Gynecology

Do health effects of menopausal estrogen therapy differ between women with bilateral oophorectomy versus those with conserved ovaries? To answer this question a group of investigators performed a subanalysis of the Women’s Health Initiative (WHI) Estrogen-Alone Trial,¹ which included 40 clinical centers across the United States. They examined estrogen therapy outcomes by bilateral salpingo-oophorectomy (BSO) status, with additional stratification by 10-year age groups in 9,939 women aged 50 to 79 years with prior hysterectomy and known oophorectomy status. In the WHI trial, women were randomly assigned to conjugated equine estrogens (CEE) 0.625 mg/d or placebo for a median of 7.2 years. Investigators assessed the incidence of coronary heart disease and invasive breast cancer (the trial’s 2 primary end points), all-cause mortality, and a “global index”—these end points plus stroke, pulmonary embolism, colorectal cancer, and hip fracture—during the intervention phase and 18-year cumulative follow-up.

OBG Management caught up with lead author JoAnn E. Manson, MD, DrPH, NCMP, to discuss the study’s results.
 

OBG Management: How many women undergo BSO with their hysterectomy?

Dr. JoAnn E. Manson, MD, DrPH, NCMP: Of the 425,000 women who undergo hysterectomy in the United States for benign reasons each year,^2,3 about 40% of them undergo BSO—so between 150,000 and 200,000 women per year undergo BSO with their hysterectomy.^4,5
 

OBG Management: Although BSO is performed with hysterectomy to minimize patients’ future ovarian cancer risk, does BSO have health risks of its own, and how has estrogen been shown to affect these risks?

Dr. Manson: First, yes, BSO has been associated with health risks, especially when it is performed at a young age, such as before age 45. It has been linked to an increased risk of heart disease, osteoporosis, cognitive decline, and all-cause mortality. According to observational studies, estrogen therapy appears to offset many of these risks, particularly those related to heart disease and osteoporosis (the evidence is less clear on cognitive deficits).⁵
 

OBG Management: What did you find in your trial when you randomly assigned women in the age groups of 50 to 79 who underwent hysterectomy with and without BSO to estrogen therapy or placebo?

Dr. Manson: The WHI is the first study to be conducted in a randomized trial setting to analyze the health risks and benefits of estrogen therapy according to whether or not women had their ovaries removed. What we found was that the woman’s age had a strong influence on the effects of estrogen therapy among women who had BSO but only a negligible effect among women who had conserved ovaries. Overall, across the full age range, the effects of estrogen therapy did not differ substantially between women who had a BSO and those who had their ovaries conserved.

However, there were major differences by age group among the women who had BSO. A significant 32% reduction in all-cause mortality emerged during the 18-year follow-up period among the younger women (below age 60) who had BSO when they received estrogen therapy as compared with placebo. By contrast, the women who had conserved ovaries did not have this significant reduction in all-cause mortality, or in most of the other outcomes on estrogen compared with placebo. Overall, the effects of estrogen therapy tended to be relatively neutral in the women with conserved ovaries.

Now, the reduction in all-cause mortality with estrogen therapy was particularly pronounced among women who had BSO before age 45. They had a 40% statistically significant reduction in all-cause mortality with estrogen therapy compared with placebo. Also, among the women with BSO, there was a strong association between the timing of estrogen initiation and the magnitude of reduction in mortality. Women who started the estrogen therapy within 10 years of having the BSO had a 34% significant reduction in all-cause mortality, and those who started estrogen more than 20 years after having their ovaries removed had no reduction in mortality.
 

Continue to: OBG Management: Do your data give support to the timing hypothesis?

OBG Management: Do your data give support to the timing hypothesis?

Dr. Manson: Yes, our findings do support a timing hypothesis that was particularly pronounced for women who underwent BSO. It was the women who had early surgical menopause (before age 45) and those who started the estrogen therapy within 10 years of having their ovaries removed who had the greatest reduction in all-cause mortality and the most favorable benefit-risk profile from hormone therapy. So, the results do lend support to the timing hypothesis.

By contrast, women who had BSO at hysterectomy and began hormone therapy at age 70 or older had net adverse effects from hormone therapy. They posted a 40% increase in the global index—which is a summary measure of adverse effects on cardiovascular disease, cancer, and other major health outcomes. So, the women with BSO who were randomized in the trial at age 70 and older, had unfavorable results from estrogen therapy and an increase in the global index, in contrast to the women who were below age 60 or within 10 years of menopause.
 

OBG Management: Given your study findings, in which women would you recommend estrogen therapy? And are there groups of women in which you would advise avoiding estrogen therapy?

Dr. Manson: Current guidelines^6,7 recommend estrogen therapy for women who have early menopause, particularly an early surgical menopause and BSO prior to the average age at natural menopause. Unless the woman has contraindications to estrogen therapy, the recommendations are to treat with estrogen until the average age of menopause—until about age 50 to 51.

Our study findings provide reassurance that, if a woman continues to have indications for estrogen (vasomotor symptoms, or other indications for estrogen therapy), there is relative safety of continuing estrogen-alone therapy through her 50s, until age 60. For example, a woman who, after the average age of menopause continues to have vasomotor symptoms, or if she has bone health problems, our study would suggest that estrogen therapy would continue to have a favorable benefit-risk profile until at least the age of 60. Decisions would have to be individualized, especially after age 60, with shared decision-making particularly important for those decisions. (Some women, depending on their risk profile, may continue to be candidates for estrogen therapy past age 60.)

So, this study provides reassurance regarding use of estrogen therapy for women in their 50s if they have had BSO. Actually, the women who had conserved ovaries also had relative safety with estrogen therapy until age 60. They just didn’t show the significant benefits for all-cause mortality. Overall, their pattern of health-related benefits and risks was neutral. Thus, if vasomotor symptom management, quality of life benefits, or bone health effects are sought, taking hormone therapy is a quite reasonable choice for these women.

By contrast, women who have had a BSO and are age 70 or older should really avoid initiating estrogen therapy because it would follow a prolonged period of estrogen deficiency, or very low estrogen levels, and these women appeared to have a net adverse effect from initiating hormone therapy (with increases in the global index found).

Continue to: OBG Management: Did taking estrogen therapy prior to trial enrollment make a difference when it came to study outcomes?

OBG Management: Did taking estrogen therapy prior to trial enrollment make a difference when it came to study outcomes?

Dr. Manson: We found minimal if any effect in our analyses. In fact, even the women who did not have prior (pre-randomization) use of estrogen therapy tended to do well on estrogen-alone therapy if they were younger than age 60. This was particularly true for the women who had BSO. Even if they had not used estrogen previously, and they were many years past the BSO, they still did well on estrogen therapy if they were below age 60.

Do health effects of menopausal estrogen therapy differ between women with bilateral oophorectomy versus those with conserved ovaries? To answer this question a group of investigators performed a subanalysis of the Women’s Health Initiative (WHI) Estrogen-Alone Trial,¹ which included 40 clinical centers across the United States. They examined estrogen therapy outcomes by bilateral salpingo-oophorectomy (BSO) status, with additional stratification by 10-year age groups in 9,939 women aged 50 to 79 years with prior hysterectomy and known oophorectomy status. In the WHI trial, women were randomly assigned to conjugated equine estrogens (CEE) 0.625 mg/d or placebo for a median of 7.2 years. Investigators assessed the incidence of coronary heart disease and invasive breast cancer (the trial’s 2 primary end points), all-cause mortality, and a “global index”—these end points plus stroke, pulmonary embolism, colorectal cancer, and hip fracture—during the intervention phase and 18-year cumulative follow-up.

OBG Management caught up with lead author JoAnn E. Manson, MD, DrPH, NCMP, to discuss the study’s results.
 

OBG Management: How many women undergo BSO with their hysterectomy?

Dr. JoAnn E. Manson, MD, DrPH, NCMP: Of the 425,000 women who undergo hysterectomy in the United States for benign reasons each year,^2,3 about 40% of them undergo BSO—so between 150,000 and 200,000 women per year undergo BSO with their hysterectomy.^4,5
 

OBG Management: Although BSO is performed with hysterectomy to minimize patients’ future ovarian cancer risk, does BSO have health risks of its own, and how has estrogen been shown to affect these risks?

Dr. Manson: First, yes, BSO has been associated with health risks, especially when it is performed at a young age, such as before age 45. It has been linked to an increased risk of heart disease, osteoporosis, cognitive decline, and all-cause mortality. According to observational studies, estrogen therapy appears to offset many of these risks, particularly those related to heart disease and osteoporosis (the evidence is less clear on cognitive deficits).⁵
 

OBG Management: What did you find in your trial when you randomly assigned women in the age groups of 50 to 79 who underwent hysterectomy with and without BSO to estrogen therapy or placebo?

Dr. Manson: The WHI is the first study to be conducted in a randomized trial setting to analyze the health risks and benefits of estrogen therapy according to whether or not women had their ovaries removed. What we found was that the woman’s age had a strong influence on the effects of estrogen therapy among women who had BSO but only a negligible effect among women who had conserved ovaries. Overall, across the full age range, the effects of estrogen therapy did not differ substantially between women who had a BSO and those who had their ovaries conserved.

However, there were major differences by age group among the women who had BSO. A significant 32% reduction in all-cause mortality emerged during the 18-year follow-up period among the younger women (below age 60) who had BSO when they received estrogen therapy as compared with placebo. By contrast, the women who had conserved ovaries did not have this significant reduction in all-cause mortality, or in most of the other outcomes on estrogen compared with placebo. Overall, the effects of estrogen therapy tended to be relatively neutral in the women with conserved ovaries.

Now, the reduction in all-cause mortality with estrogen therapy was particularly pronounced among women who had BSO before age 45. They had a 40% statistically significant reduction in all-cause mortality with estrogen therapy compared with placebo. Also, among the women with BSO, there was a strong association between the timing of estrogen initiation and the magnitude of reduction in mortality. Women who started the estrogen therapy within 10 years of having the BSO had a 34% significant reduction in all-cause mortality, and those who started estrogen more than 20 years after having their ovaries removed had no reduction in mortality.
 

Continue to: OBG Management: Do your data give support to the timing hypothesis?

OBG Management: Do your data give support to the timing hypothesis?

Dr. Manson: Yes, our findings do support a timing hypothesis that was particularly pronounced for women who underwent BSO. It was the women who had early surgical menopause (before age 45) and those who started the estrogen therapy within 10 years of having their ovaries removed who had the greatest reduction in all-cause mortality and the most favorable benefit-risk profile from hormone therapy. So, the results do lend support to the timing hypothesis.

By contrast, women who had BSO at hysterectomy and began hormone therapy at age 70 or older had net adverse effects from hormone therapy. They posted a 40% increase in the global index—which is a summary measure of adverse effects on cardiovascular disease, cancer, and other major health outcomes. So, the women with BSO who were randomized in the trial at age 70 and older, had unfavorable results from estrogen therapy and an increase in the global index, in contrast to the women who were below age 60 or within 10 years of menopause.
 

OBG Management: Given your study findings, in which women would you recommend estrogen therapy? And are there groups of women in which you would advise avoiding estrogen therapy?

Dr. Manson: Current guidelines^6,7 recommend estrogen therapy for women who have early menopause, particularly an early surgical menopause and BSO prior to the average age at natural menopause. Unless the woman has contraindications to estrogen therapy, the recommendations are to treat with estrogen until the average age of menopause—until about age 50 to 51.

Our study findings provide reassurance that, if a woman continues to have indications for estrogen (vasomotor symptoms, or other indications for estrogen therapy), there is relative safety of continuing estrogen-alone therapy through her 50s, until age 60. For example, a woman who, after the average age of menopause continues to have vasomotor symptoms, or if she has bone health problems, our study would suggest that estrogen therapy would continue to have a favorable benefit-risk profile until at least the age of 60. Decisions would have to be individualized, especially after age 60, with shared decision-making particularly important for those decisions. (Some women, depending on their risk profile, may continue to be candidates for estrogen therapy past age 60.)

So, this study provides reassurance regarding use of estrogen therapy for women in their 50s if they have had BSO. Actually, the women who had conserved ovaries also had relative safety with estrogen therapy until age 60. They just didn’t show the significant benefits for all-cause mortality. Overall, their pattern of health-related benefits and risks was neutral. Thus, if vasomotor symptom management, quality of life benefits, or bone health effects are sought, taking hormone therapy is a quite reasonable choice for these women.

By contrast, women who have had a BSO and are age 70 or older should really avoid initiating estrogen therapy because it would follow a prolonged period of estrogen deficiency, or very low estrogen levels, and these women appeared to have a net adverse effect from initiating hormone therapy (with increases in the global index found).

Continue to: OBG Management: Did taking estrogen therapy prior to trial enrollment make a difference when it came to study outcomes?

OBG Management: Did taking estrogen therapy prior to trial enrollment make a difference when it came to study outcomes?

Dr. Manson: We found minimal if any effect in our analyses. In fact, even the women who did not have prior (pre-randomization) use of estrogen therapy tended to do well on estrogen-alone therapy if they were younger than age 60. This was particularly true for the women who had BSO. Even if they had not used estrogen previously, and they were many years past the BSO, they still did well on estrogen therapy if they were below age 60.

Do health effects of menopausal estrogen therapy differ between women with bilateral oophorectomy versus those with conserved ovaries? To answer this question a group of investigators performed a subanalysis of the Women’s Health Initiative (WHI) Estrogen-Alone Trial,¹ which included 40 clinical centers across the United States. They examined estrogen therapy outcomes by bilateral salpingo-oophorectomy (BSO) status, with additional stratification by 10-year age groups in 9,939 women aged 50 to 79 years with prior hysterectomy and known oophorectomy status. In the WHI trial, women were randomly assigned to conjugated equine estrogens (CEE) 0.625 mg/d or placebo for a median of 7.2 years. Investigators assessed the incidence of coronary heart disease and invasive breast cancer (the trial’s 2 primary end points), all-cause mortality, and a “global index”—these end points plus stroke, pulmonary embolism, colorectal cancer, and hip fracture—during the intervention phase and 18-year cumulative follow-up.

OBG Management caught up with lead author JoAnn E. Manson, MD, DrPH, NCMP, to discuss the study’s results.
 

OBG Management: How many women undergo BSO with their hysterectomy?

Dr. JoAnn E. Manson, MD, DrPH, NCMP: Of the 425,000 women who undergo hysterectomy in the United States for benign reasons each year,^2,3 about 40% of them undergo BSO—so between 150,000 and 200,000 women per year undergo BSO with their hysterectomy.^4,5
 

OBG Management: Although BSO is performed with hysterectomy to minimize patients’ future ovarian cancer risk, does BSO have health risks of its own, and how has estrogen been shown to affect these risks?

Dr. Manson: First, yes, BSO has been associated with health risks, especially when it is performed at a young age, such as before age 45. It has been linked to an increased risk of heart disease, osteoporosis, cognitive decline, and all-cause mortality. According to observational studies, estrogen therapy appears to offset many of these risks, particularly those related to heart disease and osteoporosis (the evidence is less clear on cognitive deficits).⁵
 

OBG Management: What did you find in your trial when you randomly assigned women in the age groups of 50 to 79 who underwent hysterectomy with and without BSO to estrogen therapy or placebo?

Dr. Manson: The WHI is the first study to be conducted in a randomized trial setting to analyze the health risks and benefits of estrogen therapy according to whether or not women had their ovaries removed. What we found was that the woman’s age had a strong influence on the effects of estrogen therapy among women who had BSO but only a negligible effect among women who had conserved ovaries. Overall, across the full age range, the effects of estrogen therapy did not differ substantially between women who had a BSO and those who had their ovaries conserved.

However, there were major differences by age group among the women who had BSO. A significant 32% reduction in all-cause mortality emerged during the 18-year follow-up period among the younger women (below age 60) who had BSO when they received estrogen therapy as compared with placebo. By contrast, the women who had conserved ovaries did not have this significant reduction in all-cause mortality, or in most of the other outcomes on estrogen compared with placebo. Overall, the effects of estrogen therapy tended to be relatively neutral in the women with conserved ovaries.

Now, the reduction in all-cause mortality with estrogen therapy was particularly pronounced among women who had BSO before age 45. They had a 40% statistically significant reduction in all-cause mortality with estrogen therapy compared with placebo. Also, among the women with BSO, there was a strong association between the timing of estrogen initiation and the magnitude of reduction in mortality. Women who started the estrogen therapy within 10 years of having the BSO had a 34% significant reduction in all-cause mortality, and those who started estrogen more than 20 years after having their ovaries removed had no reduction in mortality.
 

Continue to: OBG Management: Do your data give support to the timing hypothesis?

OBG Management: Do your data give support to the timing hypothesis?

Dr. Manson: Yes, our findings do support a timing hypothesis that was particularly pronounced for women who underwent BSO. It was the women who had early surgical menopause (before age 45) and those who started the estrogen therapy within 10 years of having their ovaries removed who had the greatest reduction in all-cause mortality and the most favorable benefit-risk profile from hormone therapy. So, the results do lend support to the timing hypothesis.

By contrast, women who had BSO at hysterectomy and began hormone therapy at age 70 or older had net adverse effects from hormone therapy. They posted a 40% increase in the global index—which is a summary measure of adverse effects on cardiovascular disease, cancer, and other major health outcomes. So, the women with BSO who were randomized in the trial at age 70 and older, had unfavorable results from estrogen therapy and an increase in the global index, in contrast to the women who were below age 60 or within 10 years of menopause.
 

OBG Management: Given your study findings, in which women would you recommend estrogen therapy? And are there groups of women in which you would advise avoiding estrogen therapy?

Dr. Manson: Current guidelines^6,7 recommend estrogen therapy for women who have early menopause, particularly an early surgical menopause and BSO prior to the average age at natural menopause. Unless the woman has contraindications to estrogen therapy, the recommendations are to treat with estrogen until the average age of menopause—until about age 50 to 51.

Our study findings provide reassurance that, if a woman continues to have indications for estrogen (vasomotor symptoms, or other indications for estrogen therapy), there is relative safety of continuing estrogen-alone therapy through her 50s, until age 60. For example, a woman who, after the average age of menopause continues to have vasomotor symptoms, or if she has bone health problems, our study would suggest that estrogen therapy would continue to have a favorable benefit-risk profile until at least the age of 60. Decisions would have to be individualized, especially after age 60, with shared decision-making particularly important for those decisions. (Some women, depending on their risk profile, may continue to be candidates for estrogen therapy past age 60.)

So, this study provides reassurance regarding use of estrogen therapy for women in their 50s if they have had BSO. Actually, the women who had conserved ovaries also had relative safety with estrogen therapy until age 60. They just didn’t show the significant benefits for all-cause mortality. Overall, their pattern of health-related benefits and risks was neutral. Thus, if vasomotor symptom management, quality of life benefits, or bone health effects are sought, taking hormone therapy is a quite reasonable choice for these women.

By contrast, women who have had a BSO and are age 70 or older should really avoid initiating estrogen therapy because it would follow a prolonged period of estrogen deficiency, or very low estrogen levels, and these women appeared to have a net adverse effect from initiating hormone therapy (with increases in the global index found).

Continue to: OBG Management: Did taking estrogen therapy prior to trial enrollment make a difference when it came to study outcomes?

OBG Management: Did taking estrogen therapy prior to trial enrollment make a difference when it came to study outcomes?

Dr. Manson: We found minimal if any effect in our analyses. In fact, even the women who did not have prior (pre-randomization) use of estrogen therapy tended to do well on estrogen-alone therapy if they were younger than age 60. This was particularly true for the women who had BSO. Even if they had not used estrogen previously, and they were many years past the BSO, they still did well on estrogen therapy if they were below age 60.

