Leptospirosis (LS) is considered the most common and widespread zoonotic disease in the world. Numerous outbreaks have occurred in the past 10 years. Due to its technically difficult diagnosis, LS is severely underrecognized, underdiagnosed, and therefore, underreported.^1,2 The Centers for Disease Control and Prevention (CDC) estimate 100 to 150 cases of LS are identified annually in the US, with about 50% of those cases occurring in Puerto Rico (PR).³ Specifically in PR, about 15 to 100 cases of suspected LS were reported annually between 2000 and 2009, with 59 cases and 1 death reported in 2010. The data are thought to be severely underreported due to a lack of widespread diagnostic testing availability in PR and no formal veterinary and environmental surveillance programs to monitor the incidence of animal cases and actual circulating serovars.⁴

A recent systematic review of 80 studies from 34 countries on morbidity and mortality of LS revealed that the global incidence and mortality is about 1.03 million cases and 58,900 deaths every year. Almost half of the reported deaths were adult males aged 20 to 49 years.⁵ Although mild cases of LS are not associated with an elevated mortality, icteric LS with renal failure (Weil disease) carries a mortality rate of 10%.⁶ In patients who develop hemorrhagic pneumonitis, mortality may be as high as 50 to 70%.⁷ Therefore, it is pivotal that clinicians recognize the disease early, that novel modalities of treatment continue to be developed, and that their impact on patient morbidity and mortality are studied and documented.

Case Presentation

A 43-year-old man with a medical history of schizophrenia presented to the emergency department at the US Department of Veterans Affairs (VA) Caribbean Healthcare System in San Juan, PR, after experiencing 1 week of intermittent fever, myalgia, and general weakness. Emergency medical services had found him disheveled and in a rodent-infested swamp area several days before admission. Initial vital signs were within normal limits.

On physical examination, the patient was afebrile, without acute distress, but he had diffuse jaundice and mild epigastric tenderness without evidence of peritoneal irritation. His complete blood count was remarkable for leukocytosis with left shifting, adequate hemoglobin levels but with 9 × 10³ U/L platelets. The complete metabolic panel demonstrated an aspartate aminotransferase level of 564 U/L, alanine transaminase level of 462 U/L, total bilirubin of 12 mg/dL, which 10.2 mg/dL were direct bilirubin, and an alkaline phosphate of 345 U/L. Lipase levels were measured at 626 U/L. Marked coagulopathy also was present. The toxicology panel, including acetaminophen and salicylate acid levels, did not reveal the presence of any of the tested substances, and chest imaging did not demonstrate any infiltrates.

An abdominal ultrasound was negative for acute cholestatic pathologies, such as cholelithiasis, cholecystitis, or choledocholithiasis. Nonetheless, a noncontrast abdominopelvic computed tomography was remarkable for peripancreatic fat stranding, which raised suspicion for a diagnosis of pancreatitis.

Once the patient was transferred to the intensive care unit, he developed several episodes of hematemesis, leading to hemodynamical instability and severe respiratory distress. Due to anticipated respiratory failure and need for airway securement, endotracheal intubation was performed. Multiple packed red blood cells were transfused, and the patient was started in vasopressor support.

Diagnosis

A presumptive diagnosis of LS was made due to a considerable history of rodent exposure. The patient was started on broad-spectrum parenteral antibiotics, vancomycin 750 mg every 24 hours, metronidazole 500 mg every 8 hours, and ceftriaxone 2 g IV daily for adequate coverage against Leptospira spp. Despite 72 hours of antibiotic treatment, the patient’s clinical state deteriorated. He required high dosages of norepinephrine (1.5 mcg/kg/min) and vasopressin (0.03 U/min) to maintain adequate organ perfusion. Despite lung protective settings with low tidal volume and a high positive end-expiratory pressure, there was difficulty maintaining adequate oxygenation. Chest imaging was remarkable for bilateral infiltrates concerning for acute respiratory distress syndrome (ARDS).

The coagulopathy and cholestasis continued to worsen, and the renal failure progressed from nonoliguric to anuric. Because of this progression, the patient was started on continuous renal replacement therapy (CRRT) by hemodialysis. Within 24 hours of initiating CRRT, the patient’s clinical status improved dramatically. Vasopressor support was weaned, the coagulopathy resolved, and the cholestasis was improving. The patient’s respiratory status improved in such a manner that he was extubated by the seventh day after being placed on mechanical ventilation. The urine and blood samples sent for identification of Leptospira spp. through polymerase chain reaction (PCR) returned positive by the ninth day of admission. While on CRRT, the patient’s renal function eventually returned to baseline, and he was discharged 12 days after admission.

Discussion

The spirochetes of the genus Leptospira include both saprophytic and pathogenic species. These pathogenic Leptospira spp. have adapted to a grand variety of zoonotic hosts, the most important being rodents. They serve as vectors for the contraction of the disease by humans. Initial infection in rodents by Leptospira spp. causes a systemic illness followed by a persistent colonization of renal tubules from which they are excreted in the urine and into the environment. Humans, in turn, are an incidental host unable to induce a carrier state for the transmission of the pathogenic organism.¹ The time from exposure to onset of symptoms, or incubation phase, averages 7 to 12 days but may range from 3 to 30 days.⁸

LS has been described as having 2 discernable but often coexisting phases. The first, an acute febrile bacteremic phase, has been noted to last about 9 days in about 85% of patients, although a minority have persistent fever from 2 weeks to > 30 days. A second phase, the immune or inflammatory phase, is characterized by a second fever spike preceded by 1 to 5 afebrile days in which there is presence of IgM antibodies and resolution of leptospiremia but positive urine cultures.⁹ Weil disease may present as the second phase of the disease or as a single, progressive illness from its first manifestation. It is characterized by a triad of jaundice, renal failure, and hemorrhage or coagulopathy.¹⁰ Weil disease is of great concern and importance due to its associated higher mortality than that found with the mildest form of the disease.

There are studies that advocate for RRT as an intricate part of the treatment regimen in LS to remove the inflammatory cytokines produced as a reaction to the spirochete.¹¹ In tropical countries with a higher incidence of the disease, leptospirosis is an important cause of acute kidney injury (AKI), depending on multiple factors, including the AKI definition that is used.¹² Renal invasion by Leptospira spp. produces acute tubular necrosis (ATN) and cell edema during the first week and then could progress to acute interstitial nephritis (AIN) in 2 to 3 weeks. It is believed that the mechanism for the Leptospira spp. invasion of the tubules that results in damage is associated with the antigenic components in its outer membrane; the most important outer membrane protein expressed during infection is LipL32. This protein increases the production of proinflammatory proteins, such as inducible nitric oxide synthase, monocyte chemotactic protein-1 (CCL2/MCP-1), T cells, and tumor necrosis factor.¹³

Although doxycycline has been recommended for the prophylaxis and treatment of mild LS, the preferred agent and the conferred benefits of antibiotic treatment overall for the severe form of the disease has been controversial. Traditionally, penicillin G sodium has been recommended as the first-line antibiotic treatment for moderate-to-severe LS.¹⁴ Nonetheless, there has been an increasing pattern of penicillin resistance among Leptospira spp. that has prompted the study and use of alternative agents.

An open-label, randomized comparison of parenteral cefotaxime, penicillin G sodium, and doxycycline for the treatment of suspected severe leptospirosis conducted by Suputtamongkol and colleagues showed no difference in mortality, defervescence, or time to resolution of abnormal laboratory findings.¹⁵ Current CDC recommendations include the use of parenteral penicillin 1.5 MU every 6 hours as the drug of choice, with ceftriaxone 1 g administered IV every 24 hours equally as effective.³

In addition to antimicrobial therapy, supportive care has shifted to include hemodialysis in those patients who develop AKI as part of the disease. Andrade and colleagues conducted a study of 33 patients with LS in Brazil that was set to compare the impact of door-to-dialysis time and dosage of hemodialysis on mortality. In patients with a quicker door-to-dialysis time and daily hemodialysis sessions, there was a 50% (16.7% vs 66.7%) absolute mortality reduction when compared with those with delayed initiation and alternate-day hemodialysis sessions.¹¹ A follow-up prospective study compared the use of traditional sustained low-efficiency dialysis (SLED) with the use of extended SLED via hemodiafiltration in patients with LS presenting with ARDS and AKI. Although hemodiafiltration resulted in a relative decrease in serum levels of interleukin (IL)-17, IL-7, and CCL2/MCP-1, there was no significant difference in mortality.¹⁶ The most important prognostic factor in severe LS presenting with AKI and relating to RRT is a shorter door-to-dialysis time and increased dose, not the mode of dialysis clearance. Nonetheless, both RRT methods resulted in a progressive decrease in inflammatory mediators that have been associated with ATN and AIN in the context of LS.¹⁶ The authors argue that using CRRT instead of SLED via hemodiafiltration could have accentuated the effects of the reduction that inflammatory mediators may have on mortality in patients with severe LS.

Conclusions

LS continues to be of interest due to its current status as the most common zoonotic disease and its widespread prevalence throughout the globe. Novel treatment modalities for LS, specifically for Weil disease, continue to be developed with the goal of reducing the current mortality rate associated with the disease.

In endemic areas, prompt recognition is essential to initiate the recommended therapy. Parenteral antibiotics, such as penicillin G sodium and ceftriaxone, continue to be the mainstay of treatment and constitute the current CDC recommendations. Nonetheless, early initiation of CRRT has been shown to greatly reduce the mortality associated with Weil disease and, when available, should be considered in these patients.

Our patient failed to improve while receiving parenteral antibiotics alone but showed marked improvement after being placed on CRRT. Furthermore, initiation of CRRT resulted in near-complete resolution of his organ dysfunction and eventual discharge from the hospital. This case serves to further support the use of early CRRT as part of the standard of care in severe LS.

Leptospirosis (LS) is considered the most common and widespread zoonotic disease in the world. Numerous outbreaks have occurred in the past 10 years. Due to its technically difficult diagnosis, LS is severely underrecognized, underdiagnosed, and therefore, underreported.^1,2 The Centers for Disease Control and Prevention (CDC) estimate 100 to 150 cases of LS are identified annually in the US, with about 50% of those cases occurring in Puerto Rico (PR).³ Specifically in PR, about 15 to 100 cases of suspected LS were reported annually between 2000 and 2009, with 59 cases and 1 death reported in 2010. The data are thought to be severely underreported due to a lack of widespread diagnostic testing availability in PR and no formal veterinary and environmental surveillance programs to monitor the incidence of animal cases and actual circulating serovars.⁴

A recent systematic review of 80 studies from 34 countries on morbidity and mortality of LS revealed that the global incidence and mortality is about 1.03 million cases and 58,900 deaths every year. Almost half of the reported deaths were adult males aged 20 to 49 years.⁵ Although mild cases of LS are not associated with an elevated mortality, icteric LS with renal failure (Weil disease) carries a mortality rate of 10%.⁶ In patients who develop hemorrhagic pneumonitis, mortality may be as high as 50 to 70%.⁷ Therefore, it is pivotal that clinicians recognize the disease early, that novel modalities of treatment continue to be developed, and that their impact on patient morbidity and mortality are studied and documented.

Case Presentation

A 43-year-old man with a medical history of schizophrenia presented to the emergency department at the US Department of Veterans Affairs (VA) Caribbean Healthcare System in San Juan, PR, after experiencing 1 week of intermittent fever, myalgia, and general weakness. Emergency medical services had found him disheveled and in a rodent-infested swamp area several days before admission. Initial vital signs were within normal limits.

On physical examination, the patient was afebrile, without acute distress, but he had diffuse jaundice and mild epigastric tenderness without evidence of peritoneal irritation. His complete blood count was remarkable for leukocytosis with left shifting, adequate hemoglobin levels but with 9 × 10³ U/L platelets. The complete metabolic panel demonstrated an aspartate aminotransferase level of 564 U/L, alanine transaminase level of 462 U/L, total bilirubin of 12 mg/dL, which 10.2 mg/dL were direct bilirubin, and an alkaline phosphate of 345 U/L. Lipase levels were measured at 626 U/L. Marked coagulopathy also was present. The toxicology panel, including acetaminophen and salicylate acid levels, did not reveal the presence of any of the tested substances, and chest imaging did not demonstrate any infiltrates.

An abdominal ultrasound was negative for acute cholestatic pathologies, such as cholelithiasis, cholecystitis, or choledocholithiasis. Nonetheless, a noncontrast abdominopelvic computed tomography was remarkable for peripancreatic fat stranding, which raised suspicion for a diagnosis of pancreatitis.

Once the patient was transferred to the intensive care unit, he developed several episodes of hematemesis, leading to hemodynamical instability and severe respiratory distress. Due to anticipated respiratory failure and need for airway securement, endotracheal intubation was performed. Multiple packed red blood cells were transfused, and the patient was started in vasopressor support.

Diagnosis

A presumptive diagnosis of LS was made due to a considerable history of rodent exposure. The patient was started on broad-spectrum parenteral antibiotics, vancomycin 750 mg every 24 hours, metronidazole 500 mg every 8 hours, and ceftriaxone 2 g IV daily for adequate coverage against Leptospira spp. Despite 72 hours of antibiotic treatment, the patient’s clinical state deteriorated. He required high dosages of norepinephrine (1.5 mcg/kg/min) and vasopressin (0.03 U/min) to maintain adequate organ perfusion. Despite lung protective settings with low tidal volume and a high positive end-expiratory pressure, there was difficulty maintaining adequate oxygenation. Chest imaging was remarkable for bilateral infiltrates concerning for acute respiratory distress syndrome (ARDS).

The coagulopathy and cholestasis continued to worsen, and the renal failure progressed from nonoliguric to anuric. Because of this progression, the patient was started on continuous renal replacement therapy (CRRT) by hemodialysis. Within 24 hours of initiating CRRT, the patient’s clinical status improved dramatically. Vasopressor support was weaned, the coagulopathy resolved, and the cholestasis was improving. The patient’s respiratory status improved in such a manner that he was extubated by the seventh day after being placed on mechanical ventilation. The urine and blood samples sent for identification of Leptospira spp. through polymerase chain reaction (PCR) returned positive by the ninth day of admission. While on CRRT, the patient’s renal function eventually returned to baseline, and he was discharged 12 days after admission.

Discussion

The spirochetes of the genus Leptospira include both saprophytic and pathogenic species. These pathogenic Leptospira spp. have adapted to a grand variety of zoonotic hosts, the most important being rodents. They serve as vectors for the contraction of the disease by humans. Initial infection in rodents by Leptospira spp. causes a systemic illness followed by a persistent colonization of renal tubules from which they are excreted in the urine and into the environment. Humans, in turn, are an incidental host unable to induce a carrier state for the transmission of the pathogenic organism.¹ The time from exposure to onset of symptoms, or incubation phase, averages 7 to 12 days but may range from 3 to 30 days.⁸

LS has been described as having 2 discernable but often coexisting phases. The first, an acute febrile bacteremic phase, has been noted to last about 9 days in about 85% of patients, although a minority have persistent fever from 2 weeks to > 30 days. A second phase, the immune or inflammatory phase, is characterized by a second fever spike preceded by 1 to 5 afebrile days in which there is presence of IgM antibodies and resolution of leptospiremia but positive urine cultures.⁹ Weil disease may present as the second phase of the disease or as a single, progressive illness from its first manifestation. It is characterized by a triad of jaundice, renal failure, and hemorrhage or coagulopathy.¹⁰ Weil disease is of great concern and importance due to its associated higher mortality than that found with the mildest form of the disease.

There are studies that advocate for RRT as an intricate part of the treatment regimen in LS to remove the inflammatory cytokines produced as a reaction to the spirochete.¹¹ In tropical countries with a higher incidence of the disease, leptospirosis is an important cause of acute kidney injury (AKI), depending on multiple factors, including the AKI definition that is used.¹² Renal invasion by Leptospira spp. produces acute tubular necrosis (ATN) and cell edema during the first week and then could progress to acute interstitial nephritis (AIN) in 2 to 3 weeks. It is believed that the mechanism for the Leptospira spp. invasion of the tubules that results in damage is associated with the antigenic components in its outer membrane; the most important outer membrane protein expressed during infection is LipL32. This protein increases the production of proinflammatory proteins, such as inducible nitric oxide synthase, monocyte chemotactic protein-1 (CCL2/MCP-1), T cells, and tumor necrosis factor.¹³

Although doxycycline has been recommended for the prophylaxis and treatment of mild LS, the preferred agent and the conferred benefits of antibiotic treatment overall for the severe form of the disease has been controversial. Traditionally, penicillin G sodium has been recommended as the first-line antibiotic treatment for moderate-to-severe LS.¹⁴ Nonetheless, there has been an increasing pattern of penicillin resistance among Leptospira spp. that has prompted the study and use of alternative agents.

An open-label, randomized comparison of parenteral cefotaxime, penicillin G sodium, and doxycycline for the treatment of suspected severe leptospirosis conducted by Suputtamongkol and colleagues showed no difference in mortality, defervescence, or time to resolution of abnormal laboratory findings.¹⁵ Current CDC recommendations include the use of parenteral penicillin 1.5 MU every 6 hours as the drug of choice, with ceftriaxone 1 g administered IV every 24 hours equally as effective.³

In addition to antimicrobial therapy, supportive care has shifted to include hemodialysis in those patients who develop AKI as part of the disease. Andrade and colleagues conducted a study of 33 patients with LS in Brazil that was set to compare the impact of door-to-dialysis time and dosage of hemodialysis on mortality. In patients with a quicker door-to-dialysis time and daily hemodialysis sessions, there was a 50% (16.7% vs 66.7%) absolute mortality reduction when compared with those with delayed initiation and alternate-day hemodialysis sessions.¹¹ A follow-up prospective study compared the use of traditional sustained low-efficiency dialysis (SLED) with the use of extended SLED via hemodiafiltration in patients with LS presenting with ARDS and AKI. Although hemodiafiltration resulted in a relative decrease in serum levels of interleukin (IL)-17, IL-7, and CCL2/MCP-1, there was no significant difference in mortality.¹⁶ The most important prognostic factor in severe LS presenting with AKI and relating to RRT is a shorter door-to-dialysis time and increased dose, not the mode of dialysis clearance. Nonetheless, both RRT methods resulted in a progressive decrease in inflammatory mediators that have been associated with ATN and AIN in the context of LS.¹⁶ The authors argue that using CRRT instead of SLED via hemodiafiltration could have accentuated the effects of the reduction that inflammatory mediators may have on mortality in patients with severe LS.

Conclusions

LS continues to be of interest due to its current status as the most common zoonotic disease and its widespread prevalence throughout the globe. Novel treatment modalities for LS, specifically for Weil disease, continue to be developed with the goal of reducing the current mortality rate associated with the disease.

In endemic areas, prompt recognition is essential to initiate the recommended therapy. Parenteral antibiotics, such as penicillin G sodium and ceftriaxone, continue to be the mainstay of treatment and constitute the current CDC recommendations. Nonetheless, early initiation of CRRT has been shown to greatly reduce the mortality associated with Weil disease and, when available, should be considered in these patients.

Our patient failed to improve while receiving parenteral antibiotics alone but showed marked improvement after being placed on CRRT. Furthermore, initiation of CRRT resulted in near-complete resolution of his organ dysfunction and eventual discharge from the hospital. This case serves to further support the use of early CRRT as part of the standard of care in severe LS.

Leptospirosis (LS) is considered the most common and widespread zoonotic disease in the world. Numerous outbreaks have occurred in the past 10 years. Due to its technically difficult diagnosis, LS is severely underrecognized, underdiagnosed, and therefore, underreported.^1,2 The Centers for Disease Control and Prevention (CDC) estimate 100 to 150 cases of LS are identified annually in the US, with about 50% of those cases occurring in Puerto Rico (PR).³ Specifically in PR, about 15 to 100 cases of suspected LS were reported annually between 2000 and 2009, with 59 cases and 1 death reported in 2010. The data are thought to be severely underreported due to a lack of widespread diagnostic testing availability in PR and no formal veterinary and environmental surveillance programs to monitor the incidence of animal cases and actual circulating serovars.⁴

A recent systematic review of 80 studies from 34 countries on morbidity and mortality of LS revealed that the global incidence and mortality is about 1.03 million cases and 58,900 deaths every year. Almost half of the reported deaths were adult males aged 20 to 49 years.⁵ Although mild cases of LS are not associated with an elevated mortality, icteric LS with renal failure (Weil disease) carries a mortality rate of 10%.⁶ In patients who develop hemorrhagic pneumonitis, mortality may be as high as 50 to 70%.⁷ Therefore, it is pivotal that clinicians recognize the disease early, that novel modalities of treatment continue to be developed, and that their impact on patient morbidity and mortality are studied and documented.

Case Presentation

A 43-year-old man with a medical history of schizophrenia presented to the emergency department at the US Department of Veterans Affairs (VA) Caribbean Healthcare System in San Juan, PR, after experiencing 1 week of intermittent fever, myalgia, and general weakness. Emergency medical services had found him disheveled and in a rodent-infested swamp area several days before admission. Initial vital signs were within normal limits.

On physical examination, the patient was afebrile, without acute distress, but he had diffuse jaundice and mild epigastric tenderness without evidence of peritoneal irritation. His complete blood count was remarkable for leukocytosis with left shifting, adequate hemoglobin levels but with 9 × 10³ U/L platelets. The complete metabolic panel demonstrated an aspartate aminotransferase level of 564 U/L, alanine transaminase level of 462 U/L, total bilirubin of 12 mg/dL, which 10.2 mg/dL were direct bilirubin, and an alkaline phosphate of 345 U/L. Lipase levels were measured at 626 U/L. Marked coagulopathy also was present. The toxicology panel, including acetaminophen and salicylate acid levels, did not reveal the presence of any of the tested substances, and chest imaging did not demonstrate any infiltrates.

An abdominal ultrasound was negative for acute cholestatic pathologies, such as cholelithiasis, cholecystitis, or choledocholithiasis. Nonetheless, a noncontrast abdominopelvic computed tomography was remarkable for peripancreatic fat stranding, which raised suspicion for a diagnosis of pancreatitis.

Once the patient was transferred to the intensive care unit, he developed several episodes of hematemesis, leading to hemodynamical instability and severe respiratory distress. Due to anticipated respiratory failure and need for airway securement, endotracheal intubation was performed. Multiple packed red blood cells were transfused, and the patient was started in vasopressor support.

Diagnosis

A presumptive diagnosis of LS was made due to a considerable history of rodent exposure. The patient was started on broad-spectrum parenteral antibiotics, vancomycin 750 mg every 24 hours, metronidazole 500 mg every 8 hours, and ceftriaxone 2 g IV daily for adequate coverage against Leptospira spp. Despite 72 hours of antibiotic treatment, the patient’s clinical state deteriorated. He required high dosages of norepinephrine (1.5 mcg/kg/min) and vasopressin (0.03 U/min) to maintain adequate organ perfusion. Despite lung protective settings with low tidal volume and a high positive end-expiratory pressure, there was difficulty maintaining adequate oxygenation. Chest imaging was remarkable for bilateral infiltrates concerning for acute respiratory distress syndrome (ARDS).

The coagulopathy and cholestasis continued to worsen, and the renal failure progressed from nonoliguric to anuric. Because of this progression, the patient was started on continuous renal replacement therapy (CRRT) by hemodialysis. Within 24 hours of initiating CRRT, the patient’s clinical status improved dramatically. Vasopressor support was weaned, the coagulopathy resolved, and the cholestasis was improving. The patient’s respiratory status improved in such a manner that he was extubated by the seventh day after being placed on mechanical ventilation. The urine and blood samples sent for identification of Leptospira spp. through polymerase chain reaction (PCR) returned positive by the ninth day of admission. While on CRRT, the patient’s renal function eventually returned to baseline, and he was discharged 12 days after admission.

Discussion

The spirochetes of the genus Leptospira include both saprophytic and pathogenic species. These pathogenic Leptospira spp. have adapted to a grand variety of zoonotic hosts, the most important being rodents. They serve as vectors for the contraction of the disease by humans. Initial infection in rodents by Leptospira spp. causes a systemic illness followed by a persistent colonization of renal tubules from which they are excreted in the urine and into the environment. Humans, in turn, are an incidental host unable to induce a carrier state for the transmission of the pathogenic organism.¹ The time from exposure to onset of symptoms, or incubation phase, averages 7 to 12 days but may range from 3 to 30 days.⁸

LS has been described as having 2 discernable but often coexisting phases. The first, an acute febrile bacteremic phase, has been noted to last about 9 days in about 85% of patients, although a minority have persistent fever from 2 weeks to > 30 days. A second phase, the immune or inflammatory phase, is characterized by a second fever spike preceded by 1 to 5 afebrile days in which there is presence of IgM antibodies and resolution of leptospiremia but positive urine cultures.⁹ Weil disease may present as the second phase of the disease or as a single, progressive illness from its first manifestation. It is characterized by a triad of jaundice, renal failure, and hemorrhage or coagulopathy.¹⁰ Weil disease is of great concern and importance due to its associated higher mortality than that found with the mildest form of the disease.

There are studies that advocate for RRT as an intricate part of the treatment regimen in LS to remove the inflammatory cytokines produced as a reaction to the spirochete.¹¹ In tropical countries with a higher incidence of the disease, leptospirosis is an important cause of acute kidney injury (AKI), depending on multiple factors, including the AKI definition that is used.¹² Renal invasion by Leptospira spp. produces acute tubular necrosis (ATN) and cell edema during the first week and then could progress to acute interstitial nephritis (AIN) in 2 to 3 weeks. It is believed that the mechanism for the Leptospira spp. invasion of the tubules that results in damage is associated with the antigenic components in its outer membrane; the most important outer membrane protein expressed during infection is LipL32. This protein increases the production of proinflammatory proteins, such as inducible nitric oxide synthase, monocyte chemotactic protein-1 (CCL2/MCP-1), T cells, and tumor necrosis factor.¹³

Although doxycycline has been recommended for the prophylaxis and treatment of mild LS, the preferred agent and the conferred benefits of antibiotic treatment overall for the severe form of the disease has been controversial. Traditionally, penicillin G sodium has been recommended as the first-line antibiotic treatment for moderate-to-severe LS.¹⁴ Nonetheless, there has been an increasing pattern of penicillin resistance among Leptospira spp. that has prompted the study and use of alternative agents.

An open-label, randomized comparison of parenteral cefotaxime, penicillin G sodium, and doxycycline for the treatment of suspected severe leptospirosis conducted by Suputtamongkol and colleagues showed no difference in mortality, defervescence, or time to resolution of abnormal laboratory findings.¹⁵ Current CDC recommendations include the use of parenteral penicillin 1.5 MU every 6 hours as the drug of choice, with ceftriaxone 1 g administered IV every 24 hours equally as effective.³

In addition to antimicrobial therapy, supportive care has shifted to include hemodialysis in those patients who develop AKI as part of the disease. Andrade and colleagues conducted a study of 33 patients with LS in Brazil that was set to compare the impact of door-to-dialysis time and dosage of hemodialysis on mortality. In patients with a quicker door-to-dialysis time and daily hemodialysis sessions, there was a 50% (16.7% vs 66.7%) absolute mortality reduction when compared with those with delayed initiation and alternate-day hemodialysis sessions.¹¹ A follow-up prospective study compared the use of traditional sustained low-efficiency dialysis (SLED) with the use of extended SLED via hemodiafiltration in patients with LS presenting with ARDS and AKI. Although hemodiafiltration resulted in a relative decrease in serum levels of interleukin (IL)-17, IL-7, and CCL2/MCP-1, there was no significant difference in mortality.¹⁶ The most important prognostic factor in severe LS presenting with AKI and relating to RRT is a shorter door-to-dialysis time and increased dose, not the mode of dialysis clearance. Nonetheless, both RRT methods resulted in a progressive decrease in inflammatory mediators that have been associated with ATN and AIN in the context of LS.¹⁶ The authors argue that using CRRT instead of SLED via hemodiafiltration could have accentuated the effects of the reduction that inflammatory mediators may have on mortality in patients with severe LS.

Conclusions

LS continues to be of interest due to its current status as the most common zoonotic disease and its widespread prevalence throughout the globe. Novel treatment modalities for LS, specifically for Weil disease, continue to be developed with the goal of reducing the current mortality rate associated with the disease.

In endemic areas, prompt recognition is essential to initiate the recommended therapy. Parenteral antibiotics, such as penicillin G sodium and ceftriaxone, continue to be the mainstay of treatment and constitute the current CDC recommendations. Nonetheless, early initiation of CRRT has been shown to greatly reduce the mortality associated with Weil disease and, when available, should be considered in these patients.

Our patient failed to improve while receiving parenteral antibiotics alone but showed marked improvement after being placed on CRRT. Furthermore, initiation of CRRT resulted in near-complete resolution of his organ dysfunction and eventual discharge from the hospital. This case serves to further support the use of early CRRT as part of the standard of care in severe LS.

OBG Management takes the issues of systemic and structural racism incredibly seriously--not just by talking about it but by trying to highlight areas in medicine, particularly in obstetrics and gynecology, that are barriers to progress. In this new series for OBG Management, Board Member Barbara Levy, MD, faces the issues head-on, beginning with this peer-to-peer interview with Pierre Johnson, MD, ObGyn in Chicago, Illinois. Watch for future installments in upcoming issues of OBG Management.

Finding inspiration among life’s challenges

Barbara Levy, MD: I am fortunate to have met Pierre serendipitously at a training that we were both attending and was impressed by Dr. Johnson’s life story, his passion and commitment, and his dedication—not only to his personal career but also to raising up other young men of color by trying to break down barriers that face them. His life story highlights those areas of systemic and structural problems that all of us together need to address if we are going to make any progress.

Pierre Johnson, MD: Thank you, Barbara. A little about myself: I am a board-certified ObGyn, and I specialize in minimally invasive surgery. I was born on the South side of Chicago, experiencing gang violence, drugs, and substandard, underserved schools. Long story short, I had a very rough upbringing. I had a single mom and several different issues at home. I am the oldest of 5 siblings, and life was tough.

But I knew that I wanted to do something different with my life. I saw that there was a need in my community as far as health care was concerned, in particular women’s health and childbirth. I knew early on that I wanted to be an ObGyn, and the reason had a lot to do with The Cosby Show. It was the only example of a positive, successful Black man that I saw. No one graduated from college in my family. There weren’t any models of young Black excellence around me. Saying that I wanted to be a doctor planted a seed. I was 9 when my mom became pregnant with my first sibling, and it was fascinating to me. The physiology of pregnancy, and eventually childbirth, was extremely fascinating to me; it set me off on my journey to be an ObGyn.

As I got older, things didn’t get any easier. I went to high school in one of the toughest areas on the South side of Chicago. Gang violence, and violence in and of itself, were all around me, but I was able to stay focused. I went on to Xavier University in Louisiana.

Dr. Levy: There are some important things that I learned from your book and from talking to you at our first meeting. Your mom’s ObGyn, when she was pregnant with your next youngest sibling, was also a Black ObGyn. He took some time to take you under wing?

Dr. Johnson: He did. My mom’s ObGyn was a Black man. Other than The Cosby Show, that’s the only time I saw something like that. When I spoke to him, he really took the time to answer my questions and show me that he was like me; he wasn’t just a far-off mythical person, or something that I could not obtain.

Continue to: Seeing is believing when it comes to success...

Seeing is believing when it comes to success

Dr. Levy: Do you think it was important to have a role model who wasn’t a sports star?

Dr. Johnson: If you can’t see it, you can’t achieve it. He took his time to really talk to me, and it’s the little things for kids that go a long way in their life experience. I still have a relationship with him to this day. How he handled me as a kid made me realize that this is something that I could do. That was extremely important for me.

Dr. Levy: One of the structural things I think we need to point out is that the ability to see yourself as someone successful is critical. When we see 1,000 images a day and they are all White, and they are all so different from where we are that it gets incorporated into our sense of being. I think that’s really difficult for those of us of with privilege to understand what that privilege is.