FDA REMOVES ALCOHOL BAN WITH ADDYI

Sprout Pharmaceuticals announced that the US Food and Drug Administration (FDA) has removed their contraindication on alcohol use with Addyi® (flibanserin). Addyi was approved in 2015 and is an oral nonhormonal pill for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. Patients are advised to discontinue drinking alcohol at least 2 hours before taking Addyi at bedtime or skip the Addyi dose that evening.

The FDA also removed the requirement, under its Risk Evaluation and Mitigation Strategy (REMS) program, for health care practitioners or pharmacies to be certified to prescribe or dispense Addyi. Sprout says that to make all labeling elements consistent with the FDA’s findings the boxed warning will change and the medication guide will be updated and included under the REMS. 

The most commonly reported adverse events among patients taking Addyi are dizziness, sleepiness, nausea, fatigue, insomnia, and dry mouth. Addyi is contraindicated in patients taking moderate or strong cytochrome P450 3A4 (CYP3A4) inhibitors and in those with hepatic impairment.

FOR MORE INFORMATION AND THE FULL PRESCRIBING INFORMATION AND MEDICATION GUIDE, VISIT: www.addyi.com

FEZOLINETANT FOR VMS

FOR MORE INFORMATION, VISIT: http://www.clinicaltrials.gov, TRIAL IDENTIFIERS NCT04003155, NCT04003142, AND NCT04003389

SOLUTIONS FOR OUTCOME TRACKING

DrChrono and OutcomeMD announce a partnership to track and analyze patient outcome data and confounding factors. DrChrono is an electronic health record (EHR) system, and OutcomeMD is a software solution that uses literature-validated patient-reported outcome instruments to score and track a patient’s symptom severity and inform treatment decisions for users.

Via a HIPAA compliant process, patients answer a list of questions that are accessed through a web link on their mobile or desktop devices. OutcomeMD summarizes the symptoms into a score that displays to both the physician and patient. Patients’ answers and scores are pushed to the clinician’s DrChrono EHR medical note. As care progresses in the OutcomeMD platform, patients remotely track how their symptoms change, and notifications alert clinicians of patients who may need attention. The integration with DrChrono also allows patient data on confounding factors to be automatically pushed from the patient’s device into the clinician’s medical note. The partnership will enable physicians to visualize patients’ status, and all the factors involved in their care, on one screen, says DrChrono and OutcomeMD, strengthening documentation and saving time for both patients and clinicians. An integration demo video is available at https://youtu.be/jnh7YPII080.

FOR MORE INFORMATION, VISIT: www.outcomemd.com

Continue to: NEW MATERNITY GOWN...

ImageFIRST launched a new maternity gown for expecting mothers. The Comfort Care^® Maternity Gown is a lightweight, premium polyester/nylon fabric that front snaps to allow for skin-to-skin access and optional breastfeeding. The gown also includes shoulder snaps and a full cut for extra coverage and to accommodate a variety of body types, says ImageFIRST.

ImageFIRST is a national linen rental provider. It developed the Comfort Care^® Maternity Gown with input from labor and delivery departments to best meet the needs of expecting mothers. It also says that a portion of the proceeds from each gown rental will be donated to the National Pediatric Cancer Foundation. 

FOR MORE INFORMATION, VISIT: www.imagefirst.com

FDA REMOVES ALCOHOL BAN WITH ADDYI

Sprout Pharmaceuticals announced that the US Food and Drug Administration (FDA) has removed their contraindication on alcohol use with Addyi® (flibanserin). Addyi was approved in 2015 and is an oral nonhormonal pill for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. Patients are advised to discontinue drinking alcohol at least 2 hours before taking Addyi at bedtime or skip the Addyi dose that evening.

The FDA also removed the requirement, under its Risk Evaluation and Mitigation Strategy (REMS) program, for health care practitioners or pharmacies to be certified to prescribe or dispense Addyi. Sprout says that to make all labeling elements consistent with the FDA’s findings the boxed warning will change and the medication guide will be updated and included under the REMS. 

The most commonly reported adverse events among patients taking Addyi are dizziness, sleepiness, nausea, fatigue, insomnia, and dry mouth. Addyi is contraindicated in patients taking moderate or strong cytochrome P450 3A4 (CYP3A4) inhibitors and in those with hepatic impairment.

FOR MORE INFORMATION AND THE FULL PRESCRIBING INFORMATION AND MEDICATION GUIDE, VISIT: www.addyi.com

FEZOLINETANT FOR VMS

FOR MORE INFORMATION, VISIT: http://www.clinicaltrials.gov, TRIAL IDENTIFIERS NCT04003155, NCT04003142, AND NCT04003389

SOLUTIONS FOR OUTCOME TRACKING

DrChrono and OutcomeMD announce a partnership to track and analyze patient outcome data and confounding factors. DrChrono is an electronic health record (EHR) system, and OutcomeMD is a software solution that uses literature-validated patient-reported outcome instruments to score and track a patient’s symptom severity and inform treatment decisions for users.

Via a HIPAA compliant process, patients answer a list of questions that are accessed through a web link on their mobile or desktop devices. OutcomeMD summarizes the symptoms into a score that displays to both the physician and patient. Patients’ answers and scores are pushed to the clinician’s DrChrono EHR medical note. As care progresses in the OutcomeMD platform, patients remotely track how their symptoms change, and notifications alert clinicians of patients who may need attention. The integration with DrChrono also allows patient data on confounding factors to be automatically pushed from the patient’s device into the clinician’s medical note. The partnership will enable physicians to visualize patients’ status, and all the factors involved in their care, on one screen, says DrChrono and OutcomeMD, strengthening documentation and saving time for both patients and clinicians. An integration demo video is available at https://youtu.be/jnh7YPII080.

FOR MORE INFORMATION, VISIT: www.outcomemd.com

Continue to: NEW MATERNITY GOWN...

ImageFIRST launched a new maternity gown for expecting mothers. The Comfort Care^® Maternity Gown is a lightweight, premium polyester/nylon fabric that front snaps to allow for skin-to-skin access and optional breastfeeding. The gown also includes shoulder snaps and a full cut for extra coverage and to accommodate a variety of body types, says ImageFIRST.

ImageFIRST is a national linen rental provider. It developed the Comfort Care^® Maternity Gown with input from labor and delivery departments to best meet the needs of expecting mothers. It also says that a portion of the proceeds from each gown rental will be donated to the National Pediatric Cancer Foundation. 

FOR MORE INFORMATION, VISIT: www.imagefirst.com

FDA REMOVES ALCOHOL BAN WITH ADDYI

Sprout Pharmaceuticals announced that the US Food and Drug Administration (FDA) has removed their contraindication on alcohol use with Addyi® (flibanserin). Addyi was approved in 2015 and is an oral nonhormonal pill for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. Patients are advised to discontinue drinking alcohol at least 2 hours before taking Addyi at bedtime or skip the Addyi dose that evening.

The FDA also removed the requirement, under its Risk Evaluation and Mitigation Strategy (REMS) program, for health care practitioners or pharmacies to be certified to prescribe or dispense Addyi. Sprout says that to make all labeling elements consistent with the FDA’s findings the boxed warning will change and the medication guide will be updated and included under the REMS. 

The most commonly reported adverse events among patients taking Addyi are dizziness, sleepiness, nausea, fatigue, insomnia, and dry mouth. Addyi is contraindicated in patients taking moderate or strong cytochrome P450 3A4 (CYP3A4) inhibitors and in those with hepatic impairment.

FOR MORE INFORMATION AND THE FULL PRESCRIBING INFORMATION AND MEDICATION GUIDE, VISIT: www.addyi.com

FEZOLINETANT FOR VMS

FOR MORE INFORMATION, VISIT: http://www.clinicaltrials.gov, TRIAL IDENTIFIERS NCT04003155, NCT04003142, AND NCT04003389

SOLUTIONS FOR OUTCOME TRACKING

DrChrono and OutcomeMD announce a partnership to track and analyze patient outcome data and confounding factors. DrChrono is an electronic health record (EHR) system, and OutcomeMD is a software solution that uses literature-validated patient-reported outcome instruments to score and track a patient’s symptom severity and inform treatment decisions for users.

Via a HIPAA compliant process, patients answer a list of questions that are accessed through a web link on their mobile or desktop devices. OutcomeMD summarizes the symptoms into a score that displays to both the physician and patient. Patients’ answers and scores are pushed to the clinician’s DrChrono EHR medical note. As care progresses in the OutcomeMD platform, patients remotely track how their symptoms change, and notifications alert clinicians of patients who may need attention. The integration with DrChrono also allows patient data on confounding factors to be automatically pushed from the patient’s device into the clinician’s medical note. The partnership will enable physicians to visualize patients’ status, and all the factors involved in their care, on one screen, says DrChrono and OutcomeMD, strengthening documentation and saving time for both patients and clinicians. An integration demo video is available at https://youtu.be/jnh7YPII080.

FOR MORE INFORMATION, VISIT: www.outcomemd.com

Continue to: NEW MATERNITY GOWN...

ImageFIRST launched a new maternity gown for expecting mothers. The Comfort Care^® Maternity Gown is a lightweight, premium polyester/nylon fabric that front snaps to allow for skin-to-skin access and optional breastfeeding. The gown also includes shoulder snaps and a full cut for extra coverage and to accommodate a variety of body types, says ImageFIRST.

ImageFIRST is a national linen rental provider. It developed the Comfort Care^® Maternity Gown with input from labor and delivery departments to best meet the needs of expecting mothers. It also says that a portion of the proceeds from each gown rental will be donated to the National Pediatric Cancer Foundation. 

FOR MORE INFORMATION, VISIT: www.imagefirst.com

Genital lichen simplex chronicus

Lichen simplex chronicus (LSC) is an inflammatory skin condition that develops secondary to persistent rubbing or scratching of skin. Although LSC can occur anywhere on the body, genital LSC develops in association with genital itch, with the itch often described as intense and unrelenting. The itching sensation leads to scratching and rubbing of the area, which can provide temporary symptomatic relief.^1,2 However, this action of rubbing and scratching stimulates local cutaneous nerves, inducing an even more intense itch sensation. This process, identified as the ‘itch-scratch cycle,’ plays a prominent role in all cases of LSC.¹

On physical examination LSC appears as poorly defined, pink to red plaques with accentuated skin markings on bilateral labia majora. Less commonly, it can present as asymmetrical or unilateral plaques.³ LSC can extend onto labia minora, mons pubis, and medial thighs. However, the vagina is spared.¹ Excoriations, marked by their geometric, angular appearance, often can be appreciated overlying plaques of LSC. Additionally, crusting, scale, broken hairs, hyperpigmentation, and scarring may be seen in LSC.²

In this case, white discharge was noted on vaginal examination, which was suspicious for vaginal candidiasis. Wet mount examination revealed multiple candida hyphae and spores (FIGURE 2), confirming vaginal candidiasis. This vulvovaginal fungal infection caused persistent vulvar pruritus, with subsequent development of LSC due to prolonged scratching. The patient was treated with both oral fluconazole and topical mometasone ointment, for vaginal candidiasis and vulvar LSC, respectively. Mometasone ointment is categorized as a class II (high potency) topical steroid. However, it is worth noting that mometasone cream is categorized as a class IV (medium potency) topical steroid.
 

FIGURE 2 Wet mount of vaginal discharge, revealing candida hyphae and spores

Treatment

Successful treatment of LSC requires addressing 4 elements, including recognizing and treating the underlying etiology, restoring barrier function, reducing inflammation, and interrupting the itch-scratch cycle.³

Identifying the underlying etiology. Knowing the etiology of vulvar pruritus is a key step in resolution of the condition because LSC is driven by repetitive rubbing and scratching behaviors in response to the itch. The differential diagnosis for vulvar pruritus is broad. Evaluation and workup should be tailored to suit each unique patient presentation. A review of past medical history and full-body skin examination can identify a contributing inflammatory skin disease, such as atopic dermatitis, psoriasis, lichen planus, lichen sclerosus, or autoimmune vesiculobullous disease (pemphigus).^1,2 Careful review of products applied in the genital area can reveal an underlying irritant or allergic contact dermatitis. Scented soap or detergent commonly cause vulvar dermatitis.¹ A speculum examination may suggest inflammatory vaginitis or atrophic vaginitis (genitourinary syndrome of menopause); run off of vaginal discharge onto the vulvar skin can result in vulvar pruritus. Vaginal wet mount can diagnose vulvovaginal candidiasis, trichomonas infection, and bacterial vaginitis.¹ A skin scraping with mineral oil or potassium hydroxide can suggest scabies infestation or cutaneous dermatophyte infection, respectively.² Treatment of vulvar pruritus should be initiated based on diagnosis.

Restoring barrier function. The repetitive scratching and rubbing behaviors disrupt the cutaneous barrier layer and lead to stimulation of the local nerves. This creates more itch and further traumatization to the barrier. Barrier function can be restored through soaking the area, with sitz baths or damp towels. Following 20- to 30-minute soaks, a lubricant, such as petroleum jelly, should be applied to the area.³

Reducing inflammation. To reduce inflammation, topical steroids should be applied to areas of LSC.³ In severe cases, high potency topical steroids should be prescribed. Examples of high potency topical steroids include:

• clobetasol propionate 0.05%
• betamethasone dipropionate 0.05%
• halobetasol propionate 0.05%.

Ointment is the choice vehicle because it is both more potent and associated with decreased stinging sensation. High potency steroid ointment should be applied twice daily for at least 2 to 4 weeks. The transition to lower potency topical steroids, such as triamcinolone acetonide 0.1% ointment, can be made as the LSC improves.²

Interrupting the itch-scratch cycle. As noted above, persistent rubbing and scratching generates increased itch sensation. Thus, breaking the itch-scratch cycle is essential. Nighttime scratching can be improved with hydroxyzine. The effective dosage ranges between 25 and 75 mg and should be titrated up slowly every 5 to 7 days. Sedation is a major adverse effect of hydroxyzine, limiting the treatment of daytime itching. Selective serotonin reuptake inhibitors (SSRIs), such as citalopram, also have been found to be effective. Over the counter, nonsedation antihistamines have not been found to be useful in breaking the itch-scratch cycle. The clinical course of LSC is chronic (as the name implies), waxing and waning, and sometimes can be challenging to treat—some patients require years-long continued follow-up and treatment.³
 

Genital lichen simplex chronicus

Lichen simplex chronicus (LSC) is an inflammatory skin condition that develops secondary to persistent rubbing or scratching of skin. Although LSC can occur anywhere on the body, genital LSC develops in association with genital itch, with the itch often described as intense and unrelenting. The itching sensation leads to scratching and rubbing of the area, which can provide temporary symptomatic relief.^1,2 However, this action of rubbing and scratching stimulates local cutaneous nerves, inducing an even more intense itch sensation. This process, identified as the ‘itch-scratch cycle,’ plays a prominent role in all cases of LSC.¹

On physical examination LSC appears as poorly defined, pink to red plaques with accentuated skin markings on bilateral labia majora. Less commonly, it can present as asymmetrical or unilateral plaques.³ LSC can extend onto labia minora, mons pubis, and medial thighs. However, the vagina is spared.¹ Excoriations, marked by their geometric, angular appearance, often can be appreciated overlying plaques of LSC. Additionally, crusting, scale, broken hairs, hyperpigmentation, and scarring may be seen in LSC.²

In this case, white discharge was noted on vaginal examination, which was suspicious for vaginal candidiasis. Wet mount examination revealed multiple candida hyphae and spores (FIGURE 2), confirming vaginal candidiasis. This vulvovaginal fungal infection caused persistent vulvar pruritus, with subsequent development of LSC due to prolonged scratching. The patient was treated with both oral fluconazole and topical mometasone ointment, for vaginal candidiasis and vulvar LSC, respectively. Mometasone ointment is categorized as a class II (high potency) topical steroid. However, it is worth noting that mometasone cream is categorized as a class IV (medium potency) topical steroid.
 

FIGURE 2 Wet mount of vaginal discharge, revealing candida hyphae and spores

Treatment

Successful treatment of LSC requires addressing 4 elements, including recognizing and treating the underlying etiology, restoring barrier function, reducing inflammation, and interrupting the itch-scratch cycle.³

Identifying the underlying etiology. Knowing the etiology of vulvar pruritus is a key step in resolution of the condition because LSC is driven by repetitive rubbing and scratching behaviors in response to the itch. The differential diagnosis for vulvar pruritus is broad. Evaluation and workup should be tailored to suit each unique patient presentation. A review of past medical history and full-body skin examination can identify a contributing inflammatory skin disease, such as atopic dermatitis, psoriasis, lichen planus, lichen sclerosus, or autoimmune vesiculobullous disease (pemphigus).^1,2 Careful review of products applied in the genital area can reveal an underlying irritant or allergic contact dermatitis. Scented soap or detergent commonly cause vulvar dermatitis.¹ A speculum examination may suggest inflammatory vaginitis or atrophic vaginitis (genitourinary syndrome of menopause); run off of vaginal discharge onto the vulvar skin can result in vulvar pruritus. Vaginal wet mount can diagnose vulvovaginal candidiasis, trichomonas infection, and bacterial vaginitis.¹ A skin scraping with mineral oil or potassium hydroxide can suggest scabies infestation or cutaneous dermatophyte infection, respectively.² Treatment of vulvar pruritus should be initiated based on diagnosis.

Restoring barrier function. The repetitive scratching and rubbing behaviors disrupt the cutaneous barrier layer and lead to stimulation of the local nerves. This creates more itch and further traumatization to the barrier. Barrier function can be restored through soaking the area, with sitz baths or damp towels. Following 20- to 30-minute soaks, a lubricant, such as petroleum jelly, should be applied to the area.³

Reducing inflammation. To reduce inflammation, topical steroids should be applied to areas of LSC.³ In severe cases, high potency topical steroids should be prescribed. Examples of high potency topical steroids include:

• clobetasol propionate 0.05%
• betamethasone dipropionate 0.05%
• halobetasol propionate 0.05%.

Ointment is the choice vehicle because it is both more potent and associated with decreased stinging sensation. High potency steroid ointment should be applied twice daily for at least 2 to 4 weeks. The transition to lower potency topical steroids, such as triamcinolone acetonide 0.1% ointment, can be made as the LSC improves.²

Interrupting the itch-scratch cycle. As noted above, persistent rubbing and scratching generates increased itch sensation. Thus, breaking the itch-scratch cycle is essential. Nighttime scratching can be improved with hydroxyzine. The effective dosage ranges between 25 and 75 mg and should be titrated up slowly every 5 to 7 days. Sedation is a major adverse effect of hydroxyzine, limiting the treatment of daytime itching. Selective serotonin reuptake inhibitors (SSRIs), such as citalopram, also have been found to be effective. Over the counter, nonsedation antihistamines have not been found to be useful in breaking the itch-scratch cycle. The clinical course of LSC is chronic (as the name implies), waxing and waning, and sometimes can be challenging to treat—some patients require years-long continued follow-up and treatment.³
 

Genital lichen simplex chronicus

Lichen simplex chronicus (LSC) is an inflammatory skin condition that develops secondary to persistent rubbing or scratching of skin. Although LSC can occur anywhere on the body, genital LSC develops in association with genital itch, with the itch often described as intense and unrelenting. The itching sensation leads to scratching and rubbing of the area, which can provide temporary symptomatic relief.^1,2 However, this action of rubbing and scratching stimulates local cutaneous nerves, inducing an even more intense itch sensation. This process, identified as the ‘itch-scratch cycle,’ plays a prominent role in all cases of LSC.¹

On physical examination LSC appears as poorly defined, pink to red plaques with accentuated skin markings on bilateral labia majora. Less commonly, it can present as asymmetrical or unilateral plaques.³ LSC can extend onto labia minora, mons pubis, and medial thighs. However, the vagina is spared.¹ Excoriations, marked by their geometric, angular appearance, often can be appreciated overlying plaques of LSC. Additionally, crusting, scale, broken hairs, hyperpigmentation, and scarring may be seen in LSC.²

In this case, white discharge was noted on vaginal examination, which was suspicious for vaginal candidiasis. Wet mount examination revealed multiple candida hyphae and spores (FIGURE 2), confirming vaginal candidiasis. This vulvovaginal fungal infection caused persistent vulvar pruritus, with subsequent development of LSC due to prolonged scratching. The patient was treated with both oral fluconazole and topical mometasone ointment, for vaginal candidiasis and vulvar LSC, respectively. Mometasone ointment is categorized as a class II (high potency) topical steroid. However, it is worth noting that mometasone cream is categorized as a class IV (medium potency) topical steroid.
 

FIGURE 2 Wet mount of vaginal discharge, revealing candida hyphae and spores

Treatment

Successful treatment of LSC requires addressing 4 elements, including recognizing and treating the underlying etiology, restoring barrier function, reducing inflammation, and interrupting the itch-scratch cycle.³

Identifying the underlying etiology. Knowing the etiology of vulvar pruritus is a key step in resolution of the condition because LSC is driven by repetitive rubbing and scratching behaviors in response to the itch. The differential diagnosis for vulvar pruritus is broad. Evaluation and workup should be tailored to suit each unique patient presentation. A review of past medical history and full-body skin examination can identify a contributing inflammatory skin disease, such as atopic dermatitis, psoriasis, lichen planus, lichen sclerosus, or autoimmune vesiculobullous disease (pemphigus).^1,2 Careful review of products applied in the genital area can reveal an underlying irritant or allergic contact dermatitis. Scented soap or detergent commonly cause vulvar dermatitis.¹ A speculum examination may suggest inflammatory vaginitis or atrophic vaginitis (genitourinary syndrome of menopause); run off of vaginal discharge onto the vulvar skin can result in vulvar pruritus. Vaginal wet mount can diagnose vulvovaginal candidiasis, trichomonas infection, and bacterial vaginitis.¹ A skin scraping with mineral oil or potassium hydroxide can suggest scabies infestation or cutaneous dermatophyte infection, respectively.² Treatment of vulvar pruritus should be initiated based on diagnosis.

Restoring barrier function. The repetitive scratching and rubbing behaviors disrupt the cutaneous barrier layer and lead to stimulation of the local nerves. This creates more itch and further traumatization to the barrier. Barrier function can be restored through soaking the area, with sitz baths or damp towels. Following 20- to 30-minute soaks, a lubricant, such as petroleum jelly, should be applied to the area.³

Reducing inflammation. To reduce inflammation, topical steroids should be applied to areas of LSC.³ In severe cases, high potency topical steroids should be prescribed. Examples of high potency topical steroids include:

• clobetasol propionate 0.05%
• betamethasone dipropionate 0.05%
• halobetasol propionate 0.05%.

Ointment is the choice vehicle because it is both more potent and associated with decreased stinging sensation. High potency steroid ointment should be applied twice daily for at least 2 to 4 weeks. The transition to lower potency topical steroids, such as triamcinolone acetonide 0.1% ointment, can be made as the LSC improves.²

Interrupting the itch-scratch cycle. As noted above, persistent rubbing and scratching generates increased itch sensation. Thus, breaking the itch-scratch cycle is essential. Nighttime scratching can be improved with hydroxyzine. The effective dosage ranges between 25 and 75 mg and should be titrated up slowly every 5 to 7 days. Sedation is a major adverse effect of hydroxyzine, limiting the treatment of daytime itching. Selective serotonin reuptake inhibitors (SSRIs), such as citalopram, also have been found to be effective. Over the counter, nonsedation antihistamines have not been found to be useful in breaking the itch-scratch cycle. The clinical course of LSC is chronic (as the name implies), waxing and waning, and sometimes can be challenging to treat—some patients require years-long continued follow-up and treatment.³
 

Minimally invasive surgical techniques, which have revolutionized modern-day surgery, are the current standard of care for benign hysterectomies.^1-4 Many surgeons use a video-laparoscopic approach, with or without robotic assistance, to perform a hysterectomy. The development of a bladder flap or vesicovaginal surgical space is a critical step for mobilizing the bladder. When properly performed, it allows for appropriate closure of the vaginal cuff while mitigating the risk of urinary bladder damage.

In patients with no prior pelvic surgeries, this vesicovaginal anatomic space is typically developed with ease. However, in patients who have had prior cesarean deliveries (CDs), the presence of vesicouterine adhesions could make this step significantly more challenging. As a result, the risk of bladder injury is higher.^5-8

With the current tide of cesarean birth rates approaching 33% on a national scale, the presence of vesicouterine adhesions is commonly encountered.⁹ These adhesions can distort the anatomy and thereby create more difficult dissections and increase operative time, conversion to laparotomy, and inadvertent cystotomy. Such a challenge also presents an increased risk of injuring adjacent structures.

In this article, we describe an effective method of dissection that is especially useful in the setting of prior CDs. This method involves developing a "new" surgical space lateral and caudal to the vesicocervical space. 

Steps in operative planning

Preoperative evaluation. A thorough preoperative evaluation should be performed for patients planning to undergo a laparoscopic hysterectomy. This includes obtaining details of their medical and surgical history. Access to prior surgical records may help to facilitate planning of the surgical approach. Previous pelvic surgery, such as CD, anterior myomectomy, cesarean scar defect repair, endometriosis treatment, or exploratory laparotomy, may predispose these patients to develop adhesions in the anterior cul-de-sac. Our method of reverse vesicouterine fold dissection can be particularly efficacious in these settings.

Surgical preparation and laparoscopic port placement. In the operative suite, the patient is placed under general anesthesia and positioned in the dorsal lithotomy position.¹⁰ Sterile prep and drapes are used in the standard fashion. A urinary catheter is inserted to maintain a decompressed bladder. A uterine manipulator is inserted with good placement ensured.

Per our practice, we introduce laparoscopic ports in 4 locations. The first incision is made in the umbilicus for the introduction of a 10-mm laparoscope. Three subsequent 5-mm incisions are made in the left and right lower lateral quadrants and medially at the level of the suprapubic region.¹⁰ Upon laparoscopic entry, we perform a comprehensive survey of the abdominopelvic cavity. Adequate mobility of the uterus is confirmed.¹¹ Any posterior uterine adhesions or endometriosis are treated appropriately.¹²

First step in the surgical technique: Lateral dissection

We proceed by first desiccating and cutting the round ligament laterally near the inguinal canal. This technique is carried forward in a caudal direction as the areolar tissue near the obliterated umbilical artery is expanded by the pneumoperitoneum. With a vessel sealing-cutting device, we address the attachments to the adnexa. If the ovaries are to be retained, the utero-ovarian ligament is dessicated and cut. If an oophorectomy is indicated, the infundibulopelvic ligament is dessicated and cut.

Continue to: Using the tip of the vessel sealing...

Using the tip of the vessel sealing-cutting device, the space between the anterior and posterior leaves of the broad ligament is developed and opened. A grasping forceps is then used to elevate the anterior leaf of the broad ligament and maintain medial traction. A space parallel and lateral to the cervix and bladder is then created with blunt dissection.

The inferior and medial direction of this dissection is paramount to avoid injury to nearby structures in the pelvic sidewall. Gradually, this will lead to the identification of the vesciovaginal ligament and then the vesicocervical ligament. The development of these spaces allows for the lateral and inferior displacement of the ureter. These maneuvers can mitigate ureter injury by pushing it away from the planes of dissection during the hysterectomy.

Continued traction is maintained by keeping the medial aspect of the anterior leaf of the broad ligament intact. However, the posterior leaf is dissected next, which further lateralizes the ureter. Now, with the uterine vessels fully exposed, they are thoroughly dessicated and ligated. The same procedure is then performed on the contralateral side.¹¹ (See the box below for links to videos that demonstrate the techniques described here.)

Creating the “new” space

In the “new” space that was partially developed during the lateral dissection, blunt dissection is continued, using a sweeping motion from an inferior-to-superior direction, to extend this avascular space. This is performed bilaterally until both sides are connected from the inferior aspect of the vesicouterine adhesions, if present. This thorough dissection creates what we refer to as a “new” space¹¹ (FIGURE 1).

Medially, the new space is bordered by the vesicocervical-vaginal ligament, also known as the bladder pillar. Its distal landmark is the bladder. The remaining intact anterior leaf of the broad ligament lies adjacent to the space anteriorly. The inner aspect of the obliterated umbilical artery neighbors it laterally. Lastly, the vesicovaginal plane’s posterior margin is the parametrium, which is the region where the ureter courses into the bladder. The paravesical space lies lateral to the obliterated umbilical ligament.

Visualization of this new space is made possible in the laparoscopic setting. The pneumoperitoneum allows for better demarcation of the space. Additionally, laparoscopic views of the anatomic spaces differ from those of the laparotomy view because of the magnification and the insufflation of carbon dioxide gas in the spaces.^13,14 In our experience, approaching the surgery from the “new” space could significantly decrease the risk of genitourinary injuries in patients with anterior cul-de-sac adhesions (FIGURE 2).

Using the reverse vesicouterine fold dissection technique

Among patients with prior CDs, adhesions often are at the level of or superior to the prior CD scar. By creating the new space, safe dissection from a previously untouched area can be accomplished and injury to the urinary bladder can be avoided.

The reverse vesicouterine fold dissection can be performed from this space. Using the previously described blunt sweeping motion from an inferior-to-superior direction, the vesicovaginal and vesicocervical space is further developed from an unscarred plane. This will separate the lowest portion of the bladder from the vagina, cervix, and uterus in a safe manner. Similar to the technique performed during a vaginal hysterectomy, this reverse motion of developing the bladder flap avoids erroneous and blind dissection through the vesicouterine adhesions (FIGURES 3–5).

Continue to: Completing the surgery...

Completing the surgery

Once the bladder is freely mobilized and all adhesions have been dissected, the cervix is circumferentially amputated using monopolar cautery. The vaginal cuff can then be closed from either a laparoscopic or vaginal approach using polyglactin 910 (0-Vicryl) or barbed (V-Loc) suture in a running or interrupted fashion. Our practice uses a 1.5-cm margin depth with each suture. At the end of the surgery, routine cystoscopy is performed to verify distal ureteral patency.¹⁶ Postoperatively, we manage these patients using a fast-track, or enhanced recovery, model.¹⁷

An effective technique in challenging situations

Genitourinary injury is a common complication of hysterectomy.¹⁸ The proximity of the bladder and ureters to the field of dissection during a hysterectomy can be especially challenging when the anatomy is distorted by adhesion formation from prior surgeries. One study demonstrated a 1.3% incidence of urinary tract injuries during laparoscopic hysterectomy.⁶ This included 0.54% ureteral injuries, 0.71% urinary bladder injuries, and 0.06% combined bladder and ureteral injuries.⁶ Particularly among patients with a prior CD, the risk of bladder injury can be significantly heightened.¹⁸

The reverse vesicouterine fold dissection technique that we described offers multiple benefits. By starting the procedure from an untouched and avascular plane, dissection into the plane of the prior adhesions can be circumvented; thus, bleeding is limited and injury to the bladder and ureters is avoided or minimized. By using blunt and sharp dissection, thermal injury and delayed necrosis can be mitigated. Finally, with bladder mobilization well below the colpotomy site, more adequate vaginal tissue is free to be incorporated into the vaginal cuff closure, thereby limiting the risk of cuff dehiscence.¹⁶

While we have found this technique effective for patients with prior cesarean deliveries, it also may be applied to any patient who has a scarred anterior cul-de-sac. This could include patients with prior myomectomy, cesarean scar defect, or endometriosis. Despite the technique being a safeguard against bladder injury, surgeons must still use care in developing the spaces to avoid ureteral injury, especially in a setting of distorted anatomy.

Minimally invasive surgical techniques, which have revolutionized modern-day surgery, are the current standard of care for benign hysterectomies.^1-4 Many surgeons use a video-laparoscopic approach, with or without robotic assistance, to perform a hysterectomy. The development of a bladder flap or vesicovaginal surgical space is a critical step for mobilizing the bladder. When properly performed, it allows for appropriate closure of the vaginal cuff while mitigating the risk of urinary bladder damage.

In patients with no prior pelvic surgeries, this vesicovaginal anatomic space is typically developed with ease. However, in patients who have had prior cesarean deliveries (CDs), the presence of vesicouterine adhesions could make this step significantly more challenging. As a result, the risk of bladder injury is higher.^5-8

With the current tide of cesarean birth rates approaching 33% on a national scale, the presence of vesicouterine adhesions is commonly encountered.⁹ These adhesions can distort the anatomy and thereby create more difficult dissections and increase operative time, conversion to laparotomy, and inadvertent cystotomy. Such a challenge also presents an increased risk of injuring adjacent structures.

In this article, we describe an effective method of dissection that is especially useful in the setting of prior CDs. This method involves developing a "new" surgical space lateral and caudal to the vesicocervical space. 

Steps in operative planning

Preoperative evaluation. A thorough preoperative evaluation should be performed for patients planning to undergo a laparoscopic hysterectomy. This includes obtaining details of their medical and surgical history. Access to prior surgical records may help to facilitate planning of the surgical approach. Previous pelvic surgery, such as CD, anterior myomectomy, cesarean scar defect repair, endometriosis treatment, or exploratory laparotomy, may predispose these patients to develop adhesions in the anterior cul-de-sac. Our method of reverse vesicouterine fold dissection can be particularly efficacious in these settings.

Surgical preparation and laparoscopic port placement. In the operative suite, the patient is placed under general anesthesia and positioned in the dorsal lithotomy position.¹⁰ Sterile prep and drapes are used in the standard fashion. A urinary catheter is inserted to maintain a decompressed bladder. A uterine manipulator is inserted with good placement ensured.

Per our practice, we introduce laparoscopic ports in 4 locations. The first incision is made in the umbilicus for the introduction of a 10-mm laparoscope. Three subsequent 5-mm incisions are made in the left and right lower lateral quadrants and medially at the level of the suprapubic region.¹⁰ Upon laparoscopic entry, we perform a comprehensive survey of the abdominopelvic cavity. Adequate mobility of the uterus is confirmed.¹¹ Any posterior uterine adhesions or endometriosis are treated appropriately.¹²

First step in the surgical technique: Lateral dissection

We proceed by first desiccating and cutting the round ligament laterally near the inguinal canal. This technique is carried forward in a caudal direction as the areolar tissue near the obliterated umbilical artery is expanded by the pneumoperitoneum. With a vessel sealing-cutting device, we address the attachments to the adnexa. If the ovaries are to be retained, the utero-ovarian ligament is dessicated and cut. If an oophorectomy is indicated, the infundibulopelvic ligament is dessicated and cut.

Continue to: Using the tip of the vessel sealing...

Using the tip of the vessel sealing-cutting device, the space between the anterior and posterior leaves of the broad ligament is developed and opened. A grasping forceps is then used to elevate the anterior leaf of the broad ligament and maintain medial traction. A space parallel and lateral to the cervix and bladder is then created with blunt dissection.

The inferior and medial direction of this dissection is paramount to avoid injury to nearby structures in the pelvic sidewall. Gradually, this will lead to the identification of the vesciovaginal ligament and then the vesicocervical ligament. The development of these spaces allows for the lateral and inferior displacement of the ureter. These maneuvers can mitigate ureter injury by pushing it away from the planes of dissection during the hysterectomy.

Continued traction is maintained by keeping the medial aspect of the anterior leaf of the broad ligament intact. However, the posterior leaf is dissected next, which further lateralizes the ureter. Now, with the uterine vessels fully exposed, they are thoroughly dessicated and ligated. The same procedure is then performed on the contralateral side.¹¹ (See the box below for links to videos that demonstrate the techniques described here.)

Creating the “new” space

In the “new” space that was partially developed during the lateral dissection, blunt dissection is continued, using a sweeping motion from an inferior-to-superior direction, to extend this avascular space. This is performed bilaterally until both sides are connected from the inferior aspect of the vesicouterine adhesions, if present. This thorough dissection creates what we refer to as a “new” space¹¹ (FIGURE 1).

Medially, the new space is bordered by the vesicocervical-vaginal ligament, also known as the bladder pillar. Its distal landmark is the bladder. The remaining intact anterior leaf of the broad ligament lies adjacent to the space anteriorly. The inner aspect of the obliterated umbilical artery neighbors it laterally. Lastly, the vesicovaginal plane’s posterior margin is the parametrium, which is the region where the ureter courses into the bladder. The paravesical space lies lateral to the obliterated umbilical ligament.

Visualization of this new space is made possible in the laparoscopic setting. The pneumoperitoneum allows for better demarcation of the space. Additionally, laparoscopic views of the anatomic spaces differ from those of the laparotomy view because of the magnification and the insufflation of carbon dioxide gas in the spaces.^13,14 In our experience, approaching the surgery from the “new” space could significantly decrease the risk of genitourinary injuries in patients with anterior cul-de-sac adhesions (FIGURE 2).

Using the reverse vesicouterine fold dissection technique

Among patients with prior CDs, adhesions often are at the level of or superior to the prior CD scar. By creating the new space, safe dissection from a previously untouched area can be accomplished and injury to the urinary bladder can be avoided.

The reverse vesicouterine fold dissection can be performed from this space. Using the previously described blunt sweeping motion from an inferior-to-superior direction, the vesicovaginal and vesicocervical space is further developed from an unscarred plane. This will separate the lowest portion of the bladder from the vagina, cervix, and uterus in a safe manner. Similar to the technique performed during a vaginal hysterectomy, this reverse motion of developing the bladder flap avoids erroneous and blind dissection through the vesicouterine adhesions (FIGURES 3–5).

Continue to: Completing the surgery...

Completing the surgery

Once the bladder is freely mobilized and all adhesions have been dissected, the cervix is circumferentially amputated using monopolar cautery. The vaginal cuff can then be closed from either a laparoscopic or vaginal approach using polyglactin 910 (0-Vicryl) or barbed (V-Loc) suture in a running or interrupted fashion. Our practice uses a 1.5-cm margin depth with each suture. At the end of the surgery, routine cystoscopy is performed to verify distal ureteral patency.¹⁶ Postoperatively, we manage these patients using a fast-track, or enhanced recovery, model.¹⁷

An effective technique in challenging situations

Genitourinary injury is a common complication of hysterectomy.¹⁸ The proximity of the bladder and ureters to the field of dissection during a hysterectomy can be especially challenging when the anatomy is distorted by adhesion formation from prior surgeries. One study demonstrated a 1.3% incidence of urinary tract injuries during laparoscopic hysterectomy.⁶ This included 0.54% ureteral injuries, 0.71% urinary bladder injuries, and 0.06% combined bladder and ureteral injuries.⁶ Particularly among patients with a prior CD, the risk of bladder injury can be significantly heightened.¹⁸

The reverse vesicouterine fold dissection technique that we described offers multiple benefits. By starting the procedure from an untouched and avascular plane, dissection into the plane of the prior adhesions can be circumvented; thus, bleeding is limited and injury to the bladder and ureters is avoided or minimized. By using blunt and sharp dissection, thermal injury and delayed necrosis can be mitigated. Finally, with bladder mobilization well below the colpotomy site, more adequate vaginal tissue is free to be incorporated into the vaginal cuff closure, thereby limiting the risk of cuff dehiscence.¹⁶

While we have found this technique effective for patients with prior cesarean deliveries, it also may be applied to any patient who has a scarred anterior cul-de-sac. This could include patients with prior myomectomy, cesarean scar defect, or endometriosis. Despite the technique being a safeguard against bladder injury, surgeons must still use care in developing the spaces to avoid ureteral injury, especially in a setting of distorted anatomy.