Dr. Johnson: Absolutely, and I’ll even go further. In residency, 2 White females were my classmates, and both of their parents were doctors. They had grandparents who were doctors. My mom was addicted to drugs; my father was not around. They had been talking medicine since they were 5. You have to make things equitable, but in medicine it’s really not equitable. In medicine, what we don’t realize is that there is an importance for all aspects of someone’s upbringing and environment, and it’s not just what they can regurgitate on a standardized test. If a patient can’t relate to you and tell you what is wrong with them, how can you adequately treat them?

Dr. Levy: Even if they are trying to tell me, but I can’t hear it because I don’t have the language and I don’t have the background. There are really good data to show, in fact, that Black male physicians do a better job at engaging Black men to manage their hypertension.¹ When we look at the inequities in birth outcomes for women of color, indigenous women and Black women, there’s evidence that providers who come from a similar background do a better job.

Dr. Johnson: There was the study of Black infants that just came out about them dying at a 3-time higher rate in non-Black physicians’ hands.² These things need to be recognized. They need to be discussed, and they need to be identified as issues and then, realistically, we need to start talking about solutions, not get offended by what actual statistics are saying.

Foundational inequities in education

Dr. Levy: To address some of the barriers that you faced: I know that you went to a high school that was not geared toward pushing students into professional careers. Your colleagues, however, had educations that prepared them for the standardized tests and other things that they would face academically.

Dr. Johnson: People think I am kidding when I say it, but when I went into college, I didn’t know what a periodic table was. I saw it, but I had no idea what these things meant. I didn’t have any sciences or any AP classes in high school. I did well, but grades are smoke and mirrors. The true test of medicine comes with testing. From the MCATs to the boards, every step of the way there is a standardized test.

Knowledge is something that you can obtain, but test taking is a cultivated skill that happens from a very early age. Trying to teach an adult or someone in their late teens a skill that they should have learned as a kid is difficult. For me, I did not have that, so I had to program myself. I had to learn how to fundamentally take tests as an adult, where most people understand how to do that going into college and professional school.

Dr. Levy: I was impressed with your resilience. I think all of us as human beings, if we fail a test, we take it personally and think it’s about our lack of knowledge. One of the insights that you came to was that failure on those things was not that you didn’t study hard enough. In fact, you probably studied 4 times harder than most other people. You had the knowledge. Being able to get that knowledge into a standardized structured test score was the huge challenge for you.

Dr. Johnson: That’s it. I can remember taking the MCAT, and if you looked at the step 1 book, I could regurgitate to you everything on that page. However, it’s not a test about do you know it or not. It’s an understanding of the English language and how to break things down to make things fit into particular scenarios.

Continue to: A college experience focused on growth and exposure...

Dr. Levy: I was impressed by the distinction between your experience at Xavier University where there was a lot of support and guidance and help in your premed program, and what happened to you when you hit medical school.

Dr. Johnson: Xavier University in Louisiana is the number 1 institution in the country for getting minorities into professional school. They understand that they have kids that are brilliant but underprepared, and just have not had the background to actually tackle some of these tough curriculums. I always had good grades in school. But by not being challenged, I didn’t know what I didn’t really know. So now that I was seeing biology, chemistry for the first time, and trying to tackle it; there’s a failure point. I didn’t know how to take tests, and I didn’t know how to study properly. The harder I tried, the worse things got for me.

Xavier has seen that story a multitude of times. If I went to a bigger or predominantly White university, a counselor would have told me, “Well, medicine’s maybe not for you. You can’t handle a premed curriculum.” Instead, I said, “Listen, I’m studying. I’m doing all of these things, and I’m not hacking it.” And they broke it down: “Let’s get you into study groups with kids that have had these type of AP classes before. We’ll have you watch how they study,” and everything started to click. That facilitation of how to adjust to this curriculum was a godsend. It’s the only reason I’m here. I am a prime example of being brilliant enough to be able to do it, but needing the infrastructure and a system set up.

Dr. Levy: There’s a great book by Carol Dweck called Mindset that talks about education of young kids and putting them into silos so early in life; the brilliant kids go into the AP courses and the rest are labeled as inadequate. It’s assumed in a fixed mindset based on their heredity and IQ, and not based on the fact that they have not been exposed to the right things.

Xavier was growing you into the man who could, in fact, do all of those things. I think that is one of the systemic and structural issues that we have—that fixed mindset that frames a kid who is not succeeding as therefore unable to succeed, as opposed to framing that child as not having the correct tools.

New tribulations of medical school

Dr. Johnson: Absolutely. I think what Xavier did for me is to at least let me understand what I needed to do, how to comprehend and retain information, which I never had been exposed to before. Those years were very important to establishing a foundation. When going to medical school, it was like, “There’s no more excuses. What could be the problem now?” Well, now let’s talk about taking tests—a whole different skill. Xavier focused on getting me to understand how to structure my thought process and knowledge base. In medical school I had to apply those skills (because if you can’t apply them, there’s no fit).

My second through fourth year of medical school, I was the only African-American kid in my class. I was spending 20-hour days sometimes just studying, trying to overcompensate by knowing as much as I possibly could and thinking that would propel me from the test-taking standpoint. Even though I didn’t have a lot of classmates in medical school that looked like me, I did have mentors that looked similarly, who really saw potential in me. Dr. Frederick Horvath, a nephrologist in Peoria said, “What are you doing? I want you to get out of these books, and let’s go out to lunch.”

He ended up buying me some instrumental books, really talked to me, listening to my background and understanding how driven I was as a person. He took me under his wing for the rest of medical school and said, “This is how you navigate through these spaces. Yes, you need to have a fund of knowledge to be able to take these tests, but you need to start understanding how to apply it to these questions.” I’m forever grateful to Dr. Horvath for doing that because it was a point in time where I was lost and struggling.

Continue to: Hitting a stride but facing racism head-on...

Dr. Levy: You talk about the systemic and pervasive racism that was on the wards when you hit them in fourth year. If you don’t mind sharing just a little bit of that, it would help people reading this to have a better understanding of the kinds of barriers that are out there.

Dr. Johnson: Even when I talk about it today, it bothers me.

I went to medical school in Peoria, Illinois, not far from the home of the Ku Klux Klan. At that time, once you got out of Chicago it was a very brutal place, with systemic racism throughout. I was a young Black kid going through a process that not many young Black kids from the South side of Chicago go through, and you had people who had never seen anyone like me. When I was going through my clinical rotations, I knew what I was up against. I was dressed “to the T” every day, arriving early, leaving late, trying to answer questions. I would look at the evaluations, and they would be disparaging. I would look at my counterparts, how their evaluations were, and how people would respond to them, and it would be completely different.

Surgery was the part of ObGyn that I really grew to love more than anything, even more than obstetrics. When general surgery came, I wanted to take it very seriously and learn as much as I possibly could. From the beginning, I knew there was a problem because the chief resident, an older White man, wouldn’t look me in the eye or talk to me. He would make disparaging remarks. The thing that stuck out in my mind the most was when I was in the operating room transporting patients, just like a medical student did, and he came up behind me and said, “You know, Pierre, this is where a small mind and a strong back come into play.” For me, it took me to a place where I had to corral my emotions and thoughts because I just wanted to lash out and just tell him how racist and horrible that was for him to say that to me. I explained this to the powers that be, the director of the department, and they basically blew it off to the side.

When it came down to the end of the evaluation period, I passed with flying colors. But they gave me an incomplete because of that chief resident and his remarks on my evaluations. He had 3 pages of report about me as a person and as a student. He said that he had difficulty in expressing his opinions about me because of possible cultural biases that he may have had. He put “cultural biases” in an evaluation, and they looked at that and said that was enough for me to have to remediate my time. I was required to do an extra month in Pontiac, Illinois, which is even more rural than Peoria, because of a racist person that did not give me a fair opportunity because I was Black.

Like everything else in life, it was a learning experience. It’s why I fight so hard today. It’s why I’m so passionate about equity, not only in medicine but also in all aspects of society. It shows why we have police brutality and Black men dying in the streets. It shows how this happens because there are cultural and implicit biases that play out in every part of life, and we are not honest about it. Until we are honest about it and until we say that this is happening and there is something that needs to be done to address it, it’s going to continue to happen. That is my fight.

Exposing the unspoken power struggle

Dr. Levy: I couldn’t agree more. Attributing things like that to the individual, where you talk about a White man in power and a power structure that didn’t literally physically beat you but did beat you into submission. You talk about how to succeed in medical school, and how you had to suck it up and submit to something that was incredibly unfair. You understood, you were old enough, mature enough, to understand that if you fought back, you were going to lose. The only opportunity you had was to submit to that inequity and push forward.

Dr. Johnson: When I did try to fight, the chair of the department told me that either I accept the consequences or I would not graduate from medical school and be forced to do another year. That struck a chord with me. I think that happens a lot in our society, and it needs to be exposed.

Past experiences reflected in today’s society

Dr. Levy: Can you talk about what you faced in your ObGyn residency in terms of the systemic pushback, people not taking your orders, people questioning you. I know that I have heard that a great deal, and I experienced that myself as a woman.

Dr. Johnson: We look at the things that are happening now, everything from George Floyd’s murder to Colin Kaepernick taking a knee. These things are 10 years past when I first started residency. The year before I started residency, there was a noose hanging on the capitol lawn of Springfield, Illinois’ capital city. There’s systemic racism and hatred there. When I first started on the wards of my first year of ObGyn, again, I was the very first Black resident of my program’s history. Nobody could relate to me.

I went from a year-long general surgery internship at Washington Hospital Center in Washington, DC, to ObGyn residency. In the first 2 months, there were complaints of, “He’s not answering his pages. He’s not being prompt.” I went to my program director and said, “Listen, I have never had one complaint like this. There’s a problem here. And there’s a problem when I’m on the floor: When trying to give orders to nurses, they’re not taking them. I had to tell a couple of nurses, ‘I’m Dr. Johnson. Don’t call me by my first name, especially not in front of patients.’”

My director was just not hearing me, because the entire scenario was something they had never been exposed to. Systemic racism is real, and unless you experience it, it’s very difficult to accept that it is happening. But biases happen when you are not cognizant. People are used to things a certain way. Things play out in the media that make your mind think a certain way, and you don’t even realize it. You may not even want to be that way.

Continue to: Unconscious bias is a barrier to ensuring equity...

Dr. Levy: One very important point you just made is that we as the system need to be able to recognize those unconscious things, the language that we use, the disparaging remarks, the things that put people down, as well as the things that keep people out of promotion.

There are some interesting data about both race and gender and the language that we use when we write recommendations for people, that we do things unconsciously. The big message to all of us at the end is to open our minds to where those things can occur. For myself, professionally, I keep a list of words that I use when I write recommendations. I measure myself to ensure that I am using the same language for men and women, for Black and White. I think we need to overcome the system and the structure to create real equity—not equality but equity.

It begins with being real about the issues

Dr. Johnson: It’s a bigger problem than the existence of bias and racism. I think these are systemic issues that have been cultivated over centuries that have never been addressed. The true issue is that we deny that these are problems and refuse to talk about it because it makes us uncomfortable. To truly make things more equitable, we have to push our levels of comfort to be able to talk about things in a healthy manner, be open and transparent, and to start to understand how we are thinking about certain things. When you can see it, you can start to implement changes and start to change mentalities and thought processes.

For me, people say, “You don’t look like a doctor.” I get that all the time—because I have tattoos and earrings. I wear my hair in a mohawk. The image of what success looks like has been manifested through our media and culture, and it has imprinted on our minds as to how things are supposed to be. If someone doesn’t fit those molds, we start to shun them out, or we start to exhibit biases against those things. What I am trying to do is change that thought process of what a successful or a professional person looks like. It doesn’t have a look. It is not a White or Black thing. It’s an intellect, a mindset, a way of living. You have to treat every person as an individual and take all the biases out of it and understand where they are coming from and what they have to offer to the profession.

Dr. Levy: I personally was so impressed by you when I met you. I was impressed by the tattoos and the earrings, and my initial response to them was exactly that biased, “Oh, who is this person?” I checked that at the door, listened to you, and was really impressed at your surgical skill, your knowledge, your background. I am really grateful that you have been willing to spend the time to share that with everyone.

Dr. Johnson: Thank you for this discussion.

To watch the full interview between Drs. Levy and Johnson, visit: https://www.mdedge.com/obgyn/article/228507/facing-systemic-racism-health-care-inequities-medical-education. ●

OBG Management takes the issues of systemic and structural racism incredibly seriously--not just by talking about it but by trying to highlight areas in medicine, particularly in obstetrics and gynecology, that are barriers to progress. In this new series for OBG Management, Board Member Barbara Levy, MD, faces the issues head-on, beginning with this peer-to-peer interview with Pierre Johnson, MD, ObGyn in Chicago, Illinois. Watch for future installments in upcoming issues of OBG Management.

Finding inspiration among life’s challenges

Barbara Levy, MD: I am fortunate to have met Pierre serendipitously at a training that we were both attending and was impressed by Dr. Johnson’s life story, his passion and commitment, and his dedication—not only to his personal career but also to raising up other young men of color by trying to break down barriers that face them. His life story highlights those areas of systemic and structural problems that all of us together need to address if we are going to make any progress.

Pierre Johnson, MD: Thank you, Barbara. A little about myself: I am a board-certified ObGyn, and I specialize in minimally invasive surgery. I was born on the South side of Chicago, experiencing gang violence, drugs, and substandard, underserved schools. Long story short, I had a very rough upbringing. I had a single mom and several different issues at home. I am the oldest of 5 siblings, and life was tough.

But I knew that I wanted to do something different with my life. I saw that there was a need in my community as far as health care was concerned, in particular women’s health and childbirth. I knew early on that I wanted to be an ObGyn, and the reason had a lot to do with The Cosby Show. It was the only example of a positive, successful Black man that I saw. No one graduated from college in my family. There weren’t any models of young Black excellence around me. Saying that I wanted to be a doctor planted a seed. I was 9 when my mom became pregnant with my first sibling, and it was fascinating to me. The physiology of pregnancy, and eventually childbirth, was extremely fascinating to me; it set me off on my journey to be an ObGyn.

As I got older, things didn’t get any easier. I went to high school in one of the toughest areas on the South side of Chicago. Gang violence, and violence in and of itself, were all around me, but I was able to stay focused. I went on to Xavier University in Louisiana.

Dr. Levy: There are some important things that I learned from your book and from talking to you at our first meeting. Your mom’s ObGyn, when she was pregnant with your next youngest sibling, was also a Black ObGyn. He took some time to take you under wing?

Dr. Johnson: He did. My mom’s ObGyn was a Black man. Other than The Cosby Show, that’s the only time I saw something like that. When I spoke to him, he really took the time to answer my questions and show me that he was like me; he wasn’t just a far-off mythical person, or something that I could not obtain.

Continue to: Seeing is believing when it comes to success...

Seeing is believing when it comes to success

Dr. Levy: Do you think it was important to have a role model who wasn’t a sports star?

Dr. Johnson: If you can’t see it, you can’t achieve it. He took his time to really talk to me, and it’s the little things for kids that go a long way in their life experience. I still have a relationship with him to this day. How he handled me as a kid made me realize that this is something that I could do. That was extremely important for me.

Dr. Levy: One of the structural things I think we need to point out is that the ability to see yourself as someone successful is critical. When we see 1,000 images a day and they are all White, and they are all so different from where we are that it gets incorporated into our sense of being. I think that’s really difficult for those of us of with privilege to understand what that privilege is.

Dr. Johnson: Absolutely, and I’ll even go further. In residency, 2 White females were my classmates, and both of their parents were doctors. They had grandparents who were doctors. My mom was addicted to drugs; my father was not around. They had been talking medicine since they were 5. You have to make things equitable, but in medicine it’s really not equitable. In medicine, what we don’t realize is that there is an importance for all aspects of someone’s upbringing and environment, and it’s not just what they can regurgitate on a standardized test. If a patient can’t relate to you and tell you what is wrong with them, how can you adequately treat them?

Dr. Levy: Even if they are trying to tell me, but I can’t hear it because I don’t have the language and I don’t have the background. There are really good data to show, in fact, that Black male physicians do a better job at engaging Black men to manage their hypertension.¹ When we look at the inequities in birth outcomes for women of color, indigenous women and Black women, there’s evidence that providers who come from a similar background do a better job.

Dr. Johnson: There was the study of Black infants that just came out about them dying at a 3-time higher rate in non-Black physicians’ hands.² These things need to be recognized. They need to be discussed, and they need to be identified as issues and then, realistically, we need to start talking about solutions, not get offended by what actual statistics are saying.

Foundational inequities in education

Dr. Levy: To address some of the barriers that you faced: I know that you went to a high school that was not geared toward pushing students into professional careers. Your colleagues, however, had educations that prepared them for the standardized tests and other things that they would face academically.

Dr. Johnson: People think I am kidding when I say it, but when I went into college, I didn’t know what a periodic table was. I saw it, but I had no idea what these things meant. I didn’t have any sciences or any AP classes in high school. I did well, but grades are smoke and mirrors. The true test of medicine comes with testing. From the MCATs to the boards, every step of the way there is a standardized test.

Knowledge is something that you can obtain, but test taking is a cultivated skill that happens from a very early age. Trying to teach an adult or someone in their late teens a skill that they should have learned as a kid is difficult. For me, I did not have that, so I had to program myself. I had to learn how to fundamentally take tests as an adult, where most people understand how to do that going into college and professional school.

Dr. Levy: I was impressed with your resilience. I think all of us as human beings, if we fail a test, we take it personally and think it’s about our lack of knowledge. One of the insights that you came to was that failure on those things was not that you didn’t study hard enough. In fact, you probably studied 4 times harder than most other people. You had the knowledge. Being able to get that knowledge into a standardized structured test score was the huge challenge for you.

Dr. Johnson: That’s it. I can remember taking the MCAT, and if you looked at the step 1 book, I could regurgitate to you everything on that page. However, it’s not a test about do you know it or not. It’s an understanding of the English language and how to break things down to make things fit into particular scenarios.

Continue to: A college experience focused on growth and exposure...

Dr. Levy: I was impressed by the distinction between your experience at Xavier University where there was a lot of support and guidance and help in your premed program, and what happened to you when you hit medical school.

Dr. Johnson: Xavier University in Louisiana is the number 1 institution in the country for getting minorities into professional school. They understand that they have kids that are brilliant but underprepared, and just have not had the background to actually tackle some of these tough curriculums. I always had good grades in school. But by not being challenged, I didn’t know what I didn’t really know. So now that I was seeing biology, chemistry for the first time, and trying to tackle it; there’s a failure point. I didn’t know how to take tests, and I didn’t know how to study properly. The harder I tried, the worse things got for me.

Xavier has seen that story a multitude of times. If I went to a bigger or predominantly White university, a counselor would have told me, “Well, medicine’s maybe not for you. You can’t handle a premed curriculum.” Instead, I said, “Listen, I’m studying. I’m doing all of these things, and I’m not hacking it.” And they broke it down: “Let’s get you into study groups with kids that have had these type of AP classes before. We’ll have you watch how they study,” and everything started to click. That facilitation of how to adjust to this curriculum was a godsend. It’s the only reason I’m here. I am a prime example of being brilliant enough to be able to do it, but needing the infrastructure and a system set up.

Dr. Levy: There’s a great book by Carol Dweck called Mindset that talks about education of young kids and putting them into silos so early in life; the brilliant kids go into the AP courses and the rest are labeled as inadequate. It’s assumed in a fixed mindset based on their heredity and IQ, and not based on the fact that they have not been exposed to the right things.

Xavier was growing you into the man who could, in fact, do all of those things. I think that is one of the systemic and structural issues that we have—that fixed mindset that frames a kid who is not succeeding as therefore unable to succeed, as opposed to framing that child as not having the correct tools.

New tribulations of medical school

Dr. Johnson: Absolutely. I think what Xavier did for me is to at least let me understand what I needed to do, how to comprehend and retain information, which I never had been exposed to before. Those years were very important to establishing a foundation. When going to medical school, it was like, “There’s no more excuses. What could be the problem now?” Well, now let’s talk about taking tests—a whole different skill. Xavier focused on getting me to understand how to structure my thought process and knowledge base. In medical school I had to apply those skills (because if you can’t apply them, there’s no fit).

My second through fourth year of medical school, I was the only African-American kid in my class. I was spending 20-hour days sometimes just studying, trying to overcompensate by knowing as much as I possibly could and thinking that would propel me from the test-taking standpoint. Even though I didn’t have a lot of classmates in medical school that looked like me, I did have mentors that looked similarly, who really saw potential in me. Dr. Frederick Horvath, a nephrologist in Peoria said, “What are you doing? I want you to get out of these books, and let’s go out to lunch.”

He ended up buying me some instrumental books, really talked to me, listening to my background and understanding how driven I was as a person. He took me under his wing for the rest of medical school and said, “This is how you navigate through these spaces. Yes, you need to have a fund of knowledge to be able to take these tests, but you need to start understanding how to apply it to these questions.” I’m forever grateful to Dr. Horvath for doing that because it was a point in time where I was lost and struggling.

Continue to: Hitting a stride but facing racism head-on...

Dr. Levy: You talk about the systemic and pervasive racism that was on the wards when you hit them in fourth year. If you don’t mind sharing just a little bit of that, it would help people reading this to have a better understanding of the kinds of barriers that are out there.

Dr. Johnson: Even when I talk about it today, it bothers me.

I went to medical school in Peoria, Illinois, not far from the home of the Ku Klux Klan. At that time, once you got out of Chicago it was a very brutal place, with systemic racism throughout. I was a young Black kid going through a process that not many young Black kids from the South side of Chicago go through, and you had people who had never seen anyone like me. When I was going through my clinical rotations, I knew what I was up against. I was dressed “to the T” every day, arriving early, leaving late, trying to answer questions. I would look at the evaluations, and they would be disparaging. I would look at my counterparts, how their evaluations were, and how people would respond to them, and it would be completely different.

Surgery was the part of ObGyn that I really grew to love more than anything, even more than obstetrics. When general surgery came, I wanted to take it very seriously and learn as much as I possibly could. From the beginning, I knew there was a problem because the chief resident, an older White man, wouldn’t look me in the eye or talk to me. He would make disparaging remarks. The thing that stuck out in my mind the most was when I was in the operating room transporting patients, just like a medical student did, and he came up behind me and said, “You know, Pierre, this is where a small mind and a strong back come into play.” For me, it took me to a place where I had to corral my emotions and thoughts because I just wanted to lash out and just tell him how racist and horrible that was for him to say that to me. I explained this to the powers that be, the director of the department, and they basically blew it off to the side.

When it came down to the end of the evaluation period, I passed with flying colors. But they gave me an incomplete because of that chief resident and his remarks on my evaluations. He had 3 pages of report about me as a person and as a student. He said that he had difficulty in expressing his opinions about me because of possible cultural biases that he may have had. He put “cultural biases” in an evaluation, and they looked at that and said that was enough for me to have to remediate my time. I was required to do an extra month in Pontiac, Illinois, which is even more rural than Peoria, because of a racist person that did not give me a fair opportunity because I was Black.

Like everything else in life, it was a learning experience. It’s why I fight so hard today. It’s why I’m so passionate about equity, not only in medicine but also in all aspects of society. It shows why we have police brutality and Black men dying in the streets. It shows how this happens because there are cultural and implicit biases that play out in every part of life, and we are not honest about it. Until we are honest about it and until we say that this is happening and there is something that needs to be done to address it, it’s going to continue to happen. That is my fight.

Exposing the unspoken power struggle

Dr. Levy: I couldn’t agree more. Attributing things like that to the individual, where you talk about a White man in power and a power structure that didn’t literally physically beat you but did beat you into submission. You talk about how to succeed in medical school, and how you had to suck it up and submit to something that was incredibly unfair. You understood, you were old enough, mature enough, to understand that if you fought back, you were going to lose. The only opportunity you had was to submit to that inequity and push forward.

Dr. Johnson: When I did try to fight, the chair of the department told me that either I accept the consequences or I would not graduate from medical school and be forced to do another year. That struck a chord with me. I think that happens a lot in our society, and it needs to be exposed.

Past experiences reflected in today’s society

Dr. Levy: Can you talk about what you faced in your ObGyn residency in terms of the systemic pushback, people not taking your orders, people questioning you. I know that I have heard that a great deal, and I experienced that myself as a woman.

Dr. Johnson: We look at the things that are happening now, everything from George Floyd’s murder to Colin Kaepernick taking a knee. These things are 10 years past when I first started residency. The year before I started residency, there was a noose hanging on the capitol lawn of Springfield, Illinois’ capital city. There’s systemic racism and hatred there. When I first started on the wards of my first year of ObGyn, again, I was the very first Black resident of my program’s history. Nobody could relate to me.

I went from a year-long general surgery internship at Washington Hospital Center in Washington, DC, to ObGyn residency. In the first 2 months, there were complaints of, “He’s not answering his pages. He’s not being prompt.” I went to my program director and said, “Listen, I have never had one complaint like this. There’s a problem here. And there’s a problem when I’m on the floor: When trying to give orders to nurses, they’re not taking them. I had to tell a couple of nurses, ‘I’m Dr. Johnson. Don’t call me by my first name, especially not in front of patients.’”

My director was just not hearing me, because the entire scenario was something they had never been exposed to. Systemic racism is real, and unless you experience it, it’s very difficult to accept that it is happening. But biases happen when you are not cognizant. People are used to things a certain way. Things play out in the media that make your mind think a certain way, and you don’t even realize it. You may not even want to be that way.

Continue to: Unconscious bias is a barrier to ensuring equity...

Dr. Levy: One very important point you just made is that we as the system need to be able to recognize those unconscious things, the language that we use, the disparaging remarks, the things that put people down, as well as the things that keep people out of promotion.

There are some interesting data about both race and gender and the language that we use when we write recommendations for people, that we do things unconsciously. The big message to all of us at the end is to open our minds to where those things can occur. For myself, professionally, I keep a list of words that I use when I write recommendations. I measure myself to ensure that I am using the same language for men and women, for Black and White. I think we need to overcome the system and the structure to create real equity—not equality but equity.

It begins with being real about the issues

Dr. Johnson: It’s a bigger problem than the existence of bias and racism. I think these are systemic issues that have been cultivated over centuries that have never been addressed. The true issue is that we deny that these are problems and refuse to talk about it because it makes us uncomfortable. To truly make things more equitable, we have to push our levels of comfort to be able to talk about things in a healthy manner, be open and transparent, and to start to understand how we are thinking about certain things. When you can see it, you can start to implement changes and start to change mentalities and thought processes.

For me, people say, “You don’t look like a doctor.” I get that all the time—because I have tattoos and earrings. I wear my hair in a mohawk. The image of what success looks like has been manifested through our media and culture, and it has imprinted on our minds as to how things are supposed to be. If someone doesn’t fit those molds, we start to shun them out, or we start to exhibit biases against those things. What I am trying to do is change that thought process of what a successful or a professional person looks like. It doesn’t have a look. It is not a White or Black thing. It’s an intellect, a mindset, a way of living. You have to treat every person as an individual and take all the biases out of it and understand where they are coming from and what they have to offer to the profession.

Dr. Levy: I personally was so impressed by you when I met you. I was impressed by the tattoos and the earrings, and my initial response to them was exactly that biased, “Oh, who is this person?” I checked that at the door, listened to you, and was really impressed at your surgical skill, your knowledge, your background. I am really grateful that you have been willing to spend the time to share that with everyone.

Dr. Johnson: Thank you for this discussion.

To watch the full interview between Drs. Levy and Johnson, visit: https://www.mdedge.com/obgyn/article/228507/facing-systemic-racism-health-care-inequities-medical-education. ●

OBG Management takes the issues of systemic and structural racism incredibly seriously--not just by talking about it but by trying to highlight areas in medicine, particularly in obstetrics and gynecology, that are barriers to progress. In this new series for OBG Management, Board Member Barbara Levy, MD, faces the issues head-on, beginning with this peer-to-peer interview with Pierre Johnson, MD, ObGyn in Chicago, Illinois. Watch for future installments in upcoming issues of OBG Management.

Finding inspiration among life’s challenges

Barbara Levy, MD: I am fortunate to have met Pierre serendipitously at a training that we were both attending and was impressed by Dr. Johnson’s life story, his passion and commitment, and his dedication—not only to his personal career but also to raising up other young men of color by trying to break down barriers that face them. His life story highlights those areas of systemic and structural problems that all of us together need to address if we are going to make any progress.

Pierre Johnson, MD: Thank you, Barbara. A little about myself: I am a board-certified ObGyn, and I specialize in minimally invasive surgery. I was born on the South side of Chicago, experiencing gang violence, drugs, and substandard, underserved schools. Long story short, I had a very rough upbringing. I had a single mom and several different issues at home. I am the oldest of 5 siblings, and life was tough.

But I knew that I wanted to do something different with my life. I saw that there was a need in my community as far as health care was concerned, in particular women’s health and childbirth. I knew early on that I wanted to be an ObGyn, and the reason had a lot to do with The Cosby Show. It was the only example of a positive, successful Black man that I saw. No one graduated from college in my family. There weren’t any models of young Black excellence around me. Saying that I wanted to be a doctor planted a seed. I was 9 when my mom became pregnant with my first sibling, and it was fascinating to me. The physiology of pregnancy, and eventually childbirth, was extremely fascinating to me; it set me off on my journey to be an ObGyn.

As I got older, things didn’t get any easier. I went to high school in one of the toughest areas on the South side of Chicago. Gang violence, and violence in and of itself, were all around me, but I was able to stay focused. I went on to Xavier University in Louisiana.

Dr. Levy: There are some important things that I learned from your book and from talking to you at our first meeting. Your mom’s ObGyn, when she was pregnant with your next youngest sibling, was also a Black ObGyn. He took some time to take you under wing?

Dr. Johnson: He did. My mom’s ObGyn was a Black man. Other than The Cosby Show, that’s the only time I saw something like that. When I spoke to him, he really took the time to answer my questions and show me that he was like me; he wasn’t just a far-off mythical person, or something that I could not obtain.

Continue to: Seeing is believing when it comes to success...

Seeing is believing when it comes to success

Dr. Levy: Do you think it was important to have a role model who wasn’t a sports star?

Dr. Johnson: If you can’t see it, you can’t achieve it. He took his time to really talk to me, and it’s the little things for kids that go a long way in their life experience. I still have a relationship with him to this day. How he handled me as a kid made me realize that this is something that I could do. That was extremely important for me.

Dr. Levy: One of the structural things I think we need to point out is that the ability to see yourself as someone successful is critical. When we see 1,000 images a day and they are all White, and they are all so different from where we are that it gets incorporated into our sense of being. I think that’s really difficult for those of us of with privilege to understand what that privilege is.

Dr. Johnson: Absolutely, and I’ll even go further. In residency, 2 White females were my classmates, and both of their parents were doctors. They had grandparents who were doctors. My mom was addicted to drugs; my father was not around. They had been talking medicine since they were 5. You have to make things equitable, but in medicine it’s really not equitable. In medicine, what we don’t realize is that there is an importance for all aspects of someone’s upbringing and environment, and it’s not just what they can regurgitate on a standardized test. If a patient can’t relate to you and tell you what is wrong with them, how can you adequately treat them?

Dr. Levy: Even if they are trying to tell me, but I can’t hear it because I don’t have the language and I don’t have the background. There are really good data to show, in fact, that Black male physicians do a better job at engaging Black men to manage their hypertension.¹ When we look at the inequities in birth outcomes for women of color, indigenous women and Black women, there’s evidence that providers who come from a similar background do a better job.

Dr. Johnson: There was the study of Black infants that just came out about them dying at a 3-time higher rate in non-Black physicians’ hands.² These things need to be recognized. They need to be discussed, and they need to be identified as issues and then, realistically, we need to start talking about solutions, not get offended by what actual statistics are saying.

Foundational inequities in education

Dr. Levy: To address some of the barriers that you faced: I know that you went to a high school that was not geared toward pushing students into professional careers. Your colleagues, however, had educations that prepared them for the standardized tests and other things that they would face academically.