Minimally invasive surgical techniques, which have revolutionized modern-day surgery, are the current standard of care for benign hysterectomies.^1-4 Many surgeons use a video-laparoscopic approach, with or without robotic assistance, to perform a hysterectomy. The development of a bladder flap or vesicovaginal surgical space is a critical step for mobilizing the bladder. When properly performed, it allows for appropriate closure of the vaginal cuff while mitigating the risk of urinary bladder damage.

In patients with no prior pelvic surgeries, this vesicovaginal anatomic space is typically developed with ease. However, in patients who have had prior cesarean deliveries (CDs), the presence of vesicouterine adhesions could make this step significantly more challenging. As a result, the risk of bladder injury is higher.^5-8

With the current tide of cesarean birth rates approaching 33% on a national scale, the presence of vesicouterine adhesions is commonly encountered.⁹ These adhesions can distort the anatomy and thereby create more difficult dissections and increase operative time, conversion to laparotomy, and inadvertent cystotomy. Such a challenge also presents an increased risk of injuring adjacent structures.

In this article, we describe an effective method of dissection that is especially useful in the setting of prior CDs. This method involves developing a "new" surgical space lateral and caudal to the vesicocervical space. 

Steps in operative planning

Preoperative evaluation. A thorough preoperative evaluation should be performed for patients planning to undergo a laparoscopic hysterectomy. This includes obtaining details of their medical and surgical history. Access to prior surgical records may help to facilitate planning of the surgical approach. Previous pelvic surgery, such as CD, anterior myomectomy, cesarean scar defect repair, endometriosis treatment, or exploratory laparotomy, may predispose these patients to develop adhesions in the anterior cul-de-sac. Our method of reverse vesicouterine fold dissection can be particularly efficacious in these settings.

Surgical preparation and laparoscopic port placement. In the operative suite, the patient is placed under general anesthesia and positioned in the dorsal lithotomy position.¹⁰ Sterile prep and drapes are used in the standard fashion. A urinary catheter is inserted to maintain a decompressed bladder. A uterine manipulator is inserted with good placement ensured.

Per our practice, we introduce laparoscopic ports in 4 locations. The first incision is made in the umbilicus for the introduction of a 10-mm laparoscope. Three subsequent 5-mm incisions are made in the left and right lower lateral quadrants and medially at the level of the suprapubic region.¹⁰ Upon laparoscopic entry, we perform a comprehensive survey of the abdominopelvic cavity. Adequate mobility of the uterus is confirmed.¹¹ Any posterior uterine adhesions or endometriosis are treated appropriately.¹²

First step in the surgical technique: Lateral dissection

We proceed by first desiccating and cutting the round ligament laterally near the inguinal canal. This technique is carried forward in a caudal direction as the areolar tissue near the obliterated umbilical artery is expanded by the pneumoperitoneum. With a vessel sealing-cutting device, we address the attachments to the adnexa. If the ovaries are to be retained, the utero-ovarian ligament is dessicated and cut. If an oophorectomy is indicated, the infundibulopelvic ligament is dessicated and cut.

Continue to: Using the tip of the vessel sealing...

Using the tip of the vessel sealing-cutting device, the space between the anterior and posterior leaves of the broad ligament is developed and opened. A grasping forceps is then used to elevate the anterior leaf of the broad ligament and maintain medial traction. A space parallel and lateral to the cervix and bladder is then created with blunt dissection.

The inferior and medial direction of this dissection is paramount to avoid injury to nearby structures in the pelvic sidewall. Gradually, this will lead to the identification of the vesciovaginal ligament and then the vesicocervical ligament. The development of these spaces allows for the lateral and inferior displacement of the ureter. These maneuvers can mitigate ureter injury by pushing it away from the planes of dissection during the hysterectomy.

Continued traction is maintained by keeping the medial aspect of the anterior leaf of the broad ligament intact. However, the posterior leaf is dissected next, which further lateralizes the ureter. Now, with the uterine vessels fully exposed, they are thoroughly dessicated and ligated. The same procedure is then performed on the contralateral side.¹¹ (See the box below for links to videos that demonstrate the techniques described here.)

Creating the “new” space

In the “new” space that was partially developed during the lateral dissection, blunt dissection is continued, using a sweeping motion from an inferior-to-superior direction, to extend this avascular space. This is performed bilaterally until both sides are connected from the inferior aspect of the vesicouterine adhesions, if present. This thorough dissection creates what we refer to as a “new” space¹¹ (FIGURE 1).

Medially, the new space is bordered by the vesicocervical-vaginal ligament, also known as the bladder pillar. Its distal landmark is the bladder. The remaining intact anterior leaf of the broad ligament lies adjacent to the space anteriorly. The inner aspect of the obliterated umbilical artery neighbors it laterally. Lastly, the vesicovaginal plane’s posterior margin is the parametrium, which is the region where the ureter courses into the bladder. The paravesical space lies lateral to the obliterated umbilical ligament.

Visualization of this new space is made possible in the laparoscopic setting. The pneumoperitoneum allows for better demarcation of the space. Additionally, laparoscopic views of the anatomic spaces differ from those of the laparotomy view because of the magnification and the insufflation of carbon dioxide gas in the spaces.^13,14 In our experience, approaching the surgery from the “new” space could significantly decrease the risk of genitourinary injuries in patients with anterior cul-de-sac adhesions (FIGURE 2).

Using the reverse vesicouterine fold dissection technique

Among patients with prior CDs, adhesions often are at the level of or superior to the prior CD scar. By creating the new space, safe dissection from a previously untouched area can be accomplished and injury to the urinary bladder can be avoided.

The reverse vesicouterine fold dissection can be performed from this space. Using the previously described blunt sweeping motion from an inferior-to-superior direction, the vesicovaginal and vesicocervical space is further developed from an unscarred plane. This will separate the lowest portion of the bladder from the vagina, cervix, and uterus in a safe manner. Similar to the technique performed during a vaginal hysterectomy, this reverse motion of developing the bladder flap avoids erroneous and blind dissection through the vesicouterine adhesions (FIGURES 3–5).

Continue to: Completing the surgery...

Completing the surgery

Once the bladder is freely mobilized and all adhesions have been dissected, the cervix is circumferentially amputated using monopolar cautery. The vaginal cuff can then be closed from either a laparoscopic or vaginal approach using polyglactin 910 (0-Vicryl) or barbed (V-Loc) suture in a running or interrupted fashion. Our practice uses a 1.5-cm margin depth with each suture. At the end of the surgery, routine cystoscopy is performed to verify distal ureteral patency.¹⁶ Postoperatively, we manage these patients using a fast-track, or enhanced recovery, model.¹⁷

An effective technique in challenging situations

Genitourinary injury is a common complication of hysterectomy.¹⁸ The proximity of the bladder and ureters to the field of dissection during a hysterectomy can be especially challenging when the anatomy is distorted by adhesion formation from prior surgeries. One study demonstrated a 1.3% incidence of urinary tract injuries during laparoscopic hysterectomy.⁶ This included 0.54% ureteral injuries, 0.71% urinary bladder injuries, and 0.06% combined bladder and ureteral injuries.⁶ Particularly among patients with a prior CD, the risk of bladder injury can be significantly heightened.¹⁸

The reverse vesicouterine fold dissection technique that we described offers multiple benefits. By starting the procedure from an untouched and avascular plane, dissection into the plane of the prior adhesions can be circumvented; thus, bleeding is limited and injury to the bladder and ureters is avoided or minimized. By using blunt and sharp dissection, thermal injury and delayed necrosis can be mitigated. Finally, with bladder mobilization well below the colpotomy site, more adequate vaginal tissue is free to be incorporated into the vaginal cuff closure, thereby limiting the risk of cuff dehiscence.¹⁶

While we have found this technique effective for patients with prior cesarean deliveries, it also may be applied to any patient who has a scarred anterior cul-de-sac. This could include patients with prior myomectomy, cesarean scar defect, or endometriosis. Despite the technique being a safeguard against bladder injury, surgeons must still use care in developing the spaces to avoid ureteral injury, especially in a setting of distorted anatomy.

The most recently concluded term of the US Supreme Court, which began on October 1, 2018, yielded a number of decisions of interest to health care professionals and to ObGyns in particular. Although the term was viewed by some observers as less consequential than other recent terms, a review of the cases decided paints a picture of a more important term than some commentators expected.

When the term began, the Court had only 8 justices—1 short of a full bench: Judge Brett Kavanaugh had not yet been confirmed by the Senate. He was confirmed on October 6, by a 50-48 vote, and Justice Kavanaugh immediately joined the Court and began to hear and decide cases.

Increasingly, important decisions affect medical practice

From the nature of practice (abortion), to payment for service (Medicare reimbursement), resolution of disputes (arbitration), and fraud and abuse (the federal False Claims Act), the decisions of the Court will have an impact on many areas of medical practice. Organized medicine increasingly has recognized the significance of the work of the Court; nowhere has this been more clearly demonstrated than with amicus curiae (friend of the court) briefs filed by medical organizations.

Amicus curiae briefs. These briefs are filed by persons or organizations not a party to a case the Court is hearing. Their legitimate purpose is to inform the Court of 1) special information within the expertise of the amicus (or amici, plural) or 2) consequences of the decision that might not be apparent from arguments made by the parties to the case. Sometimes, the Court cites amicus briefs for having provided important information about the case.

Filing amicus briefs is time-consuming and expensive; organizations do not file them for trivial reasons. Organizations frequently join together to file a joint brief, to share expenses and express to the Court a stronger position.

Three categories of health professionals file amicus briefs in ObGyn-related cases:

• Major national organizations, often representing broad interests of health care professions or institutions (the American Medical Association [AMA], the Association of American Medical Colleges, and the American Hospital Association [AHA]), have filed a number of amicus briefs over the years.
• Specialty boards increasingly file amicus briefs. For example, the American College of Obstetricians and Gynecologists (ACOG) and the American Society for Reproductive Medicine have filed briefs related to abortion issues.
• In reproductive issues, the American Association of Pro-Life Obstetricians and Gynecologists, the American College of Pediatricians, and the Christian Medical & Dental Associations have been active amicus filers—frequently taking positions different than, even inconsistent with, amicus briefs filed by major specialty boards.

Amicus briefs filed by medical associations provide strong clues to what is important to clinicians. We have looked at such briefs to help us identify topics and cases from the just-concluded term that can be of particular interest to you.

Continue to: Surveying the shadow docket...

Surveying the shadow docket. As part of our review of the past term, we also looked at the so-called shadow docket, which includes decisions regarding writs of certiorari (which cases it agrees to hear); stays (usually delaying implementation of a law); or denials of stays. (Persuading the Court to hear a case is not easy: It hears approximately 70 cases per year out of as many as 7,000 applications to be heard.)

Abortion ruling

At stake. A number of states recently enacted a variety of provisions that might make an abortion more difficult to obtain. Some of the cases challenging these restrictions are making their way through lower courts, and one day might be argued before the Supreme Court. However, the Court has not (yet) agreed to hear the substance of many new abortion-related provisions.

Box v Planned Parenthood of Indiana and Kentucky, Inc.

The Court decided only 1 abortion restriction case this term.¹ The Indiana law in question included 2 provisions that the Court considered:

Disposal of remains. The law regulated the manner in which abortion providers can dispose of fetal remains (ie, they cannot be treated as “infectious and pathologic waste”).

Motivation for seeking abortion. The Indiana law makes it illegal for an abortion provider to perform an abortion when the provider knows that the mother is seeking that abortion “solely” because of the fetus’s race, sex, diagnosis of Down syndrome, disability, or related characteristics.

Final rulings. The Court held that the disposal-of-remains provision is constitutional. The provision is “rationally related to the state’s interest in proper disposal of fetal remains.”² Planned Parenthood had not raised the issue of whether the law might impose an undue burden on a woman’s right to obtain an abortion, so the Court did not decide that issue.

The Court did not consider the constitutionality of the part of the law proscribing certain reasons for seeking an otherwise legal abortion; instead, it awaits lower courts’ review of the issue. Justice Clarence Thomas wrote an extensive concurring opinion suggesting that this law is intended to avoid abortion to achieve eugenic goals.³

Key developments from the shadow docket

The Court issued a stay preventing a Louisiana statute that requires physicians who perform abortions to have admitting privileges at a nearby hospital from going into effect, pending the outcome of litigation about that law.⁴ Four dissenters noted that all 4 physicians who perform abortions in Louisiana have such privileges. Chief Justice Roberts was the fifth vote to grant the stay. This case likely will make its way back to the Court, as will a number of other state laws being adopted. The issue may be back as soon as the term just starting.

The Court is also considering whether to take another Indiana case, Box v Planned Parenthood of Indiana and Kentucky, Inc. (Box II). This case involves an Indiana ultrasonography viewing option as part of the abortion consent process.⁵

The Court declined to hear cases from Louisiana and Kansas in which the states had cut off Medicaid funding to Planned Parenthood. Lower courts had stopped the implementation of those laws.⁶ The legal issue was whether private parties, as opposed to the federal government, had standing to bring the case. For now, the decision of the lower courts to stop implementation of the funding cutoff is in effect. There is a split in the Circuit Courts on the issue, however, making it likely that the Supreme Court will have to resolve it sooner or later.

Health care organizations have filed a number of amicus briefs in these and other cases involving new abortion regulations. ACOG and others filed a brief opposing a Louisiana law that requires abortion providers to have admitting privileges at a nearby facility,⁷ and a brief opposing a similar Oklahoma law.⁸ The Association of Pro-Life Obstetricians and Gynecologists and others filed amicus curiae briefs in Box II⁹ and in an Alabama case involving so-called dismemberment abortion.¹⁰

Continue to: Medicare payments...

Medicare payments

Azar, Secretary of Health and Human Services v Allina Health Services, et al¹¹

This case drew interest—and many amicus briefs—from health care providers, including the AMA and the AHA.^12,13 There was good reason for their interest: First, the case involved more than $3 billion in reimbursements; second, it represented a potentially important precedent about the rights of providers and patients to comment on Medicare reimbursement changes. The question involved the technical calculation of additional payments made to institutions that serve a disproportionate number of low-income patients (known as Medicare Fractions).

At stake. The issue was a statutory requirement for a 60-day public notice and comment period for rules that “change a substantive legal standard” governing the scope of benefits, eligibility, or payment for services.¹⁴ In 2014, the Secretary of the Department of Health and Human Services (HHS) in the Obama administration posted a spreadsheet announcing Medicare fractions rates for hospitals (for 2012)—without formal notice or comment regarding the formula used. (The spreadsheet listed what each qualifying institution would receive, but it was based on a formula that, as noted, had not been subject to public notice and comment.) The AMA and AHA briefs emphasized the importance of a notice and comment period, especially when Medicare reimbursement is involved.

Final ruling. The Court held that the HHS process violated the notice and comment provision, thereby invalidating the policy underlying the so-called spreadsheet reimbursement. The decision was significant: This was a careful statutory interpretation of the 60-day notice and comment period, not the reimbursement policy itself. Presumably, had the HHS Secretary provided for sufficient notice and comment, the formula used would have met the requirements for issuing reimbursement formulas.

Key points. Hospitals will collectively receive $3 or $4 billion as a consequence of the ruling. Perhaps more importantly, the decision signals that HHS is going to have to take seriously the requirement that it publish Medicare-related reimbursement policies for the 60-day period.

Liability under the False Claims Act

The False Claims Act (FCA) protects the federal government from fraudulent claims for payment and for shoddy goods and services. It incentivizes (by a percentage of recovery) private parties to bring cases to enforce the law.¹⁵ (Of course, the federal government also enforces the Act.)

At stake. The FCA has been of considerable concern to the AHA, the Association of American Medical Colleges, and other health care organizations—understandably so.¹⁶ As the AHA informed the Court in an amicus brief, “The prevalence of [FCA] cases has ballooned over the past three decades.... These suits disproportionately target healthcare entities.... Of the 767 new FCA cases filed in 2018, for example, 506 involved healthcare defendants.”¹⁷

Final ruling. The Court considered an ambiguity in the statute of limitations for these actions and the Court unanimously ruled to permit an extended time in which qui tam actions (private actions under the law) can be filed.¹⁸

Key points. As long a period as 10 years can pass between the time an FCA violation occurs and an action is brought. This decision is likely to increase the number of FCA actions against health care providers because the case can be filed many years after the conduct that gave rise to the complaint.

Continue to: Registering sex offenders...

Registering sex offenders

The Court upheld the constitutionality of the federal Sex Offender Registration and Notification Act (SORNA).¹⁹ Sex offenders must register and periodically report, in person, to law enforcement in every state in which the offender works, studies, or resides.

At stake. The case involved the applicability of SORNA registration obligations to those convicted of sex offenses before SORNA was adopted (pre-Act offenders).²⁰ The court upheld registration requirements for pre-Act offenders.

Arbitration

The Court continued its practice of deciding at least one case each term that emphasizes that federal law requires that courts rather strictly enforce agreements to arbitrate (instead of to litigate) future disputes.²¹ In another case, the Court ruled that there can be “class” or “joint” arbitration only if the agreement to arbitrate a dispute clearly permits such class arbitration.²²

Pharma’s liability regarding product risk

The Court somewhat limited the liability of pharmaceutical companies for failing to provide adequate warning about the risk that their products pose. The case against Merck involved 500 patients who took denosumab (Fosamax) and suffered atypical femoral fractures.²³

At stake. Because prescribing information (in which warnings are provided) must be approved by the US Food and Drug Administration (FDA), the legal test is: Would the FDA have refused to approve a change in the warning if Merck had “fully informed the FDA of the justifications for the warning” required by state law to avoid liability?^24,25 Lower-court judges (not juries) will be expected to apply this test in the future.

The doctor and the death penalty

The Court has established a rule that, when a prisoner facing capital punishment objects to a form of execution because it is too painful, he has to propose an alternative that is reasonably available. In one case,²⁶ a physician, an expert witness for the prisoner, did not answer some essential relative-pain questions (ie, would one procedure be more painful than another?).

At stake. The AMA filed an amicus brief in this case, indicating that it is unethical for physicians to participate in an execution. The brief noted that “testimony used to determine which method of execution would reduce physical suffering would constitute physician participation in capital punishment and would be unethical.”²⁷

The expert witness’s failure to answer the question on relative pain had the unfortunate result of reducing the likelihood that the prisoner would prevail in his request for an alternative method of execution.

Analysis

Despite obvious disagreements about big issues (notably, abortion and the death penalty) the Court maintained a courteous and civil demeanor—something not always seen nowadays in other branches of government. Here are facts about the Court’s term just concluded:

• The Court issued 72 merits opinions (about average).
• Only 39% of decisions were unanimous (compared with the average of 49% in recent terms).
• On the other hand, 26% of decisions were split 5 to 4 (compared with a 10% recent average).
• In those 5 to 4 decisions, Justices were in the majority as follows²⁸: Justice Gorsuch, 65%; Justice Kavanaugh, 61%; Justice Thomas, 60%; Chief Justice Roberts and Justices Ginsburg and Alito, each 55%; Justice Breyer, 50%; and Justices Sotomayor and Kagan each at 45%.
• There were 57 dissenting opinions—up from 48 in the previous term.
• What is referred to as “the liberal-conservative split” might seem more profound than it really is: “Every conservative member of the court at some point voted to form a majority with the liberal justices. And every liberal at least once left behind all of his or her usual voting partners to join the conservatives.”²⁹

Continue to: Last, it was a year of personal health issues for...

Last, it was a year of personal health issues for the Court: Justice Ginsburg had a diagnosis of lung cancer and was absent, following surgery, in January. Of retired Justices, Sandra Day O’Connor suffers from dementia and former Justice John Paul Stevens died.

In closing

The Court has accepted approximately 50 cases for the current term, which began on October 7. The first 2 days of the term were spent on arguments about, first, whether a state can abolish the insanity defense and, second, whether nondiscrimination laws (“based on sex”) prohibit discrimination based on sexual orientation or transgender status. Cases also will deal with Patient Protection and Affordable Care Act payments to providers; the Deferred Action for Childhood Arrivals, or DACA; the death penalty; and international child custody disputes. The Court will be accepting more cases for several months. It promises to be a very interesting term.

The most recently concluded term of the US Supreme Court, which began on October 1, 2018, yielded a number of decisions of interest to health care professionals and to ObGyns in particular. Although the term was viewed by some observers as less consequential than other recent terms, a review of the cases decided paints a picture of a more important term than some commentators expected.

When the term began, the Court had only 8 justices—1 short of a full bench: Judge Brett Kavanaugh had not yet been confirmed by the Senate. He was confirmed on October 6, by a 50-48 vote, and Justice Kavanaugh immediately joined the Court and began to hear and decide cases.

Increasingly, important decisions affect medical practice

From the nature of practice (abortion), to payment for service (Medicare reimbursement), resolution of disputes (arbitration), and fraud and abuse (the federal False Claims Act), the decisions of the Court will have an impact on many areas of medical practice. Organized medicine increasingly has recognized the significance of the work of the Court; nowhere has this been more clearly demonstrated than with amicus curiae (friend of the court) briefs filed by medical organizations.

Amicus curiae briefs. These briefs are filed by persons or organizations not a party to a case the Court is hearing. Their legitimate purpose is to inform the Court of 1) special information within the expertise of the amicus (or amici, plural) or 2) consequences of the decision that might not be apparent from arguments made by the parties to the case. Sometimes, the Court cites amicus briefs for having provided important information about the case.

Filing amicus briefs is time-consuming and expensive; organizations do not file them for trivial reasons. Organizations frequently join together to file a joint brief, to share expenses and express to the Court a stronger position.

Three categories of health professionals file amicus briefs in ObGyn-related cases:

• Major national organizations, often representing broad interests of health care professions or institutions (the American Medical Association [AMA], the Association of American Medical Colleges, and the American Hospital Association [AHA]), have filed a number of amicus briefs over the years.
• Specialty boards increasingly file amicus briefs. For example, the American College of Obstetricians and Gynecologists (ACOG) and the American Society for Reproductive Medicine have filed briefs related to abortion issues.
• In reproductive issues, the American Association of Pro-Life Obstetricians and Gynecologists, the American College of Pediatricians, and the Christian Medical & Dental Associations have been active amicus filers—frequently taking positions different than, even inconsistent with, amicus briefs filed by major specialty boards.

Amicus briefs filed by medical associations provide strong clues to what is important to clinicians. We have looked at such briefs to help us identify topics and cases from the just-concluded term that can be of particular interest to you.

Continue to: Surveying the shadow docket...

Surveying the shadow docket. As part of our review of the past term, we also looked at the so-called shadow docket, which includes decisions regarding writs of certiorari (which cases it agrees to hear); stays (usually delaying implementation of a law); or denials of stays. (Persuading the Court to hear a case is not easy: It hears approximately 70 cases per year out of as many as 7,000 applications to be heard.)

Abortion ruling

At stake. A number of states recently enacted a variety of provisions that might make an abortion more difficult to obtain. Some of the cases challenging these restrictions are making their way through lower courts, and one day might be argued before the Supreme Court. However, the Court has not (yet) agreed to hear the substance of many new abortion-related provisions.

Box v Planned Parenthood of Indiana and Kentucky, Inc.

The Court decided only 1 abortion restriction case this term.¹ The Indiana law in question included 2 provisions that the Court considered:

Disposal of remains. The law regulated the manner in which abortion providers can dispose of fetal remains (ie, they cannot be treated as “infectious and pathologic waste”).

Motivation for seeking abortion. The Indiana law makes it illegal for an abortion provider to perform an abortion when the provider knows that the mother is seeking that abortion “solely” because of the fetus’s race, sex, diagnosis of Down syndrome, disability, or related characteristics.

Final rulings. The Court held that the disposal-of-remains provision is constitutional. The provision is “rationally related to the state’s interest in proper disposal of fetal remains.”² Planned Parenthood had not raised the issue of whether the law might impose an undue burden on a woman’s right to obtain an abortion, so the Court did not decide that issue.

The Court did not consider the constitutionality of the part of the law proscribing certain reasons for seeking an otherwise legal abortion; instead, it awaits lower courts’ review of the issue. Justice Clarence Thomas wrote an extensive concurring opinion suggesting that this law is intended to avoid abortion to achieve eugenic goals.³

Key developments from the shadow docket

The Court issued a stay preventing a Louisiana statute that requires physicians who perform abortions to have admitting privileges at a nearby hospital from going into effect, pending the outcome of litigation about that law.⁴ Four dissenters noted that all 4 physicians who perform abortions in Louisiana have such privileges. Chief Justice Roberts was the fifth vote to grant the stay. This case likely will make its way back to the Court, as will a number of other state laws being adopted. The issue may be back as soon as the term just starting.

The Court is also considering whether to take another Indiana case, Box v Planned Parenthood of Indiana and Kentucky, Inc. (Box II). This case involves an Indiana ultrasonography viewing option as part of the abortion consent process.⁵

The Court declined to hear cases from Louisiana and Kansas in which the states had cut off Medicaid funding to Planned Parenthood. Lower courts had stopped the implementation of those laws.⁶ The legal issue was whether private parties, as opposed to the federal government, had standing to bring the case. For now, the decision of the lower courts to stop implementation of the funding cutoff is in effect. There is a split in the Circuit Courts on the issue, however, making it likely that the Supreme Court will have to resolve it sooner or later.

Health care organizations have filed a number of amicus briefs in these and other cases involving new abortion regulations. ACOG and others filed a brief opposing a Louisiana law that requires abortion providers to have admitting privileges at a nearby facility,⁷ and a brief opposing a similar Oklahoma law.⁸ The Association of Pro-Life Obstetricians and Gynecologists and others filed amicus curiae briefs in Box II⁹ and in an Alabama case involving so-called dismemberment abortion.¹⁰

Continue to: Medicare payments...

Medicare payments

Azar, Secretary of Health and Human Services v Allina Health Services, et al¹¹

This case drew interest—and many amicus briefs—from health care providers, including the AMA and the AHA.^12,13 There was good reason for their interest: First, the case involved more than $3 billion in reimbursements; second, it represented a potentially important precedent about the rights of providers and patients to comment on Medicare reimbursement changes. The question involved the technical calculation of additional payments made to institutions that serve a disproportionate number of low-income patients (known as Medicare Fractions).

At stake. The issue was a statutory requirement for a 60-day public notice and comment period for rules that “change a substantive legal standard” governing the scope of benefits, eligibility, or payment for services.¹⁴ In 2014, the Secretary of the Department of Health and Human Services (HHS) in the Obama administration posted a spreadsheet announcing Medicare fractions rates for hospitals (for 2012)—without formal notice or comment regarding the formula used. (The spreadsheet listed what each qualifying institution would receive, but it was based on a formula that, as noted, had not been subject to public notice and comment.) The AMA and AHA briefs emphasized the importance of a notice and comment period, especially when Medicare reimbursement is involved.

Final ruling. The Court held that the HHS process violated the notice and comment provision, thereby invalidating the policy underlying the so-called spreadsheet reimbursement. The decision was significant: This was a careful statutory interpretation of the 60-day notice and comment period, not the reimbursement policy itself. Presumably, had the HHS Secretary provided for sufficient notice and comment, the formula used would have met the requirements for issuing reimbursement formulas.

Key points. Hospitals will collectively receive $3 or $4 billion as a consequence of the ruling. Perhaps more importantly, the decision signals that HHS is going to have to take seriously the requirement that it publish Medicare-related reimbursement policies for the 60-day period.

Liability under the False Claims Act

The False Claims Act (FCA) protects the federal government from fraudulent claims for payment and for shoddy goods and services. It incentivizes (by a percentage of recovery) private parties to bring cases to enforce the law.¹⁵ (Of course, the federal government also enforces the Act.)

At stake. The FCA has been of considerable concern to the AHA, the Association of American Medical Colleges, and other health care organizations—understandably so.¹⁶ As the AHA informed the Court in an amicus brief, “The prevalence of [FCA] cases has ballooned over the past three decades.... These suits disproportionately target healthcare entities.... Of the 767 new FCA cases filed in 2018, for example, 506 involved healthcare defendants.”¹⁷

Final ruling. The Court considered an ambiguity in the statute of limitations for these actions and the Court unanimously ruled to permit an extended time in which qui tam actions (private actions under the law) can be filed.¹⁸

Key points. As long a period as 10 years can pass between the time an FCA violation occurs and an action is brought. This decision is likely to increase the number of FCA actions against health care providers because the case can be filed many years after the conduct that gave rise to the complaint.

Continue to: Registering sex offenders...

Registering sex offenders

The Court upheld the constitutionality of the federal Sex Offender Registration and Notification Act (SORNA).¹⁹ Sex offenders must register and periodically report, in person, to law enforcement in every state in which the offender works, studies, or resides.

At stake. The case involved the applicability of SORNA registration obligations to those convicted of sex offenses before SORNA was adopted (pre-Act offenders).²⁰ The court upheld registration requirements for pre-Act offenders.

Arbitration

The Court continued its practice of deciding at least one case each term that emphasizes that federal law requires that courts rather strictly enforce agreements to arbitrate (instead of to litigate) future disputes.²¹ In another case, the Court ruled that there can be “class” or “joint” arbitration only if the agreement to arbitrate a dispute clearly permits such class arbitration.²²

Pharma’s liability regarding product risk

The Court somewhat limited the liability of pharmaceutical companies for failing to provide adequate warning about the risk that their products pose. The case against Merck involved 500 patients who took denosumab (Fosamax) and suffered atypical femoral fractures.²³

At stake. Because prescribing information (in which warnings are provided) must be approved by the US Food and Drug Administration (FDA), the legal test is: Would the FDA have refused to approve a change in the warning if Merck had “fully informed the FDA of the justifications for the warning” required by state law to avoid liability?^24,25 Lower-court judges (not juries) will be expected to apply this test in the future.

The doctor and the death penalty

The Court has established a rule that, when a prisoner facing capital punishment objects to a form of execution because it is too painful, he has to propose an alternative that is reasonably available. In one case,²⁶ a physician, an expert witness for the prisoner, did not answer some essential relative-pain questions (ie, would one procedure be more painful than another?).

At stake. The AMA filed an amicus brief in this case, indicating that it is unethical for physicians to participate in an execution. The brief noted that “testimony used to determine which method of execution would reduce physical suffering would constitute physician participation in capital punishment and would be unethical.”²⁷

The expert witness’s failure to answer the question on relative pain had the unfortunate result of reducing the likelihood that the prisoner would prevail in his request for an alternative method of execution.

Analysis

Despite obvious disagreements about big issues (notably, abortion and the death penalty) the Court maintained a courteous and civil demeanor—something not always seen nowadays in other branches of government. Here are facts about the Court’s term just concluded:

• The Court issued 72 merits opinions (about average).
• Only 39% of decisions were unanimous (compared with the average of 49% in recent terms).
• On the other hand, 26% of decisions were split 5 to 4 (compared with a 10% recent average).
• In those 5 to 4 decisions, Justices were in the majority as follows²⁸: Justice Gorsuch, 65%; Justice Kavanaugh, 61%; Justice Thomas, 60%; Chief Justice Roberts and Justices Ginsburg and Alito, each 55%; Justice Breyer, 50%; and Justices Sotomayor and Kagan each at 45%.
• There were 57 dissenting opinions—up from 48 in the previous term.
• What is referred to as “the liberal-conservative split” might seem more profound than it really is: “Every conservative member of the court at some point voted to form a majority with the liberal justices. And every liberal at least once left behind all of his or her usual voting partners to join the conservatives.”²⁹

Continue to: Last, it was a year of personal health issues for...

Last, it was a year of personal health issues for the Court: Justice Ginsburg had a diagnosis of lung cancer and was absent, following surgery, in January. Of retired Justices, Sandra Day O’Connor suffers from dementia and former Justice John Paul Stevens died.

In closing

The Court has accepted approximately 50 cases for the current term, which began on October 7. The first 2 days of the term were spent on arguments about, first, whether a state can abolish the insanity defense and, second, whether nondiscrimination laws (“based on sex”) prohibit discrimination based on sexual orientation or transgender status. Cases also will deal with Patient Protection and Affordable Care Act payments to providers; the Deferred Action for Childhood Arrivals, or DACA; the death penalty; and international child custody disputes. The Court will be accepting more cases for several months. It promises to be a very interesting term.

The most recently concluded term of the US Supreme Court, which began on October 1, 2018, yielded a number of decisions of interest to health care professionals and to ObGyns in particular. Although the term was viewed by some observers as less consequential than other recent terms, a review of the cases decided paints a picture of a more important term than some commentators expected.

When the term began, the Court had only 8 justices—1 short of a full bench: Judge Brett Kavanaugh had not yet been confirmed by the Senate. He was confirmed on October 6, by a 50-48 vote, and Justice Kavanaugh immediately joined the Court and began to hear and decide cases.

Increasingly, important decisions affect medical practice

From the nature of practice (abortion), to payment for service (Medicare reimbursement), resolution of disputes (arbitration), and fraud and abuse (the federal False Claims Act), the decisions of the Court will have an impact on many areas of medical practice. Organized medicine increasingly has recognized the significance of the work of the Court; nowhere has this been more clearly demonstrated than with amicus curiae (friend of the court) briefs filed by medical organizations.

Amicus curiae briefs. These briefs are filed by persons or organizations not a party to a case the Court is hearing. Their legitimate purpose is to inform the Court of 1) special information within the expertise of the amicus (or amici, plural) or 2) consequences of the decision that might not be apparent from arguments made by the parties to the case. Sometimes, the Court cites amicus briefs for having provided important information about the case.

Filing amicus briefs is time-consuming and expensive; organizations do not file them for trivial reasons. Organizations frequently join together to file a joint brief, to share expenses and express to the Court a stronger position.

Three categories of health professionals file amicus briefs in ObGyn-related cases:

• Major national organizations, often representing broad interests of health care professions or institutions (the American Medical Association [AMA], the Association of American Medical Colleges, and the American Hospital Association [AHA]), have filed a number of amicus briefs over the years.
• Specialty boards increasingly file amicus briefs. For example, the American College of Obstetricians and Gynecologists (ACOG) and the American Society for Reproductive Medicine have filed briefs related to abortion issues.
• In reproductive issues, the American Association of Pro-Life Obstetricians and Gynecologists, the American College of Pediatricians, and the Christian Medical & Dental Associations have been active amicus filers—frequently taking positions different than, even inconsistent with, amicus briefs filed by major specialty boards.

Amicus briefs filed by medical associations provide strong clues to what is important to clinicians. We have looked at such briefs to help us identify topics and cases from the just-concluded term that can be of particular interest to you.

Continue to: Surveying the shadow docket...

Surveying the shadow docket. As part of our review of the past term, we also looked at the so-called shadow docket, which includes decisions regarding writs of certiorari (which cases it agrees to hear); stays (usually delaying implementation of a law); or denials of stays. (Persuading the Court to hear a case is not easy: It hears approximately 70 cases per year out of as many as 7,000 applications to be heard.)

Abortion ruling

At stake. A number of states recently enacted a variety of provisions that might make an abortion more difficult to obtain. Some of the cases challenging these restrictions are making their way through lower courts, and one day might be argued before the Supreme Court. However, the Court has not (yet) agreed to hear the substance of many new abortion-related provisions.

Box v Planned Parenthood of Indiana and Kentucky, Inc.

The Court decided only 1 abortion restriction case this term.¹ The Indiana law in question included 2 provisions that the Court considered:

Disposal of remains. The law regulated the manner in which abortion providers can dispose of fetal remains (ie, they cannot be treated as “infectious and pathologic waste”).

Motivation for seeking abortion. The Indiana law makes it illegal for an abortion provider to perform an abortion when the provider knows that the mother is seeking that abortion “solely” because of the fetus’s race, sex, diagnosis of Down syndrome, disability, or related characteristics.

Final rulings. The Court held that the disposal-of-remains provision is constitutional. The provision is “rationally related to the state’s interest in proper disposal of fetal remains.”² Planned Parenthood had not raised the issue of whether the law might impose an undue burden on a woman’s right to obtain an abortion, so the Court did not decide that issue.

The Court did not consider the constitutionality of the part of the law proscribing certain reasons for seeking an otherwise legal abortion; instead, it awaits lower courts’ review of the issue. Justice Clarence Thomas wrote an extensive concurring opinion suggesting that this law is intended to avoid abortion to achieve eugenic goals.³

Key developments from the shadow docket

The Court issued a stay preventing a Louisiana statute that requires physicians who perform abortions to have admitting privileges at a nearby hospital from going into effect, pending the outcome of litigation about that law.⁴ Four dissenters noted that all 4 physicians who perform abortions in Louisiana have such privileges. Chief Justice Roberts was the fifth vote to grant the stay. This case likely will make its way back to the Court, as will a number of other state laws being adopted. The issue may be back as soon as the term just starting.

The Court is also considering whether to take another Indiana case, Box v Planned Parenthood of Indiana and Kentucky, Inc. (Box II). This case involves an Indiana ultrasonography viewing option as part of the abortion consent process.⁵

The Court declined to hear cases from Louisiana and Kansas in which the states had cut off Medicaid funding to Planned Parenthood. Lower courts had stopped the implementation of those laws.⁶ The legal issue was whether private parties, as opposed to the federal government, had standing to bring the case. For now, the decision of the lower courts to stop implementation of the funding cutoff is in effect. There is a split in the Circuit Courts on the issue, however, making it likely that the Supreme Court will have to resolve it sooner or later.

Health care organizations have filed a number of amicus briefs in these and other cases involving new abortion regulations. ACOG and others filed a brief opposing a Louisiana law that requires abortion providers to have admitting privileges at a nearby facility,⁷ and a brief opposing a similar Oklahoma law.⁸ The Association of Pro-Life Obstetricians and Gynecologists and others filed amicus curiae briefs in Box II⁹ and in an Alabama case involving so-called dismemberment abortion.¹⁰

Continue to: Medicare payments...

Medicare payments

Azar, Secretary of Health and Human Services v Allina Health Services, et al¹¹

This case drew interest—and many amicus briefs—from health care providers, including the AMA and the AHA.^12,13 There was good reason for their interest: First, the case involved more than $3 billion in reimbursements; second, it represented a potentially important precedent about the rights of providers and patients to comment on Medicare reimbursement changes. The question involved the technical calculation of additional payments made to institutions that serve a disproportionate number of low-income patients (known as Medicare Fractions).

At stake. The issue was a statutory requirement for a 60-day public notice and comment period for rules that “change a substantive legal standard” governing the scope of benefits, eligibility, or payment for services.¹⁴ In 2014, the Secretary of the Department of Health and Human Services (HHS) in the Obama administration posted a spreadsheet announcing Medicare fractions rates for hospitals (for 2012)—without formal notice or comment regarding the formula used. (The spreadsheet listed what each qualifying institution would receive, but it was based on a formula that, as noted, had not been subject to public notice and comment.) The AMA and AHA briefs emphasized the importance of a notice and comment period, especially when Medicare reimbursement is involved.