Dr. Johnson: People think I am kidding when I say it, but when I went into college, I didn’t know what a periodic table was. I saw it, but I had no idea what these things meant. I didn’t have any sciences or any AP classes in high school. I did well, but grades are smoke and mirrors. The true test of medicine comes with testing. From the MCATs to the boards, every step of the way there is a standardized test.

Knowledge is something that you can obtain, but test taking is a cultivated skill that happens from a very early age. Trying to teach an adult or someone in their late teens a skill that they should have learned as a kid is difficult. For me, I did not have that, so I had to program myself. I had to learn how to fundamentally take tests as an adult, where most people understand how to do that going into college and professional school.

Dr. Levy: I was impressed with your resilience. I think all of us as human beings, if we fail a test, we take it personally and think it’s about our lack of knowledge. One of the insights that you came to was that failure on those things was not that you didn’t study hard enough. In fact, you probably studied 4 times harder than most other people. You had the knowledge. Being able to get that knowledge into a standardized structured test score was the huge challenge for you.

Dr. Johnson: That’s it. I can remember taking the MCAT, and if you looked at the step 1 book, I could regurgitate to you everything on that page. However, it’s not a test about do you know it or not. It’s an understanding of the English language and how to break things down to make things fit into particular scenarios.

Continue to: A college experience focused on growth and exposure...

Dr. Levy: I was impressed by the distinction between your experience at Xavier University where there was a lot of support and guidance and help in your premed program, and what happened to you when you hit medical school.

Dr. Johnson: Xavier University in Louisiana is the number 1 institution in the country for getting minorities into professional school. They understand that they have kids that are brilliant but underprepared, and just have not had the background to actually tackle some of these tough curriculums. I always had good grades in school. But by not being challenged, I didn’t know what I didn’t really know. So now that I was seeing biology, chemistry for the first time, and trying to tackle it; there’s a failure point. I didn’t know how to take tests, and I didn’t know how to study properly. The harder I tried, the worse things got for me.

Xavier has seen that story a multitude of times. If I went to a bigger or predominantly White university, a counselor would have told me, “Well, medicine’s maybe not for you. You can’t handle a premed curriculum.” Instead, I said, “Listen, I’m studying. I’m doing all of these things, and I’m not hacking it.” And they broke it down: “Let’s get you into study groups with kids that have had these type of AP classes before. We’ll have you watch how they study,” and everything started to click. That facilitation of how to adjust to this curriculum was a godsend. It’s the only reason I’m here. I am a prime example of being brilliant enough to be able to do it, but needing the infrastructure and a system set up.

Dr. Levy: There’s a great book by Carol Dweck called Mindset that talks about education of young kids and putting them into silos so early in life; the brilliant kids go into the AP courses and the rest are labeled as inadequate. It’s assumed in a fixed mindset based on their heredity and IQ, and not based on the fact that they have not been exposed to the right things.

Xavier was growing you into the man who could, in fact, do all of those things. I think that is one of the systemic and structural issues that we have—that fixed mindset that frames a kid who is not succeeding as therefore unable to succeed, as opposed to framing that child as not having the correct tools.

New tribulations of medical school

Dr. Johnson: Absolutely. I think what Xavier did for me is to at least let me understand what I needed to do, how to comprehend and retain information, which I never had been exposed to before. Those years were very important to establishing a foundation. When going to medical school, it was like, “There’s no more excuses. What could be the problem now?” Well, now let’s talk about taking tests—a whole different skill. Xavier focused on getting me to understand how to structure my thought process and knowledge base. In medical school I had to apply those skills (because if you can’t apply them, there’s no fit).

My second through fourth year of medical school, I was the only African-American kid in my class. I was spending 20-hour days sometimes just studying, trying to overcompensate by knowing as much as I possibly could and thinking that would propel me from the test-taking standpoint. Even though I didn’t have a lot of classmates in medical school that looked like me, I did have mentors that looked similarly, who really saw potential in me. Dr. Frederick Horvath, a nephrologist in Peoria said, “What are you doing? I want you to get out of these books, and let’s go out to lunch.”

He ended up buying me some instrumental books, really talked to me, listening to my background and understanding how driven I was as a person. He took me under his wing for the rest of medical school and said, “This is how you navigate through these spaces. Yes, you need to have a fund of knowledge to be able to take these tests, but you need to start understanding how to apply it to these questions.” I’m forever grateful to Dr. Horvath for doing that because it was a point in time where I was lost and struggling.

Continue to: Hitting a stride but facing racism head-on...

Dr. Levy: You talk about the systemic and pervasive racism that was on the wards when you hit them in fourth year. If you don’t mind sharing just a little bit of that, it would help people reading this to have a better understanding of the kinds of barriers that are out there.

Dr. Johnson: Even when I talk about it today, it bothers me.

I went to medical school in Peoria, Illinois, not far from the home of the Ku Klux Klan. At that time, once you got out of Chicago it was a very brutal place, with systemic racism throughout. I was a young Black kid going through a process that not many young Black kids from the South side of Chicago go through, and you had people who had never seen anyone like me. When I was going through my clinical rotations, I knew what I was up against. I was dressed “to the T” every day, arriving early, leaving late, trying to answer questions. I would look at the evaluations, and they would be disparaging. I would look at my counterparts, how their evaluations were, and how people would respond to them, and it would be completely different.

Surgery was the part of ObGyn that I really grew to love more than anything, even more than obstetrics. When general surgery came, I wanted to take it very seriously and learn as much as I possibly could. From the beginning, I knew there was a problem because the chief resident, an older White man, wouldn’t look me in the eye or talk to me. He would make disparaging remarks. The thing that stuck out in my mind the most was when I was in the operating room transporting patients, just like a medical student did, and he came up behind me and said, “You know, Pierre, this is where a small mind and a strong back come into play.” For me, it took me to a place where I had to corral my emotions and thoughts because I just wanted to lash out and just tell him how racist and horrible that was for him to say that to me. I explained this to the powers that be, the director of the department, and they basically blew it off to the side.

When it came down to the end of the evaluation period, I passed with flying colors. But they gave me an incomplete because of that chief resident and his remarks on my evaluations. He had 3 pages of report about me as a person and as a student. He said that he had difficulty in expressing his opinions about me because of possible cultural biases that he may have had. He put “cultural biases” in an evaluation, and they looked at that and said that was enough for me to have to remediate my time. I was required to do an extra month in Pontiac, Illinois, which is even more rural than Peoria, because of a racist person that did not give me a fair opportunity because I was Black.

Like everything else in life, it was a learning experience. It’s why I fight so hard today. It’s why I’m so passionate about equity, not only in medicine but also in all aspects of society. It shows why we have police brutality and Black men dying in the streets. It shows how this happens because there are cultural and implicit biases that play out in every part of life, and we are not honest about it. Until we are honest about it and until we say that this is happening and there is something that needs to be done to address it, it’s going to continue to happen. That is my fight.

Exposing the unspoken power struggle

Dr. Levy: I couldn’t agree more. Attributing things like that to the individual, where you talk about a White man in power and a power structure that didn’t literally physically beat you but did beat you into submission. You talk about how to succeed in medical school, and how you had to suck it up and submit to something that was incredibly unfair. You understood, you were old enough, mature enough, to understand that if you fought back, you were going to lose. The only opportunity you had was to submit to that inequity and push forward.

Dr. Johnson: When I did try to fight, the chair of the department told me that either I accept the consequences or I would not graduate from medical school and be forced to do another year. That struck a chord with me. I think that happens a lot in our society, and it needs to be exposed.

Past experiences reflected in today’s society

Dr. Levy: Can you talk about what you faced in your ObGyn residency in terms of the systemic pushback, people not taking your orders, people questioning you. I know that I have heard that a great deal, and I experienced that myself as a woman.

Dr. Johnson: We look at the things that are happening now, everything from George Floyd’s murder to Colin Kaepernick taking a knee. These things are 10 years past when I first started residency. The year before I started residency, there was a noose hanging on the capitol lawn of Springfield, Illinois’ capital city. There’s systemic racism and hatred there. When I first started on the wards of my first year of ObGyn, again, I was the very first Black resident of my program’s history. Nobody could relate to me.

I went from a year-long general surgery internship at Washington Hospital Center in Washington, DC, to ObGyn residency. In the first 2 months, there were complaints of, “He’s not answering his pages. He’s not being prompt.” I went to my program director and said, “Listen, I have never had one complaint like this. There’s a problem here. And there’s a problem when I’m on the floor: When trying to give orders to nurses, they’re not taking them. I had to tell a couple of nurses, ‘I’m Dr. Johnson. Don’t call me by my first name, especially not in front of patients.’”

My director was just not hearing me, because the entire scenario was something they had never been exposed to. Systemic racism is real, and unless you experience it, it’s very difficult to accept that it is happening. But biases happen when you are not cognizant. People are used to things a certain way. Things play out in the media that make your mind think a certain way, and you don’t even realize it. You may not even want to be that way.

Continue to: Unconscious bias is a barrier to ensuring equity...

Dr. Levy: One very important point you just made is that we as the system need to be able to recognize those unconscious things, the language that we use, the disparaging remarks, the things that put people down, as well as the things that keep people out of promotion.

There are some interesting data about both race and gender and the language that we use when we write recommendations for people, that we do things unconsciously. The big message to all of us at the end is to open our minds to where those things can occur. For myself, professionally, I keep a list of words that I use when I write recommendations. I measure myself to ensure that I am using the same language for men and women, for Black and White. I think we need to overcome the system and the structure to create real equity—not equality but equity.

It begins with being real about the issues

Dr. Johnson: It’s a bigger problem than the existence of bias and racism. I think these are systemic issues that have been cultivated over centuries that have never been addressed. The true issue is that we deny that these are problems and refuse to talk about it because it makes us uncomfortable. To truly make things more equitable, we have to push our levels of comfort to be able to talk about things in a healthy manner, be open and transparent, and to start to understand how we are thinking about certain things. When you can see it, you can start to implement changes and start to change mentalities and thought processes.

For me, people say, “You don’t look like a doctor.” I get that all the time—because I have tattoos and earrings. I wear my hair in a mohawk. The image of what success looks like has been manifested through our media and culture, and it has imprinted on our minds as to how things are supposed to be. If someone doesn’t fit those molds, we start to shun them out, or we start to exhibit biases against those things. What I am trying to do is change that thought process of what a successful or a professional person looks like. It doesn’t have a look. It is not a White or Black thing. It’s an intellect, a mindset, a way of living. You have to treat every person as an individual and take all the biases out of it and understand where they are coming from and what they have to offer to the profession.

Dr. Levy: I personally was so impressed by you when I met you. I was impressed by the tattoos and the earrings, and my initial response to them was exactly that biased, “Oh, who is this person?” I checked that at the door, listened to you, and was really impressed at your surgical skill, your knowledge, your background. I am really grateful that you have been willing to spend the time to share that with everyone.

Dr. Johnson: Thank you for this discussion.

To watch the full interview between Drs. Levy and Johnson, visit: https://www.mdedge.com/obgyn/article/228507/facing-systemic-racism-health-care-inequities-medical-education. ●

Over the last 30 years, surgical correction of the common condition pelvic organ prolapse (POP) and stress urinary incontinence (SUI) has become so routine and straightforward that many gynecologists and urogynecologists choose surgery as their first choice for treating these conditions, withholding it only from the riskiest patients or from those who, for a variety of reasons, do not choose surgery. Moreover, as generalist gynecologists increasingly refer patients with POP or incontinence to their urogynecologist colleagues, they increasingly lack the skills, or have not been trained, to use conservative treatment strategies for these disorders. Thus, pessaries—devices constructed of inert plastic, silicone, or latex and placed inside the vagina to support prolapsed pelvic structures—frequently are not part of the general gynecologist’s armamentarium.

When properly selected, however, pessaries used for indicated purposes and correctly fitted are an excellent, inexpensive, low-risk, and noninvasive tool that can provide immediate relief not only of POP but also of SUI and defecatory difficulties. As an alternative to surgery, pessaries are especially valuable, because the other major nonsurgical modality for treatment of POP and incontinence—pelvic floor muscle training—often is not covered by insurance (making it expensive for patients), takes many weekly sessions to complete (which can make access challenging), and frequently is not readily available.¹

POP is very common. An estimated 15% to 30% of women in North America have some degree of prolapse, and more than 500,000 surgeries for this condition are performed in the United States each year.² Risk factors for POP include:

• vaginal childbirth, especially higher parity
• advancing age
• high body mass index (BMI)
• prior hysterectomy
• raised intra-abdominal pressure, such as from obesity, chronic cough, or heavy lifting.

In addition to the discomfort caused by the herniation of pelvic and vaginal structures, POP also is associated with urinary incontinence (73%), urinary urgency and frequency (86%), and fecal incontinence (31%).³

Moreover, according to the US Census Bureau, the number of American women aged 65 or older will double to more than 40 million by 2030.⁴ This will greatly increase the population of women at risk for POP who may be candidates for pessary use. It therefore behooves gynecologists to become familiar with the correct usage, fitting, and maintenance of this effective, nonsurgical mode of treatment for POP.

In this article, I discuss why pessaries are a good option for many patients with POP, review the types of pessaries available, and offer guidance on how to choose the right pessary for an individual patient’s needs. In addition, the box at the end of this article provides an interesting timeline of pessary history dating back to antiquity.

Next month in Part 2 of this article, I cover how to fit a pessary; device aftercare; potential complications of use; and effectiveness of pessaries for POP, SUI, preterm labor prevention, and defecatory disorders.

Continue to: Potential candidates for pessary use...

Potential candidates for pessary use

Almost all women with POP—and in many cases accompanying SUI—are potential candidates for a pessary. In fact, many urogynecologists believe that a trial of pessary usage should be the first treatment modality offered for POP.⁵ Women who cannot use a pessary include those with an extremely short vagina (<6 cm) and those who have severely eroded vaginal mucosa. In the latter situation, the mucosa can be treated with estrogen cream for several weeks and, once the tissue has healed, a pessary can be fitted.

Given that surgical repair is generally a straightforward, one-time procedure that obviates the need for long-term use of an artificial device worn internally, why might a patient or her physician opt for a pessary instead?

Some of the many reasons include:

• Many patients prefer to avoid surgery.
• Many patients are not appropriate candidates for surgery because they have significant comorbid risk factors or high BMI.
• Patients may have recurrent prolapse or incontinence and wish to avoid repeat surgery.
• Patients with SUI may have heard of the occurrence of mesh erosion and wish to avoid that possibility.
• Women who live in low-resource environments or countries where elective surgical care is relatively unavailable may not have the option of surgery.

A clinician might also recommend pessary use:

• as a diagnostic tool to attempt to assess the potential results of vaginal repair surgery
• to estimate the potential effectiveness of a midurethral sling procedure; several investigators have found this to be approximately as accurate as urodynamic testing^6,7
• as prophylaxis for pregnant women with either a history of preterm cervical dilation or a short cervix detected on ultrasonography
• for pregnant women with POP that is worsening and becoming increasingly uncomfortable
• for women with POP who wish to have more children
• for short-term use while a patient is delaying or awaiting POP surgery or to allow time for other medical issues to resolve
• for patients who wish only intermittent, temporary support while exercising or engaging in sports.

Patient acceptance may be contingent on counseling

Numerous studies show that women who choose pessaries to treat POP are generally older than women who elect surgery. Still, patient acceptance of a trial of pessary use depends much on the counseling and information she receives. Properly informed, many patients with POP will opt for a trial of pessary placement. One study showed that, of women with untreated POP, 36% preferred pessary placement to surgery.⁸ Other investigators reported that when women with symptomatic POP had the benefits of a pessary versus surgery explained to them, nearly two-thirds opted for a pessary as their mode of treatment.⁹

Exceptions to pessary use

Fortunately, there are relatively few contraindications to pessary use. These are vaginal or pelvic infection and an exposed foreign body in the vagina, such as eroded vaginal mesh. In addition, patients at risk for nonadherence with follow-up care are poor candidates, as it could lead to missing such problems as mucosal erosion, ulceration, or even (extremely rarely) fistula formation. Pessaries may be inappropriate for sexually active women who on their own are unable to remove and reinsert pessary types that do not allow for intercourse while in place (see below).

Continue to: Types of pessaries...

Types of pessaries

The numerous kinds of pessaries available fall into 3 general categories: support, space filling, and lever, and devices within each group have modifications and variations. As with most areas of prescribing and treatment in medicine, it is best to become very familiar with just a few kinds of pessaries, know their indications, and use them when appropriate.

Most pessaries are constructed of inert silicone which, unlike earlier rubber pessaries, does not absorb odor or discharge. They are easy to clean, long lasting, and are autoclavable and hypoallergenic.

Support pessaries

Support pessaries look like contraceptive diaphragms. They are easy to place and remove, are comfortable, and do an excellent job correcting moderate POP. They also can control or eliminate symptoms of SUI by the pressure they exert on the urethra and their alteration of the urethrovesicular angle.

Ring pessaries. The most commonly used type of pessary, the ring pessary,¹⁰ comes in 4 variations:

• a simple open ring
• a ring with a web of material, called a “support shield,” that fills the ring
• an open ring with a firm 2-cm “incontinence knob” attached that is positioned over the urethra
• a ring with support shield and incontinence knob.

When in position, the deepest edge of a ring pessary fits behind the cervix (or in the vaginal apex for women who have had a hysterectomy) while the front of the ring slips into place behind the pubic symphysis, just like a diaphragm. When a ring with an incontinence knob is used, the ring is rotated until the knob is directly over the urethra.

Sexual intercourse is possible with any of the ring pessaries in place. Of the various types of pessaries, the ring pessary is the easiest to insert and remove. Some women tie a piece of dental floss to the edge of the ring to make its removal even easier.

The ring pessary is available in sizes 0 (44.5 mm) to 13 (127 mm). For most women a size 3, 4, or 5 ring pessary fits well.

The Marland pessary is similar to the ring pessary with the addition of a wedge-shaped piece of material approximately 3 cm in height that arises from half of the ring. It rarely is used in the United States because most American gynecologists are unfamiliar with it, and there is little evidence that it is more effective than the ring pessary.¹¹

The Shaatz pessary is a rigid round pessary, smaller in diameter than the standard ring pessary, and similar to the Gellhorn pessary (discussed below) but without a stem. It is placed the same way one places a ring pessary but with its concave surface up against the cervix or, if there is no cervix, against the upper anterior vaginal wall. Its main benefit is that it provides firmer support than the ring pessary. This pessary is not widely used in the United States.

The Gehrung pessary looks like a flat strip of material that has been bent into the shape of a “U.” It is designed to correct severe cystoceles and rectoceles. For insertion, the edges at the open end of the pessary are squeezed together and the pessary is inserted with the closed part of the “U” facing the anterior vaginal wall. The upper edge is advanced until it rests in the anterior fornix of the vagina (or in the vaginal apex in women who have had a hysterectomy). Although it is more efficacious than some other pessaries for control of vaginal wall prolapse, its unfamiliarity to clinicians and its unusual shape result in it being used rarely.

Continue to: Space-filling pessaries...

Space-filling pessaries

Space-filling pessaries are used when more severe degrees of prolapse are present than can be managed by the ring or other support pessaries. This is especially the case when the vagina is so capacious or the introitus so lax that a standard ring pessary cannot be kept in place, resulting in frequent expulsions.

Space-filling pessaries are 3 dimensional and work by filling the vagina with a relatively large object that prevents the cervix/vaginal apex from dropping down and the vaginal walls from prolapsing. They have a special role for women who:

• are posthysterectomy and have an enterocele and/or vaginal apex prolapse
• have significant rectoceles for which support pessaries are not effective
• have a wide vaginal hiatus and thus are prone to expel support pessaries.

Space-filling pessaries do have some drawbacks compared with support pessaries. For example, they do not help in controlling SUI, and they are difficult for patients to remove on their own for cleaning. In addition, sexual intercourse is impossible with a space-filling pessary in place.

The Gellhorn pessary is the most common of the space-filling pessaries, and it is the one gynecologists and urogynecologists most often use for severe prolapse. It has a concave disc that fits up against the cervix or vaginal apex and a solid stem that points down the vagina. The stem itself is supported by the perineal body. It offers excellent support for severe uterine and vaginal wall prolapse, as long as the perineal body is intact. The stem stabilizes the disc portion of the pessary and prevents pessary expulsion. Gellhorn pessaries are available with long or short stems.

The Gellhorn is inserted into the vagina by folding the stem 90 degrees until it is in the same plane as the disc. With lubricated fingers, the patient’s perineal body is depressed and the disc of the pessary is folded and slid in. The disc is then placed up against the cervix or vaginal apex with the stem pointing down the vagina and tucked just inside the posterior edge of the introitus.

Removing the Gellhorn pessary can be problematic and is difficult for patients to do on their own. Clinicians often must use a ring forceps to grasp the stem of the pessary in order to bring it into the lower vagina, where the stem is folded up against the disc and the entire pessary removed. As with all space-filling pessaries, the Gellhorn must be taken out prior to intercourse.

The Gellhorn pessary is available in sizes that range from a disc diameter of 1.5 to 3.75 inches. Those measuring 2.5, 2.75, or 3 inches are used most commonly.

The cube pessary is a soft, dice-shaped piece of silicone with an indentation in each of its 6 sides. It is used for severe prolapse.

Squeezing the cube allows for easier insertion into the vagina; once it is at the top of the vagina, the cube expands back to its normal shape. The indentations on each side of the cube attach to the vaginal walls with moderate suction, which helps to keep the pessary in place. Because of the suction, the cube pessary can be used in cases of severe prolapse when other pessaries will not stay in place; a drawback is that the suction created by the indented sides can cause vaginal mucosal erosion.¹⁰ Ideally, the cube pessary should be removed every night for cleansing as discharge and accompanying odor can accumulate. The string attached to the cube pessary aids in its removal.

The cube pessary is available in sizes 0 to 7, with edge lengths that range from 1 to 2.25 inches.

The donut pessary, as its name suggests, has the form of a large donut. It can be compressed slightly to help with insertion. Because it occupies a large space within the vagina, it is used (like the cube pessary) for treatment of severe prolapse. The size and shape of the donut pessary, however, can make it difficult for patients to insert and take out on their own.

The donut pessary is available in sizes 0 (51 mm) to 8 (95 mm).

The inflatable pessary has the same basic shape as the donut pessary and serves the same purpose: It acts as a large semisoft object that fills the vagina to support the vaginal walls and cervix (or vaginal apex) in cases of severe prolapse. The inflatable pessary differs in that it has a valve on a stem through which air can be inserted and removed. This allows the uninflated pessary to be placed relatively easily into the vagina and then pumped full of air to the dimensions necessary to prevent vaginal, cervical, uterine, or apex prolapse. Air likewise can be removed to facilitate pessary removal.

One drawback of the inflatable pessary is that it is made of latex and thus cannot be used by anyone with a latex allergy. Also, as latex retains discharge and odors, this pessary should be removed and washed daily.

The inflatable pessary is available in sizes that range from 2 to 2.75 inches in 0.25-inch increments.

Continue to: Space-filling pessaries...

In addition to the more commonly used support and space-filling pessaries, there is a third kind that is rarely used in current practice: the lever pessaries. These pessaries—the Hodge, the Smith, and the Risser—are rectangles made of inert plastic that are folded into 3 planes to facilitate positioning in the vagina. The narrower of the 2 shorter ends of the folded rectangle is placed behind the cervix or at the vaginal apex while the other short end is placed behind the symphysis pubis.

Although sometimes used to correct POP in nonpregnant women, the lever pessary’s main purpose is to antivert a retroflexed uterus and to support the cervix and uterus in cases of prolapse during pregnancy or impending cervical incompetence.

The 3 lever pessaries differ in terms of whether the narrow ends of the pessary are straight or curved and wider or narrower.

How to choose the right pessary for your patient

If a patient’s POP or urinary incontinence symptoms would best be treated with a pessary, the next step is to select the pessary type and size best suited for that patient’s needs and the size that should be prescribed. While there is controversy among experts as to whether or not certain pessaries are better than others for different indications,¹² most gynecologists and urogynecologists who use pessaries on a regular basis agree on the following:

1. Support pessaries will meet the needs of most women with moderate POP and/or SUI. These include the ring pessary with or without the support shield and with or without an incontinence knob. A support pessary is the go-to pessary in most cases. Most women find it comfortable to wear, it is easy to put in and take out, and sexual intercourse is possible with the pessary in place.

2. The specific degree of a patient’s prolapse and/or incontinence dictates whether or not to prescribe the support shield feature or the incontinence knob with a ring pessary. The shield helps support a prolapsed cervix and uterus when they are present.^5,13 The knob is a useful feature if incontinence is a prominent symptom.

3. The Gellhorn pessary is usually the first choice for more severe prolapse. As long as there is some degree of posterior perineal support, this pessary does an excellent job of correcting even severe prolapse whether of a cervix and uterus or of vaginal walls and apex. It does require the patient to have some practice and dexterity for inserting and removing it on her own; individuals not comfortable or physically able to do so will need to have the pessary removed and cleaned by a clinician on a regular basis in the office. (Part 2 of this article will discuss pessary cleansing intervals).

4. Space-filling pessaries (such as the cube and donut) are useful when there is a severe degree of prolapse and insufficient perineal support to maintain a Gellhorn pessary. In practice, they are generally used less frequently—which is unfortunate, as they are a potentially useful solution for older women with severe prolapse who might not be candidates for surgical repair. As mentioned, both the cube and donut pessaries require more frequent removal for cleaning.

5. In unusual cases, the use of 2 pessaries simultaneously may resolve a difficult problem, such as when a pessary is the only option for treatment, the prolapse is severe, or it is impossible to find a pessary that resists being expelled from the vagina.¹⁴ A space-filling pessary in the most cephalad aspect of the vagina used in conjunction with a ring pessary with support shield below it can sometimes resolve even the worst cases of prolapse.

Continue to: Stay tuned...

Stay tuned

Part 2 of this article next month will provide more information on pessaries, including fitting, aftercare, potential complications, and effectiveness in various disorders. ●

Over the last 30 years, surgical correction of the common condition pelvic organ prolapse (POP) and stress urinary incontinence (SUI) has become so routine and straightforward that many gynecologists and urogynecologists choose surgery as their first choice for treating these conditions, withholding it only from the riskiest patients or from those who, for a variety of reasons, do not choose surgery. Moreover, as generalist gynecologists increasingly refer patients with POP or incontinence to their urogynecologist colleagues, they increasingly lack the skills, or have not been trained, to use conservative treatment strategies for these disorders. Thus, pessaries—devices constructed of inert plastic, silicone, or latex and placed inside the vagina to support prolapsed pelvic structures—frequently are not part of the general gynecologist’s armamentarium.

When properly selected, however, pessaries used for indicated purposes and correctly fitted are an excellent, inexpensive, low-risk, and noninvasive tool that can provide immediate relief not only of POP but also of SUI and defecatory difficulties. As an alternative to surgery, pessaries are especially valuable, because the other major nonsurgical modality for treatment of POP and incontinence—pelvic floor muscle training—often is not covered by insurance (making it expensive for patients), takes many weekly sessions to complete (which can make access challenging), and frequently is not readily available.¹

POP is very common. An estimated 15% to 30% of women in North America have some degree of prolapse, and more than 500,000 surgeries for this condition are performed in the United States each year.² Risk factors for POP include:

• vaginal childbirth, especially higher parity
• advancing age
• high body mass index (BMI)
• prior hysterectomy
• raised intra-abdominal pressure, such as from obesity, chronic cough, or heavy lifting.

In addition to the discomfort caused by the herniation of pelvic and vaginal structures, POP also is associated with urinary incontinence (73%), urinary urgency and frequency (86%), and fecal incontinence (31%).³

Moreover, according to the US Census Bureau, the number of American women aged 65 or older will double to more than 40 million by 2030.⁴ This will greatly increase the population of women at risk for POP who may be candidates for pessary use. It therefore behooves gynecologists to become familiar with the correct usage, fitting, and maintenance of this effective, nonsurgical mode of treatment for POP.

In this article, I discuss why pessaries are a good option for many patients with POP, review the types of pessaries available, and offer guidance on how to choose the right pessary for an individual patient’s needs. In addition, the box at the end of this article provides an interesting timeline of pessary history dating back to antiquity.

Next month in Part 2 of this article, I cover how to fit a pessary; device aftercare; potential complications of use; and effectiveness of pessaries for POP, SUI, preterm labor prevention, and defecatory disorders.

Continue to: Potential candidates for pessary use...

Potential candidates for pessary use

Almost all women with POP—and in many cases accompanying SUI—are potential candidates for a pessary. In fact, many urogynecologists believe that a trial of pessary usage should be the first treatment modality offered for POP.⁵ Women who cannot use a pessary include those with an extremely short vagina (<6 cm) and those who have severely eroded vaginal mucosa. In the latter situation, the mucosa can be treated with estrogen cream for several weeks and, once the tissue has healed, a pessary can be fitted.

Given that surgical repair is generally a straightforward, one-time procedure that obviates the need for long-term use of an artificial device worn internally, why might a patient or her physician opt for a pessary instead?

Some of the many reasons include:

• Many patients prefer to avoid surgery.
• Many patients are not appropriate candidates for surgery because they have significant comorbid risk factors or high BMI.
• Patients may have recurrent prolapse or incontinence and wish to avoid repeat surgery.
• Patients with SUI may have heard of the occurrence of mesh erosion and wish to avoid that possibility.
• Women who live in low-resource environments or countries where elective surgical care is relatively unavailable may not have the option of surgery.

A clinician might also recommend pessary use:

• as a diagnostic tool to attempt to assess the potential results of vaginal repair surgery
• to estimate the potential effectiveness of a midurethral sling procedure; several investigators have found this to be approximately as accurate as urodynamic testing^6,7
• as prophylaxis for pregnant women with either a history of preterm cervical dilation or a short cervix detected on ultrasonography
• for pregnant women with POP that is worsening and becoming increasingly uncomfortable
• for women with POP who wish to have more children
• for short-term use while a patient is delaying or awaiting POP surgery or to allow time for other medical issues to resolve
• for patients who wish only intermittent, temporary support while exercising or engaging in sports.

Patient acceptance may be contingent on counseling

Numerous studies show that women who choose pessaries to treat POP are generally older than women who elect surgery. Still, patient acceptance of a trial of pessary use depends much on the counseling and information she receives. Properly informed, many patients with POP will opt for a trial of pessary placement. One study showed that, of women with untreated POP, 36% preferred pessary placement to surgery.⁸ Other investigators reported that when women with symptomatic POP had the benefits of a pessary versus surgery explained to them, nearly two-thirds opted for a pessary as their mode of treatment.⁹

Exceptions to pessary use

Fortunately, there are relatively few contraindications to pessary use. These are vaginal or pelvic infection and an exposed foreign body in the vagina, such as eroded vaginal mesh. In addition, patients at risk for nonadherence with follow-up care are poor candidates, as it could lead to missing such problems as mucosal erosion, ulceration, or even (extremely rarely) fistula formation. Pessaries may be inappropriate for sexually active women who on their own are unable to remove and reinsert pessary types that do not allow for intercourse while in place (see below).

Continue to: Types of pessaries...

Types of pessaries

The numerous kinds of pessaries available fall into 3 general categories: support, space filling, and lever, and devices within each group have modifications and variations. As with most areas of prescribing and treatment in medicine, it is best to become very familiar with just a few kinds of pessaries, know their indications, and use them when appropriate.

Most pessaries are constructed of inert silicone which, unlike earlier rubber pessaries, does not absorb odor or discharge. They are easy to clean, long lasting, and are autoclavable and hypoallergenic.

Support pessaries

Support pessaries look like contraceptive diaphragms. They are easy to place and remove, are comfortable, and do an excellent job correcting moderate POP. They also can control or eliminate symptoms of SUI by the pressure they exert on the urethra and their alteration of the urethrovesicular angle.

Ring pessaries. The most commonly used type of pessary, the ring pessary,¹⁰ comes in 4 variations:

• a simple open ring
• a ring with a web of material, called a “support shield,” that fills the ring
• an open ring with a firm 2-cm “incontinence knob” attached that is positioned over the urethra
• a ring with support shield and incontinence knob.

When in position, the deepest edge of a ring pessary fits behind the cervix (or in the vaginal apex for women who have had a hysterectomy) while the front of the ring slips into place behind the pubic symphysis, just like a diaphragm. When a ring with an incontinence knob is used, the ring is rotated until the knob is directly over the urethra.

Sexual intercourse is possible with any of the ring pessaries in place. Of the various types of pessaries, the ring pessary is the easiest to insert and remove. Some women tie a piece of dental floss to the edge of the ring to make its removal even easier.

The ring pessary is available in sizes 0 (44.5 mm) to 13 (127 mm). For most women a size 3, 4, or 5 ring pessary fits well.

The Marland pessary is similar to the ring pessary with the addition of a wedge-shaped piece of material approximately 3 cm in height that arises from half of the ring. It rarely is used in the United States because most American gynecologists are unfamiliar with it, and there is little evidence that it is more effective than the ring pessary.¹¹

The Shaatz pessary is a rigid round pessary, smaller in diameter than the standard ring pessary, and similar to the Gellhorn pessary (discussed below) but without a stem. It is placed the same way one places a ring pessary but with its concave surface up against the cervix or, if there is no cervix, against the upper anterior vaginal wall. Its main benefit is that it provides firmer support than the ring pessary. This pessary is not widely used in the United States.

The Gehrung pessary looks like a flat strip of material that has been bent into the shape of a “U.” It is designed to correct severe cystoceles and rectoceles. For insertion, the edges at the open end of the pessary are squeezed together and the pessary is inserted with the closed part of the “U” facing the anterior vaginal wall. The upper edge is advanced until it rests in the anterior fornix of the vagina (or in the vaginal apex in women who have had a hysterectomy). Although it is more efficacious than some other pessaries for control of vaginal wall prolapse, its unfamiliarity to clinicians and its unusual shape result in it being used rarely.

Continue to: Space-filling pessaries...

Space-filling pessaries

Space-filling pessaries are used when more severe degrees of prolapse are present than can be managed by the ring or other support pessaries. This is especially the case when the vagina is so capacious or the introitus so lax that a standard ring pessary cannot be kept in place, resulting in frequent expulsions.

Space-filling pessaries are 3 dimensional and work by filling the vagina with a relatively large object that prevents the cervix/vaginal apex from dropping down and the vaginal walls from prolapsing. They have a special role for women who:

• are posthysterectomy and have an enterocele and/or vaginal apex prolapse
• have significant rectoceles for which support pessaries are not effective
• have a wide vaginal hiatus and thus are prone to expel support pessaries.

Space-filling pessaries do have some drawbacks compared with support pessaries. For example, they do not help in controlling SUI, and they are difficult for patients to remove on their own for cleaning. In addition, sexual intercourse is impossible with a space-filling pessary in place.

The Gellhorn pessary is the most common of the space-filling pessaries, and it is the one gynecologists and urogynecologists most often use for severe prolapse. It has a concave disc that fits up against the cervix or vaginal apex and a solid stem that points down the vagina. The stem itself is supported by the perineal body. It offers excellent support for severe uterine and vaginal wall prolapse, as long as the perineal body is intact. The stem stabilizes the disc portion of the pessary and prevents pessary expulsion. Gellhorn pessaries are available with long or short stems.

The Gellhorn is inserted into the vagina by folding the stem 90 degrees until it is in the same plane as the disc. With lubricated fingers, the patient’s perineal body is depressed and the disc of the pessary is folded and slid in. The disc is then placed up against the cervix or vaginal apex with the stem pointing down the vagina and tucked just inside the posterior edge of the introitus.

Removing the Gellhorn pessary can be problematic and is difficult for patients to do on their own. Clinicians often must use a ring forceps to grasp the stem of the pessary in order to bring it into the lower vagina, where the stem is folded up against the disc and the entire pessary removed. As with all space-filling pessaries, the Gellhorn must be taken out prior to intercourse.

The Gellhorn pessary is available in sizes that range from a disc diameter of 1.5 to 3.75 inches. Those measuring 2.5, 2.75, or 3 inches are used most commonly.

The cube pessary is a soft, dice-shaped piece of silicone with an indentation in each of its 6 sides. It is used for severe prolapse.

Squeezing the cube allows for easier insertion into the vagina; once it is at the top of the vagina, the cube expands back to its normal shape. The indentations on each side of the cube attach to the vaginal walls with moderate suction, which helps to keep the pessary in place. Because of the suction, the cube pessary can be used in cases of severe prolapse when other pessaries will not stay in place; a drawback is that the suction created by the indented sides can cause vaginal mucosal erosion.¹⁰ Ideally, the cube pessary should be removed every night for cleansing as discharge and accompanying odor can accumulate. The string attached to the cube pessary aids in its removal.

The cube pessary is available in sizes 0 to 7, with edge lengths that range from 1 to 2.25 inches.

The donut pessary, as its name suggests, has the form of a large donut. It can be compressed slightly to help with insertion. Because it occupies a large space within the vagina, it is used (like the cube pessary) for treatment of severe prolapse. The size and shape of the donut pessary, however, can make it difficult for patients to insert and take out on their own.

The donut pessary is available in sizes 0 (51 mm) to 8 (95 mm).

The inflatable pessary has the same basic shape as the donut pessary and serves the same purpose: It acts as a large semisoft object that fills the vagina to support the vaginal walls and cervix (or vaginal apex) in cases of severe prolapse. The inflatable pessary differs in that it has a valve on a stem through which air can be inserted and removed. This allows the uninflated pessary to be placed relatively easily into the vagina and then pumped full of air to the dimensions necessary to prevent vaginal, cervical, uterine, or apex prolapse. Air likewise can be removed to facilitate pessary removal.

One drawback of the inflatable pessary is that it is made of latex and thus cannot be used by anyone with a latex allergy. Also, as latex retains discharge and odors, this pessary should be removed and washed daily.

The inflatable pessary is available in sizes that range from 2 to 2.75 inches in 0.25-inch increments.

Continue to: Space-filling pessaries...

In addition to the more commonly used support and space-filling pessaries, there is a third kind that is rarely used in current practice: the lever pessaries. These pessaries—the Hodge, the Smith, and the Risser—are rectangles made of inert plastic that are folded into 3 planes to facilitate positioning in the vagina. The narrower of the 2 shorter ends of the folded rectangle is placed behind the cervix or at the vaginal apex while the other short end is placed behind the symphysis pubis.

Although sometimes used to correct POP in nonpregnant women, the lever pessary’s main purpose is to antivert a retroflexed uterus and to support the cervix and uterus in cases of prolapse during pregnancy or impending cervical incompetence.

The 3 lever pessaries differ in terms of whether the narrow ends of the pessary are straight or curved and wider or narrower.

How to choose the right pessary for your patient

If a patient’s POP or urinary incontinence symptoms would best be treated with a pessary, the next step is to select the pessary type and size best suited for that patient’s needs and the size that should be prescribed. While there is controversy among experts as to whether or not certain pessaries are better than others for different indications,¹² most gynecologists and urogynecologists who use pessaries on a regular basis agree on the following:

1. Support pessaries will meet the needs of most women with moderate POP and/or SUI. These include the ring pessary with or without the support shield and with or without an incontinence knob. A support pessary is the go-to pessary in most cases. Most women find it comfortable to wear, it is easy to put in and take out, and sexual intercourse is possible with the pessary in place.

2. The specific degree of a patient’s prolapse and/or incontinence dictates whether or not to prescribe the support shield feature or the incontinence knob with a ring pessary. The shield helps support a prolapsed cervix and uterus when they are present.^5,13 The knob is a useful feature if incontinence is a prominent symptom.

3. The Gellhorn pessary is usually the first choice for more severe prolapse. As long as there is some degree of posterior perineal support, this pessary does an excellent job of correcting even severe prolapse whether of a cervix and uterus or of vaginal walls and apex. It does require the patient to have some practice and dexterity for inserting and removing it on her own; individuals not comfortable or physically able to do so will need to have the pessary removed and cleaned by a clinician on a regular basis in the office. (Part 2 of this article will discuss pessary cleansing intervals).

4. Space-filling pessaries (such as the cube and donut) are useful when there is a severe degree of prolapse and insufficient perineal support to maintain a Gellhorn pessary. In practice, they are generally used less frequently—which is unfortunate, as they are a potentially useful solution for older women with severe prolapse who might not be candidates for surgical repair. As mentioned, both the cube and donut pessaries require more frequent removal for cleaning.

5. In unusual cases, the use of 2 pessaries simultaneously may resolve a difficult problem, such as when a pessary is the only option for treatment, the prolapse is severe, or it is impossible to find a pessary that resists being expelled from the vagina.¹⁴ A space-filling pessary in the most cephalad aspect of the vagina used in conjunction with a ring pessary with support shield below it can sometimes resolve even the worst cases of prolapse.

Continue to: Stay tuned...

Stay tuned

Part 2 of this article next month will provide more information on pessaries, including fitting, aftercare, potential complications, and effectiveness in various disorders. ●

Over the last 30 years, surgical correction of the common condition pelvic organ prolapse (POP) and stress urinary incontinence (SUI) has become so routine and straightforward that many gynecologists and urogynecologists choose surgery as their first choice for treating these conditions, withholding it only from the riskiest patients or from those who, for a variety of reasons, do not choose surgery. Moreover, as generalist gynecologists increasingly refer patients with POP or incontinence to their urogynecologist colleagues, they increasingly lack the skills, or have not been trained, to use conservative treatment strategies for these disorders. Thus, pessaries—devices constructed of inert plastic, silicone, or latex and placed inside the vagina to support prolapsed pelvic structures—frequently are not part of the general gynecologist’s armamentarium.

When properly selected, however, pessaries used for indicated purposes and correctly fitted are an excellent, inexpensive, low-risk, and noninvasive tool that can provide immediate relief not only of POP but also of SUI and defecatory difficulties. As an alternative to surgery, pessaries are especially valuable, because the other major nonsurgical modality for treatment of POP and incontinence—pelvic floor muscle training—often is not covered by insurance (making it expensive for patients), takes many weekly sessions to complete (which can make access challenging), and frequently is not readily available.¹

POP is very common. An estimated 15% to 30% of women in North America have some degree of prolapse, and more than 500,000 surgeries for this condition are performed in the United States each year.² Risk factors for POP include:

• vaginal childbirth, especially higher parity
• advancing age
• high body mass index (BMI)
• prior hysterectomy
• raised intra-abdominal pressure, such as from obesity, chronic cough, or heavy lifting.

In addition to the discomfort caused by the herniation of pelvic and vaginal structures, POP also is associated with urinary incontinence (73%), urinary urgency and frequency (86%), and fecal incontinence (31%).³

Moreover, according to the US Census Bureau, the number of American women aged 65 or older will double to more than 40 million by 2030.⁴ This will greatly increase the population of women at risk for POP who may be candidates for pessary use. It therefore behooves gynecologists to become familiar with the correct usage, fitting, and maintenance of this effective, nonsurgical mode of treatment for POP.

In this article, I discuss why pessaries are a good option for many patients with POP, review the types of pessaries available, and offer guidance on how to choose the right pessary for an individual patient’s needs. In addition, the box at the end of this article provides an interesting timeline of pessary history dating back to antiquity.

Next month in Part 2 of this article, I cover how to fit a pessary; device aftercare; potential complications of use; and effectiveness of pessaries for POP, SUI, preterm labor prevention, and defecatory disorders.

Continue to: Potential candidates for pessary use...

Potential candidates for pessary use

Almost all women with POP—and in many cases accompanying SUI—are potential candidates for a pessary. In fact, many urogynecologists believe that a trial of pessary usage should be the first treatment modality offered for POP.⁵ Women who cannot use a pessary include those with an extremely short vagina (<6 cm) and those who have severely eroded vaginal mucosa. In the latter situation, the mucosa can be treated with estrogen cream for several weeks and, once the tissue has healed, a pessary can be fitted.

Given that surgical repair is generally a straightforward, one-time procedure that obviates the need for long-term use of an artificial device worn internally, why might a patient or her physician opt for a pessary instead?

Some of the many reasons include:

• Many patients prefer to avoid surgery.
• Many patients are not appropriate candidates for surgery because they have significant comorbid risk factors or high BMI.
• Patients may have recurrent prolapse or incontinence and wish to avoid repeat surgery.
• Patients with SUI may have heard of the occurrence of mesh erosion and wish to avoid that possibility.
• Women who live in low-resource environments or countries where elective surgical care is relatively unavailable may not have the option of surgery.

A clinician might also recommend pessary use:

• as a diagnostic tool to attempt to assess the potential results of vaginal repair surgery
• to estimate the potential effectiveness of a midurethral sling procedure; several investigators have found this to be approximately as accurate as urodynamic testing^6,7
• as prophylaxis for pregnant women with either a history of preterm cervical dilation or a short cervix detected on ultrasonography
• for pregnant women with POP that is worsening and becoming increasingly uncomfortable
• for women with POP who wish to have more children
• for short-term use while a patient is delaying or awaiting POP surgery or to allow time for other medical issues to resolve
• for patients who wish only intermittent, temporary support while exercising or engaging in sports.

Patient acceptance may be contingent on counseling

Numerous studies show that women who choose pessaries to treat POP are generally older than women who elect surgery. Still, patient acceptance of a trial of pessary use depends much on the counseling and information she receives. Properly informed, many patients with POP will opt for a trial of pessary placement. One study showed that, of women with untreated POP, 36% preferred pessary placement to surgery.⁸ Other investigators reported that when women with symptomatic POP had the benefits of a pessary versus surgery explained to them, nearly two-thirds opted for a pessary as their mode of treatment.⁹

Exceptions to pessary use

Fortunately, there are relatively few contraindications to pessary use. These are vaginal or pelvic infection and an exposed foreign body in the vagina, such as eroded vaginal mesh. In addition, patients at risk for nonadherence with follow-up care are poor candidates, as it could lead to missing such problems as mucosal erosion, ulceration, or even (extremely rarely) fistula formation. Pessaries may be inappropriate for sexually active women who on their own are unable to remove and reinsert pessary types that do not allow for intercourse while in place (see below).

Continue to: Types of pessaries...

Types of pessaries

The numerous kinds of pessaries available fall into 3 general categories: support, space filling, and lever, and devices within each group have modifications and variations. As with most areas of prescribing and treatment in medicine, it is best to become very familiar with just a few kinds of pessaries, know their indications, and use them when appropriate.

Most pessaries are constructed of inert silicone which, unlike earlier rubber pessaries, does not absorb odor or discharge. They are easy to clean, long lasting, and are autoclavable and hypoallergenic.

Support pessaries

Support pessaries look like contraceptive diaphragms. They are easy to place and remove, are comfortable, and do an excellent job correcting moderate POP. They also can control or eliminate symptoms of SUI by the pressure they exert on the urethra and their alteration of the urethrovesicular angle.

Ring pessaries. The most commonly used type of pessary, the ring pessary,¹⁰ comes in 4 variations:

• a simple open ring
• a ring with a web of material, called a “support shield,” that fills the ring
• an open ring with a firm 2-cm “incontinence knob” attached that is positioned over the urethra
• a ring with support shield and incontinence knob.

When in position, the deepest edge of a ring pessary fits behind the cervix (or in the vaginal apex for women who have had a hysterectomy) while the front of the ring slips into place behind the pubic symphysis, just like a diaphragm. When a ring with an incontinence knob is used, the ring is rotated until the knob is directly over the urethra.

Sexual intercourse is possible with any of the ring pessaries in place. Of the various types of pessaries, the ring pessary is the easiest to insert and remove. Some women tie a piece of dental floss to the edge of the ring to make its removal even easier.

The ring pessary is available in sizes 0 (44.5 mm) to 13 (127 mm). For most women a size 3, 4, or 5 ring pessary fits well.

The Marland pessary is similar to the ring pessary with the addition of a wedge-shaped piece of material approximately 3 cm in height that arises from half of the ring. It rarely is used in the United States because most American gynecologists are unfamiliar with it, and there is little evidence that it is more effective than the ring pessary.¹¹

The Shaatz pessary is a rigid round pessary, smaller in diameter than the standard ring pessary, and similar to the Gellhorn pessary (discussed below) but without a stem. It is placed the same way one places a ring pessary but with its concave surface up against the cervix or, if there is no cervix, against the upper anterior vaginal wall. Its main benefit is that it provides firmer support than the ring pessary. This pessary is not widely used in the United States.

The Gehrung pessary looks like a flat strip of material that has been bent into the shape of a “U.” It is designed to correct severe cystoceles and rectoceles. For insertion, the edges at the open end of the pessary are squeezed together and the pessary is inserted with the closed part of the “U” facing the anterior vaginal wall. The upper edge is advanced until it rests in the anterior fornix of the vagina (or in the vaginal apex in women who have had a hysterectomy). Although it is more efficacious than some other pessaries for control of vaginal wall prolapse, its unfamiliarity to clinicians and its unusual shape result in it being used rarely.

Continue to: Space-filling pessaries...

Space-filling pessaries

Space-filling pessaries are used when more severe degrees of prolapse are present than can be managed by the ring or other support pessaries. This is especially the case when the vagina is so capacious or the introitus so lax that a standard ring pessary cannot be kept in place, resulting in frequent expulsions.

Space-filling pessaries are 3 dimensional and work by filling the vagina with a relatively large object that prevents the cervix/vaginal apex from dropping down and the vaginal walls from prolapsing. They have a special role for women who:

• are posthysterectomy and have an enterocele and/or vaginal apex prolapse
• have significant rectoceles for which support pessaries are not effective
• have a wide vaginal hiatus and thus are prone to expel support pessaries.

Space-filling pessaries do have some drawbacks compared with support pessaries. For example, they do not help in controlling SUI, and they are difficult for patients to remove on their own for cleaning. In addition, sexual intercourse is impossible with a space-filling pessary in place.

The Gellhorn pessary is the most common of the space-filling pessaries, and it is the one gynecologists and urogynecologists most often use for severe prolapse. It has a concave disc that fits up against the cervix or vaginal apex and a solid stem that points down the vagina. The stem itself is supported by the perineal body. It offers excellent support for severe uterine and vaginal wall prolapse, as long as the perineal body is intact. The stem stabilizes the disc portion of the pessary and prevents pessary expulsion. Gellhorn pessaries are available with long or short stems.

The Gellhorn is inserted into the vagina by folding the stem 90 degrees until it is in the same plane as the disc. With lubricated fingers, the patient’s perineal body is depressed and the disc of the pessary is folded and slid in. The disc is then placed up against the cervix or vaginal apex with the stem pointing down the vagina and tucked just inside the posterior edge of the introitus.

Removing the Gellhorn pessary can be problematic and is difficult for patients to do on their own. Clinicians often must use a ring forceps to grasp the stem of the pessary in order to bring it into the lower vagina, where the stem is folded up against the disc and the entire pessary removed. As with all space-filling pessaries, the Gellhorn must be taken out prior to intercourse.

The Gellhorn pessary is available in sizes that range from a disc diameter of 1.5 to 3.75 inches. Those measuring 2.5, 2.75, or 3 inches are used most commonly.

The cube pessary is a soft, dice-shaped piece of silicone with an indentation in each of its 6 sides. It is used for severe prolapse.

Squeezing the cube allows for easier insertion into the vagina; once it is at the top of the vagina, the cube expands back to its normal shape. The indentations on each side of the cube attach to the vaginal walls with moderate suction, which helps to keep the pessary in place. Because of the suction, the cube pessary can be used in cases of severe prolapse when other pessaries will not stay in place; a drawback is that the suction created by the indented sides can cause vaginal mucosal erosion.¹⁰ Ideally, the cube pessary should be removed every night for cleansing as discharge and accompanying odor can accumulate. The string attached to the cube pessary aids in its removal.

The cube pessary is available in sizes 0 to 7, with edge lengths that range from 1 to 2.25 inches.

The donut pessary, as its name suggests, has the form of a large donut. It can be compressed slightly to help with insertion. Because it occupies a large space within the vagina, it is used (like the cube pessary) for treatment of severe prolapse. The size and shape of the donut pessary, however, can make it difficult for patients to insert and take out on their own.

The donut pessary is available in sizes 0 (51 mm) to 8 (95 mm).

The inflatable pessary has the same basic shape as the donut pessary and serves the same purpose: It acts as a large semisoft object that fills the vagina to support the vaginal walls and cervix (or vaginal apex) in cases of severe prolapse. The inflatable pessary differs in that it has a valve on a stem through which air can be inserted and removed. This allows the uninflated pessary to be placed relatively easily into the vagina and then pumped full of air to the dimensions necessary to prevent vaginal, cervical, uterine, or apex prolapse. Air likewise can be removed to facilitate pessary removal.

One drawback of the inflatable pessary is that it is made of latex and thus cannot be used by anyone with a latex allergy. Also, as latex retains discharge and odors, this pessary should be removed and washed daily.

The inflatable pessary is available in sizes that range from 2 to 2.75 inches in 0.25-inch increments.

Continue to: Space-filling pessaries...

In addition to the more commonly used support and space-filling pessaries, there is a third kind that is rarely used in current practice: the lever pessaries. These pessaries—the Hodge, the Smith, and the Risser—are rectangles made of inert plastic that are folded into 3 planes to facilitate positioning in the vagina. The narrower of the 2 shorter ends of the folded rectangle is placed behind the cervix or at the vaginal apex while the other short end is placed behind the symphysis pubis.

Although sometimes used to correct POP in nonpregnant women, the lever pessary’s main purpose is to antivert a retroflexed uterus and to support the cervix and uterus in cases of prolapse during pregnancy or impending cervical incompetence.

The 3 lever pessaries differ in terms of whether the narrow ends of the pessary are straight or curved and wider or narrower.

How to choose the right pessary for your patient

If a patient’s POP or urinary incontinence symptoms would best be treated with a pessary, the next step is to select the pessary type and size best suited for that patient’s needs and the size that should be prescribed. While there is controversy among experts as to whether or not certain pessaries are better than others for different indications,¹² most gynecologists and urogynecologists who use pessaries on a regular basis agree on the following:

1. Support pessaries will meet the needs of most women with moderate POP and/or SUI. These include the ring pessary with or without the support shield and with or without an incontinence knob. A support pessary is the go-to pessary in most cases. Most women find it comfortable to wear, it is easy to put in and take out, and sexual intercourse is possible with the pessary in place.

2. The specific degree of a patient’s prolapse and/or incontinence dictates whether or not to prescribe the support shield feature or the incontinence knob with a ring pessary. The shield helps support a prolapsed cervix and uterus when they are present.^5,13 The knob is a useful feature if incontinence is a prominent symptom.

3. The Gellhorn pessary is usually the first choice for more severe prolapse. As long as there is some degree of posterior perineal support, this pessary does an excellent job of correcting even severe prolapse whether of a cervix and uterus or of vaginal walls and apex. It does require the patient to have some practice and dexterity for inserting and removing it on her own; individuals not comfortable or physically able to do so will need to have the pessary removed and cleaned by a clinician on a regular basis in the office. (Part 2 of this article will discuss pessary cleansing intervals).

4. Space-filling pessaries (such as the cube and donut) are useful when there is a severe degree of prolapse and insufficient perineal support to maintain a Gellhorn pessary. In practice, they are generally used less frequently—which is unfortunate, as they are a potentially useful solution for older women with severe prolapse who might not be candidates for surgical repair. As mentioned, both the cube and donut pessaries require more frequent removal for cleaning.

5. In unusual cases, the use of 2 pessaries simultaneously may resolve a difficult problem, such as when a pessary is the only option for treatment, the prolapse is severe, or it is impossible to find a pessary that resists being expelled from the vagina.¹⁴ A space-filling pessary in the most cephalad aspect of the vagina used in conjunction with a ring pessary with support shield below it can sometimes resolve even the worst cases of prolapse.

Continue to: Stay tuned...

Stay tuned

Part 2 of this article next month will provide more information on pessaries, including fitting, aftercare, potential complications, and effectiveness in various disorders. ●

CASE Patient questions need for preoperative tests

A healthy 42-year-old woman (G2P2) with abnormal uterine bleeding and a 2-cm endometrial polyp is scheduled for hysteroscopic polypectomy. After your preoperative clinic visit, the patient receives her paperwork containing information about preoperative lab work and diagnostic studies. You are asked to come into the room because she has further questions. When you arrive, the patient holds the papers out and asks, “Is all this blood work and a chest x-ray necessary? I thought I was healthy and this was a fairly simple surgery. Is there more I should be worried about?”

How would you respond?

The goal of preoperative testing is to determine which patients may be at an increased risk for experiencing an adverse perioperative event, taking into account both the inherent risks of the surgical procedure and the health of the individual patient. In the literature, the general consensus is that physicians rely too heavily on unnecessary laboratory and diagnostic testing during their preoperative assessment.¹ More than 50% of patients who underwent preoperative evaluation had at least 1 unindicated test.² These tests may result in a high frequency of abnormal findings, with less than 3% of abnormalities having clinical value or leading to a change in management.³

With health care costs accounting for almost 20% of the gross domestic product in the United States (totaling about $3.5 billion in 2017), performing unindicated preoperative testing contributes to the economic burden on health care systems, with an estimated cost of $3 to $18 million annually.^4,5 In addition, unindicated tests can increase patient anxiety and necessitate follow-up testing, possibly exposing physicians to increased liability if abnormal results are not adequately investigated.⁶

It is time to rethink our use of routine preoperative testing.

Which tests to consider—or not: Evidence-based guidance

Professional societies, including the American Board of Internal Medicine’s Choosing Wisely campaign, promote a move away from routine testing to avoid unnecessary visits and studies. In addition, the American Society of Anesthesiologists (ASA) has published recommendations to guide preoperative testing.⁷ To stratify patients’ surgical risk according to their pre-existing health conditions, the ASA created a physical status classification system (TABLE 1).⁸

In addition to individual patient characteristics, some guidelines similarly stratify surgical procedures into minor, intermediate, and major risk. The modified Johns Hopkins surgical criteria allocates surgical risk based on expected blood loss, insensible loss, and the inherent risk of a procedure separate from anesthesia (TABLE 2).⁹ Despite these guidelines, physicians responsible for preoperative evaluations continue to order laboratory and diagnostic tests that are not indicated, often over concerns of case delays or cancellations.^10,11

The following evidence-based recommendations provide guidance to gynecologists performing surgery for benign indications to determine which preoperative studies should be performed.

Serum chemistries

Basic metabolic panel (BMP). In both contemporary studies and earlier prospective studies, a preoperative BMP has a low likelihood of changing the surgical procedure or the patient’s management, especially in patients who are classified as ASA I and are undergoing minor- and intermediate-risk procedures.^12,13 Therefore, we recommend a BMP for patients in class ASA II or higher who are undergoing intermediate-risk or major surgery.¹⁴

Thyroid function. A basic tenet of preoperative evaluation is that asymptomatic patients should not be diagnosed according to lab values prior to surgical intervention. Therefore, we do not recommend routine preoperative thyroid function testing in patients without a history of thyroid disease.¹⁰ For patients with known thyroid disease, a thyroid stimulating hormone (TSH) level should be evaluated prior to major surgery, or with any changes in medication dose or symptoms, within the past year.¹⁵

Liver function tests (LFTs). Routine screening of asymptomatic individuals without risk factors for liver disease is not recommended because there is a significantly lower incidence of abnormal lab values for LFTs than for other lab tests.¹⁶ We recommend LFTs only in symptomatic patients or patients diagnosed with severe liver disease undergoing intermediate-risk or major procedures.¹⁴

Hemoglobin A1c (HbA1c). Poorly controlled diabetes is a risk factor for poor wound healing, hospital readmission, prolonged hospitalization, and adverse events following surgery.¹⁷ We recommend that HbA1c levels be drawn only for patients with known diabetes undergoing intermediate-risk or major surgery who do not have an available lab value within the past 3 months.¹⁴

Continue to: Hematologic studies...

Hematologic studies

Complete blood count (CBC). Many patients undergoing gynecologic procedures may have unreported or undiagnosed anemia secondary to abnormal uterine bleeding, which also may encompass heavy menstrual bleeding. With an abnormal CBC likely to affect preoperative management, assessment of preoperative hemoglobin levels is critical so that hemoglobin levels can be appropriately corrected before surgery. We therefore recommend obtaining a CBC for patients in class ASA II or higher who are undergoing intermediate-risk or major surgery.^10,14

Coagulation studies. Preoperative coagulation studies are unlikely to uncover previously undiagnosed inherited coagulopathies, which are generally uncommon in the general population, and they do not predict operative bleeding when ordered unnecessarily.^18,19 Therefore, we recommend preoperative coagulation studies only in patients 1) currently on anticoagulation therapy undergoing intermediate-risk or major surgery or 2) in class ASA III or higher with bleeding disorders or cirrhosis undergoing intermediate-risk or major surgery.¹⁴

Type and screen (T&S). Complicated algorithms have been proposed to determine when a preoperative T&S is necessary, but these may be impractical for busy gynecologists.²⁰ We recommend a T&S within 72 hours, or on the day, of surgery for all patients undergoing major surgery, including hysterectomy, or with an anticipated blood loss of more than 500 mL; routine crossmatching of blood is not recommended.^10,14

Urologic studies

Urine pregnancy test. Although the probability of a positive pregnancy test is likely very low, its occurrence frequently leads to the cancellation of surgery. We therefore recommend a preoperative urine pregnancy test, particularly in reproductive-aged patients with unknown pregnancy status or unreliable contraceptive habits.¹⁴ Preoperative urine pregnancy testing, even in patients who report sexual inactivity, ideally should be individualized and based on risk of fetal harm during or subsequent to surgery. Surgeries involving the uterus, or those involving possible teratogens like radiation, also should be considered when making recommendations for testing.

Urinalysis and urine culture. In asymptomatic patients undergoing general gynecologic procedures, a routine preoperative urinalysis and urine culture are of little value.¹⁸ However, among patients undergoing a urogynecologic surgical procedure, the risk of a postoperative urinary tract infection is higher than among patients undergoing a nonurogynecologic procedure.^21,22 Therefore, we typically do not recommend routine preoperative urinalysis or urine culture, but a preoperative urine culture may be beneficial in patients undergoing urogynecologic surgery.¹⁴

Continue to: Diagnostic studies...

Electrocardiography (ECG). The absolute difference in cardiovascular death is less than 1% among patients with and without ECG abnormalities undergoing a noncardiac procedure with minimal to moderate risk; therefore, routine ECG for low-risk patients should not be performed.²³ Instead, ECG should be performed in patients with known coronary artery disease or structural heart disease and in patients aged 65 years and older, since age older than 65 years is an independent predictor of significant ECG abnormalities.^24,25 We therefore recommend that the following individuals have an ECG within the last 12 months: patients aged 65 years and older, patients in class ASA II or higher with cardiovascular disease, and patients in class ASA III or higher undergoing general anesthesia. If there is a change in cardiovascular health since the most recent ECG—even if it was performed within 12 months—a repeat ECG is warranted.^10,14

Chest x-ray. Despite a high rate of abnormalities seen on routine and indicated chest x-rays, there is no significant difference in perioperative pulmonary complications among patients with a normal or abnormal chest x-ray.¹⁶ Rather than changing surgical management, these abnormal results are more likely to lead to the cancellation or postponement of a surgical procedure.⁷ We therefore recommend against routine preoperative chest x-ray.¹⁴

The bottom line

Preoperative testing serves as an additional component of surgical planning. The fact is, however, that abnormal test results are common and frequently do not correlate with surgical outcomes.²⁶ Instead, they can lead to unnecessary surgical procedure cancellations or postponements, undue anxiety in patients, increased liability among physicians, and rising health care costs.^5-7

Rather than overly relying on routine laboratory or diagnostic studies, the history and physical examination should continue to be the cornerstone for surgeons responsible for assessing surgical risk. With individualized risk assessment, specific, indicated testing rather than routine nonspecific testing can be obtained.^10,14 In short, low-risk patients undergoing noncardiac surgery are unlikely to benefit from preoperative ECG, chest x-ray, or routine laboratory testing without clinical indication. ●

CASE Patient questions need for preoperative tests

A healthy 42-year-old woman (G2P2) with abnormal uterine bleeding and a 2-cm endometrial polyp is scheduled for hysteroscopic polypectomy. After your preoperative clinic visit, the patient receives her paperwork containing information about preoperative lab work and diagnostic studies. You are asked to come into the room because she has further questions. When you arrive, the patient holds the papers out and asks, “Is all this blood work and a chest x-ray necessary? I thought I was healthy and this was a fairly simple surgery. Is there more I should be worried about?”