Final ruling. The Court held that the HHS process violated the notice and comment provision, thereby invalidating the policy underlying the so-called spreadsheet reimbursement. The decision was significant: This was a careful statutory interpretation of the 60-day notice and comment period, not the reimbursement policy itself. Presumably, had the HHS Secretary provided for sufficient notice and comment, the formula used would have met the requirements for issuing reimbursement formulas.

Key points. Hospitals will collectively receive $3 or $4 billion as a consequence of the ruling. Perhaps more importantly, the decision signals that HHS is going to have to take seriously the requirement that it publish Medicare-related reimbursement policies for the 60-day period.

Liability under the False Claims Act

The False Claims Act (FCA) protects the federal government from fraudulent claims for payment and for shoddy goods and services. It incentivizes (by a percentage of recovery) private parties to bring cases to enforce the law.¹⁵ (Of course, the federal government also enforces the Act.)

At stake. The FCA has been of considerable concern to the AHA, the Association of American Medical Colleges, and other health care organizations—understandably so.¹⁶ As the AHA informed the Court in an amicus brief, “The prevalence of [FCA] cases has ballooned over the past three decades.... These suits disproportionately target healthcare entities.... Of the 767 new FCA cases filed in 2018, for example, 506 involved healthcare defendants.”¹⁷

Final ruling. The Court considered an ambiguity in the statute of limitations for these actions and the Court unanimously ruled to permit an extended time in which qui tam actions (private actions under the law) can be filed.¹⁸

Key points. As long a period as 10 years can pass between the time an FCA violation occurs and an action is brought. This decision is likely to increase the number of FCA actions against health care providers because the case can be filed many years after the conduct that gave rise to the complaint.

Continue to: Registering sex offenders...

Registering sex offenders

The Court upheld the constitutionality of the federal Sex Offender Registration and Notification Act (SORNA).¹⁹ Sex offenders must register and periodically report, in person, to law enforcement in every state in which the offender works, studies, or resides.

At stake. The case involved the applicability of SORNA registration obligations to those convicted of sex offenses before SORNA was adopted (pre-Act offenders).²⁰ The court upheld registration requirements for pre-Act offenders.

Arbitration

The Court continued its practice of deciding at least one case each term that emphasizes that federal law requires that courts rather strictly enforce agreements to arbitrate (instead of to litigate) future disputes.²¹ In another case, the Court ruled that there can be “class” or “joint” arbitration only if the agreement to arbitrate a dispute clearly permits such class arbitration.²²

Pharma’s liability regarding product risk

The Court somewhat limited the liability of pharmaceutical companies for failing to provide adequate warning about the risk that their products pose. The case against Merck involved 500 patients who took denosumab (Fosamax) and suffered atypical femoral fractures.²³

At stake. Because prescribing information (in which warnings are provided) must be approved by the US Food and Drug Administration (FDA), the legal test is: Would the FDA have refused to approve a change in the warning if Merck had “fully informed the FDA of the justifications for the warning” required by state law to avoid liability?^24,25 Lower-court judges (not juries) will be expected to apply this test in the future.

The doctor and the death penalty

The Court has established a rule that, when a prisoner facing capital punishment objects to a form of execution because it is too painful, he has to propose an alternative that is reasonably available. In one case,²⁶ a physician, an expert witness for the prisoner, did not answer some essential relative-pain questions (ie, would one procedure be more painful than another?).

At stake. The AMA filed an amicus brief in this case, indicating that it is unethical for physicians to participate in an execution. The brief noted that “testimony used to determine which method of execution would reduce physical suffering would constitute physician participation in capital punishment and would be unethical.”²⁷

The expert witness’s failure to answer the question on relative pain had the unfortunate result of reducing the likelihood that the prisoner would prevail in his request for an alternative method of execution.

Analysis

Despite obvious disagreements about big issues (notably, abortion and the death penalty) the Court maintained a courteous and civil demeanor—something not always seen nowadays in other branches of government. Here are facts about the Court’s term just concluded:

• The Court issued 72 merits opinions (about average).
• Only 39% of decisions were unanimous (compared with the average of 49% in recent terms).
• On the other hand, 26% of decisions were split 5 to 4 (compared with a 10% recent average).
• In those 5 to 4 decisions, Justices were in the majority as follows²⁸: Justice Gorsuch, 65%; Justice Kavanaugh, 61%; Justice Thomas, 60%; Chief Justice Roberts and Justices Ginsburg and Alito, each 55%; Justice Breyer, 50%; and Justices Sotomayor and Kagan each at 45%.
• There were 57 dissenting opinions—up from 48 in the previous term.
• What is referred to as “the liberal-conservative split” might seem more profound than it really is: “Every conservative member of the court at some point voted to form a majority with the liberal justices. And every liberal at least once left behind all of his or her usual voting partners to join the conservatives.”²⁹

Continue to: Last, it was a year of personal health issues for...

Last, it was a year of personal health issues for the Court: Justice Ginsburg had a diagnosis of lung cancer and was absent, following surgery, in January. Of retired Justices, Sandra Day O’Connor suffers from dementia and former Justice John Paul Stevens died.

In closing

The Court has accepted approximately 50 cases for the current term, which began on October 7. The first 2 days of the term were spent on arguments about, first, whether a state can abolish the insanity defense and, second, whether nondiscrimination laws (“based on sex”) prohibit discrimination based on sexual orientation or transgender status. Cases also will deal with Patient Protection and Affordable Care Act payments to providers; the Deferred Action for Childhood Arrivals, or DACA; the death penalty; and international child custody disputes. The Court will be accepting more cases for several months. It promises to be a very interesting term.

Case 1 Multiparous woman presents with heavy regular menses

Over the past several years, a 34-year-old woman has noted increasing intensity and duration of menstrual flow, which now persists for 8 days and includes clots “the size of quarters” and soaks a pad within 1 hour. Sometimes she misses or leaves work on her heaviest days of flow. She reports that menstrual cramps prior to and during flow are increasingly bothersome and do not respond adequately to ibuprofen. She intermittently uses condoms for contraception. She does not wish to be pregnant currently; however, she recently entered into a new relationship and may wish to conceive in the future.

On bimanual examination, the uterus appears bulky. Her hemoglobin is 10.9 g/dL with low mean corpuscular volume and a serum ferritin level indicating iron depletion. Pelvic ultrasonography suggests uterine adenomyosis; no fibroids are imaged (FIGURE 1).

You advise the patient to take ferrous sulfate 325 mg every other day. After discussion with the patient regarding different treatment options, she chooses to proceed with placement of a 52-mg levonorgestrel (LNG) intrauterine device (IUD; Mirena or Liletta).

Case 2 Older adolescent presents with irregular bleeding

A 19-year-old patient reports approximately 6 bleeding episodes each year. She reports the duration of her bleeding as variable, and sometimes the bleeding is heavy with small clots passed. She has been previously diagnosed with polycystic ovary syndrome (PCOS). Combination estrogen-progestin oral contraceptives have been prescribed several times in the past, but she always has discontinued them due to nausea. The patient is in a same-sex relationship and does not anticipate being sexually active with a male. She reports having to shave her mustache and chin twice weekly for the past 1 to 2 years.

On physical examination, the patient is obese (body mass index [BMI], 32 kg/m²), facial acne and hirsutism are present, and hair extends from the mons toward the umbilicus. Bimanual examination reveals a normal size, mobile, nontender uterus without obvious adnexal pathology. Pelvic ultrasonography demonstrates a normal-appearing uterus with multiplanar endometrium (consistent with proliferative changes) (FIGURE 2). Ovarian imaging demonstrates ≥12 follicles per image (FIGURE 3).

About one-third of all women experience abnormal uterine bleeding (AUB) sometime during their lifetime and AUB can impair quality of life.¹ Surgical management, including hysterectomy and endometrial ablation, plays an important role in the management of AUB in patients who do not desire future pregnancies. However, many cases of AUB occur in women who may not have completed childbearing or in women who prefer to avoid surgery.² AUB can be managed effectively medically in most cases.¹ Accordingly, in this review, we focus on nonsurgical management of AUB.

Continue to: Because previously used terms, including...

Because previously used terms, including menorrhagia and meno-metrorrhagia, were inconsistently defined and confusing, the International Federation of Gynecology and Obstetrics introduced updated terminology in 2011 to better describe and characterize AUB in nonpregnant women. Heavy menstrual bleeding (HMB) refers to ovulatory (cyclic) bleeding that is more than 8 days’ duration, or sufficiently heavy to impair a woman’s quality of life. HMB is a pattern of AUB distinct from the irregular bleeding pattern typically caused by ovulatory dysfunction (AUB-O).¹

Clinical evaluation

Obtain menstrual history. In addition to a medical, surgical, and gynecologic history, a thorough menstrual history should be obtained to further characterize the patient’s bleeding pattern. In contrast to the cyclical or ovulatory bleeding seen with HMB, bleeding associated with inconsistent ovulation (AUB-O) is unpredictable or irregular, and is commonly associated with PCOS. AUB-O is also encountered in recently menarchal girls (secondary to immaturity of the hypothalamic-pituitary-gonadal axis) and in those who are perimenopausal. In addition, medications that can induce hyperprolactinemia (such as certain antipsychotics) can cause AUB-O.

Evaluate for all sources of bleeding. Be sure to evaluate for extrauterine causes of bleeding, including the cervix, vagina, vulva, or the urinary or gastrointestinal tracts for bleeding. Intermenstrual bleeding occurring between normal regular menses may be caused by an endometrial polyp, submucosal fibroid, endometritis, or an IUD. The patient report of postcoital bleeding suggests that cervical disease (cervicitis, polyp, or malignancy) may be present. Uterine leiomyoma or adenomyosis represent common causes of HMB. However, HMB also may be caused by a copper IUD, coagulation disorders (including von Willebrand disease), or use of anticoagulant medications. Hormonal contraceptives also can cause irregular bleeding.

Perform a pelvic examination and measure vital signs. The presence of fever suggests the possible presence of pelvic inflammatory disease (PID), while orthostatic hypotension raises the possibility of hypovolemia. When vaginal speculum examination is performed, a cervical cause of abnormal bleeding may be noted. The presence of fresh or old blood or finding clots in the vaginal vault or at the cervical os are all consistent with AUB. A bimanual examination that reveals an enlarged or lobular uterus suggests leiomyoma or adenomyosis. Cervical or adnexal tenderness is often noted in women with PID, which itself may be associated with endometritis. The presence of hyperandrogenic signs on physical examination (eg, acne, hirsutism, or clitoromegaly) suggests PCOS. The finding of galactorrhea suggests that hyperprolactinemia may be present.

Laboratory assessment

Test for pregnancy, cervical disease, and sexually transmitted infection when appropriate. Pregnancy testing is appropriate for women with AUB aged 55 years or younger. If patients with AUB are not up to date with normal cervical cancer screening results, cervical cytology and/or human papillomavirus testing should be performed. Testing for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis should be performed in patients:

• younger than 25 years
• when the history indicates new or multiple sexual partners, or
• when vaginal discharge, cervicitis, cervical motion, or adnexal tenderness is present.

Continue to: Obtain a complete blood count and serum ferritin levels...

Obtain a complete blood count and serum ferritin levels. In women presenting with HMB, iron depletion and iron deficiency anemia are common. The finding of leukocytosis raises the possibility of PID or postpartum endometritis. In women with presumptive AUB-O, checking the levels of thyroid-stimulating hormone, free T4, and prolactin should be performed.

Screen for a hemostasis disorder. Women with excessive menstrual bleeding should be clinically screened for an underlying disorder of hemostasis (TABLE 1).³ When a hemostasis disorder is suspected, initial laboratory evaluation includes a partial thromboplastin time, prothrombin time, activated partial thromboplastin time, and fibrinogen. Women who have a positive clinical screen for a possible bleeding disorder or abnormal initial laboratory test results for disorders of hemostasis should undergo further laboratory evaluation, including von Willebrand factor antigen, ristocetin cofactor assay, and factor VIII. Consultation with a hematologist should be considered in these cases.

Perform endometrial biopsy when indicated

After excluding pregnancy, endometrial biopsy (through pipelle biospy or brush sampling; FIGURE 4) should be performed in women with AUB who are at increased risk for endometrial neoplasia. The prevalence of endometrial neoplasia is substantially higher among women ≥45 years of age⁴ and among patients with AUB who are also obese (BMI, ≥30 kg/m²).⁵ In addition, AUB patients with unopposed estrogen exposure (presumed anovulation/PCOS), as well as those with persistent AUB or failed medical management, should undergo endometrial biopsy.⁶

Utilize transvaginal ultrasonography

Transvaginal ultrasonography is often useful in the evaluation of patients with AUB, as it may identify uterine fibroids or adenomyosis, suggest intracavitary pathology (such as an endometrial polyp or submucosal fibroid), or raise the possibility of PCOS. In virginal patients or those in whom vaginal ultrasound is not appropriate, abdominal pelvic ultrasonography represents appropriate imaging. If unenhanced ultrasound suggests endometrial polyps or fibroids within the endometrial cavity, an office-based saline infusion sonogram (sonohysterogram) (FIGURE 5) or hysteroscopy should be performed. Targeted endometrial sampling and biopsy of intracavitary pathology can be performed at the time of hysteroscopy.

Treatment

When HMB impairs quality of life, is bothersome to the patient, or results in anemia, treatment is appropriate. Although bleeding episodes in women with AUB-O may be infrequent (as with Case 2), treatment prevents heavy or prolonged bleeding episodes as well as endometrial neoplasia that may otherwise occur in anovulatory women.

Many women with AUB can be managed medically. However, treatment choices will vary with respect to the patient’s desire for future fertility, medical comorbidities, personal preferences, and financial barriers. While many women may prefer outpatient medical management (TABLE 2),^7-14 others might desire surgical therapy, including endometrial ablation or hysterectomy.

Oral contraceptives

Combination estrogen-progestin oral contraceptives represent appropriate initial therapy for many women in the reproductive-age group with AUB, whether women have HMB or AUB-O. However, contraceptive doses of estrogen are not appropriate for some women with risk factors for cardiovascular disease, including those who smoke cigarettes and are age ≥35 years or those who have hypertension (TABLE 3).^15,16

Continue to: Menopausal dosages of HT...

Menopausal dosages of HT

If use of contraceptive doses of estrogen is not appropriate, continuous off-label use of menopausal combination formulations (physiologic dosage) of hormonal therapy (HT; ie, lower doses of estrogen than contraceptives) may be effective in reducing or eliminating AUB. Options for menopausal combination formulations include generic ethinyl estradiol 5 µg/norethindrone acetate 1 mg or estradiol 1 mg/norethindrone acetate 0.5 mg.⁷ High-dose oral progestin therapy (norethindrone acetate 5 mg tablet once daily or medroxyprogesterone acetate 10 mg tablets 1–3 times daily) also can be used when combination contraceptives are contraindicated and may be more effective than lower-dose combination formulations.

Package labeling, as well as some guidelines, indicate that oral progestins used to treat AUB should be taken cyclically.⁸ However, continuous daily use is easier for many patients and may be more effective in reducing bleeding. Accordingly, we counsel patients with AUB who are using progestins and who do not wish to conceive to take these medications continuously. High-dose oral progestin therapy may cause bloating, dysphoria, and increased appetite/weight gain. Women initiating hormonal management (including the progestin IUDs detailed below) for AUB should be counseled that irregular or even continuous light bleeding/spotting is common initially, but this bleeding pattern typically decreases with continued use.

IUDs

The LNG 52 mg IUD (Mirena or Liletta) effectively treats HMB, reducing bleeding in a manner comparable to that of endometrial ablation.^9,10 The Mirena IUD is approved for treatment of HMB in women desiring intrauterine contraception. In contrast to oral medications, use of progestin IUDs does not involve daily administration and may represent an attractive option for women with HMB who would like to avoid surgery or preserve fertility. With ongoing use, continuous oral or intrauterine hormonal management may result in amenorrhea in some women with AUB.

When the LNG 52 mg IUD is used to treat HMB, the menstrual suppression impact may begin to attenuate after approximately 4 years of use; in this setting, replacing the IUD often restores effective menstrual suppression.¹¹ The LNG 52 mg IUD effectively suppresses menses in women with coagulation disorders; if menstrual suppression with the progestin IUD is not adequate in this setting, it may be appropriate to add an oral combination estrogen-progestin contraceptive or high-dose oral progestin.^11,12

NSAIDs and tranexamic acid

Off-label use of nonsteroidal anti-inflammatory drugs (naproxen 500–1,000 mg daily for 5 days beginning at the onset of menstrual flow or tranexamic acid two 650-mg tablets 3 times daily for up to 5 days during episodes of heavy flow) can suppress HMB and is useful for women who prefer to avoid or have contraindications to hormonal treatments.^13,14 Unfortunately, these agents are not as effective as hormonal management in treating AUB.

Iron supplementation is often needed

Iron depletion commonly results from HMB, often resulting in iron deficiency anemia. When iron depletion (readily identified by checking a serum ferritin level) or iron deficiency anemia is identified, iron supplementation should be recommended. Every-other-day administration of iron supplements maximizes iron absorption while minimizing the adverse effects of unabsorbed iron, such as nausea. Sixty mg of elemental iron (ferrous sulfate 325 mg) administered every other day represents an inexpensive and effective treatment for iron deficiency/anemia.¹⁷ In patients who cannot tolerate oral iron supplementation or for those in whom oral therapy is not appropriate or effective, newer intravenous iron formulations are safe and effective.¹⁸

Continue to: Case 1 Follow-up...

Case 1 Follow-up

The patient noted marked improvement in her menstrual cramps following LNG-containing IUD placement. Although she also reported that she no longer experienced heavy menstrual flow or cramps, she was bothered by frequent, unpredictable light bleeding/spotting. You prescribed norethindrone acetate (NETA) 5-mg tablet orally once daily, to be used in addition to her IUD. After using the IUD with concomitant NETA for 2 months’ duration, she noted that her bleeding/spotting almost completely resolved; however, she did report feeling irritable with use of the progestin tablets. She subsequently stopped the NETA tablets and, after 6 months of additional follow-up, reported only minimal spotting and no cramps.

At this later follow-up visit, you noted that her hemoglobin level increased to 12.6 g/dL, and the ferritin level no longer indicated iron depletion. After the IUD had been in place for 4 years, she reported that she was beginning to experience frequent light bleeding again. A follow-up vaginal sonogram noted a well-positioned IUD, there was no suggestion of intracavitary pathology, and adenomyosis continued to be imaged. She underwent IUD removal and placement of a new LNG 52 mg IUD. This resulted in marked reduction in her bleeding.

Case 2 Follow-up

Two weeks after beginning continuous oral progestin therapy, the patient called reporting frequent irregular bleeding. She was reassured that this was not unexpected and encouraged to continue oral progestin therapy. During a 3-month follow-up visit, the patient noted little, if any, bleeding over the previous 2 months and was pleased with this result. She continued to note acne and hirsutism and asked about the possibility of adding spironolactone to her oral progestin regimen.

Case 1 Multiparous woman presents with heavy regular menses

Over the past several years, a 34-year-old woman has noted increasing intensity and duration of menstrual flow, which now persists for 8 days and includes clots “the size of quarters” and soaks a pad within 1 hour. Sometimes she misses or leaves work on her heaviest days of flow. She reports that menstrual cramps prior to and during flow are increasingly bothersome and do not respond adequately to ibuprofen. She intermittently uses condoms for contraception. She does not wish to be pregnant currently; however, she recently entered into a new relationship and may wish to conceive in the future.

On bimanual examination, the uterus appears bulky. Her hemoglobin is 10.9 g/dL with low mean corpuscular volume and a serum ferritin level indicating iron depletion. Pelvic ultrasonography suggests uterine adenomyosis; no fibroids are imaged (FIGURE 1).