How would you respond?

The goal of preoperative testing is to determine which patients may be at an increased risk for experiencing an adverse perioperative event, taking into account both the inherent risks of the surgical procedure and the health of the individual patient. In the literature, the general consensus is that physicians rely too heavily on unnecessary laboratory and diagnostic testing during their preoperative assessment.¹ More than 50% of patients who underwent preoperative evaluation had at least 1 unindicated test.² These tests may result in a high frequency of abnormal findings, with less than 3% of abnormalities having clinical value or leading to a change in management.³

With health care costs accounting for almost 20% of the gross domestic product in the United States (totaling about $3.5 billion in 2017), performing unindicated preoperative testing contributes to the economic burden on health care systems, with an estimated cost of $3 to $18 million annually.^4,5 In addition, unindicated tests can increase patient anxiety and necessitate follow-up testing, possibly exposing physicians to increased liability if abnormal results are not adequately investigated.⁶

It is time to rethink our use of routine preoperative testing.

Which tests to consider—or not: Evidence-based guidance

Professional societies, including the American Board of Internal Medicine’s Choosing Wisely campaign, promote a move away from routine testing to avoid unnecessary visits and studies. In addition, the American Society of Anesthesiologists (ASA) has published recommendations to guide preoperative testing.⁷ To stratify patients’ surgical risk according to their pre-existing health conditions, the ASA created a physical status classification system (TABLE 1).⁸

In addition to individual patient characteristics, some guidelines similarly stratify surgical procedures into minor, intermediate, and major risk. The modified Johns Hopkins surgical criteria allocates surgical risk based on expected blood loss, insensible loss, and the inherent risk of a procedure separate from anesthesia (TABLE 2).⁹ Despite these guidelines, physicians responsible for preoperative evaluations continue to order laboratory and diagnostic tests that are not indicated, often over concerns of case delays or cancellations.^10,11

The following evidence-based recommendations provide guidance to gynecologists performing surgery for benign indications to determine which preoperative studies should be performed.

Serum chemistries

Basic metabolic panel (BMP). In both contemporary studies and earlier prospective studies, a preoperative BMP has a low likelihood of changing the surgical procedure or the patient’s management, especially in patients who are classified as ASA I and are undergoing minor- and intermediate-risk procedures.^12,13 Therefore, we recommend a BMP for patients in class ASA II or higher who are undergoing intermediate-risk or major surgery.¹⁴

Thyroid function. A basic tenet of preoperative evaluation is that asymptomatic patients should not be diagnosed according to lab values prior to surgical intervention. Therefore, we do not recommend routine preoperative thyroid function testing in patients without a history of thyroid disease.¹⁰ For patients with known thyroid disease, a thyroid stimulating hormone (TSH) level should be evaluated prior to major surgery, or with any changes in medication dose or symptoms, within the past year.¹⁵

Liver function tests (LFTs). Routine screening of asymptomatic individuals without risk factors for liver disease is not recommended because there is a significantly lower incidence of abnormal lab values for LFTs than for other lab tests.¹⁶ We recommend LFTs only in symptomatic patients or patients diagnosed with severe liver disease undergoing intermediate-risk or major procedures.¹⁴

Hemoglobin A1c (HbA1c). Poorly controlled diabetes is a risk factor for poor wound healing, hospital readmission, prolonged hospitalization, and adverse events following surgery.¹⁷ We recommend that HbA1c levels be drawn only for patients with known diabetes undergoing intermediate-risk or major surgery who do not have an available lab value within the past 3 months.¹⁴

Continue to: Hematologic studies...

Hematologic studies

Complete blood count (CBC). Many patients undergoing gynecologic procedures may have unreported or undiagnosed anemia secondary to abnormal uterine bleeding, which also may encompass heavy menstrual bleeding. With an abnormal CBC likely to affect preoperative management, assessment of preoperative hemoglobin levels is critical so that hemoglobin levels can be appropriately corrected before surgery. We therefore recommend obtaining a CBC for patients in class ASA II or higher who are undergoing intermediate-risk or major surgery.^10,14

Coagulation studies. Preoperative coagulation studies are unlikely to uncover previously undiagnosed inherited coagulopathies, which are generally uncommon in the general population, and they do not predict operative bleeding when ordered unnecessarily.^18,19 Therefore, we recommend preoperative coagulation studies only in patients 1) currently on anticoagulation therapy undergoing intermediate-risk or major surgery or 2) in class ASA III or higher with bleeding disorders or cirrhosis undergoing intermediate-risk or major surgery.¹⁴

Type and screen (T&S). Complicated algorithms have been proposed to determine when a preoperative T&S is necessary, but these may be impractical for busy gynecologists.²⁰ We recommend a T&S within 72 hours, or on the day, of surgery for all patients undergoing major surgery, including hysterectomy, or with an anticipated blood loss of more than 500 mL; routine crossmatching of blood is not recommended.^10,14

Urologic studies

Urine pregnancy test. Although the probability of a positive pregnancy test is likely very low, its occurrence frequently leads to the cancellation of surgery. We therefore recommend a preoperative urine pregnancy test, particularly in reproductive-aged patients with unknown pregnancy status or unreliable contraceptive habits.¹⁴ Preoperative urine pregnancy testing, even in patients who report sexual inactivity, ideally should be individualized and based on risk of fetal harm during or subsequent to surgery. Surgeries involving the uterus, or those involving possible teratogens like radiation, also should be considered when making recommendations for testing.

Urinalysis and urine culture. In asymptomatic patients undergoing general gynecologic procedures, a routine preoperative urinalysis and urine culture are of little value.¹⁸ However, among patients undergoing a urogynecologic surgical procedure, the risk of a postoperative urinary tract infection is higher than among patients undergoing a nonurogynecologic procedure.^21,22 Therefore, we typically do not recommend routine preoperative urinalysis or urine culture, but a preoperative urine culture may be beneficial in patients undergoing urogynecologic surgery.¹⁴

Continue to: Diagnostic studies...

Electrocardiography (ECG). The absolute difference in cardiovascular death is less than 1% among patients with and without ECG abnormalities undergoing a noncardiac procedure with minimal to moderate risk; therefore, routine ECG for low-risk patients should not be performed.²³ Instead, ECG should be performed in patients with known coronary artery disease or structural heart disease and in patients aged 65 years and older, since age older than 65 years is an independent predictor of significant ECG abnormalities.^24,25 We therefore recommend that the following individuals have an ECG within the last 12 months: patients aged 65 years and older, patients in class ASA II or higher with cardiovascular disease, and patients in class ASA III or higher undergoing general anesthesia. If there is a change in cardiovascular health since the most recent ECG—even if it was performed within 12 months—a repeat ECG is warranted.^10,14

Chest x-ray. Despite a high rate of abnormalities seen on routine and indicated chest x-rays, there is no significant difference in perioperative pulmonary complications among patients with a normal or abnormal chest x-ray.¹⁶ Rather than changing surgical management, these abnormal results are more likely to lead to the cancellation or postponement of a surgical procedure.⁷ We therefore recommend against routine preoperative chest x-ray.¹⁴

The bottom line

Preoperative testing serves as an additional component of surgical planning. The fact is, however, that abnormal test results are common and frequently do not correlate with surgical outcomes.²⁶ Instead, they can lead to unnecessary surgical procedure cancellations or postponements, undue anxiety in patients, increased liability among physicians, and rising health care costs.^5-7

Rather than overly relying on routine laboratory or diagnostic studies, the history and physical examination should continue to be the cornerstone for surgeons responsible for assessing surgical risk. With individualized risk assessment, specific, indicated testing rather than routine nonspecific testing can be obtained.^10,14 In short, low-risk patients undergoing noncardiac surgery are unlikely to benefit from preoperative ECG, chest x-ray, or routine laboratory testing without clinical indication. ●

CASE Patient questions need for preoperative tests

A healthy 42-year-old woman (G2P2) with abnormal uterine bleeding and a 2-cm endometrial polyp is scheduled for hysteroscopic polypectomy. After your preoperative clinic visit, the patient receives her paperwork containing information about preoperative lab work and diagnostic studies. You are asked to come into the room because she has further questions. When you arrive, the patient holds the papers out and asks, “Is all this blood work and a chest x-ray necessary? I thought I was healthy and this was a fairly simple surgery. Is there more I should be worried about?”

How would you respond?

The goal of preoperative testing is to determine which patients may be at an increased risk for experiencing an adverse perioperative event, taking into account both the inherent risks of the surgical procedure and the health of the individual patient. In the literature, the general consensus is that physicians rely too heavily on unnecessary laboratory and diagnostic testing during their preoperative assessment.¹ More than 50% of patients who underwent preoperative evaluation had at least 1 unindicated test.² These tests may result in a high frequency of abnormal findings, with less than 3% of abnormalities having clinical value or leading to a change in management.³

With health care costs accounting for almost 20% of the gross domestic product in the United States (totaling about $3.5 billion in 2017), performing unindicated preoperative testing contributes to the economic burden on health care systems, with an estimated cost of $3 to $18 million annually.^4,5 In addition, unindicated tests can increase patient anxiety and necessitate follow-up testing, possibly exposing physicians to increased liability if abnormal results are not adequately investigated.⁶

It is time to rethink our use of routine preoperative testing.

Which tests to consider—or not: Evidence-based guidance

Professional societies, including the American Board of Internal Medicine’s Choosing Wisely campaign, promote a move away from routine testing to avoid unnecessary visits and studies. In addition, the American Society of Anesthesiologists (ASA) has published recommendations to guide preoperative testing.⁷ To stratify patients’ surgical risk according to their pre-existing health conditions, the ASA created a physical status classification system (TABLE 1).⁸

In addition to individual patient characteristics, some guidelines similarly stratify surgical procedures into minor, intermediate, and major risk. The modified Johns Hopkins surgical criteria allocates surgical risk based on expected blood loss, insensible loss, and the inherent risk of a procedure separate from anesthesia (TABLE 2).⁹ Despite these guidelines, physicians responsible for preoperative evaluations continue to order laboratory and diagnostic tests that are not indicated, often over concerns of case delays or cancellations.^10,11

The following evidence-based recommendations provide guidance to gynecologists performing surgery for benign indications to determine which preoperative studies should be performed.

Serum chemistries

Basic metabolic panel (BMP). In both contemporary studies and earlier prospective studies, a preoperative BMP has a low likelihood of changing the surgical procedure or the patient’s management, especially in patients who are classified as ASA I and are undergoing minor- and intermediate-risk procedures.^12,13 Therefore, we recommend a BMP for patients in class ASA II or higher who are undergoing intermediate-risk or major surgery.¹⁴

Thyroid function. A basic tenet of preoperative evaluation is that asymptomatic patients should not be diagnosed according to lab values prior to surgical intervention. Therefore, we do not recommend routine preoperative thyroid function testing in patients without a history of thyroid disease.¹⁰ For patients with known thyroid disease, a thyroid stimulating hormone (TSH) level should be evaluated prior to major surgery, or with any changes in medication dose or symptoms, within the past year.¹⁵

Liver function tests (LFTs). Routine screening of asymptomatic individuals without risk factors for liver disease is not recommended because there is a significantly lower incidence of abnormal lab values for LFTs than for other lab tests.¹⁶ We recommend LFTs only in symptomatic patients or patients diagnosed with severe liver disease undergoing intermediate-risk or major procedures.¹⁴

Hemoglobin A1c (HbA1c). Poorly controlled diabetes is a risk factor for poor wound healing, hospital readmission, prolonged hospitalization, and adverse events following surgery.¹⁷ We recommend that HbA1c levels be drawn only for patients with known diabetes undergoing intermediate-risk or major surgery who do not have an available lab value within the past 3 months.¹⁴

Continue to: Hematologic studies...

Hematologic studies

Complete blood count (CBC). Many patients undergoing gynecologic procedures may have unreported or undiagnosed anemia secondary to abnormal uterine bleeding, which also may encompass heavy menstrual bleeding. With an abnormal CBC likely to affect preoperative management, assessment of preoperative hemoglobin levels is critical so that hemoglobin levels can be appropriately corrected before surgery. We therefore recommend obtaining a CBC for patients in class ASA II or higher who are undergoing intermediate-risk or major surgery.^10,14

Coagulation studies. Preoperative coagulation studies are unlikely to uncover previously undiagnosed inherited coagulopathies, which are generally uncommon in the general population, and they do not predict operative bleeding when ordered unnecessarily.^18,19 Therefore, we recommend preoperative coagulation studies only in patients 1) currently on anticoagulation therapy undergoing intermediate-risk or major surgery or 2) in class ASA III or higher with bleeding disorders or cirrhosis undergoing intermediate-risk or major surgery.¹⁴

Type and screen (T&S). Complicated algorithms have been proposed to determine when a preoperative T&S is necessary, but these may be impractical for busy gynecologists.²⁰ We recommend a T&S within 72 hours, or on the day, of surgery for all patients undergoing major surgery, including hysterectomy, or with an anticipated blood loss of more than 500 mL; routine crossmatching of blood is not recommended.^10,14

Urologic studies

Urine pregnancy test. Although the probability of a positive pregnancy test is likely very low, its occurrence frequently leads to the cancellation of surgery. We therefore recommend a preoperative urine pregnancy test, particularly in reproductive-aged patients with unknown pregnancy status or unreliable contraceptive habits.¹⁴ Preoperative urine pregnancy testing, even in patients who report sexual inactivity, ideally should be individualized and based on risk of fetal harm during or subsequent to surgery. Surgeries involving the uterus, or those involving possible teratogens like radiation, also should be considered when making recommendations for testing.

Urinalysis and urine culture. In asymptomatic patients undergoing general gynecologic procedures, a routine preoperative urinalysis and urine culture are of little value.¹⁸ However, among patients undergoing a urogynecologic surgical procedure, the risk of a postoperative urinary tract infection is higher than among patients undergoing a nonurogynecologic procedure.^21,22 Therefore, we typically do not recommend routine preoperative urinalysis or urine culture, but a preoperative urine culture may be beneficial in patients undergoing urogynecologic surgery.¹⁴

Continue to: Diagnostic studies...

Electrocardiography (ECG). The absolute difference in cardiovascular death is less than 1% among patients with and without ECG abnormalities undergoing a noncardiac procedure with minimal to moderate risk; therefore, routine ECG for low-risk patients should not be performed.²³ Instead, ECG should be performed in patients with known coronary artery disease or structural heart disease and in patients aged 65 years and older, since age older than 65 years is an independent predictor of significant ECG abnormalities.^24,25 We therefore recommend that the following individuals have an ECG within the last 12 months: patients aged 65 years and older, patients in class ASA II or higher with cardiovascular disease, and patients in class ASA III or higher undergoing general anesthesia. If there is a change in cardiovascular health since the most recent ECG—even if it was performed within 12 months—a repeat ECG is warranted.^10,14

Chest x-ray. Despite a high rate of abnormalities seen on routine and indicated chest x-rays, there is no significant difference in perioperative pulmonary complications among patients with a normal or abnormal chest x-ray.¹⁶ Rather than changing surgical management, these abnormal results are more likely to lead to the cancellation or postponement of a surgical procedure.⁷ We therefore recommend against routine preoperative chest x-ray.¹⁴

The bottom line

Preoperative testing serves as an additional component of surgical planning. The fact is, however, that abnormal test results are common and frequently do not correlate with surgical outcomes.²⁶ Instead, they can lead to unnecessary surgical procedure cancellations or postponements, undue anxiety in patients, increased liability among physicians, and rising health care costs.^5-7

Rather than overly relying on routine laboratory or diagnostic studies, the history and physical examination should continue to be the cornerstone for surgeons responsible for assessing surgical risk. With individualized risk assessment, specific, indicated testing rather than routine nonspecific testing can be obtained.^10,14 In short, low-risk patients undergoing noncardiac surgery are unlikely to benefit from preoperative ECG, chest x-ray, or routine laboratory testing without clinical indication. ●

In the era of long-acting reversible contraceptives (LARCs), the pill can seem obsolete. However, it is still the second most commonly used birth control method in the United States, chosen by 19% of female contraceptive users as of 2015–2017.¹ It also has noncontraceptive benefits, so it is important that obstetrician-gynecologists are well-versed in its uses. In this article, I will focus on combined oral contraceptives (COCs; TABLE 1), reviewing the major risks, benefits, and adverse effects of COCs before focusing on recommendations for particular formulations of COCs for various patient populations.

Benefits and risks

There are numerous noncontraceptive benefits of COCs, including menstrual cycle regulation; reduced risk of ovarian, endometrial, and colorectal cancer; and treatment of menorrhagia, dysmenorrhea, acne, menstrual migraine, premenstrual syndrome and premenstrual dysphoric disorder, pelvic pain due to endometriosis, and hirsutism.

Common patient concerns

In terms of adverse effects, there are more potential unwanted effects of concern to women than there are ones validated in the literature. Accepted adverse effects include nausea, breast tenderness, and decreased libido. However, one of the most common concerns voiced during contraceptive counseling is that COCs will cause weight gain. A 2014 Cochrane review identified 49 trials studying the weight gain question.² Of those, only 4 had a placebo or nonintervention group. Of these 4, there was no significant difference in weight change between the COC-receiving group and the control group. When patients bring up their concerns, it may help to remind them that women tend to gain weight over time whether or not they are taking a COC.

Another common concern is that COCs cause mood changes. A 2016 review by Schaffir and colleagues sheds some light on this topic,³ albeit limited by the paucity of prospective studies. This review identified only 1 randomized controlled trial comparing depression incidence among women initiating a COC versus a placebo. There was no difference in the incidence of depression among the groups at 3 months. Among 4 large retrospective studies of women using COCs, the agents either had no or a beneficial effect on mood. Schaffir’s review reports that there may be greater mood adverse effects with COCs among women with underlying mood disorders.

Patients may worry that COC use will permanently impair their fertility or delay return to fertility after discontinuation. Research does indicate that return of fertility after stopping COCs often takes several months (compared with immediate fertility after discontinuing a barrier method). However, there still seem to be comparable conception rates within 12 months after discontinuing COCs as there are after discontinuing other common nonhormonal or hormonal contraceptive methods. Fertility is not impacted by the duration of COC use. In addition, return to fertility seems to be comparable after discontinuation of extended cycle or continuous COCs compared with traditional-cycle COCs.⁴

COC safety

Known major risks of COCs include venous thromboembolism (VTE). The risk of VTE is about double among COC users than among nonpregnant nonusers: 3–9 per 10,000 woman-years compared with 1–5.⁵ In a study by the US Food and Drug Administration, drospirenone-containing COCs had double the risk of VTE than other COCs. However, the position of the American College of Obstetricians and Gynecologists on this increased risk of VTE with drospirenone-containing pills is that it is “possible” and “minimal.”⁵ It is important to remember that an alternative to COC use is pregnancy, in which the VTE risk is about double that among COC users, at 5–20 per 10,000 woman-years. This risk increases further in the postpartum period, to 40–65 per 10,000 woman-years.⁵

Another known major risk of COCs is arterial embolic disease, including cerebrovascular accidents and myocardial infarctions. Women at increased risk for these complications include those with hypertension, diabetes, and/or obesity and women who are aged 35 or older and smoke. Interestingly, women with migraines with aura are at increased risk for stroke but not for myocardial infarction. These women increase their risk of stroke 2- to 4-fold if they use COCs.

Continue to: Different pills for different problems...

Different pills for different problems

With so many pills on the market, it is important for clinicians to know how to choose a particular pill for a particular patient. The following discussion assumes that the patient in question desires a COC for contraception, then offers guidance on how to choose a pill with patient-specific noncontraceptive benefits (TABLE 2).

• Introvale and Seasonique, both extended-cycle formulations
• Amethyst, which is formulated without placebo pills so that it can be used continuously
• any other COC prescribed with instructions for the patient to skip placebo pills.

An extrapolated benefit to extended-cycle or continuous COCs use for heavy menstrual bleeding is addressing anemia.

For premenstrual dysphoric disorder, the only randomized controlled trials showing improvement involve drospirenone-ethinyl estradiol pills (Yaz and Yasmin).⁷ There is also evidence that extended cyclic or continuous use of these formulations is more impactful for premenstrual dysphoric disorder than a traditional cycle.⁸

Keeping migraine avoidance and prevention in mind. Various studies have looked at the impact of different COC formulations on menstrual-related symptoms. There is evidence of greater improvement in headache, bloating, and dysmenorrhea with extended cyclic or continuous use compared with traditional cyclic use.⁶

In terms of headache, let us delve into menstrual migraine in particular. Menstrual migraines occur sometime between 2 days prior to 2 days after the first day of menses and are linked to a sharp drop in estrogen levels. COCs are contraindicated in women with menstrual migraines with aura because of the increased stroke risk. For women with menstrual migraines without aura, COCs can prevent migraines. Prevention depends on minimizing fluctuations in estrogen levels; any change in estrogen level greater than 10 µg of ethinyl estradiol may trigger an estrogen-related migraine. All currently available regimens of COCs that comprise 21 days of active pills and 7 days of placebo involve a drop of more than 10 µg. Options that involve a drop of 10 µg or less include any continuous formulation, the extended formulation LoSeasonique (levonorgestrel 0.1 mg and ethinyl estradiol 20 µg for 84 days, then ethinyl estradiol 10 µg for 7 days), and Lo Loestrin (ethinyl estradiol 10 µg and norethindrone 1 mg for 24 days, then ethinyl estradiol 10 µg for 2 days, then placebo for 2 days).⁹

What’s best for acne-prone patients? All COCs should improve acne by increasing levels of sex hormone binding globulin. However, some comparative studies have shown drospirenone-containing COCs to be the most effective for acne. This finding makes sense in light of studies demonstrating antiandrogenic effects of drospirenone.¹⁰

Managing PCOS symptoms. It seems logical, by extension, that drospirenone-containing COCs would be particularly beneficial for treating hirsutism associated with polycystic ovary syndrome (PCOS). Other low‒androgenic-potential progestins, such as a third-generation progestin (norgestimate or desogestrel), might similarly be hypothesized to be advantageous. However, there is currently insufficient evidence to recommend any one COC formulation over another for the indication of PCOS.¹¹

Ovarian cysts: Can COCs be helpful? COCs are commonly prescribed by gynecologists for patients with functional ovarian cysts. It is important to note that COCs have not been found to hasten the resolution of existing cysts, so they should not be used for this purpose.¹² Studies of early COCs, which had high doses of estrogen (on the order of 50 µg), showed lower rates of cysts among users. This effect seems to be attenuated with the lower-estrogen-dose pills that are currently available, but there still appears to be benefit. Therefore, for a patient prone to cysts who desires an oral contraceptive, a COC containing estrogen 35 µg is likely to be the most beneficial of COCs currently on the market.^13,14

Lower-dosage COCs in perimenopause may be beneficial. COCs can ameliorate perimenopausal symptoms including abnormal uterine bleeding and vasomotor symptoms. Clinicians are often hesitant to prescribe COCs for perimenopausal women because of increased risk of VTE, stroke, myocardial infarction, and breast cancer with increasing age. However, age alone is not a contraindication to any contraceptive method. An extended cyclic or continuous regimen COC may be the best choice for a perimenopausal woman in order to avoid vasomotor symptoms that occur during hormone-free intervals. In addition, given the increasing risk of adverse effects like VTE with estrogen dose, a lower estrogen formulation is advisable.¹⁵

Patients with epilepsy who are taking antiepileptic drugs (AEDs) are a special population when it comes to COCs. Certain AEDs induce hepatic enzymes involved in the metabolism and protein binding of COCs, which can result in contraceptive failure. Strong inducers are carbamazepine, oxcarbazepine, perampanel, phenobarbital, phenytoin, and primidone. Weak inducers are clobazam, eslicarbazepine, felbamate, lamotrigine, rufinamide, and topiramate. Women taking any of the above AEDs are recommended to choose a different form of contraception than a COC. However, if they are limited to COCs for some reason, a preparation containing estrogen 50 µg is recommended. It is speculated that the efficacy and adverse effects of COCs with increased hormone doses, used in combination with enzyme-inducing AEDs, should be comparable to those with standard doses when not combined with AEDs; however, this speculation is unproven.¹⁶ There are few COCs on the market with estrogen doses of 50 µg, but a couple of examples are Kelnor and Ogestrel.

Additional factors have to be considered with concurrent COC use with the AED lamotrigine since COCs increase clearance of this agent. Therefore, patients taking lamotrigine who start COCs will need an increase in lamotrigine dose. To avoid fluctuations in lamotrigine serum levels, use of a continuous COC is recommended.¹⁷

Continue to: Pill types to minimize adverse effects or risks...

For women who desire to use a COC for contraception but who are at risk for a particular complication or are bothered by a particular adverse effect, ObGyns can optimize the choice of pill (TABLE 3). For example, women who have adverse effects of nausea and/or breast tenderness may benefit from reducing the estrogen dose to 20 µg or lower.¹⁸

Considering VTE

As discussed previously, VTE is a risk with all COCs, but some pills confer greater risk than others. For one, VTE risk increases with estrogen dose. In addition, VTE risk depends on the type of progestin. Drospirenone and third-generation progestins (norgestimate, gestodene, and desogestrel) confer a higher risk of VTE than first- or second-generation progestins. For example, a pill with estradiol 30 µg and either a third-generation progestin or drospirenone has a 50% to 80% higher risk of VTE compared with a pill with estradiol 30 µg and levonorgestrel.

For patients at particularly high risk for VTE, COCs are contraindicated. For patients for whom COCs are considered medically appropriate but who are at higher risk (eg, obese women), it is wise to use a pill containing a first-generation (norethindrone) or second-generation progestin (levonorgestrel) combined with the lowest dose of estrogen that has tolerable adverse effects.¹⁹

What about hypertension concerns?

Let us turn our attention briefly to hypertension and its relation to COC use. While the American College of Cardiology and the American Heart Association redefined hypertension in 2017 using a threshold of 130/80 mm Hg, the American College of Obstetricians and Gynecologists (ACOG) considers hypertension to be 140/90 mm Hg in terms of safety of using COCs. ACOG states, “women with blood pressure below 140/90 mm Hg may use any hormonal contraceptive method.”²⁰ In women with hypertension in the range of 140‒159 mm Hg systolic or 90‒99 mm Hg diastolic, COCs are category 3 according to the US Medical Eligibility Criteria for Contraceptive Use, meaning that the risks usually outweigh the benefits. For women with blood pressures of 160/110 mm Hg or greater, COCs are category 4 (contraindicated). If a woman with mild hypertension is started on a COC, a drospirenone-containing pill may be the best choice because of its diuretic effects. While other contemporary COCs have been associated with a mild increase in blood pressure, drospirenone-containing pills have not shown this association.²¹

Continue to: At issue: Break-through bleeding, mood, and weight gain...

At issue: Break-through bleeding, mood, and weight gain

For women bothered by intermenstrual bleeding, use of a COC with a third-generation progestin may be preferable to use of one with a first- or second-generation. It may be because of decreased abnormal bleeding that COCs with third-generation progestins have lower discontinuation rates.²² In addition, COCs containing estrogen 20 µg or less are associated with more intermenstrual bleeding than those with more than 20 µg estrogen.²³ Keep in mind that it is common with any COC to have intermenstrual bleeding for the first several months.

For women with pre-existing mood disorders or who report mood changes with COCs, it appears that fluctuations in hormone levels are problematic. Consistently, there is evidence that monophasic pills are preferable to multiphasic and that extended cyclic or continuous use is preferable to traditional cyclic use for mitigating mood adverse effects. There is mixed evidence on whether a low dose of ethinyl estradiol is better for mood.³

Although it is discussed above that randomized controlled trials have not shown an association between COC use and weight gain, many women remain concerned. For these women, a drospirenone-containing COC may be the best choice. Drospirenone has antimineralocorticoid activity, so it may help prevent water retention.

A brief word about multiphasic COCs. While these pills were designed to mimic physiologic hormone fluctuations and minimize hormonal adverse effects, there is insufficient evidence to compare their effects to those of monophasic pills.²⁴ Without such evidence, there is little reason to recommend a multiphasic pill to a patient over the more straightforward monophasic formulation.

Conclusion

There are more nuances to prescribing an optimal COC for a patient than may initially come to mind. It is useful to remember that any formulation of pill may be prescribed in an extended or continuous fashion, and there are benefits for such use for premenstrual dysphoric disorder, heavy menstrual bleeding, perimenopause, and menstrual symptoms. Although there are numerous brands of COCs available, a small cadre will suffice for almost all purposes. Such a “toolbox” of pills could include a pill formatted for continuous use (Seasonique), a low estrogen pill (Loestrin), a drospirenone-containing pill (Yaz), and a pill containing a third-generation progestin and a higher dose of estrogen (Sprintec). ●

In the era of long-acting reversible contraceptives (LARCs), the pill can seem obsolete. However, it is still the second most commonly used birth control method in the United States, chosen by 19% of female contraceptive users as of 2015–2017.¹ It also has noncontraceptive benefits, so it is important that obstetrician-gynecologists are well-versed in its uses. In this article, I will focus on combined oral contraceptives (COCs; TABLE 1), reviewing the major risks, benefits, and adverse effects of COCs before focusing on recommendations for particular formulations of COCs for various patient populations.

Benefits and risks

There are numerous noncontraceptive benefits of COCs, including menstrual cycle regulation; reduced risk of ovarian, endometrial, and colorectal cancer; and treatment of menorrhagia, dysmenorrhea, acne, menstrual migraine, premenstrual syndrome and premenstrual dysphoric disorder, pelvic pain due to endometriosis, and hirsutism.

Common patient concerns

In terms of adverse effects, there are more potential unwanted effects of concern to women than there are ones validated in the literature. Accepted adverse effects include nausea, breast tenderness, and decreased libido. However, one of the most common concerns voiced during contraceptive counseling is that COCs will cause weight gain. A 2014 Cochrane review identified 49 trials studying the weight gain question.² Of those, only 4 had a placebo or nonintervention group. Of these 4, there was no significant difference in weight change between the COC-receiving group and the control group. When patients bring up their concerns, it may help to remind them that women tend to gain weight over time whether or not they are taking a COC.

Another common concern is that COCs cause mood changes. A 2016 review by Schaffir and colleagues sheds some light on this topic,³ albeit limited by the paucity of prospective studies. This review identified only 1 randomized controlled trial comparing depression incidence among women initiating a COC versus a placebo. There was no difference in the incidence of depression among the groups at 3 months. Among 4 large retrospective studies of women using COCs, the agents either had no or a beneficial effect on mood. Schaffir’s review reports that there may be greater mood adverse effects with COCs among women with underlying mood disorders.

Patients may worry that COC use will permanently impair their fertility or delay return to fertility after discontinuation. Research does indicate that return of fertility after stopping COCs often takes several months (compared with immediate fertility after discontinuing a barrier method). However, there still seem to be comparable conception rates within 12 months after discontinuing COCs as there are after discontinuing other common nonhormonal or hormonal contraceptive methods. Fertility is not impacted by the duration of COC use. In addition, return to fertility seems to be comparable after discontinuation of extended cycle or continuous COCs compared with traditional-cycle COCs.⁴

COC safety

Known major risks of COCs include venous thromboembolism (VTE). The risk of VTE is about double among COC users than among nonpregnant nonusers: 3–9 per 10,000 woman-years compared with 1–5.⁵ In a study by the US Food and Drug Administration, drospirenone-containing COCs had double the risk of VTE than other COCs. However, the position of the American College of Obstetricians and Gynecologists on this increased risk of VTE with drospirenone-containing pills is that it is “possible” and “minimal.”⁵ It is important to remember that an alternative to COC use is pregnancy, in which the VTE risk is about double that among COC users, at 5–20 per 10,000 woman-years. This risk increases further in the postpartum period, to 40–65 per 10,000 woman-years.⁵

Another known major risk of COCs is arterial embolic disease, including cerebrovascular accidents and myocardial infarctions. Women at increased risk for these complications include those with hypertension, diabetes, and/or obesity and women who are aged 35 or older and smoke. Interestingly, women with migraines with aura are at increased risk for stroke but not for myocardial infarction. These women increase their risk of stroke 2- to 4-fold if they use COCs.

Continue to: Different pills for different problems...

Different pills for different problems

With so many pills on the market, it is important for clinicians to know how to choose a particular pill for a particular patient. The following discussion assumes that the patient in question desires a COC for contraception, then offers guidance on how to choose a pill with patient-specific noncontraceptive benefits (TABLE 2).

• Introvale and Seasonique, both extended-cycle formulations
• Amethyst, which is formulated without placebo pills so that it can be used continuously
• any other COC prescribed with instructions for the patient to skip placebo pills.

An extrapolated benefit to extended-cycle or continuous COCs use for heavy menstrual bleeding is addressing anemia.

For premenstrual dysphoric disorder, the only randomized controlled trials showing improvement involve drospirenone-ethinyl estradiol pills (Yaz and Yasmin).⁷ There is also evidence that extended cyclic or continuous use of these formulations is more impactful for premenstrual dysphoric disorder than a traditional cycle.⁸

Keeping migraine avoidance and prevention in mind. Various studies have looked at the impact of different COC formulations on menstrual-related symptoms. There is evidence of greater improvement in headache, bloating, and dysmenorrhea with extended cyclic or continuous use compared with traditional cyclic use.⁶

In terms of headache, let us delve into menstrual migraine in particular. Menstrual migraines occur sometime between 2 days prior to 2 days after the first day of menses and are linked to a sharp drop in estrogen levels. COCs are contraindicated in women with menstrual migraines with aura because of the increased stroke risk. For women with menstrual migraines without aura, COCs can prevent migraines. Prevention depends on minimizing fluctuations in estrogen levels; any change in estrogen level greater than 10 µg of ethinyl estradiol may trigger an estrogen-related migraine. All currently available regimens of COCs that comprise 21 days of active pills and 7 days of placebo involve a drop of more than 10 µg. Options that involve a drop of 10 µg or less include any continuous formulation, the extended formulation LoSeasonique (levonorgestrel 0.1 mg and ethinyl estradiol 20 µg for 84 days, then ethinyl estradiol 10 µg for 7 days), and Lo Loestrin (ethinyl estradiol 10 µg and norethindrone 1 mg for 24 days, then ethinyl estradiol 10 µg for 2 days, then placebo for 2 days).⁹

What’s best for acne-prone patients? All COCs should improve acne by increasing levels of sex hormone binding globulin. However, some comparative studies have shown drospirenone-containing COCs to be the most effective for acne. This finding makes sense in light of studies demonstrating antiandrogenic effects of drospirenone.¹⁰

Managing PCOS symptoms. It seems logical, by extension, that drospirenone-containing COCs would be particularly beneficial for treating hirsutism associated with polycystic ovary syndrome (PCOS). Other low‒androgenic-potential progestins, such as a third-generation progestin (norgestimate or desogestrel), might similarly be hypothesized to be advantageous. However, there is currently insufficient evidence to recommend any one COC formulation over another for the indication of PCOS.¹¹

Ovarian cysts: Can COCs be helpful? COCs are commonly prescribed by gynecologists for patients with functional ovarian cysts. It is important to note that COCs have not been found to hasten the resolution of existing cysts, so they should not be used for this purpose.¹² Studies of early COCs, which had high doses of estrogen (on the order of 50 µg), showed lower rates of cysts among users. This effect seems to be attenuated with the lower-estrogen-dose pills that are currently available, but there still appears to be benefit. Therefore, for a patient prone to cysts who desires an oral contraceptive, a COC containing estrogen 35 µg is likely to be the most beneficial of COCs currently on the market.^13,14

Lower-dosage COCs in perimenopause may be beneficial. COCs can ameliorate perimenopausal symptoms including abnormal uterine bleeding and vasomotor symptoms. Clinicians are often hesitant to prescribe COCs for perimenopausal women because of increased risk of VTE, stroke, myocardial infarction, and breast cancer with increasing age. However, age alone is not a contraindication to any contraceptive method. An extended cyclic or continuous regimen COC may be the best choice for a perimenopausal woman in order to avoid vasomotor symptoms that occur during hormone-free intervals. In addition, given the increasing risk of adverse effects like VTE with estrogen dose, a lower estrogen formulation is advisable.¹⁵

Patients with epilepsy who are taking antiepileptic drugs (AEDs) are a special population when it comes to COCs. Certain AEDs induce hepatic enzymes involved in the metabolism and protein binding of COCs, which can result in contraceptive failure. Strong inducers are carbamazepine, oxcarbazepine, perampanel, phenobarbital, phenytoin, and primidone. Weak inducers are clobazam, eslicarbazepine, felbamate, lamotrigine, rufinamide, and topiramate. Women taking any of the above AEDs are recommended to choose a different form of contraception than a COC. However, if they are limited to COCs for some reason, a preparation containing estrogen 50 µg is recommended. It is speculated that the efficacy and adverse effects of COCs with increased hormone doses, used in combination with enzyme-inducing AEDs, should be comparable to those with standard doses when not combined with AEDs; however, this speculation is unproven.¹⁶ There are few COCs on the market with estrogen doses of 50 µg, but a couple of examples are Kelnor and Ogestrel.

Additional factors have to be considered with concurrent COC use with the AED lamotrigine since COCs increase clearance of this agent. Therefore, patients taking lamotrigine who start COCs will need an increase in lamotrigine dose. To avoid fluctuations in lamotrigine serum levels, use of a continuous COC is recommended.¹⁷

Continue to: Pill types to minimize adverse effects or risks...

For women who desire to use a COC for contraception but who are at risk for a particular complication or are bothered by a particular adverse effect, ObGyns can optimize the choice of pill (TABLE 3). For example, women who have adverse effects of nausea and/or breast tenderness may benefit from reducing the estrogen dose to 20 µg or lower.¹⁸

Considering VTE

As discussed previously, VTE is a risk with all COCs, but some pills confer greater risk than others. For one, VTE risk increases with estrogen dose. In addition, VTE risk depends on the type of progestin. Drospirenone and third-generation progestins (norgestimate, gestodene, and desogestrel) confer a higher risk of VTE than first- or second-generation progestins. For example, a pill with estradiol 30 µg and either a third-generation progestin or drospirenone has a 50% to 80% higher risk of VTE compared with a pill with estradiol 30 µg and levonorgestrel.

For patients at particularly high risk for VTE, COCs are contraindicated. For patients for whom COCs are considered medically appropriate but who are at higher risk (eg, obese women), it is wise to use a pill containing a first-generation (norethindrone) or second-generation progestin (levonorgestrel) combined with the lowest dose of estrogen that has tolerable adverse effects.¹⁹

What about hypertension concerns?

Let us turn our attention briefly to hypertension and its relation to COC use. While the American College of Cardiology and the American Heart Association redefined hypertension in 2017 using a threshold of 130/80 mm Hg, the American College of Obstetricians and Gynecologists (ACOG) considers hypertension to be 140/90 mm Hg in terms of safety of using COCs. ACOG states, “women with blood pressure below 140/90 mm Hg may use any hormonal contraceptive method.”²⁰ In women with hypertension in the range of 140‒159 mm Hg systolic or 90‒99 mm Hg diastolic, COCs are category 3 according to the US Medical Eligibility Criteria for Contraceptive Use, meaning that the risks usually outweigh the benefits. For women with blood pressures of 160/110 mm Hg or greater, COCs are category 4 (contraindicated). If a woman with mild hypertension is started on a COC, a drospirenone-containing pill may be the best choice because of its diuretic effects. While other contemporary COCs have been associated with a mild increase in blood pressure, drospirenone-containing pills have not shown this association.²¹

Continue to: At issue: Break-through bleeding, mood, and weight gain...

At issue: Break-through bleeding, mood, and weight gain

For women bothered by intermenstrual bleeding, use of a COC with a third-generation progestin may be preferable to use of one with a first- or second-generation. It may be because of decreased abnormal bleeding that COCs with third-generation progestins have lower discontinuation rates.²² In addition, COCs containing estrogen 20 µg or less are associated with more intermenstrual bleeding than those with more than 20 µg estrogen.²³ Keep in mind that it is common with any COC to have intermenstrual bleeding for the first several months.

For women with pre-existing mood disorders or who report mood changes with COCs, it appears that fluctuations in hormone levels are problematic. Consistently, there is evidence that monophasic pills are preferable to multiphasic and that extended cyclic or continuous use is preferable to traditional cyclic use for mitigating mood adverse effects. There is mixed evidence on whether a low dose of ethinyl estradiol is better for mood.³

Although it is discussed above that randomized controlled trials have not shown an association between COC use and weight gain, many women remain concerned. For these women, a drospirenone-containing COC may be the best choice. Drospirenone has antimineralocorticoid activity, so it may help prevent water retention.

A brief word about multiphasic COCs. While these pills were designed to mimic physiologic hormone fluctuations and minimize hormonal adverse effects, there is insufficient evidence to compare their effects to those of monophasic pills.²⁴ Without such evidence, there is little reason to recommend a multiphasic pill to a patient over the more straightforward monophasic formulation.

Conclusion

There are more nuances to prescribing an optimal COC for a patient than may initially come to mind. It is useful to remember that any formulation of pill may be prescribed in an extended or continuous fashion, and there are benefits for such use for premenstrual dysphoric disorder, heavy menstrual bleeding, perimenopause, and menstrual symptoms. Although there are numerous brands of COCs available, a small cadre will suffice for almost all purposes. Such a “toolbox” of pills could include a pill formatted for continuous use (Seasonique), a low estrogen pill (Loestrin), a drospirenone-containing pill (Yaz), and a pill containing a third-generation progestin and a higher dose of estrogen (Sprintec). ●

In the era of long-acting reversible contraceptives (LARCs), the pill can seem obsolete. However, it is still the second most commonly used birth control method in the United States, chosen by 19% of female contraceptive users as of 2015–2017.¹ It also has noncontraceptive benefits, so it is important that obstetrician-gynecologists are well-versed in its uses. In this article, I will focus on combined oral contraceptives (COCs; TABLE 1), reviewing the major risks, benefits, and adverse effects of COCs before focusing on recommendations for particular formulations of COCs for various patient populations.

Benefits and risks

There are numerous noncontraceptive benefits of COCs, including menstrual cycle regulation; reduced risk of ovarian, endometrial, and colorectal cancer; and treatment of menorrhagia, dysmenorrhea, acne, menstrual migraine, premenstrual syndrome and premenstrual dysphoric disorder, pelvic pain due to endometriosis, and hirsutism.

Common patient concerns

In terms of adverse effects, there are more potential unwanted effects of concern to women than there are ones validated in the literature. Accepted adverse effects include nausea, breast tenderness, and decreased libido. However, one of the most common concerns voiced during contraceptive counseling is that COCs will cause weight gain. A 2014 Cochrane review identified 49 trials studying the weight gain question.² Of those, only 4 had a placebo or nonintervention group. Of these 4, there was no significant difference in weight change between the COC-receiving group and the control group. When patients bring up their concerns, it may help to remind them that women tend to gain weight over time whether or not they are taking a COC.

Another common concern is that COCs cause mood changes. A 2016 review by Schaffir and colleagues sheds some light on this topic,³ albeit limited by the paucity of prospective studies. This review identified only 1 randomized controlled trial comparing depression incidence among women initiating a COC versus a placebo. There was no difference in the incidence of depression among the groups at 3 months. Among 4 large retrospective studies of women using COCs, the agents either had no or a beneficial effect on mood. Schaffir’s review reports that there may be greater mood adverse effects with COCs among women with underlying mood disorders.

Patients may worry that COC use will permanently impair their fertility or delay return to fertility after discontinuation. Research does indicate that return of fertility after stopping COCs often takes several months (compared with immediate fertility after discontinuing a barrier method). However, there still seem to be comparable conception rates within 12 months after discontinuing COCs as there are after discontinuing other common nonhormonal or hormonal contraceptive methods. Fertility is not impacted by the duration of COC use. In addition, return to fertility seems to be comparable after discontinuation of extended cycle or continuous COCs compared with traditional-cycle COCs.⁴

COC safety

Known major risks of COCs include venous thromboembolism (VTE). The risk of VTE is about double among COC users than among nonpregnant nonusers: 3–9 per 10,000 woman-years compared with 1–5.⁵ In a study by the US Food and Drug Administration, drospirenone-containing COCs had double the risk of VTE than other COCs. However, the position of the American College of Obstetricians and Gynecologists on this increased risk of VTE with drospirenone-containing pills is that it is “possible” and “minimal.”⁵ It is important to remember that an alternative to COC use is pregnancy, in which the VTE risk is about double that among COC users, at 5–20 per 10,000 woman-years. This risk increases further in the postpartum period, to 40–65 per 10,000 woman-years.⁵

Another known major risk of COCs is arterial embolic disease, including cerebrovascular accidents and myocardial infarctions. Women at increased risk for these complications include those with hypertension, diabetes, and/or obesity and women who are aged 35 or older and smoke. Interestingly, women with migraines with aura are at increased risk for stroke but not for myocardial infarction. These women increase their risk of stroke 2- to 4-fold if they use COCs.

Continue to: Different pills for different problems...

Different pills for different problems

With so many pills on the market, it is important for clinicians to know how to choose a particular pill for a particular patient. The following discussion assumes that the patient in question desires a COC for contraception, then offers guidance on how to choose a pill with patient-specific noncontraceptive benefits (TABLE 2).

• Introvale and Seasonique, both extended-cycle formulations
• Amethyst, which is formulated without placebo pills so that it can be used continuously
• any other COC prescribed with instructions for the patient to skip placebo pills.

An extrapolated benefit to extended-cycle or continuous COCs use for heavy menstrual bleeding is addressing anemia.

For premenstrual dysphoric disorder, the only randomized controlled trials showing improvement involve drospirenone-ethinyl estradiol pills (Yaz and Yasmin).⁷ There is also evidence that extended cyclic or continuous use of these formulations is more impactful for premenstrual dysphoric disorder than a traditional cycle.⁸

Keeping migraine avoidance and prevention in mind. Various studies have looked at the impact of different COC formulations on menstrual-related symptoms. There is evidence of greater improvement in headache, bloating, and dysmenorrhea with extended cyclic or continuous use compared with traditional cyclic use.⁶

In terms of headache, let us delve into menstrual migraine in particular. Menstrual migraines occur sometime between 2 days prior to 2 days after the first day of menses and are linked to a sharp drop in estrogen levels. COCs are contraindicated in women with menstrual migraines with aura because of the increased stroke risk. For women with menstrual migraines without aura, COCs can prevent migraines. Prevention depends on minimizing fluctuations in estrogen levels; any change in estrogen level greater than 10 µg of ethinyl estradiol may trigger an estrogen-related migraine. All currently available regimens of COCs that comprise 21 days of active pills and 7 days of placebo involve a drop of more than 10 µg. Options that involve a drop of 10 µg or less include any continuous formulation, the extended formulation LoSeasonique (levonorgestrel 0.1 mg and ethinyl estradiol 20 µg for 84 days, then ethinyl estradiol 10 µg for 7 days), and Lo Loestrin (ethinyl estradiol 10 µg and norethindrone 1 mg for 24 days, then ethinyl estradiol 10 µg for 2 days, then placebo for 2 days).⁹

What’s best for acne-prone patients? All COCs should improve acne by increasing levels of sex hormone binding globulin. However, some comparative studies have shown drospirenone-containing COCs to be the most effective for acne. This finding makes sense in light of studies demonstrating antiandrogenic effects of drospirenone.¹⁰

Managing PCOS symptoms. It seems logical, by extension, that drospirenone-containing COCs would be particularly beneficial for treating hirsutism associated with polycystic ovary syndrome (PCOS). Other low‒androgenic-potential progestins, such as a third-generation progestin (norgestimate or desogestrel), might similarly be hypothesized to be advantageous. However, there is currently insufficient evidence to recommend any one COC formulation over another for the indication of PCOS.¹¹

Ovarian cysts: Can COCs be helpful? COCs are commonly prescribed by gynecologists for patients with functional ovarian cysts. It is important to note that COCs have not been found to hasten the resolution of existing cysts, so they should not be used for this purpose.¹² Studies of early COCs, which had high doses of estrogen (on the order of 50 µg), showed lower rates of cysts among users. This effect seems to be attenuated with the lower-estrogen-dose pills that are currently available, but there still appears to be benefit. Therefore, for a patient prone to cysts who desires an oral contraceptive, a COC containing estrogen 35 µg is likely to be the most beneficial of COCs currently on the market.^13,14

Lower-dosage COCs in perimenopause may be beneficial. COCs can ameliorate perimenopausal symptoms including abnormal uterine bleeding and vasomotor symptoms. Clinicians are often hesitant to prescribe COCs for perimenopausal women because of increased risk of VTE, stroke, myocardial infarction, and breast cancer with increasing age. However, age alone is not a contraindication to any contraceptive method. An extended cyclic or continuous regimen COC may be the best choice for a perimenopausal woman in order to avoid vasomotor symptoms that occur during hormone-free intervals. In addition, given the increasing risk of adverse effects like VTE with estrogen dose, a lower estrogen formulation is advisable.¹⁵

Patients with epilepsy who are taking antiepileptic drugs (AEDs) are a special population when it comes to COCs. Certain AEDs induce hepatic enzymes involved in the metabolism and protein binding of COCs, which can result in contraceptive failure. Strong inducers are carbamazepine, oxcarbazepine, perampanel, phenobarbital, phenytoin, and primidone. Weak inducers are clobazam, eslicarbazepine, felbamate, lamotrigine, rufinamide, and topiramate. Women taking any of the above AEDs are recommended to choose a different form of contraception than a COC. However, if they are limited to COCs for some reason, a preparation containing estrogen 50 µg is recommended. It is speculated that the efficacy and adverse effects of COCs with increased hormone doses, used in combination with enzyme-inducing AEDs, should be comparable to those with standard doses when not combined with AEDs; however, this speculation is unproven.¹⁶ There are few COCs on the market with estrogen doses of 50 µg, but a couple of examples are Kelnor and Ogestrel.

Additional factors have to be considered with concurrent COC use with the AED lamotrigine since COCs increase clearance of this agent. Therefore, patients taking lamotrigine who start COCs will need an increase in lamotrigine dose. To avoid fluctuations in lamotrigine serum levels, use of a continuous COC is recommended.¹⁷

Continue to: Pill types to minimize adverse effects or risks...

For women who desire to use a COC for contraception but who are at risk for a particular complication or are bothered by a particular adverse effect, ObGyns can optimize the choice of pill (TABLE 3). For example, women who have adverse effects of nausea and/or breast tenderness may benefit from reducing the estrogen dose to 20 µg or lower.¹⁸

Considering VTE

As discussed previously, VTE is a risk with all COCs, but some pills confer greater risk than others. For one, VTE risk increases with estrogen dose. In addition, VTE risk depends on the type of progestin. Drospirenone and third-generation progestins (norgestimate, gestodene, and desogestrel) confer a higher risk of VTE than first- or second-generation progestins. For example, a pill with estradiol 30 µg and either a third-generation progestin or drospirenone has a 50% to 80% higher risk of VTE compared with a pill with estradiol 30 µg and levonorgestrel.

For patients at particularly high risk for VTE, COCs are contraindicated. For patients for whom COCs are considered medically appropriate but who are at higher risk (eg, obese women), it is wise to use a pill containing a first-generation (norethindrone) or second-generation progestin (levonorgestrel) combined with the lowest dose of estrogen that has tolerable adverse effects.¹⁹

What about hypertension concerns?

Let us turn our attention briefly to hypertension and its relation to COC use. While the American College of Cardiology and the American Heart Association redefined hypertension in 2017 using a threshold of 130/80 mm Hg, the American College of Obstetricians and Gynecologists (ACOG) considers hypertension to be 140/90 mm Hg in terms of safety of using COCs. ACOG states, “women with blood pressure below 140/90 mm Hg may use any hormonal contraceptive method.”²⁰ In women with hypertension in the range of 140‒159 mm Hg systolic or 90‒99 mm Hg diastolic, COCs are category 3 according to the US Medical Eligibility Criteria for Contraceptive Use, meaning that the risks usually outweigh the benefits. For women with blood pressures of 160/110 mm Hg or greater, COCs are category 4 (contraindicated). If a woman with mild hypertension is started on a COC, a drospirenone-containing pill may be the best choice because of its diuretic effects. While other contemporary COCs have been associated with a mild increase in blood pressure, drospirenone-containing pills have not shown this association.²¹

Continue to: At issue: Break-through bleeding, mood, and weight gain...

At issue: Break-through bleeding, mood, and weight gain

For women bothered by intermenstrual bleeding, use of a COC with a third-generation progestin may be preferable to use of one with a first- or second-generation. It may be because of decreased abnormal bleeding that COCs with third-generation progestins have lower discontinuation rates.²² In addition, COCs containing estrogen 20 µg or less are associated with more intermenstrual bleeding than those with more than 20 µg estrogen.²³ Keep in mind that it is common with any COC to have intermenstrual bleeding for the first several months.

For women with pre-existing mood disorders or who report mood changes with COCs, it appears that fluctuations in hormone levels are problematic. Consistently, there is evidence that monophasic pills are preferable to multiphasic and that extended cyclic or continuous use is preferable to traditional cyclic use for mitigating mood adverse effects. There is mixed evidence on whether a low dose of ethinyl estradiol is better for mood.³

Although it is discussed above that randomized controlled trials have not shown an association between COC use and weight gain, many women remain concerned. For these women, a drospirenone-containing COC may be the best choice. Drospirenone has antimineralocorticoid activity, so it may help prevent water retention.

A brief word about multiphasic COCs. While these pills were designed to mimic physiologic hormone fluctuations and minimize hormonal adverse effects, there is insufficient evidence to compare their effects to those of monophasic pills.²⁴ Without such evidence, there is little reason to recommend a multiphasic pill to a patient over the more straightforward monophasic formulation.

Conclusion

There are more nuances to prescribing an optimal COC for a patient than may initially come to mind. It is useful to remember that any formulation of pill may be prescribed in an extended or continuous fashion, and there are benefits for such use for premenstrual dysphoric disorder, heavy menstrual bleeding, perimenopause, and menstrual symptoms. Although there are numerous brands of COCs available, a small cadre will suffice for almost all purposes. Such a “toolbox” of pills could include a pill formatted for continuous use (Seasonique), a low estrogen pill (Loestrin), a drospirenone-containing pill (Yaz), and a pill containing a third-generation progestin and a higher dose of estrogen (Sprintec). ●

Endometrial cancer is the most common gynecologic ma­lignancy, with approximately 59,000 cases diagnosed annually,¹ and a lifetime risk of approximately 3.1% in the United States.² Type I endometrial cancer includes tumors with endometrioid histology that are grade 1 or 2. Type II endometrial cancer includes tumors that have grade 3 endometrioid or nonendometrioid histology, including serous, clear cell, mucinous, squamous transitional cell, mesonephric, and undifferentiated tumors.³ Type I endometrial cancer is hormone sensitive, generally stimulated by estrogen and suppressed by progestins.

Endometrial cancer is diagnosed at a mean age of 63 years,⁴ and only 15% of cases occur before age 50.⁵ Women with an elevated body mass index (BMI) have a markedly increased risk of both Types I and II endometrial cancer (TABLE).⁶ Hence, endometrial cancer is highly prevalent in obese postmenopausal women. For these women health interventions that may reduce the risk of developing endometrial cancer include dieting, physical activity, bariatric surgery, and progestin therapy.

Educating patients is a priority

Many women do not know that postmenopausal bleeding is a sign of endometrial cancer. All postmenopausal women should be advised that if they develop vaginal bleeding they need to be evaluated by a clinician.⁷ Women who are knowledgeable about the link between postmenopausal vaginal bleeding and endometrial cancer can be encouraged to share this information with their postmenopausal friends in order to reach more people with this important information. All obese postmenopausal women should be advised that weight loss and increased physical activity can reduce the risk of developing endometrial cancer.

How weight loss and physical activity affect risk

Intentional weight loss has been reported to reduce the risk of endometrial cancer in postmenopausal women. As part of the Women’s Health Initiative observational study, 36,794 postmenopausal women aged 50 to 79 years with a uterus had their body weight and height measured at entry into the study and after 3 years of follow-up.⁸ During the 11 years following study entry, there were 566 incident cases of endometrial cancer. Compared with women who had a stable weight, intentional weight loss of ≥5% was associated with a 40% reduction in the risk of endometrial cancer (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.42–0.86). Compared with women who had a stable weight, women who had weight gain ≥10% had an increased risk of endometrial cancer (HR, 1.26; 95% CI, 1.00–1.57).

High levels of physical activity may be associated with a decreased risk of endometrial cancer. In one study, compared with a sedentary lifestyle, higher levels of physical activity were reported to be associated with a decreased risk of endometrial cancer.⁹

Continue to: How bariatric surgery affects risk...

Many cancers are associated with obesity, including endometrial, breast, colon, pancreas, gallbladder, and renal. Obesity is associated with increased conversion of androgens to estrogens in fat tissue, stimulating excessive endometrial proliferation and increasing the risk of endometrial hyperplasia and cancer. Bariatric surgery reliably causes sustained weight reduction. Multiple studies have reported that bariatric surgery reduces the risk of endometrial cancer.

Schauer and colleagues used data from the Kaiser Permanente health system to identify 22,198 obese people who had undergone bariatric surgery and 66,427 matched controls who were obese but did not have surgery.¹⁰ The study population was 81% female, with a mean age of 45 years and a mean BMI of 45 kg/m². After an average 3.5 years of follow-up there were 2,542 incident cases of cancer, including 322 cases of endometrial cancer. Compared with conventional weight loss treatment, bariatric surgery reduced the risk of endometrial cancer by 50% (HR, 0.50; 95% CI, 0.37–0.67; P<.001).¹⁰ In addition, bariatric surgery reduced the risk of colon and pancreatic cancer by 41% and 54%, respectively.¹⁰

In the Swedish Obese Subjects (SOS) study, 1,420 women who underwent bariatric surgery and 1,447 matched controls who received conventional obesity treatment were followed for 18 years.¹¹ At study entry, the mean age of the women was approximately 48 years, and the mean BMI was approximately 42 kg/m². In follow-up there were 76 incident cases of endometrial cancer. Compared with women receiving conventional obesity treatment, women who had bariatric surgery had a non–statistically significant 49% decrease in the risk of developing endometrial cancer (HR, 0.51; 95% CI, 0.24–1.10)

In a systematic review of 5 additional studies (not including publications 10 or 11) of the impact of bariatric surgery on the risk of developing endometrial cancer, the surgery was associated with a 68% risk reduction (odds ratio [OR], 0.32; 95% CI, 0.16–0.63) compared with matched obese women that did not have surgery.¹²

Although there are no randomized prospective studies showing that bariatric surgery reduces the risk of endometrial cancer, the weight of the observation evidence is strong. In addition, bariatric surgery was reported to reduce all-cause mortality in the SOS study.¹³ Hence, for obese postmenopausal women, if lifestyle changes do not result in sustained weight loss, bariatric surgery may be an optimal approach to improving health outcomes.

Continue to: Progestin treatment and endometrial cancer risk...

Estrogen stimulates endometrial cell proliferation. Hence, unopposed chronic exposure to estrogen is a major risk factor for developing endometrial hyperplasia and cancer. Progestins block the proliferative effect of estrogen and cause cell differentiation, resulting in stromal decidualization. Progestins also reduce the concentration of estrogen and progesterone receptors and increase the activity of enzymes that convert estradiol to estrone, blocking estrogen-induced endometrial proliferation.¹⁴

In women with endometrial hyperplasia, progestins have been shown to be effective in resolving the hyperplasia in approximately 80% of cases. Both oral progestins and the 52-mg levonorgestrel-containing intrauterine device (LNG-IUD) have been reported to be effective in the treatment of endometrial hyperplasia. In a Cochrane systematic review and meta-analysis, the 52-mg LNG-IUD was reported to be somewhat more effective in resolving endometrial hyperplasia than cyclic oral progestins (89% vs 72%, respectively).¹⁵

Other studies have also reported that the 52 mg LNG-IUD was more effective than oral progestin therapy for women with complex atypical endometrial hyperplasia.¹⁶ There are no large randomized clinical trials of progestin therapy on prevention for future development of endometrial cancer in obese postmenopausal women who have a normal endometrial histology. However, for an obese perimenopausal woman, insertion of a 52-mg LNG-IUD may help to minimize excessive uterine bleeding during the menopause transition and reduce the risk of developing endometrial hyperplasia during the early postmenopause.

We can help our patients reduce their risk of endometrial cancer

Obese postmenopausal women are at increased risk for developing endometrial cancer. Gynecologists play an important role in the prevention and early detection of endometrial cancer. We can make a difference and improve the health of our obese peri- and postmenopausal women by recommending interventions that reduce the risk of endometrial cancer, thereby improving the health of our patients. ●

Endometrial cancer is the most common gynecologic ma­lignancy, with approximately 59,000 cases diagnosed annually,¹ and a lifetime risk of approximately 3.1% in the United States.² Type I endometrial cancer includes tumors with endometrioid histology that are grade 1 or 2. Type II endometrial cancer includes tumors that have grade 3 endometrioid or nonendometrioid histology, including serous, clear cell, mucinous, squamous transitional cell, mesonephric, and undifferentiated tumors.³ Type I endometrial cancer is hormone sensitive, generally stimulated by estrogen and suppressed by progestins.

Endometrial cancer is diagnosed at a mean age of 63 years,⁴ and only 15% of cases occur before age 50.⁵ Women with an elevated body mass index (BMI) have a markedly increased risk of both Types I and II endometrial cancer (TABLE).⁶ Hence, endometrial cancer is highly prevalent in obese postmenopausal women. For these women health interventions that may reduce the risk of developing endometrial cancer include dieting, physical activity, bariatric surgery, and progestin therapy.

Educating patients is a priority

Many women do not know that postmenopausal bleeding is a sign of endometrial cancer. All postmenopausal women should be advised that if they develop vaginal bleeding they need to be evaluated by a clinician.⁷ Women who are knowledgeable about the link between postmenopausal vaginal bleeding and endometrial cancer can be encouraged to share this information with their postmenopausal friends in order to reach more people with this important information. All obese postmenopausal women should be advised that weight loss and increased physical activity can reduce the risk of developing endometrial cancer.

How weight loss and physical activity affect risk

Intentional weight loss has been reported to reduce the risk of endometrial cancer in postmenopausal women. As part of the Women’s Health Initiative observational study, 36,794 postmenopausal women aged 50 to 79 years with a uterus had their body weight and height measured at entry into the study and after 3 years of follow-up.⁸ During the 11 years following study entry, there were 566 incident cases of endometrial cancer. Compared with women who had a stable weight, intentional weight loss of ≥5% was associated with a 40% reduction in the risk of endometrial cancer (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.42–0.86). Compared with women who had a stable weight, women who had weight gain ≥10% had an increased risk of endometrial cancer (HR, 1.26; 95% CI, 1.00–1.57).

High levels of physical activity may be associated with a decreased risk of endometrial cancer. In one study, compared with a sedentary lifestyle, higher levels of physical activity were reported to be associated with a decreased risk of endometrial cancer.⁹

Continue to: How bariatric surgery affects risk...

Many cancers are associated with obesity, including endometrial, breast, colon, pancreas, gallbladder, and renal. Obesity is associated with increased conversion of androgens to estrogens in fat tissue, stimulating excessive endometrial proliferation and increasing the risk of endometrial hyperplasia and cancer. Bariatric surgery reliably causes sustained weight reduction. Multiple studies have reported that bariatric surgery reduces the risk of endometrial cancer.