You advise the patient to take ferrous sulfate 325 mg every other day. After discussion with the patient regarding different treatment options, she chooses to proceed with placement of a 52-mg levonorgestrel (LNG) intrauterine device (IUD; Mirena or Liletta).

Case 2 Older adolescent presents with irregular bleeding

A 19-year-old patient reports approximately 6 bleeding episodes each year. She reports the duration of her bleeding as variable, and sometimes the bleeding is heavy with small clots passed. She has been previously diagnosed with polycystic ovary syndrome (PCOS). Combination estrogen-progestin oral contraceptives have been prescribed several times in the past, but she always has discontinued them due to nausea. The patient is in a same-sex relationship and does not anticipate being sexually active with a male. She reports having to shave her mustache and chin twice weekly for the past 1 to 2 years.

On physical examination, the patient is obese (body mass index [BMI], 32 kg/m²), facial acne and hirsutism are present, and hair extends from the mons toward the umbilicus. Bimanual examination reveals a normal size, mobile, nontender uterus without obvious adnexal pathology. Pelvic ultrasonography demonstrates a normal-appearing uterus with multiplanar endometrium (consistent with proliferative changes) (FIGURE 2). Ovarian imaging demonstrates ≥12 follicles per image (FIGURE 3).

About one-third of all women experience abnormal uterine bleeding (AUB) sometime during their lifetime and AUB can impair quality of life.¹ Surgical management, including hysterectomy and endometrial ablation, plays an important role in the management of AUB in patients who do not desire future pregnancies. However, many cases of AUB occur in women who may not have completed childbearing or in women who prefer to avoid surgery.² AUB can be managed effectively medically in most cases.¹ Accordingly, in this review, we focus on nonsurgical management of AUB.

Continue to: Because previously used terms, including...

Because previously used terms, including menorrhagia and meno-metrorrhagia, were inconsistently defined and confusing, the International Federation of Gynecology and Obstetrics introduced updated terminology in 2011 to better describe and characterize AUB in nonpregnant women. Heavy menstrual bleeding (HMB) refers to ovulatory (cyclic) bleeding that is more than 8 days’ duration, or sufficiently heavy to impair a woman’s quality of life. HMB is a pattern of AUB distinct from the irregular bleeding pattern typically caused by ovulatory dysfunction (AUB-O).¹

Clinical evaluation

Obtain menstrual history. In addition to a medical, surgical, and gynecologic history, a thorough menstrual history should be obtained to further characterize the patient’s bleeding pattern. In contrast to the cyclical or ovulatory bleeding seen with HMB, bleeding associated with inconsistent ovulation (AUB-O) is unpredictable or irregular, and is commonly associated with PCOS. AUB-O is also encountered in recently menarchal girls (secondary to immaturity of the hypothalamic-pituitary-gonadal axis) and in those who are perimenopausal. In addition, medications that can induce hyperprolactinemia (such as certain antipsychotics) can cause AUB-O.

Evaluate for all sources of bleeding. Be sure to evaluate for extrauterine causes of bleeding, including the cervix, vagina, vulva, or the urinary or gastrointestinal tracts for bleeding. Intermenstrual bleeding occurring between normal regular menses may be caused by an endometrial polyp, submucosal fibroid, endometritis, or an IUD. The patient report of postcoital bleeding suggests that cervical disease (cervicitis, polyp, or malignancy) may be present. Uterine leiomyoma or adenomyosis represent common causes of HMB. However, HMB also may be caused by a copper IUD, coagulation disorders (including von Willebrand disease), or use of anticoagulant medications. Hormonal contraceptives also can cause irregular bleeding.

Perform a pelvic examination and measure vital signs. The presence of fever suggests the possible presence of pelvic inflammatory disease (PID), while orthostatic hypotension raises the possibility of hypovolemia. When vaginal speculum examination is performed, a cervical cause of abnormal bleeding may be noted. The presence of fresh or old blood or finding clots in the vaginal vault or at the cervical os are all consistent with AUB. A bimanual examination that reveals an enlarged or lobular uterus suggests leiomyoma or adenomyosis. Cervical or adnexal tenderness is often noted in women with PID, which itself may be associated with endometritis. The presence of hyperandrogenic signs on physical examination (eg, acne, hirsutism, or clitoromegaly) suggests PCOS. The finding of galactorrhea suggests that hyperprolactinemia may be present.

Laboratory assessment

Test for pregnancy, cervical disease, and sexually transmitted infection when appropriate. Pregnancy testing is appropriate for women with AUB aged 55 years or younger. If patients with AUB are not up to date with normal cervical cancer screening results, cervical cytology and/or human papillomavirus testing should be performed. Testing for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis should be performed in patients:

• younger than 25 years
• when the history indicates new or multiple sexual partners, or
• when vaginal discharge, cervicitis, cervical motion, or adnexal tenderness is present.

Continue to: Obtain a complete blood count and serum ferritin levels...

Obtain a complete blood count and serum ferritin levels. In women presenting with HMB, iron depletion and iron deficiency anemia are common. The finding of leukocytosis raises the possibility of PID or postpartum endometritis. In women with presumptive AUB-O, checking the levels of thyroid-stimulating hormone, free T4, and prolactin should be performed.

Screen for a hemostasis disorder. Women with excessive menstrual bleeding should be clinically screened for an underlying disorder of hemostasis (TABLE 1).³ When a hemostasis disorder is suspected, initial laboratory evaluation includes a partial thromboplastin time, prothrombin time, activated partial thromboplastin time, and fibrinogen. Women who have a positive clinical screen for a possible bleeding disorder or abnormal initial laboratory test results for disorders of hemostasis should undergo further laboratory evaluation, including von Willebrand factor antigen, ristocetin cofactor assay, and factor VIII. Consultation with a hematologist should be considered in these cases.

Perform endometrial biopsy when indicated

After excluding pregnancy, endometrial biopsy (through pipelle biospy or brush sampling; FIGURE 4) should be performed in women with AUB who are at increased risk for endometrial neoplasia. The prevalence of endometrial neoplasia is substantially higher among women ≥45 years of age⁴ and among patients with AUB who are also obese (BMI, ≥30 kg/m²).⁵ In addition, AUB patients with unopposed estrogen exposure (presumed anovulation/PCOS), as well as those with persistent AUB or failed medical management, should undergo endometrial biopsy.⁶

Utilize transvaginal ultrasonography

Transvaginal ultrasonography is often useful in the evaluation of patients with AUB, as it may identify uterine fibroids or adenomyosis, suggest intracavitary pathology (such as an endometrial polyp or submucosal fibroid), or raise the possibility of PCOS. In virginal patients or those in whom vaginal ultrasound is not appropriate, abdominal pelvic ultrasonography represents appropriate imaging. If unenhanced ultrasound suggests endometrial polyps or fibroids within the endometrial cavity, an office-based saline infusion sonogram (sonohysterogram) (FIGURE 5) or hysteroscopy should be performed. Targeted endometrial sampling and biopsy of intracavitary pathology can be performed at the time of hysteroscopy.

Treatment

When HMB impairs quality of life, is bothersome to the patient, or results in anemia, treatment is appropriate. Although bleeding episodes in women with AUB-O may be infrequent (as with Case 2), treatment prevents heavy or prolonged bleeding episodes as well as endometrial neoplasia that may otherwise occur in anovulatory women.

Many women with AUB can be managed medically. However, treatment choices will vary with respect to the patient’s desire for future fertility, medical comorbidities, personal preferences, and financial barriers. While many women may prefer outpatient medical management (TABLE 2),^7-14 others might desire surgical therapy, including endometrial ablation or hysterectomy.

Oral contraceptives

Combination estrogen-progestin oral contraceptives represent appropriate initial therapy for many women in the reproductive-age group with AUB, whether women have HMB or AUB-O. However, contraceptive doses of estrogen are not appropriate for some women with risk factors for cardiovascular disease, including those who smoke cigarettes and are age ≥35 years or those who have hypertension (TABLE 3).^15,16

Continue to: Menopausal dosages of HT...

Menopausal dosages of HT

If use of contraceptive doses of estrogen is not appropriate, continuous off-label use of menopausal combination formulations (physiologic dosage) of hormonal therapy (HT; ie, lower doses of estrogen than contraceptives) may be effective in reducing or eliminating AUB. Options for menopausal combination formulations include generic ethinyl estradiol 5 µg/norethindrone acetate 1 mg or estradiol 1 mg/norethindrone acetate 0.5 mg.⁷ High-dose oral progestin therapy (norethindrone acetate 5 mg tablet once daily or medroxyprogesterone acetate 10 mg tablets 1–3 times daily) also can be used when combination contraceptives are contraindicated and may be more effective than lower-dose combination formulations.

Package labeling, as well as some guidelines, indicate that oral progestins used to treat AUB should be taken cyclically.⁸ However, continuous daily use is easier for many patients and may be more effective in reducing bleeding. Accordingly, we counsel patients with AUB who are using progestins and who do not wish to conceive to take these medications continuously. High-dose oral progestin therapy may cause bloating, dysphoria, and increased appetite/weight gain. Women initiating hormonal management (including the progestin IUDs detailed below) for AUB should be counseled that irregular or even continuous light bleeding/spotting is common initially, but this bleeding pattern typically decreases with continued use.

IUDs

The LNG 52 mg IUD (Mirena or Liletta) effectively treats HMB, reducing bleeding in a manner comparable to that of endometrial ablation.^9,10 The Mirena IUD is approved for treatment of HMB in women desiring intrauterine contraception. In contrast to oral medications, use of progestin IUDs does not involve daily administration and may represent an attractive option for women with HMB who would like to avoid surgery or preserve fertility. With ongoing use, continuous oral or intrauterine hormonal management may result in amenorrhea in some women with AUB.

When the LNG 52 mg IUD is used to treat HMB, the menstrual suppression impact may begin to attenuate after approximately 4 years of use; in this setting, replacing the IUD often restores effective menstrual suppression.¹¹ The LNG 52 mg IUD effectively suppresses menses in women with coagulation disorders; if menstrual suppression with the progestin IUD is not adequate in this setting, it may be appropriate to add an oral combination estrogen-progestin contraceptive or high-dose oral progestin.^11,12

NSAIDs and tranexamic acid

Off-label use of nonsteroidal anti-inflammatory drugs (naproxen 500–1,000 mg daily for 5 days beginning at the onset of menstrual flow or tranexamic acid two 650-mg tablets 3 times daily for up to 5 days during episodes of heavy flow) can suppress HMB and is useful for women who prefer to avoid or have contraindications to hormonal treatments.^13,14 Unfortunately, these agents are not as effective as hormonal management in treating AUB.

Iron supplementation is often needed

Iron depletion commonly results from HMB, often resulting in iron deficiency anemia. When iron depletion (readily identified by checking a serum ferritin level) or iron deficiency anemia is identified, iron supplementation should be recommended. Every-other-day administration of iron supplements maximizes iron absorption while minimizing the adverse effects of unabsorbed iron, such as nausea. Sixty mg of elemental iron (ferrous sulfate 325 mg) administered every other day represents an inexpensive and effective treatment for iron deficiency/anemia.¹⁷ In patients who cannot tolerate oral iron supplementation or for those in whom oral therapy is not appropriate or effective, newer intravenous iron formulations are safe and effective.¹⁸

Continue to: Case 1 Follow-up...

Case 1 Follow-up

The patient noted marked improvement in her menstrual cramps following LNG-containing IUD placement. Although she also reported that she no longer experienced heavy menstrual flow or cramps, she was bothered by frequent, unpredictable light bleeding/spotting. You prescribed norethindrone acetate (NETA) 5-mg tablet orally once daily, to be used in addition to her IUD. After using the IUD with concomitant NETA for 2 months’ duration, she noted that her bleeding/spotting almost completely resolved; however, she did report feeling irritable with use of the progestin tablets. She subsequently stopped the NETA tablets and, after 6 months of additional follow-up, reported only minimal spotting and no cramps.

At this later follow-up visit, you noted that her hemoglobin level increased to 12.6 g/dL, and the ferritin level no longer indicated iron depletion. After the IUD had been in place for 4 years, she reported that she was beginning to experience frequent light bleeding again. A follow-up vaginal sonogram noted a well-positioned IUD, there was no suggestion of intracavitary pathology, and adenomyosis continued to be imaged. She underwent IUD removal and placement of a new LNG 52 mg IUD. This resulted in marked reduction in her bleeding.

Case 2 Follow-up

Two weeks after beginning continuous oral progestin therapy, the patient called reporting frequent irregular bleeding. She was reassured that this was not unexpected and encouraged to continue oral progestin therapy. During a 3-month follow-up visit, the patient noted little, if any, bleeding over the previous 2 months and was pleased with this result. She continued to note acne and hirsutism and asked about the possibility of adding spironolactone to her oral progestin regimen.

Case 1 Multiparous woman presents with heavy regular menses

Over the past several years, a 34-year-old woman has noted increasing intensity and duration of menstrual flow, which now persists for 8 days and includes clots “the size of quarters” and soaks a pad within 1 hour. Sometimes she misses or leaves work on her heaviest days of flow. She reports that menstrual cramps prior to and during flow are increasingly bothersome and do not respond adequately to ibuprofen. She intermittently uses condoms for contraception. She does not wish to be pregnant currently; however, she recently entered into a new relationship and may wish to conceive in the future.

On bimanual examination, the uterus appears bulky. Her hemoglobin is 10.9 g/dL with low mean corpuscular volume and a serum ferritin level indicating iron depletion. Pelvic ultrasonography suggests uterine adenomyosis; no fibroids are imaged (FIGURE 1).

You advise the patient to take ferrous sulfate 325 mg every other day. After discussion with the patient regarding different treatment options, she chooses to proceed with placement of a 52-mg levonorgestrel (LNG) intrauterine device (IUD; Mirena or Liletta).

Case 2 Older adolescent presents with irregular bleeding

A 19-year-old patient reports approximately 6 bleeding episodes each year. She reports the duration of her bleeding as variable, and sometimes the bleeding is heavy with small clots passed. She has been previously diagnosed with polycystic ovary syndrome (PCOS). Combination estrogen-progestin oral contraceptives have been prescribed several times in the past, but she always has discontinued them due to nausea. The patient is in a same-sex relationship and does not anticipate being sexually active with a male. She reports having to shave her mustache and chin twice weekly for the past 1 to 2 years.

On physical examination, the patient is obese (body mass index [BMI], 32 kg/m²), facial acne and hirsutism are present, and hair extends from the mons toward the umbilicus. Bimanual examination reveals a normal size, mobile, nontender uterus without obvious adnexal pathology. Pelvic ultrasonography demonstrates a normal-appearing uterus with multiplanar endometrium (consistent with proliferative changes) (FIGURE 2). Ovarian imaging demonstrates ≥12 follicles per image (FIGURE 3).

About one-third of all women experience abnormal uterine bleeding (AUB) sometime during their lifetime and AUB can impair quality of life.¹ Surgical management, including hysterectomy and endometrial ablation, plays an important role in the management of AUB in patients who do not desire future pregnancies. However, many cases of AUB occur in women who may not have completed childbearing or in women who prefer to avoid surgery.² AUB can be managed effectively medically in most cases.¹ Accordingly, in this review, we focus on nonsurgical management of AUB.

Continue to: Because previously used terms, including...

Because previously used terms, including menorrhagia and meno-metrorrhagia, were inconsistently defined and confusing, the International Federation of Gynecology and Obstetrics introduced updated terminology in 2011 to better describe and characterize AUB in nonpregnant women. Heavy menstrual bleeding (HMB) refers to ovulatory (cyclic) bleeding that is more than 8 days’ duration, or sufficiently heavy to impair a woman’s quality of life. HMB is a pattern of AUB distinct from the irregular bleeding pattern typically caused by ovulatory dysfunction (AUB-O).¹

Clinical evaluation

Obtain menstrual history. In addition to a medical, surgical, and gynecologic history, a thorough menstrual history should be obtained to further characterize the patient’s bleeding pattern. In contrast to the cyclical or ovulatory bleeding seen with HMB, bleeding associated with inconsistent ovulation (AUB-O) is unpredictable or irregular, and is commonly associated with PCOS. AUB-O is also encountered in recently menarchal girls (secondary to immaturity of the hypothalamic-pituitary-gonadal axis) and in those who are perimenopausal. In addition, medications that can induce hyperprolactinemia (such as certain antipsychotics) can cause AUB-O.

Evaluate for all sources of bleeding. Be sure to evaluate for extrauterine causes of bleeding, including the cervix, vagina, vulva, or the urinary or gastrointestinal tracts for bleeding. Intermenstrual bleeding occurring between normal regular menses may be caused by an endometrial polyp, submucosal fibroid, endometritis, or an IUD. The patient report of postcoital bleeding suggests that cervical disease (cervicitis, polyp, or malignancy) may be present. Uterine leiomyoma or adenomyosis represent common causes of HMB. However, HMB also may be caused by a copper IUD, coagulation disorders (including von Willebrand disease), or use of anticoagulant medications. Hormonal contraceptives also can cause irregular bleeding.

Perform a pelvic examination and measure vital signs. The presence of fever suggests the possible presence of pelvic inflammatory disease (PID), while orthostatic hypotension raises the possibility of hypovolemia. When vaginal speculum examination is performed, a cervical cause of abnormal bleeding may be noted. The presence of fresh or old blood or finding clots in the vaginal vault or at the cervical os are all consistent with AUB. A bimanual examination that reveals an enlarged or lobular uterus suggests leiomyoma or adenomyosis. Cervical or adnexal tenderness is often noted in women with PID, which itself may be associated with endometritis. The presence of hyperandrogenic signs on physical examination (eg, acne, hirsutism, or clitoromegaly) suggests PCOS. The finding of galactorrhea suggests that hyperprolactinemia may be present.

Laboratory assessment

Test for pregnancy, cervical disease, and sexually transmitted infection when appropriate. Pregnancy testing is appropriate for women with AUB aged 55 years or younger. If patients with AUB are not up to date with normal cervical cancer screening results, cervical cytology and/or human papillomavirus testing should be performed. Testing for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis should be performed in patients:

• younger than 25 years
• when the history indicates new or multiple sexual partners, or
• when vaginal discharge, cervicitis, cervical motion, or adnexal tenderness is present.

Continue to: Obtain a complete blood count and serum ferritin levels...

Obtain a complete blood count and serum ferritin levels. In women presenting with HMB, iron depletion and iron deficiency anemia are common. The finding of leukocytosis raises the possibility of PID or postpartum endometritis. In women with presumptive AUB-O, checking the levels of thyroid-stimulating hormone, free T4, and prolactin should be performed.

Screen for a hemostasis disorder. Women with excessive menstrual bleeding should be clinically screened for an underlying disorder of hemostasis (TABLE 1).³ When a hemostasis disorder is suspected, initial laboratory evaluation includes a partial thromboplastin time, prothrombin time, activated partial thromboplastin time, and fibrinogen. Women who have a positive clinical screen for a possible bleeding disorder or abnormal initial laboratory test results for disorders of hemostasis should undergo further laboratory evaluation, including von Willebrand factor antigen, ristocetin cofactor assay, and factor VIII. Consultation with a hematologist should be considered in these cases.