Schauer and colleagues used data from the Kaiser Permanente health system to identify 22,198 obese people who had undergone bariatric surgery and 66,427 matched controls who were obese but did not have surgery.¹⁰ The study population was 81% female, with a mean age of 45 years and a mean BMI of 45 kg/m². After an average 3.5 years of follow-up there were 2,542 incident cases of cancer, including 322 cases of endometrial cancer. Compared with conventional weight loss treatment, bariatric surgery reduced the risk of endometrial cancer by 50% (HR, 0.50; 95% CI, 0.37–0.67; P<.001).¹⁰ In addition, bariatric surgery reduced the risk of colon and pancreatic cancer by 41% and 54%, respectively.¹⁰

In the Swedish Obese Subjects (SOS) study, 1,420 women who underwent bariatric surgery and 1,447 matched controls who received conventional obesity treatment were followed for 18 years.¹¹ At study entry, the mean age of the women was approximately 48 years, and the mean BMI was approximately 42 kg/m². In follow-up there were 76 incident cases of endometrial cancer. Compared with women receiving conventional obesity treatment, women who had bariatric surgery had a non–statistically significant 49% decrease in the risk of developing endometrial cancer (HR, 0.51; 95% CI, 0.24–1.10)

In a systematic review of 5 additional studies (not including publications 10 or 11) of the impact of bariatric surgery on the risk of developing endometrial cancer, the surgery was associated with a 68% risk reduction (odds ratio [OR], 0.32; 95% CI, 0.16–0.63) compared with matched obese women that did not have surgery.¹²

Although there are no randomized prospective studies showing that bariatric surgery reduces the risk of endometrial cancer, the weight of the observation evidence is strong. In addition, bariatric surgery was reported to reduce all-cause mortality in the SOS study.¹³ Hence, for obese postmenopausal women, if lifestyle changes do not result in sustained weight loss, bariatric surgery may be an optimal approach to improving health outcomes.

Continue to: Progestin treatment and endometrial cancer risk...

Estrogen stimulates endometrial cell proliferation. Hence, unopposed chronic exposure to estrogen is a major risk factor for developing endometrial hyperplasia and cancer. Progestins block the proliferative effect of estrogen and cause cell differentiation, resulting in stromal decidualization. Progestins also reduce the concentration of estrogen and progesterone receptors and increase the activity of enzymes that convert estradiol to estrone, blocking estrogen-induced endometrial proliferation.¹⁴

In women with endometrial hyperplasia, progestins have been shown to be effective in resolving the hyperplasia in approximately 80% of cases. Both oral progestins and the 52-mg levonorgestrel-containing intrauterine device (LNG-IUD) have been reported to be effective in the treatment of endometrial hyperplasia. In a Cochrane systematic review and meta-analysis, the 52-mg LNG-IUD was reported to be somewhat more effective in resolving endometrial hyperplasia than cyclic oral progestins (89% vs 72%, respectively).¹⁵

Other studies have also reported that the 52 mg LNG-IUD was more effective than oral progestin therapy for women with complex atypical endometrial hyperplasia.¹⁶ There are no large randomized clinical trials of progestin therapy on prevention for future development of endometrial cancer in obese postmenopausal women who have a normal endometrial histology. However, for an obese perimenopausal woman, insertion of a 52-mg LNG-IUD may help to minimize excessive uterine bleeding during the menopause transition and reduce the risk of developing endometrial hyperplasia during the early postmenopause.

We can help our patients reduce their risk of endometrial cancer

Obese postmenopausal women are at increased risk for developing endometrial cancer. Gynecologists play an important role in the prevention and early detection of endometrial cancer. We can make a difference and improve the health of our obese peri- and postmenopausal women by recommending interventions that reduce the risk of endometrial cancer, thereby improving the health of our patients. ●

Endometrial cancer is the most common gynecologic ma­lignancy, with approximately 59,000 cases diagnosed annually,¹ and a lifetime risk of approximately 3.1% in the United States.² Type I endometrial cancer includes tumors with endometrioid histology that are grade 1 or 2. Type II endometrial cancer includes tumors that have grade 3 endometrioid or nonendometrioid histology, including serous, clear cell, mucinous, squamous transitional cell, mesonephric, and undifferentiated tumors.³ Type I endometrial cancer is hormone sensitive, generally stimulated by estrogen and suppressed by progestins.

Endometrial cancer is diagnosed at a mean age of 63 years,⁴ and only 15% of cases occur before age 50.⁵ Women with an elevated body mass index (BMI) have a markedly increased risk of both Types I and II endometrial cancer (TABLE).⁶ Hence, endometrial cancer is highly prevalent in obese postmenopausal women. For these women health interventions that may reduce the risk of developing endometrial cancer include dieting, physical activity, bariatric surgery, and progestin therapy.

Educating patients is a priority

Many women do not know that postmenopausal bleeding is a sign of endometrial cancer. All postmenopausal women should be advised that if they develop vaginal bleeding they need to be evaluated by a clinician.⁷ Women who are knowledgeable about the link between postmenopausal vaginal bleeding and endometrial cancer can be encouraged to share this information with their postmenopausal friends in order to reach more people with this important information. All obese postmenopausal women should be advised that weight loss and increased physical activity can reduce the risk of developing endometrial cancer.

How weight loss and physical activity affect risk

Intentional weight loss has been reported to reduce the risk of endometrial cancer in postmenopausal women. As part of the Women’s Health Initiative observational study, 36,794 postmenopausal women aged 50 to 79 years with a uterus had their body weight and height measured at entry into the study and after 3 years of follow-up.⁸ During the 11 years following study entry, there were 566 incident cases of endometrial cancer. Compared with women who had a stable weight, intentional weight loss of ≥5% was associated with a 40% reduction in the risk of endometrial cancer (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.42–0.86). Compared with women who had a stable weight, women who had weight gain ≥10% had an increased risk of endometrial cancer (HR, 1.26; 95% CI, 1.00–1.57).

High levels of physical activity may be associated with a decreased risk of endometrial cancer. In one study, compared with a sedentary lifestyle, higher levels of physical activity were reported to be associated with a decreased risk of endometrial cancer.⁹

Continue to: How bariatric surgery affects risk...

Many cancers are associated with obesity, including endometrial, breast, colon, pancreas, gallbladder, and renal. Obesity is associated with increased conversion of androgens to estrogens in fat tissue, stimulating excessive endometrial proliferation and increasing the risk of endometrial hyperplasia and cancer. Bariatric surgery reliably causes sustained weight reduction. Multiple studies have reported that bariatric surgery reduces the risk of endometrial cancer.

Schauer and colleagues used data from the Kaiser Permanente health system to identify 22,198 obese people who had undergone bariatric surgery and 66,427 matched controls who were obese but did not have surgery.¹⁰ The study population was 81% female, with a mean age of 45 years and a mean BMI of 45 kg/m². After an average 3.5 years of follow-up there were 2,542 incident cases of cancer, including 322 cases of endometrial cancer. Compared with conventional weight loss treatment, bariatric surgery reduced the risk of endometrial cancer by 50% (HR, 0.50; 95% CI, 0.37–0.67; P<.001).¹⁰ In addition, bariatric surgery reduced the risk of colon and pancreatic cancer by 41% and 54%, respectively.¹⁰

In the Swedish Obese Subjects (SOS) study, 1,420 women who underwent bariatric surgery and 1,447 matched controls who received conventional obesity treatment were followed for 18 years.¹¹ At study entry, the mean age of the women was approximately 48 years, and the mean BMI was approximately 42 kg/m². In follow-up there were 76 incident cases of endometrial cancer. Compared with women receiving conventional obesity treatment, women who had bariatric surgery had a non–statistically significant 49% decrease in the risk of developing endometrial cancer (HR, 0.51; 95% CI, 0.24–1.10)

In a systematic review of 5 additional studies (not including publications 10 or 11) of the impact of bariatric surgery on the risk of developing endometrial cancer, the surgery was associated with a 68% risk reduction (odds ratio [OR], 0.32; 95% CI, 0.16–0.63) compared with matched obese women that did not have surgery.¹²

Although there are no randomized prospective studies showing that bariatric surgery reduces the risk of endometrial cancer, the weight of the observation evidence is strong. In addition, bariatric surgery was reported to reduce all-cause mortality in the SOS study.¹³ Hence, for obese postmenopausal women, if lifestyle changes do not result in sustained weight loss, bariatric surgery may be an optimal approach to improving health outcomes.

Continue to: Progestin treatment and endometrial cancer risk...

Estrogen stimulates endometrial cell proliferation. Hence, unopposed chronic exposure to estrogen is a major risk factor for developing endometrial hyperplasia and cancer. Progestins block the proliferative effect of estrogen and cause cell differentiation, resulting in stromal decidualization. Progestins also reduce the concentration of estrogen and progesterone receptors and increase the activity of enzymes that convert estradiol to estrone, blocking estrogen-induced endometrial proliferation.¹⁴

In women with endometrial hyperplasia, progestins have been shown to be effective in resolving the hyperplasia in approximately 80% of cases. Both oral progestins and the 52-mg levonorgestrel-containing intrauterine device (LNG-IUD) have been reported to be effective in the treatment of endometrial hyperplasia. In a Cochrane systematic review and meta-analysis, the 52-mg LNG-IUD was reported to be somewhat more effective in resolving endometrial hyperplasia than cyclic oral progestins (89% vs 72%, respectively).¹⁵

Other studies have also reported that the 52 mg LNG-IUD was more effective than oral progestin therapy for women with complex atypical endometrial hyperplasia.¹⁶ There are no large randomized clinical trials of progestin therapy on prevention for future development of endometrial cancer in obese postmenopausal women who have a normal endometrial histology. However, for an obese perimenopausal woman, insertion of a 52-mg LNG-IUD may help to minimize excessive uterine bleeding during the menopause transition and reduce the risk of developing endometrial hyperplasia during the early postmenopause.

We can help our patients reduce their risk of endometrial cancer

Obese postmenopausal women are at increased risk for developing endometrial cancer. Gynecologists play an important role in the prevention and early detection of endometrial cancer. We can make a difference and improve the health of our obese peri- and postmenopausal women by recommending interventions that reduce the risk of endometrial cancer, thereby improving the health of our patients. ●

More than 34 million adults in the US have type 2 diabetes mellitus (T2DM), a chronic progressive disease identified by worsening hyperglycemia and micro- and macrovascular complications.¹ Consequently, 12.2% of the US adult population is currently at risk for macrovascular diseases, such as stroke and coronary artery disease (CAD) and microvascular diseases, such as neuropathy and diabetic nephropathy.¹

T2DM is the most common comorbid risk factor for chronic kidney disease (CKD) and the leading cause of end-stage renal disease (ESRD). As of 2017, about 750,000 Americans have CKD stage 5 requiring dialysis, and 50% of these patients have preexisting diabetic nephropathy.² Rates of mortality and morbidity are observed to be higher in patients with both CKD and T2DM compared with patients with CKD without T2DM.² Previous clinical trials, including the United Kingdom Prospective Diabetes Study of 1998, have proven that optimal glycemic control decreases the risk of complications of T2DM (ie, nephropathy) in the general population.³ Conversely, tight glycemic control that targets hemoglobin A_1c (HbA_1c) < 7%, in patients with T2DM with ESRD has not shown the same benefits and may lead to worse outcomes. It is postulated that this may be due to the increased incidence of hypoglycemia in this patient population.⁴

Dialysis has varying effects on patients both with and without T2DM. While patients with ESRD without T2DM have the potential to develop impaired glucose tolerance and T2DM, about 33% of patients with T2DM on dialysis actually have HbA_1c < 6%.⁵ In these patients, glycemic control improves spontaneously as their disease progresses, leading to a decrease or cessation of insulin or other antidiabetic medications. This phenomenon, known as burnt-out diabetes, is characterized by (1) alterations in glucose homeostasis and normoglycemia without antidiabetic treatment; (2) HbA_1c levels < 6% despite having established T2DM; (3) decline in insulin requirements or cessation of insulin altogether; and (4) spontaneous hypoglycemia.

There is a misconception that burnt-out diabetes is a favorable condition due to the alteration of the natural course of T2DM. Although this may be true, patients with this condition are prone to develop hypoglycemic episodes and may be linked to poor survival outcomes due to low HbA_1c.^6,7

Since Kalantar-Zadeh and colleagues presented a 2009 case study, there has been a lack of research regarding this unique condition.⁸ The purpose of this case study is to shed further light on burnt-out diabetes and present a patient case pertaining to the challenges of glycemic control in ESRD.

Case Presentation

Mr. A is a 49-year-old Hispanic male veteran with a history of ESRD on hemodialysis (HD) for 6 years, anemia of CKD, and T2DM for 22 years. The patient also has an extensive cardiovascular disease history, including hypertension, hyperlipidemia, and CAD status post-4-vessel coronary artery bypass graft in December 2014. The patient receives in-home HD Monday, Wednesday, and Friday and is on the wait list for kidney transplantation. The patient’s T2DM is managed by a primary care clinical pharmacy specialist (CPS) at the Michael E. DeBakey Veteran Affairs Medical Center (MEDVAMC) in Houston, Texas.

Mr. A’s antidiabetic regimen is 45 units of subcutaneous insulin glargine every morning; insulin aspart sliding scale (about 15-27 units) subcutaneous 3 times daily with meals; and saxagliptin 2.5 mg by mouth once daily.

At a follow-up visit with the CPS, Mr. A stated, “I feel fine except for the occasional low blood sugar episode.” The patient’s most recent HbA_1c was 6.1%, and he reported medication adherence and no signs or symptoms of hyperglycemia (ie, polydipsia, polyphagia, nocturia, visual disturbances). Mr. A reported no use of alcohol, tobacco, or illicit drugs. He walks 1 mile every other day and participates in self-monitoring blood glucose (SMBG) about 2 to 3 times daily (Table 1).

Analysis

Few articles on potential contributors to burnt-out diabetes have been published.^6,7 These articles discuss decreased renal and hepatic clearance of insulin (which increases its half-life) hypoglycemia during HD, and low HbA_1c due to preexisting anemia. Inappropriately low HbA_1c levels may be secondary to, but not limited to, hemolysis, recent blood transfusion, acute blood loss, and medications, such as erythropoietin-stimulating agents (ESAs).⁹ The conditions that affect red blood cell turnover are common in patients with advanced CKD and may result in discrepancies in HbA_1c levels.

Glycated hemoglobin is a series of minor hemoglobin components formed by the adduction of various carbohydrate molecules to hemoglobin. HbA_1c is the largest fraction formed and the most consistent index of the concentration of glucose in the blood.¹⁰ Hence, HbA_1c is the traditional indicator of overall glycemic control. The current HbA_1c goals recommended by the American Diabetes Association are derived from landmark trials conducted with patients in the general adult diabetic non-CKD population. However, hemoglobin measurements can be confounded by conditions present in ESRD and tend to underestimate glucose measurements in patients with T2DM on HD. Despite this, HbA_1c is still regarded as a reasonable measure of glycemic control even in patients with ESRD; however, alternative markers of glycemia may be preferable.¹¹

Although HbA_1c is the gold standard, there are other laboratory measures of average glycemic control available. Fructosamine is a ketoamine formed when glucose binds to serum proteins. When these proteins are exposed to high concentrations of glucose, they experience increased glycation. Fructosamine assays measure the total glycated serum proteins, of which albumin accounts for about 90%.¹¹ Because the half-life of serum proteins is about 20 days, fructosamine levels can reflect glycemic control over a 2- to 3-week period. This is advantageous in conditions that affect the average age of red blood cells, in pregnancy where frequent monitoring and measures of short-term glucose control are especially important, and in the evaluation of a medication adjustment in the management of T2DM. However, this test is not without its limitations. It is less reliable in settings of decreased protein levels (eg, liver disease), there is a lack of availability in routine practice, and reference levels have not been established.¹¹

Hypoglycemic Episodes

At the 2-month follow-up visit with the CPS, Mr. A reported having 5 hypoglycemic episodes in the past 30 days. He also stated he would forget to take his insulin aspart dose before dinner about 3 to 4 times a week but would take it 30 to 60 minutes after the meal. Mr. A did not bring his glucometer or SMBG readings to the visit, but he indicated that his blood glucose levels continued to fluctuate and were elevated when consuming carbohydrates.

Laboratory tests 1 month prior to the 2-month follow-up visit showed HbA_1c of 7.3%, which had increased from his previous level of 6.1%. He was counseled on the proper administration of insulin aspart and lifestyle modifications. A fructosamine level was ordered at this visit to further assess his glycemic control. A follow-up appointment and laboratory workup (fructosamine and HbA_1c) were scheduled for 2 months from the visit (Table 3).

Mr. A was educated on the unreliability of his HbA_1c levels secondary to his condition of ESRD on HD. He was counseled on the purpose of fructosamine and how it may be a better predictor of his glycemic control and morbidity. Mr. A continued to be followed closely by the primary care CPS for T2DM management.

Discussion

Management of T2DM in patients with ESRD presents challenges for clinicians in determining HbA_1c goals and selecting appropriate medication options. The 2012 Kidney Disease Outcomes Quality Initiative (KDOQI) diabetes guideline does not recommend treatment for patients with substantially reduced kidney function to a target HbA_1c < 7% due to risk of hypoglycemia.¹³ Although a target HbA_1c > 7% is suggested for these patients, little is known about appropriate glycemic control in these patients as there is a paucity of prospective, randomized clinical trials that include patients with advanced CKD.¹³

Moreover, many oral antidiabetic medications and their metabolites are cleared by the kidneys and, therefore, pose with potential harm for patients with CKD. Because of this, insulin is the medication of choice for patients with ESRD.⁷ Although insulin requirements may diminish with worsening kidney function, insulin provides the safest method of glycemic control. Insulin dosing can be individualized according to a patient’s renal status as there is no uniformity in renal dose adjustments. There are some noninsulin antidiabetic agents that can be used in ESRD, but use of these agents requires close monitoring and evaluation of the medication’s pharmacokinetics (Table 4). Overall, medication management can be a difficult task for patients with T2DM and ESRD, but antidiabetic regimens may be reduced or discontinued altogether in burnt-out diabetes.

Conclusions

Patients with T2DM and ESRD on dialysis may have higher morbidity and mortality rates than the rates of those without T2DM. It has been shown in various studies that very low HbA_1c (< 5%) and high HbA_1c (> 8%) are associated with poor survival. Some patients with T2DM on dialysis may experience burnt-out diabetes in which they may have normoglycemia and a HbA_1c below goal; despite these facts, this condition is not positive and can be linked to bad outcomes. In patients with T2DM and ESRD, insulin is the antidiabetic medication of choice, and we recommend a HbA_1c target of 6 to 8%. In this patient population, consider using fructosamine levels or other measures of glycemic control to supplement HbA_1c and glucose values to provide a better assessment of glycemic control, morbidity, and mortality. Larger clinical trials are needed to assist in answering questions regarding mortality and optimal HbA_1c targets in burnt-out diabetes.

More than 34 million adults in the US have type 2 diabetes mellitus (T2DM), a chronic progressive disease identified by worsening hyperglycemia and micro- and macrovascular complications.¹ Consequently, 12.2% of the US adult population is currently at risk for macrovascular diseases, such as stroke and coronary artery disease (CAD) and microvascular diseases, such as neuropathy and diabetic nephropathy.¹

T2DM is the most common comorbid risk factor for chronic kidney disease (CKD) and the leading cause of end-stage renal disease (ESRD). As of 2017, about 750,000 Americans have CKD stage 5 requiring dialysis, and 50% of these patients have preexisting diabetic nephropathy.² Rates of mortality and morbidity are observed to be higher in patients with both CKD and T2DM compared with patients with CKD without T2DM.² Previous clinical trials, including the United Kingdom Prospective Diabetes Study of 1998, have proven that optimal glycemic control decreases the risk of complications of T2DM (ie, nephropathy) in the general population.³ Conversely, tight glycemic control that targets hemoglobin A_1c (HbA_1c) < 7%, in patients with T2DM with ESRD has not shown the same benefits and may lead to worse outcomes. It is postulated that this may be due to the increased incidence of hypoglycemia in this patient population.⁴

Dialysis has varying effects on patients both with and without T2DM. While patients with ESRD without T2DM have the potential to develop impaired glucose tolerance and T2DM, about 33% of patients with T2DM on dialysis actually have HbA_1c < 6%.⁵ In these patients, glycemic control improves spontaneously as their disease progresses, leading to a decrease or cessation of insulin or other antidiabetic medications. This phenomenon, known as burnt-out diabetes, is characterized by (1) alterations in glucose homeostasis and normoglycemia without antidiabetic treatment; (2) HbA_1c levels < 6% despite having established T2DM; (3) decline in insulin requirements or cessation of insulin altogether; and (4) spontaneous hypoglycemia.

There is a misconception that burnt-out diabetes is a favorable condition due to the alteration of the natural course of T2DM. Although this may be true, patients with this condition are prone to develop hypoglycemic episodes and may be linked to poor survival outcomes due to low HbA_1c.^6,7

Since Kalantar-Zadeh and colleagues presented a 2009 case study, there has been a lack of research regarding this unique condition.⁸ The purpose of this case study is to shed further light on burnt-out diabetes and present a patient case pertaining to the challenges of glycemic control in ESRD.

Case Presentation

Mr. A is a 49-year-old Hispanic male veteran with a history of ESRD on hemodialysis (HD) for 6 years, anemia of CKD, and T2DM for 22 years. The patient also has an extensive cardiovascular disease history, including hypertension, hyperlipidemia, and CAD status post-4-vessel coronary artery bypass graft in December 2014. The patient receives in-home HD Monday, Wednesday, and Friday and is on the wait list for kidney transplantation. The patient’s T2DM is managed by a primary care clinical pharmacy specialist (CPS) at the Michael E. DeBakey Veteran Affairs Medical Center (MEDVAMC) in Houston, Texas.

Mr. A’s antidiabetic regimen is 45 units of subcutaneous insulin glargine every morning; insulin aspart sliding scale (about 15-27 units) subcutaneous 3 times daily with meals; and saxagliptin 2.5 mg by mouth once daily.

At a follow-up visit with the CPS, Mr. A stated, “I feel fine except for the occasional low blood sugar episode.” The patient’s most recent HbA_1c was 6.1%, and he reported medication adherence and no signs or symptoms of hyperglycemia (ie, polydipsia, polyphagia, nocturia, visual disturbances). Mr. A reported no use of alcohol, tobacco, or illicit drugs. He walks 1 mile every other day and participates in self-monitoring blood glucose (SMBG) about 2 to 3 times daily (Table 1).

Analysis

Few articles on potential contributors to burnt-out diabetes have been published.^6,7 These articles discuss decreased renal and hepatic clearance of insulin (which increases its half-life) hypoglycemia during HD, and low HbA_1c due to preexisting anemia. Inappropriately low HbA_1c levels may be secondary to, but not limited to, hemolysis, recent blood transfusion, acute blood loss, and medications, such as erythropoietin-stimulating agents (ESAs).⁹ The conditions that affect red blood cell turnover are common in patients with advanced CKD and may result in discrepancies in HbA_1c levels.

Glycated hemoglobin is a series of minor hemoglobin components formed by the adduction of various carbohydrate molecules to hemoglobin. HbA_1c is the largest fraction formed and the most consistent index of the concentration of glucose in the blood.¹⁰ Hence, HbA_1c is the traditional indicator of overall glycemic control. The current HbA_1c goals recommended by the American Diabetes Association are derived from landmark trials conducted with patients in the general adult diabetic non-CKD population. However, hemoglobin measurements can be confounded by conditions present in ESRD and tend to underestimate glucose measurements in patients with T2DM on HD. Despite this, HbA_1c is still regarded as a reasonable measure of glycemic control even in patients with ESRD; however, alternative markers of glycemia may be preferable.¹¹

Although HbA_1c is the gold standard, there are other laboratory measures of average glycemic control available. Fructosamine is a ketoamine formed when glucose binds to serum proteins. When these proteins are exposed to high concentrations of glucose, they experience increased glycation. Fructosamine assays measure the total glycated serum proteins, of which albumin accounts for about 90%.¹¹ Because the half-life of serum proteins is about 20 days, fructosamine levels can reflect glycemic control over a 2- to 3-week period. This is advantageous in conditions that affect the average age of red blood cells, in pregnancy where frequent monitoring and measures of short-term glucose control are especially important, and in the evaluation of a medication adjustment in the management of T2DM. However, this test is not without its limitations. It is less reliable in settings of decreased protein levels (eg, liver disease), there is a lack of availability in routine practice, and reference levels have not been established.¹¹

Hypoglycemic Episodes

At the 2-month follow-up visit with the CPS, Mr. A reported having 5 hypoglycemic episodes in the past 30 days. He also stated he would forget to take his insulin aspart dose before dinner about 3 to 4 times a week but would take it 30 to 60 minutes after the meal. Mr. A did not bring his glucometer or SMBG readings to the visit, but he indicated that his blood glucose levels continued to fluctuate and were elevated when consuming carbohydrates.

Laboratory tests 1 month prior to the 2-month follow-up visit showed HbA_1c of 7.3%, which had increased from his previous level of 6.1%. He was counseled on the proper administration of insulin aspart and lifestyle modifications. A fructosamine level was ordered at this visit to further assess his glycemic control. A follow-up appointment and laboratory workup (fructosamine and HbA_1c) were scheduled for 2 months from the visit (Table 3).

Mr. A was educated on the unreliability of his HbA_1c levels secondary to his condition of ESRD on HD. He was counseled on the purpose of fructosamine and how it may be a better predictor of his glycemic control and morbidity. Mr. A continued to be followed closely by the primary care CPS for T2DM management.

Discussion

Management of T2DM in patients with ESRD presents challenges for clinicians in determining HbA_1c goals and selecting appropriate medication options. The 2012 Kidney Disease Outcomes Quality Initiative (KDOQI) diabetes guideline does not recommend treatment for patients with substantially reduced kidney function to a target HbA_1c < 7% due to risk of hypoglycemia.¹³ Although a target HbA_1c > 7% is suggested for these patients, little is known about appropriate glycemic control in these patients as there is a paucity of prospective, randomized clinical trials that include patients with advanced CKD.¹³

Moreover, many oral antidiabetic medications and their metabolites are cleared by the kidneys and, therefore, pose with potential harm for patients with CKD. Because of this, insulin is the medication of choice for patients with ESRD.⁷ Although insulin requirements may diminish with worsening kidney function, insulin provides the safest method of glycemic control. Insulin dosing can be individualized according to a patient’s renal status as there is no uniformity in renal dose adjustments. There are some noninsulin antidiabetic agents that can be used in ESRD, but use of these agents requires close monitoring and evaluation of the medication’s pharmacokinetics (Table 4). Overall, medication management can be a difficult task for patients with T2DM and ESRD, but antidiabetic regimens may be reduced or discontinued altogether in burnt-out diabetes.

Conclusions

Patients with T2DM and ESRD on dialysis may have higher morbidity and mortality rates than the rates of those without T2DM. It has been shown in various studies that very low HbA_1c (< 5%) and high HbA_1c (> 8%) are associated with poor survival. Some patients with T2DM on dialysis may experience burnt-out diabetes in which they may have normoglycemia and a HbA_1c below goal; despite these facts, this condition is not positive and can be linked to bad outcomes. In patients with T2DM and ESRD, insulin is the antidiabetic medication of choice, and we recommend a HbA_1c target of 6 to 8%. In this patient population, consider using fructosamine levels or other measures of glycemic control to supplement HbA_1c and glucose values to provide a better assessment of glycemic control, morbidity, and mortality. Larger clinical trials are needed to assist in answering questions regarding mortality and optimal HbA_1c targets in burnt-out diabetes.

More than 34 million adults in the US have type 2 diabetes mellitus (T2DM), a chronic progressive disease identified by worsening hyperglycemia and micro- and macrovascular complications.¹ Consequently, 12.2% of the US adult population is currently at risk for macrovascular diseases, such as stroke and coronary artery disease (CAD) and microvascular diseases, such as neuropathy and diabetic nephropathy.¹

T2DM is the most common comorbid risk factor for chronic kidney disease (CKD) and the leading cause of end-stage renal disease (ESRD). As of 2017, about 750,000 Americans have CKD stage 5 requiring dialysis, and 50% of these patients have preexisting diabetic nephropathy.² Rates of mortality and morbidity are observed to be higher in patients with both CKD and T2DM compared with patients with CKD without T2DM.² Previous clinical trials, including the United Kingdom Prospective Diabetes Study of 1998, have proven that optimal glycemic control decreases the risk of complications of T2DM (ie, nephropathy) in the general population.³ Conversely, tight glycemic control that targets hemoglobin A_1c (HbA_1c) < 7%, in patients with T2DM with ESRD has not shown the same benefits and may lead to worse outcomes. It is postulated that this may be due to the increased incidence of hypoglycemia in this patient population.⁴

Dialysis has varying effects on patients both with and without T2DM. While patients with ESRD without T2DM have the potential to develop impaired glucose tolerance and T2DM, about 33% of patients with T2DM on dialysis actually have HbA_1c < 6%.⁵ In these patients, glycemic control improves spontaneously as their disease progresses, leading to a decrease or cessation of insulin or other antidiabetic medications. This phenomenon, known as burnt-out diabetes, is characterized by (1) alterations in glucose homeostasis and normoglycemia without antidiabetic treatment; (2) HbA_1c levels < 6% despite having established T2DM; (3) decline in insulin requirements or cessation of insulin altogether; and (4) spontaneous hypoglycemia.

There is a misconception that burnt-out diabetes is a favorable condition due to the alteration of the natural course of T2DM. Although this may be true, patients with this condition are prone to develop hypoglycemic episodes and may be linked to poor survival outcomes due to low HbA_1c.^6,7

Since Kalantar-Zadeh and colleagues presented a 2009 case study, there has been a lack of research regarding this unique condition.⁸ The purpose of this case study is to shed further light on burnt-out diabetes and present a patient case pertaining to the challenges of glycemic control in ESRD.

Case Presentation

Mr. A is a 49-year-old Hispanic male veteran with a history of ESRD on hemodialysis (HD) for 6 years, anemia of CKD, and T2DM for 22 years. The patient also has an extensive cardiovascular disease history, including hypertension, hyperlipidemia, and CAD status post-4-vessel coronary artery bypass graft in December 2014. The patient receives in-home HD Monday, Wednesday, and Friday and is on the wait list for kidney transplantation. The patient’s T2DM is managed by a primary care clinical pharmacy specialist (CPS) at the Michael E. DeBakey Veteran Affairs Medical Center (MEDVAMC) in Houston, Texas.

Mr. A’s antidiabetic regimen is 45 units of subcutaneous insulin glargine every morning; insulin aspart sliding scale (about 15-27 units) subcutaneous 3 times daily with meals; and saxagliptin 2.5 mg by mouth once daily.

At a follow-up visit with the CPS, Mr. A stated, “I feel fine except for the occasional low blood sugar episode.” The patient’s most recent HbA_1c was 6.1%, and he reported medication adherence and no signs or symptoms of hyperglycemia (ie, polydipsia, polyphagia, nocturia, visual disturbances). Mr. A reported no use of alcohol, tobacco, or illicit drugs. He walks 1 mile every other day and participates in self-monitoring blood glucose (SMBG) about 2 to 3 times daily (Table 1).

Analysis

Few articles on potential contributors to burnt-out diabetes have been published.^6,7 These articles discuss decreased renal and hepatic clearance of insulin (which increases its half-life) hypoglycemia during HD, and low HbA_1c due to preexisting anemia. Inappropriately low HbA_1c levels may be secondary to, but not limited to, hemolysis, recent blood transfusion, acute blood loss, and medications, such as erythropoietin-stimulating agents (ESAs).⁹ The conditions that affect red blood cell turnover are common in patients with advanced CKD and may result in discrepancies in HbA_1c levels.

Glycated hemoglobin is a series of minor hemoglobin components formed by the adduction of various carbohydrate molecules to hemoglobin. HbA_1c is the largest fraction formed and the most consistent index of the concentration of glucose in the blood.¹⁰ Hence, HbA_1c is the traditional indicator of overall glycemic control. The current HbA_1c goals recommended by the American Diabetes Association are derived from landmark trials conducted with patients in the general adult diabetic non-CKD population. However, hemoglobin measurements can be confounded by conditions present in ESRD and tend to underestimate glucose measurements in patients with T2DM on HD. Despite this, HbA_1c is still regarded as a reasonable measure of glycemic control even in patients with ESRD; however, alternative markers of glycemia may be preferable.¹¹

Although HbA_1c is the gold standard, there are other laboratory measures of average glycemic control available. Fructosamine is a ketoamine formed when glucose binds to serum proteins. When these proteins are exposed to high concentrations of glucose, they experience increased glycation. Fructosamine assays measure the total glycated serum proteins, of which albumin accounts for about 90%.¹¹ Because the half-life of serum proteins is about 20 days, fructosamine levels can reflect glycemic control over a 2- to 3-week period. This is advantageous in conditions that affect the average age of red blood cells, in pregnancy where frequent monitoring and measures of short-term glucose control are especially important, and in the evaluation of a medication adjustment in the management of T2DM. However, this test is not without its limitations. It is less reliable in settings of decreased protein levels (eg, liver disease), there is a lack of availability in routine practice, and reference levels have not been established.¹¹

Hypoglycemic Episodes

At the 2-month follow-up visit with the CPS, Mr. A reported having 5 hypoglycemic episodes in the past 30 days. He also stated he would forget to take his insulin aspart dose before dinner about 3 to 4 times a week but would take it 30 to 60 minutes after the meal. Mr. A did not bring his glucometer or SMBG readings to the visit, but he indicated that his blood glucose levels continued to fluctuate and were elevated when consuming carbohydrates.

Laboratory tests 1 month prior to the 2-month follow-up visit showed HbA_1c of 7.3%, which had increased from his previous level of 6.1%. He was counseled on the proper administration of insulin aspart and lifestyle modifications. A fructosamine level was ordered at this visit to further assess his glycemic control. A follow-up appointment and laboratory workup (fructosamine and HbA_1c) were scheduled for 2 months from the visit (Table 3).

Mr. A was educated on the unreliability of his HbA_1c levels secondary to his condition of ESRD on HD. He was counseled on the purpose of fructosamine and how it may be a better predictor of his glycemic control and morbidity. Mr. A continued to be followed closely by the primary care CPS for T2DM management.

Discussion

Management of T2DM in patients with ESRD presents challenges for clinicians in determining HbA_1c goals and selecting appropriate medication options. The 2012 Kidney Disease Outcomes Quality Initiative (KDOQI) diabetes guideline does not recommend treatment for patients with substantially reduced kidney function to a target HbA_1c < 7% due to risk of hypoglycemia.¹³ Although a target HbA_1c > 7% is suggested for these patients, little is known about appropriate glycemic control in these patients as there is a paucity of prospective, randomized clinical trials that include patients with advanced CKD.¹³

Moreover, many oral antidiabetic medications and their metabolites are cleared by the kidneys and, therefore, pose with potential harm for patients with CKD. Because of this, insulin is the medication of choice for patients with ESRD.⁷ Although insulin requirements may diminish with worsening kidney function, insulin provides the safest method of glycemic control. Insulin dosing can be individualized according to a patient’s renal status as there is no uniformity in renal dose adjustments. There are some noninsulin antidiabetic agents that can be used in ESRD, but use of these agents requires close monitoring and evaluation of the medication’s pharmacokinetics (Table 4). Overall, medication management can be a difficult task for patients with T2DM and ESRD, but antidiabetic regimens may be reduced or discontinued altogether in burnt-out diabetes.

Conclusions

Patients with T2DM and ESRD on dialysis may have higher morbidity and mortality rates than the rates of those without T2DM. It has been shown in various studies that very low HbA_1c (< 5%) and high HbA_1c (> 8%) are associated with poor survival. Some patients with T2DM on dialysis may experience burnt-out diabetes in which they may have normoglycemia and a HbA_1c below goal; despite these facts, this condition is not positive and can be linked to bad outcomes. In patients with T2DM and ESRD, insulin is the antidiabetic medication of choice, and we recommend a HbA_1c target of 6 to 8%. In this patient population, consider using fructosamine levels or other measures of glycemic control to supplement HbA_1c and glucose values to provide a better assessment of glycemic control, morbidity, and mortality. Larger clinical trials are needed to assist in answering questions regarding mortality and optimal HbA_1c targets in burnt-out diabetes.

Some who read Federal Practitioner regularly may recall that since 2017, I have been dedicating the December and January editorials to a more substantive version of the popular best and worst awards that appear in the media this time of year. Everything from the most comfortable slippers to the weirdest lawsuits is scored annually. In an effort to elevate the ranking routine, this column has reviewed and evaluated ethical and unethical events and decisions in the 3 federal health care systems Federal Practitioner primarily serves. In previous years it was a challenge requiring research and deliberation to select the most inspiring and troubling occurrences in the world of federal health care. This year neither great effort or prolonged study was required as the choice was immediate and obvious—the year itself. A year in which our individual identities as health care professionals serving in the US Department of Defense, US Department of Veterans Affairs (VA), and US Public Health Service is subsumed in our realities as citizens of a nation in crisis.

The opening lines of A Tale of Two Cities have become such a literary platitude taken out of the context of the novel that the terror and fascination with which Dickens wrote these oft-quoted lines has been diluted and dulled.¹ In citing the entire paragraph as the epigraph, I hope to recapture the moral seriousness of its message, which is so relevant in 2020. While protesting the widespread injustice that fueled the progress of London’s industrial revolution, Dickens also feared such discontent would ignite a bloody uprising as it had done in Paris.¹ This passage is a classic example of the literary device of parallelism that so perfectly expressed Dickens’ reflections on the trajectory of the unprecedented historical impact of the French Revolution. A parallelism that also aptly captures the contemporary contrasts and comparisons of the best and worst of 2020.

It is estimated that at least 66% of those eligible to vote did so on November 3, 2020, the highest turnout in more than a century, demonstrating the strength of the United States as a representative democracy.² It is not about partisan politics, it is that more than 150 million citizens braved the winter, the virus, and potential intimidation to cast a ballot for their values.³ Still, America has never been more divided, and Dickens’ fear of political upheaval has never been more real in our country, or at least since the Civil War.

As I write this editorial, manufacturers for 2 vaccines have submitted phase 3 trial data to the US Food and Drug Administration for Emergency Use Authorizations and a third consortium may follow suit soon. Scientists report that the 2 vaccines, which were developed in less than a year, have high efficacy rates (> 90%) with only modest adverse effects.⁴ It is an unparalleled, really unimaginable, scientific feat. Americans’ characteristic gift for logistical efficiency and scientific innovation faces daunting administrative and technical barriers to achieve a similar viral victory, yet we may have faced even more formidable odds in World War II.

As of December 4, 2020, Johns Hopkins University reports that more than 275,000 Americans have died of coronavirus.⁵ The United States is on track to reach 200,000 cases a day with the signature holiday season of family festivities brutally morphed into gatherings of contagion.⁶ Hospitals across the country are running out of intensive care beds and nurses and doctors to staff them. Unlike the Spring surge in the Northeast, cases are rising in 49 states, and there is nowhere in the land from which respite and reinforcements can come.⁷

Thousands of health care professionals are exhausted, many with COVID-19 or recovering from it, morally distressed, and emotionally spent. Masks and social distancing are no longer public health essentials but elements of a culture war. Those same nurses, doctors, and public health officers still show up day after night for what is much closer to war than work. They struggle to prevent patients from going on ventilators they may never come off and use the few available therapies to keep as many patients alive as possible—whether those patients believe in COVID-19, wore a mask, no matter who they voted for—because that is what it means to practice health care according to a code of ethics.

In March 2020, I pledged to devote every editorial to COVID-19 for as long as the pandemic lasted, as one small candle for all those who have died of COVID-19, who are suffering as survivors of it, and who take risks and labor to deliver essential services from groceries to intensive care. Prudent public health officials wisely advise that the vaccine(s) are not a miracle cure to revive a depleted country, in part because it may undermine life-saving public health measures.⁸ And so the columns will continue in 2021 to illuminate the ethical issues of the pandemic as they affect all of us as federal health care professionals and Americans.

The Tale of Two Cities chapter that begins with the “best of times, and the worst of times” is entitled “Recalled to Life.” Let that be our hope and prayer for the coming year.

Some who read Federal Practitioner regularly may recall that since 2017, I have been dedicating the December and January editorials to a more substantive version of the popular best and worst awards that appear in the media this time of year. Everything from the most comfortable slippers to the weirdest lawsuits is scored annually. In an effort to elevate the ranking routine, this column has reviewed and evaluated ethical and unethical events and decisions in the 3 federal health care systems Federal Practitioner primarily serves. In previous years it was a challenge requiring research and deliberation to select the most inspiring and troubling occurrences in the world of federal health care. This year neither great effort or prolonged study was required as the choice was immediate and obvious—the year itself. A year in which our individual identities as health care professionals serving in the US Department of Defense, US Department of Veterans Affairs (VA), and US Public Health Service is subsumed in our realities as citizens of a nation in crisis.

The opening lines of A Tale of Two Cities have become such a literary platitude taken out of the context of the novel that the terror and fascination with which Dickens wrote these oft-quoted lines has been diluted and dulled.¹ In citing the entire paragraph as the epigraph, I hope to recapture the moral seriousness of its message, which is so relevant in 2020. While protesting the widespread injustice that fueled the progress of London’s industrial revolution, Dickens also feared such discontent would ignite a bloody uprising as it had done in Paris.¹ This passage is a classic example of the literary device of parallelism that so perfectly expressed Dickens’ reflections on the trajectory of the unprecedented historical impact of the French Revolution. A parallelism that also aptly captures the contemporary contrasts and comparisons of the best and worst of 2020.

It is estimated that at least 66% of those eligible to vote did so on November 3, 2020, the highest turnout in more than a century, demonstrating the strength of the United States as a representative democracy.² It is not about partisan politics, it is that more than 150 million citizens braved the winter, the virus, and potential intimidation to cast a ballot for their values.³ Still, America has never been more divided, and Dickens’ fear of political upheaval has never been more real in our country, or at least since the Civil War.

As I write this editorial, manufacturers for 2 vaccines have submitted phase 3 trial data to the US Food and Drug Administration for Emergency Use Authorizations and a third consortium may follow suit soon. Scientists report that the 2 vaccines, which were developed in less than a year, have high efficacy rates (> 90%) with only modest adverse effects.⁴ It is an unparalleled, really unimaginable, scientific feat. Americans’ characteristic gift for logistical efficiency and scientific innovation faces daunting administrative and technical barriers to achieve a similar viral victory, yet we may have faced even more formidable odds in World War II.

As of December 4, 2020, Johns Hopkins University reports that more than 275,000 Americans have died of coronavirus.⁵ The United States is on track to reach 200,000 cases a day with the signature holiday season of family festivities brutally morphed into gatherings of contagion.⁶ Hospitals across the country are running out of intensive care beds and nurses and doctors to staff them. Unlike the Spring surge in the Northeast, cases are rising in 49 states, and there is nowhere in the land from which respite and reinforcements can come.⁷

Thousands of health care professionals are exhausted, many with COVID-19 or recovering from it, morally distressed, and emotionally spent. Masks and social distancing are no longer public health essentials but elements of a culture war. Those same nurses, doctors, and public health officers still show up day after night for what is much closer to war than work. They struggle to prevent patients from going on ventilators they may never come off and use the few available therapies to keep as many patients alive as possible—whether those patients believe in COVID-19, wore a mask, no matter who they voted for—because that is what it means to practice health care according to a code of ethics.

In March 2020, I pledged to devote every editorial to COVID-19 for as long as the pandemic lasted, as one small candle for all those who have died of COVID-19, who are suffering as survivors of it, and who take risks and labor to deliver essential services from groceries to intensive care. Prudent public health officials wisely advise that the vaccine(s) are not a miracle cure to revive a depleted country, in part because it may undermine life-saving public health measures.⁸ And so the columns will continue in 2021 to illuminate the ethical issues of the pandemic as they affect all of us as federal health care professionals and Americans.

The Tale of Two Cities chapter that begins with the “best of times, and the worst of times” is entitled “Recalled to Life.” Let that be our hope and prayer for the coming year.

Some who read Federal Practitioner regularly may recall that since 2017, I have been dedicating the December and January editorials to a more substantive version of the popular best and worst awards that appear in the media this time of year. Everything from the most comfortable slippers to the weirdest lawsuits is scored annually. In an effort to elevate the ranking routine, this column has reviewed and evaluated ethical and unethical events and decisions in the 3 federal health care systems Federal Practitioner primarily serves. In previous years it was a challenge requiring research and deliberation to select the most inspiring and troubling occurrences in the world of federal health care. This year neither great effort or prolonged study was required as the choice was immediate and obvious—the year itself. A year in which our individual identities as health care professionals serving in the US Department of Defense, US Department of Veterans Affairs (VA), and US Public Health Service is subsumed in our realities as citizens of a nation in crisis.

The opening lines of A Tale of Two Cities have become such a literary platitude taken out of the context of the novel that the terror and fascination with which Dickens wrote these oft-quoted lines has been diluted and dulled.¹ In citing the entire paragraph as the epigraph, I hope to recapture the moral seriousness of its message, which is so relevant in 2020. While protesting the widespread injustice that fueled the progress of London’s industrial revolution, Dickens also feared such discontent would ignite a bloody uprising as it had done in Paris.¹ This passage is a classic example of the literary device of parallelism that so perfectly expressed Dickens’ reflections on the trajectory of the unprecedented historical impact of the French Revolution. A parallelism that also aptly captures the contemporary contrasts and comparisons of the best and worst of 2020.

It is estimated that at least 66% of those eligible to vote did so on November 3, 2020, the highest turnout in more than a century, demonstrating the strength of the United States as a representative democracy.² It is not about partisan politics, it is that more than 150 million citizens braved the winter, the virus, and potential intimidation to cast a ballot for their values.³ Still, America has never been more divided, and Dickens’ fear of political upheaval has never been more real in our country, or at least since the Civil War.

As I write this editorial, manufacturers for 2 vaccines have submitted phase 3 trial data to the US Food and Drug Administration for Emergency Use Authorizations and a third consortium may follow suit soon. Scientists report that the 2 vaccines, which were developed in less than a year, have high efficacy rates (> 90%) with only modest adverse effects.⁴ It is an unparalleled, really unimaginable, scientific feat. Americans’ characteristic gift for logistical efficiency and scientific innovation faces daunting administrative and technical barriers to achieve a similar viral victory, yet we may have faced even more formidable odds in World War II.

As of December 4, 2020, Johns Hopkins University reports that more than 275,000 Americans have died of coronavirus.⁵ The United States is on track to reach 200,000 cases a day with the signature holiday season of family festivities brutally morphed into gatherings of contagion.⁶ Hospitals across the country are running out of intensive care beds and nurses and doctors to staff them. Unlike the Spring surge in the Northeast, cases are rising in 49 states, and there is nowhere in the land from which respite and reinforcements can come.⁷

Thousands of health care professionals are exhausted, many with COVID-19 or recovering from it, morally distressed, and emotionally spent. Masks and social distancing are no longer public health essentials but elements of a culture war. Those same nurses, doctors, and public health officers still show up day after night for what is much closer to war than work. They struggle to prevent patients from going on ventilators they may never come off and use the few available therapies to keep as many patients alive as possible—whether those patients believe in COVID-19, wore a mask, no matter who they voted for—because that is what it means to practice health care according to a code of ethics.

In March 2020, I pledged to devote every editorial to COVID-19 for as long as the pandemic lasted, as one small candle for all those who have died of COVID-19, who are suffering as survivors of it, and who take risks and labor to deliver essential services from groceries to intensive care. Prudent public health officials wisely advise that the vaccine(s) are not a miracle cure to revive a depleted country, in part because it may undermine life-saving public health measures.⁸ And so the columns will continue in 2021 to illuminate the ethical issues of the pandemic as they affect all of us as federal health care professionals and Americans.

The Tale of Two Cities chapter that begins with the “best of times, and the worst of times” is entitled “Recalled to Life.” Let that be our hope and prayer for the coming year.

In the 1990s, researchers found that patients undergoing any type of surgical procedure were more than twice as likely to die if they developed postsurgical infection.¹ Work to reduce surgical site infection (SSI) has and does continue, with perioperative antibiotics representing a good part of that effort. The American College of Obstetricians and Gynecologists currently recommends such antibiotic therapy for women undergoing laparotomy and laparoscopic hysterectomy.² ACOG does not, however, recommend prophylactic antibiotics for myomectomy procedures.³ Rates of infection for hysterectomy have been reported to be 3.9% for abdominal and 1.4% for minimally invasive approaches.⁴

To determine the current use of antibiotics during myomectomy and associated rates of SSI at their institutions, Dipti Banerjee, MD, and colleagues conducted a retrospective analysis of women undergoing laparoscopic or abdominal myomectomy between February 2013 and December 2017 at the University of California, Los Angeles and Hoag Memorial Hospital in Orange County, California. They presented their study results at AAGL’s 49th Global Congress on MIGS, held virtually November 6-14, 2020.³

Rate of SSI after myomectomy

A total of 620 women underwent laparoscopic myomectomy and 563 underwent open myomectomy during the study period. Antibiotics were used in 76.9% of cases. SSI developed within 6 weeks of surgery in 34 women (2.9%) overall. The women undergoing abdominal myomectomy without antibiotics were more likely to experience SSI than the women who received antibiotics (odds ratio [OR], 4.89; confidence interval [CI], 1.80–13.27; P = .0006). For laparoscopic myomectomy, antibiotic use did not affect the odds of developing SSI (OR, 1.08; CI, 0.35–3.35).

Antibiotics were more likely to be used in certain cases

Antibiotics were more likely to be administered for patients who:

• were obese (body mass index ≥30 kg/m²) (P = .009)
• underwent previous abdominal surgery (P = .001)
• underwent laparotomy (P <.0001)
• had endometrial cavity entry (P <.0001)
• had >1 fibroid (P = .0004) or an aggregate fibroid weight >500 g (P <.0001).

More data on antibiotics for myomectomy

In a retrospective study conducted at 2 academic hospitals in Boston, Massachusetts, 1,211 women underwent myomectomy from 2009 to 2016. (Exclusions were use of vaginal or hysteroscopic myomectomy, chromopertubation, or conversion to hysterectomy.) More than 92% of the women received perioperative antibiotics at the time of surgery. Although demographics were similar between women receiving and not receiving antibiotics, women who received antibiotics were more likely to have longer operative times (median 140 vs 85 min), a greater myoma burden (7 vs 2 myomas removed and weight 255 vs 53 g), and lose blood during the procedure (137 vs 50 mL). These women also were 4 times less likely to have surgical site infection (adjusted OR, 3.77; 95% CI, 1.30–10.97; P = .015).^5,6

Banerjee and colleagues say that their California study demonstrates “that the majority of surgeons elect to use antibiotics prophylactically” during myomectomy, despite current ACOG guidelines, and that their findings of benefit for abdominal myomectomy but not for laparoscopic myomectomy should inform future guidance on antibiotics for myomectomy surgery.³

In the 1990s, researchers found that patients undergoing any type of surgical procedure were more than twice as likely to die if they developed postsurgical infection.¹ Work to reduce surgical site infection (SSI) has and does continue, with perioperative antibiotics representing a good part of that effort. The American College of Obstetricians and Gynecologists currently recommends such antibiotic therapy for women undergoing laparotomy and laparoscopic hysterectomy.² ACOG does not, however, recommend prophylactic antibiotics for myomectomy procedures.³ Rates of infection for hysterectomy have been reported to be 3.9% for abdominal and 1.4% for minimally invasive approaches.⁴

To determine the current use of antibiotics during myomectomy and associated rates of SSI at their institutions, Dipti Banerjee, MD, and colleagues conducted a retrospective analysis of women undergoing laparoscopic or abdominal myomectomy between February 2013 and December 2017 at the University of California, Los Angeles and Hoag Memorial Hospital in Orange County, California. They presented their study results at AAGL’s 49th Global Congress on MIGS, held virtually November 6-14, 2020.³

Rate of SSI after myomectomy

A total of 620 women underwent laparoscopic myomectomy and 563 underwent open myomectomy during the study period. Antibiotics were used in 76.9% of cases. SSI developed within 6 weeks of surgery in 34 women (2.9%) overall. The women undergoing abdominal myomectomy without antibiotics were more likely to experience SSI than the women who received antibiotics (odds ratio [OR], 4.89; confidence interval [CI], 1.80–13.27; P = .0006). For laparoscopic myomectomy, antibiotic use did not affect the odds of developing SSI (OR, 1.08; CI, 0.35–3.35).

Antibiotics were more likely to be used in certain cases

Antibiotics were more likely to be administered for patients who:

• were obese (body mass index ≥30 kg/m²) (P = .009)
• underwent previous abdominal surgery (P = .001)
• underwent laparotomy (P <.0001)
• had endometrial cavity entry (P <.0001)
• had >1 fibroid (P = .0004) or an aggregate fibroid weight >500 g (P <.0001).

More data on antibiotics for myomectomy

In a retrospective study conducted at 2 academic hospitals in Boston, Massachusetts, 1,211 women underwent myomectomy from 2009 to 2016. (Exclusions were use of vaginal or hysteroscopic myomectomy, chromopertubation, or conversion to hysterectomy.) More than 92% of the women received perioperative antibiotics at the time of surgery. Although demographics were similar between women receiving and not receiving antibiotics, women who received antibiotics were more likely to have longer operative times (median 140 vs 85 min), a greater myoma burden (7 vs 2 myomas removed and weight 255 vs 53 g), and lose blood during the procedure (137 vs 50 mL). These women also were 4 times less likely to have surgical site infection (adjusted OR, 3.77; 95% CI, 1.30–10.97; P = .015).^5,6

Banerjee and colleagues say that their California study demonstrates “that the majority of surgeons elect to use antibiotics prophylactically” during myomectomy, despite current ACOG guidelines, and that their findings of benefit for abdominal myomectomy but not for laparoscopic myomectomy should inform future guidance on antibiotics for myomectomy surgery.³

In the 1990s, researchers found that patients undergoing any type of surgical procedure were more than twice as likely to die if they developed postsurgical infection.¹ Work to reduce surgical site infection (SSI) has and does continue, with perioperative antibiotics representing a good part of that effort. The American College of Obstetricians and Gynecologists currently recommends such antibiotic therapy for women undergoing laparotomy and laparoscopic hysterectomy.² ACOG does not, however, recommend prophylactic antibiotics for myomectomy procedures.³ Rates of infection for hysterectomy have been reported to be 3.9% for abdominal and 1.4% for minimally invasive approaches.⁴

To determine the current use of antibiotics during myomectomy and associated rates of SSI at their institutions, Dipti Banerjee, MD, and colleagues conducted a retrospective analysis of women undergoing laparoscopic or abdominal myomectomy between February 2013 and December 2017 at the University of California, Los Angeles and Hoag Memorial Hospital in Orange County, California. They presented their study results at AAGL’s 49th Global Congress on MIGS, held virtually November 6-14, 2020.³

Rate of SSI after myomectomy

A total of 620 women underwent laparoscopic myomectomy and 563 underwent open myomectomy during the study period. Antibiotics were used in 76.9% of cases. SSI developed within 6 weeks of surgery in 34 women (2.9%) overall. The women undergoing abdominal myomectomy without antibiotics were more likely to experience SSI than the women who received antibiotics (odds ratio [OR], 4.89; confidence interval [CI], 1.80–13.27; P = .0006). For laparoscopic myomectomy, antibiotic use did not affect the odds of developing SSI (OR, 1.08; CI, 0.35–3.35).

Antibiotics were more likely to be used in certain cases

Antibiotics were more likely to be administered for patients who:

• were obese (body mass index ≥30 kg/m²) (P = .009)
• underwent previous abdominal surgery (P = .001)
• underwent laparotomy (P <.0001)
• had endometrial cavity entry (P <.0001)
• had >1 fibroid (P = .0004) or an aggregate fibroid weight >500 g (P <.0001).

More data on antibiotics for myomectomy

In a retrospective study conducted at 2 academic hospitals in Boston, Massachusetts, 1,211 women underwent myomectomy from 2009 to 2016. (Exclusions were use of vaginal or hysteroscopic myomectomy, chromopertubation, or conversion to hysterectomy.) More than 92% of the women received perioperative antibiotics at the time of surgery. Although demographics were similar between women receiving and not receiving antibiotics, women who received antibiotics were more likely to have longer operative times (median 140 vs 85 min), a greater myoma burden (7 vs 2 myomas removed and weight 255 vs 53 g), and lose blood during the procedure (137 vs 50 mL). These women also were 4 times less likely to have surgical site infection (adjusted OR, 3.77; 95% CI, 1.30–10.97; P = .015).^5,6

Banerjee and colleagues say that their California study demonstrates “that the majority of surgeons elect to use antibiotics prophylactically” during myomectomy, despite current ACOG guidelines, and that their findings of benefit for abdominal myomectomy but not for laparoscopic myomectomy should inform future guidance on antibiotics for myomectomy surgery.³

The Food and Drug Administration has approved setmelanotide (Imcivree, Rhythm Pharmaceuticals) for weight management in adults and children as young as 6 years with obesity because of proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing.

Individuals with these rare genetic causes of severe obesity have a normal weight at birth but develop persistent severe obesity within months because of insatiable hunger (hyperphagia). 

Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for these disorders.

“Many patients and families who live with these diseases face an often-burdensome stigma associated with severe obesity. To manage this obesity and control disruptive food-seeking behavior, caregivers often lock cabinets and refrigerators and significantly limit social activities,” said Jennifer Miller, MD, a pediatric endocrinologist at University of Florida Health, Gainesville, in a press release issued by the company.

“This FDA approval marks an important turning point, providing a much needed therapy and supporting the use of genetic testing to identify and properly diagnose patients with these rare genetic diseases of obesity,” she noted.

David Meeker, MD, chair, president, and CEO of Rhythm Pharmaceuticals, added: “We are advancing a first-in-class, precision medicine that is designed to directly address the underlying cause of obesities driven by genetic deficits in the MC4R pathway.”

Setmelanotide was evaluated in two phase 3 clinical trials. In one trial, 80% of patients with obesity caused by POMC or PCSK1 deficiency achieved greater than 10% weight loss after 1 year of treatment.

In the other trial, 45.5% of patients with obesity caused by LEPR deficiency achieved greater than 10% weight loss with 1 year of treatment.

Results for the two trials were recently published in The Lancet Diabetes & Endocrinology and discussed at the ObesityWeek Interactive 2020 meeting.

Setmelanotide was generally well tolerated in both trials. The most common adverse events were injection-site reactions, skin hyperpigmentation, and nausea.

The drug label notes that disturbances in sexual arousal, depression, and suicidal ideation; skin pigmentation; and darkening of preexisting nevi may occur with setmelanotide treatment.

The drug label also notes a risk for serious adverse reactions because of benzyl alcohol preservative in neonates and low-birth-weight infants. Setmelanotide is not approved for use in neonates or infants.

The company expects the drug to be commercially available in the United States in the first quarter of 2021.

Setmelanotide for the treatment of obesity associated with rare genetic defects had FDA breakthrough therapy designation as well as orphan drug designation.

The company is also evaluating setmelanotide for reduction in hunger and body weight in a pivotal phase 3 trial in people living with Bardet-Biedl or Alström syndrome, and top-line data are due soon.

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration has approved setmelanotide (Imcivree, Rhythm Pharmaceuticals) for weight management in adults and children as young as 6 years with obesity because of proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing.

Individuals with these rare genetic causes of severe obesity have a normal weight at birth but develop persistent severe obesity within months because of insatiable hunger (hyperphagia). 

Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for these disorders.

“Many patients and families who live with these diseases face an often-burdensome stigma associated with severe obesity. To manage this obesity and control disruptive food-seeking behavior, caregivers often lock cabinets and refrigerators and significantly limit social activities,” said Jennifer Miller, MD, a pediatric endocrinologist at University of Florida Health, Gainesville, in a press release issued by the company.

“This FDA approval marks an important turning point, providing a much needed therapy and supporting the use of genetic testing to identify and properly diagnose patients with these rare genetic diseases of obesity,” she noted.

David Meeker, MD, chair, president, and CEO of Rhythm Pharmaceuticals, added: “We are advancing a first-in-class, precision medicine that is designed to directly address the underlying cause of obesities driven by genetic deficits in the MC4R pathway.”

Setmelanotide was evaluated in two phase 3 clinical trials. In one trial, 80% of patients with obesity caused by POMC or PCSK1 deficiency achieved greater than 10% weight loss after 1 year of treatment.

In the other trial, 45.5% of patients with obesity caused by LEPR deficiency achieved greater than 10% weight loss with 1 year of treatment.

Results for the two trials were recently published in The Lancet Diabetes & Endocrinology and discussed at the ObesityWeek Interactive 2020 meeting.

Setmelanotide was generally well tolerated in both trials. The most common adverse events were injection-site reactions, skin hyperpigmentation, and nausea.

The drug label notes that disturbances in sexual arousal, depression, and suicidal ideation; skin pigmentation; and darkening of preexisting nevi may occur with setmelanotide treatment.

The drug label also notes a risk for serious adverse reactions because of benzyl alcohol preservative in neonates and low-birth-weight infants. Setmelanotide is not approved for use in neonates or infants.

The company expects the drug to be commercially available in the United States in the first quarter of 2021.

Setmelanotide for the treatment of obesity associated with rare genetic defects had FDA breakthrough therapy designation as well as orphan drug designation.

The company is also evaluating setmelanotide for reduction in hunger and body weight in a pivotal phase 3 trial in people living with Bardet-Biedl or Alström syndrome, and top-line data are due soon.

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration has approved setmelanotide (Imcivree, Rhythm Pharmaceuticals) for weight management in adults and children as young as 6 years with obesity because of proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing.

Individuals with these rare genetic causes of severe obesity have a normal weight at birth but develop persistent severe obesity within months because of insatiable hunger (hyperphagia). 

Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for these disorders.

“Many patients and families who live with these diseases face an often-burdensome stigma associated with severe obesity. To manage this obesity and control disruptive food-seeking behavior, caregivers often lock cabinets and refrigerators and significantly limit social activities,” said Jennifer Miller, MD, a pediatric endocrinologist at University of Florida Health, Gainesville, in a press release issued by the company.

“This FDA approval marks an important turning point, providing a much needed therapy and supporting the use of genetic testing to identify and properly diagnose patients with these rare genetic diseases of obesity,” she noted.

David Meeker, MD, chair, president, and CEO of Rhythm Pharmaceuticals, added: “We are advancing a first-in-class, precision medicine that is designed to directly address the underlying cause of obesities driven by genetic deficits in the MC4R pathway.”

Setmelanotide was evaluated in two phase 3 clinical trials. In one trial, 80% of patients with obesity caused by POMC or PCSK1 deficiency achieved greater than 10% weight loss after 1 year of treatment.

In the other trial, 45.5% of patients with obesity caused by LEPR deficiency achieved greater than 10% weight loss with 1 year of treatment.

Results for the two trials were recently published in The Lancet Diabetes & Endocrinology and discussed at the ObesityWeek Interactive 2020 meeting.

Setmelanotide was generally well tolerated in both trials. The most common adverse events were injection-site reactions, skin hyperpigmentation, and nausea.

The drug label notes that disturbances in sexual arousal, depression, and suicidal ideation; skin pigmentation; and darkening of preexisting nevi may occur with setmelanotide treatment.

The drug label also notes a risk for serious adverse reactions because of benzyl alcohol preservative in neonates and low-birth-weight infants. Setmelanotide is not approved for use in neonates or infants.

The company expects the drug to be commercially available in the United States in the first quarter of 2021.

Setmelanotide for the treatment of obesity associated with rare genetic defects had FDA breakthrough therapy designation as well as orphan drug designation.

The company is also evaluating setmelanotide for reduction in hunger and body weight in a pivotal phase 3 trial in people living with Bardet-Biedl or Alström syndrome, and top-line data are due soon.

A version of this article originally appeared on Medscape.com.