Perform endometrial biopsy when indicated

After excluding pregnancy, endometrial biopsy (through pipelle biospy or brush sampling; FIGURE 4) should be performed in women with AUB who are at increased risk for endometrial neoplasia. The prevalence of endometrial neoplasia is substantially higher among women ≥45 years of age⁴ and among patients with AUB who are also obese (BMI, ≥30 kg/m²).⁵ In addition, AUB patients with unopposed estrogen exposure (presumed anovulation/PCOS), as well as those with persistent AUB or failed medical management, should undergo endometrial biopsy.⁶

Utilize transvaginal ultrasonography

Transvaginal ultrasonography is often useful in the evaluation of patients with AUB, as it may identify uterine fibroids or adenomyosis, suggest intracavitary pathology (such as an endometrial polyp or submucosal fibroid), or raise the possibility of PCOS. In virginal patients or those in whom vaginal ultrasound is not appropriate, abdominal pelvic ultrasonography represents appropriate imaging. If unenhanced ultrasound suggests endometrial polyps or fibroids within the endometrial cavity, an office-based saline infusion sonogram (sonohysterogram) (FIGURE 5) or hysteroscopy should be performed. Targeted endometrial sampling and biopsy of intracavitary pathology can be performed at the time of hysteroscopy.

Treatment

When HMB impairs quality of life, is bothersome to the patient, or results in anemia, treatment is appropriate. Although bleeding episodes in women with AUB-O may be infrequent (as with Case 2), treatment prevents heavy or prolonged bleeding episodes as well as endometrial neoplasia that may otherwise occur in anovulatory women.

Many women with AUB can be managed medically. However, treatment choices will vary with respect to the patient’s desire for future fertility, medical comorbidities, personal preferences, and financial barriers. While many women may prefer outpatient medical management (TABLE 2),^7-14 others might desire surgical therapy, including endometrial ablation or hysterectomy.

Oral contraceptives

Combination estrogen-progestin oral contraceptives represent appropriate initial therapy for many women in the reproductive-age group with AUB, whether women have HMB or AUB-O. However, contraceptive doses of estrogen are not appropriate for some women with risk factors for cardiovascular disease, including those who smoke cigarettes and are age ≥35 years or those who have hypertension (TABLE 3).^15,16

Continue to: Menopausal dosages of HT...

Menopausal dosages of HT

If use of contraceptive doses of estrogen is not appropriate, continuous off-label use of menopausal combination formulations (physiologic dosage) of hormonal therapy (HT; ie, lower doses of estrogen than contraceptives) may be effective in reducing or eliminating AUB. Options for menopausal combination formulations include generic ethinyl estradiol 5 µg/norethindrone acetate 1 mg or estradiol 1 mg/norethindrone acetate 0.5 mg.⁷ High-dose oral progestin therapy (norethindrone acetate 5 mg tablet once daily or medroxyprogesterone acetate 10 mg tablets 1–3 times daily) also can be used when combination contraceptives are contraindicated and may be more effective than lower-dose combination formulations.

Package labeling, as well as some guidelines, indicate that oral progestins used to treat AUB should be taken cyclically.⁸ However, continuous daily use is easier for many patients and may be more effective in reducing bleeding. Accordingly, we counsel patients with AUB who are using progestins and who do not wish to conceive to take these medications continuously. High-dose oral progestin therapy may cause bloating, dysphoria, and increased appetite/weight gain. Women initiating hormonal management (including the progestin IUDs detailed below) for AUB should be counseled that irregular or even continuous light bleeding/spotting is common initially, but this bleeding pattern typically decreases with continued use.

IUDs

The LNG 52 mg IUD (Mirena or Liletta) effectively treats HMB, reducing bleeding in a manner comparable to that of endometrial ablation.^9,10 The Mirena IUD is approved for treatment of HMB in women desiring intrauterine contraception. In contrast to oral medications, use of progestin IUDs does not involve daily administration and may represent an attractive option for women with HMB who would like to avoid surgery or preserve fertility. With ongoing use, continuous oral or intrauterine hormonal management may result in amenorrhea in some women with AUB.

When the LNG 52 mg IUD is used to treat HMB, the menstrual suppression impact may begin to attenuate after approximately 4 years of use; in this setting, replacing the IUD often restores effective menstrual suppression.¹¹ The LNG 52 mg IUD effectively suppresses menses in women with coagulation disorders; if menstrual suppression with the progestin IUD is not adequate in this setting, it may be appropriate to add an oral combination estrogen-progestin contraceptive or high-dose oral progestin.^11,12

NSAIDs and tranexamic acid

Off-label use of nonsteroidal anti-inflammatory drugs (naproxen 500–1,000 mg daily for 5 days beginning at the onset of menstrual flow or tranexamic acid two 650-mg tablets 3 times daily for up to 5 days during episodes of heavy flow) can suppress HMB and is useful for women who prefer to avoid or have contraindications to hormonal treatments.^13,14 Unfortunately, these agents are not as effective as hormonal management in treating AUB.

Iron supplementation is often needed

Iron depletion commonly results from HMB, often resulting in iron deficiency anemia. When iron depletion (readily identified by checking a serum ferritin level) or iron deficiency anemia is identified, iron supplementation should be recommended. Every-other-day administration of iron supplements maximizes iron absorption while minimizing the adverse effects of unabsorbed iron, such as nausea. Sixty mg of elemental iron (ferrous sulfate 325 mg) administered every other day represents an inexpensive and effective treatment for iron deficiency/anemia.¹⁷ In patients who cannot tolerate oral iron supplementation or for those in whom oral therapy is not appropriate or effective, newer intravenous iron formulations are safe and effective.¹⁸

Continue to: Case 1 Follow-up...

Case 1 Follow-up

The patient noted marked improvement in her menstrual cramps following LNG-containing IUD placement. Although she also reported that she no longer experienced heavy menstrual flow or cramps, she was bothered by frequent, unpredictable light bleeding/spotting. You prescribed norethindrone acetate (NETA) 5-mg tablet orally once daily, to be used in addition to her IUD. After using the IUD with concomitant NETA for 2 months’ duration, she noted that her bleeding/spotting almost completely resolved; however, she did report feeling irritable with use of the progestin tablets. She subsequently stopped the NETA tablets and, after 6 months of additional follow-up, reported only minimal spotting and no cramps.

At this later follow-up visit, you noted that her hemoglobin level increased to 12.6 g/dL, and the ferritin level no longer indicated iron depletion. After the IUD had been in place for 4 years, she reported that she was beginning to experience frequent light bleeding again. A follow-up vaginal sonogram noted a well-positioned IUD, there was no suggestion of intracavitary pathology, and adenomyosis continued to be imaged. She underwent IUD removal and placement of a new LNG 52 mg IUD. This resulted in marked reduction in her bleeding.

Case 2 Follow-up

Two weeks after beginning continuous oral progestin therapy, the patient called reporting frequent irregular bleeding. She was reassured that this was not unexpected and encouraged to continue oral progestin therapy. During a 3-month follow-up visit, the patient noted little, if any, bleeding over the previous 2 months and was pleased with this result. She continued to note acne and hirsutism and asked about the possibility of adding spironolactone to her oral progestin regimen.

Patients discharged with plug-unplug catheters after pelvic reconstructive surgery did not have adverse effects and reported less difficulty with catheter management and activities of daily living than women who were discharged with a continuous drainage catheter, a study has found.

“Plug-unplug catheter management technique is an acceptable method that does not appear to cause adverse events and may be considered for short-term catheterization after pelvic reconstructive surgery,” said Sarah Boyd, MD,* of the division of urogynecology at Hartford (Conn.) Hospital, and coinvestigators wrote in Obstetrics & Gynecology.

A total of 63 women who had a failed postoperative voiding trial after surgery for prolapse, with or without a concomitant incontinence procedure, were randomized to receive a 16-French transurethral catheter that was either attached to a leg bag (31 patients) or capped with a plastic plug (32 patients). Women in the second group – the plug-unplug group – were instructed to intermittently drain the bladder by uncapping the catheter when they felt the urge to void, or in the absence of urge, every 4 hours. All were scheduled for an outpatient voiding trial 5-7 days after discharge.

The first 30 study participants who did not require postoperative catheterization were assigned to a “reference,” or control, arm.

All patients in the study completed an activity assessment scale that covers both sedentary and ambulatory activities and is validated in women undergoing pelvic reconstructive surgery (Female Pelvic Med Reconstr Surg. 2012 Jul-Aug;18[4]:205-10); scores on the activity assessment scale (0-100) served as the primary outcome. Patients also answered questionnaires about their satisfaction and postoperative pain – and in the catheter arms, their experiences with the catheter.

The investigators found no difference in postoperative activity assessment scale scores (plug-unplug, 70; continuous drainage, 68; and reference arm, 79), However, patients with a continuous catheter indicated in the other evaluations that they had more difficulty managing the catheter and felt it impeded activities and the wearing of clothing they would otherwise use.

The activity scale, the investigators noted, may not have captured differences in activity during the first week postoperatively because patients are commonly instructed to restrict some of the activities assessed in the scale.

Regarding infection, there was no difference in the rate of positive urine cultures or treatment for urinary tract infection between the catheter arms during a 3-month follow-up period, “despite the theoretical concern that plugging and unplugging a catheter disrupts the closed catheter system, thus increasing the risk of infection,” the investigators wrote. However, the study was not powered to detect a difference in the risk of infection as it was for the primary outcome.

There was no difference between the catheter arms in the percentage of women who used narcotic or nonnarcotic pain medication, and overall patient satisfaction was similar.

The majority of patients passed their outpatient voiding trials at the initial postoperative visit (72% plug-unplug and 58% continuous). “Interestingly, patients in the plug-unplug arm had significantly higher voided volumes and almost half of the [postvoid residual volume] at the [5-7 day postoperative voiding trial] compared with the continuous drainage arm.” This suggests, Dr. Boyd and colleagues wrote, that patients using the plug-unplug catheter “could have undergone a voiding trial sooner.”

Offering patients options for catheter management is “valuable,” and providing them with a technique that is “easier to manage may decrease the catheter burden and improve patient experience,” the investigators added.

Luis E. Sanz, MD, director of urogynecology and pelvic reconstructive surgery at Virginia Hospital Center, Arlington, said, “I think that the plug and unplug drainage bladder catheter after reconstructive surgery is much more physiologic and ‘user friendly’ than continuous drainage. And [there is] no need for a leg bag, which is very inconvenient to the patient.”

Dr. Sanz, an Ob.Gyn. News Editorial Advisory Board member who was not involved in the study, was asked to provide a comment.

The authors did not report any potential conflicts of interest.

[email protected]

SOURCE: Boyd SS et al. Obstet Gynecol. 2019;134:1037-45.

* Correction, 10/24/2019: an earlier version misstated the chief investigator's name, which is Sarah Boyd, MD.

Patients discharged with plug-unplug catheters after pelvic reconstructive surgery did not have adverse effects and reported less difficulty with catheter management and activities of daily living than women who were discharged with a continuous drainage catheter, a study has found.

“Plug-unplug catheter management technique is an acceptable method that does not appear to cause adverse events and may be considered for short-term catheterization after pelvic reconstructive surgery,” said Sarah Boyd, MD,* of the division of urogynecology at Hartford (Conn.) Hospital, and coinvestigators wrote in Obstetrics & Gynecology.

A total of 63 women who had a failed postoperative voiding trial after surgery for prolapse, with or without a concomitant incontinence procedure, were randomized to receive a 16-French transurethral catheter that was either attached to a leg bag (31 patients) or capped with a plastic plug (32 patients). Women in the second group – the plug-unplug group – were instructed to intermittently drain the bladder by uncapping the catheter when they felt the urge to void, or in the absence of urge, every 4 hours. All were scheduled for an outpatient voiding trial 5-7 days after discharge.

The first 30 study participants who did not require postoperative catheterization were assigned to a “reference,” or control, arm.

All patients in the study completed an activity assessment scale that covers both sedentary and ambulatory activities and is validated in women undergoing pelvic reconstructive surgery (Female Pelvic Med Reconstr Surg. 2012 Jul-Aug;18[4]:205-10); scores on the activity assessment scale (0-100) served as the primary outcome. Patients also answered questionnaires about their satisfaction and postoperative pain – and in the catheter arms, their experiences with the catheter.

The investigators found no difference in postoperative activity assessment scale scores (plug-unplug, 70; continuous drainage, 68; and reference arm, 79), However, patients with a continuous catheter indicated in the other evaluations that they had more difficulty managing the catheter and felt it impeded activities and the wearing of clothing they would otherwise use.

The activity scale, the investigators noted, may not have captured differences in activity during the first week postoperatively because patients are commonly instructed to restrict some of the activities assessed in the scale.

Regarding infection, there was no difference in the rate of positive urine cultures or treatment for urinary tract infection between the catheter arms during a 3-month follow-up period, “despite the theoretical concern that plugging and unplugging a catheter disrupts the closed catheter system, thus increasing the risk of infection,” the investigators wrote. However, the study was not powered to detect a difference in the risk of infection as it was for the primary outcome.

There was no difference between the catheter arms in the percentage of women who used narcotic or nonnarcotic pain medication, and overall patient satisfaction was similar.

The majority of patients passed their outpatient voiding trials at the initial postoperative visit (72% plug-unplug and 58% continuous). “Interestingly, patients in the plug-unplug arm had significantly higher voided volumes and almost half of the [postvoid residual volume] at the [5-7 day postoperative voiding trial] compared with the continuous drainage arm.” This suggests, Dr. Boyd and colleagues wrote, that patients using the plug-unplug catheter “could have undergone a voiding trial sooner.”

Offering patients options for catheter management is “valuable,” and providing them with a technique that is “easier to manage may decrease the catheter burden and improve patient experience,” the investigators added.

Luis E. Sanz, MD, director of urogynecology and pelvic reconstructive surgery at Virginia Hospital Center, Arlington, said, “I think that the plug and unplug drainage bladder catheter after reconstructive surgery is much more physiologic and ‘user friendly’ than continuous drainage. And [there is] no need for a leg bag, which is very inconvenient to the patient.”

Dr. Sanz, an Ob.Gyn. News Editorial Advisory Board member who was not involved in the study, was asked to provide a comment.

The authors did not report any potential conflicts of interest.

[email protected]

SOURCE: Boyd SS et al. Obstet Gynecol. 2019;134:1037-45.

* Correction, 10/24/2019: an earlier version misstated the chief investigator's name, which is Sarah Boyd, MD.

Patients discharged with plug-unplug catheters after pelvic reconstructive surgery did not have adverse effects and reported less difficulty with catheter management and activities of daily living than women who were discharged with a continuous drainage catheter, a study has found.

“Plug-unplug catheter management technique is an acceptable method that does not appear to cause adverse events and may be considered for short-term catheterization after pelvic reconstructive surgery,” said Sarah Boyd, MD,* of the division of urogynecology at Hartford (Conn.) Hospital, and coinvestigators wrote in Obstetrics & Gynecology.

A total of 63 women who had a failed postoperative voiding trial after surgery for prolapse, with or without a concomitant incontinence procedure, were randomized to receive a 16-French transurethral catheter that was either attached to a leg bag (31 patients) or capped with a plastic plug (32 patients). Women in the second group – the plug-unplug group – were instructed to intermittently drain the bladder by uncapping the catheter when they felt the urge to void, or in the absence of urge, every 4 hours. All were scheduled for an outpatient voiding trial 5-7 days after discharge.

The first 30 study participants who did not require postoperative catheterization were assigned to a “reference,” or control, arm.

All patients in the study completed an activity assessment scale that covers both sedentary and ambulatory activities and is validated in women undergoing pelvic reconstructive surgery (Female Pelvic Med Reconstr Surg. 2012 Jul-Aug;18[4]:205-10); scores on the activity assessment scale (0-100) served as the primary outcome. Patients also answered questionnaires about their satisfaction and postoperative pain – and in the catheter arms, their experiences with the catheter.

The investigators found no difference in postoperative activity assessment scale scores (plug-unplug, 70; continuous drainage, 68; and reference arm, 79), However, patients with a continuous catheter indicated in the other evaluations that they had more difficulty managing the catheter and felt it impeded activities and the wearing of clothing they would otherwise use.

The activity scale, the investigators noted, may not have captured differences in activity during the first week postoperatively because patients are commonly instructed to restrict some of the activities assessed in the scale.

Regarding infection, there was no difference in the rate of positive urine cultures or treatment for urinary tract infection between the catheter arms during a 3-month follow-up period, “despite the theoretical concern that plugging and unplugging a catheter disrupts the closed catheter system, thus increasing the risk of infection,” the investigators wrote. However, the study was not powered to detect a difference in the risk of infection as it was for the primary outcome.

There was no difference between the catheter arms in the percentage of women who used narcotic or nonnarcotic pain medication, and overall patient satisfaction was similar.

The majority of patients passed their outpatient voiding trials at the initial postoperative visit (72% plug-unplug and 58% continuous). “Interestingly, patients in the plug-unplug arm had significantly higher voided volumes and almost half of the [postvoid residual volume] at the [5-7 day postoperative voiding trial] compared with the continuous drainage arm.” This suggests, Dr. Boyd and colleagues wrote, that patients using the plug-unplug catheter “could have undergone a voiding trial sooner.”

Offering patients options for catheter management is “valuable,” and providing them with a technique that is “easier to manage may decrease the catheter burden and improve patient experience,” the investigators added.

Luis E. Sanz, MD, director of urogynecology and pelvic reconstructive surgery at Virginia Hospital Center, Arlington, said, “I think that the plug and unplug drainage bladder catheter after reconstructive surgery is much more physiologic and ‘user friendly’ than continuous drainage. And [there is] no need for a leg bag, which is very inconvenient to the patient.”

Dr. Sanz, an Ob.Gyn. News Editorial Advisory Board member who was not involved in the study, was asked to provide a comment.

The authors did not report any potential conflicts of interest.

[email protected]

SOURCE: Boyd SS et al. Obstet Gynecol. 2019;134:1037-45.

* Correction, 10/24/2019: an earlier version misstated the chief investigator's name, which is Sarah Boyd, MD.

PHILADELPHIA – Factors such as primary fibroid volume, fibroid stage, and uterine volume did not appear to affect the efficacy of elagolix in improving heavy menstrual bleeding associated with uterine fibroids, according to results presented at the annual meeting of the American Society for Reproductive Medicine.

Ayman Al-Hendy, MD, PhD, director of translational research at the University of Illinois at Chicago, and associates, analyzed a pooled subgroup of 790 patients from the Elaris UF-1 and UF-2 trials who received elagolix twice daily at a dose of 300 mg (199 patients), elagolix 300 mg twice daily with add-back therapy (1 mg of estradiol plus 0.5 mg of norethindrone acetate; 395 patients), and a placebo group (196 patients) for treatment of heavy menstrual bleeding. Patients were premenopausal women aged 18-51 years with more than 80 mL of menstrual blood loss per cycle. The study design included a washout period, followed by a 2.5-month to 3.5-month screening period, and patients were randomized to 6 months of treatment with placebo, elagolix alone, or elagolix with add-back therapy in a 1:1:2 ratio. Researchers evaluated whether patients had less than 80 mL of menstrual blood loss per cycle and a 50% or more reduction in menstrual blood loss per cycle by the end of the study.

In a subgroup analysis, they also analyzed primary fibroid volume, fibroid stage, and uterine volume. The median primary fibroid volume was 36.2 cm³ (range, 1.0-1,081.5 cm³). Fibroid location was classified using the International Federation of Gynecology and Obstetrics (FIGO) staging system, and researchers placed fibroids into FIGO 0-3, FIGO 4, and FIGO 5-8 groups. At baseline, characteristics between groups were similar, but the patients who received elagolix alone had a lower number of fibroids classified as FIGO 0-3 and had a greater percentage of fibroids less than 36.2 cm³. The median uterine volume was 356.5 cm³ (range, 71.6-3,347.9 cm³).

At final follow-up, 81% of patients receiving elagolix alone and 72% of patients receiving elagolix with add-back therapy responded to treatment, compared with placebo (9%).

Patients receiving elagolix plus add-back therapy responded to treatment better than placebo, and there were no significant differences in outcomes in terms of FIGO stage: Response was as follows for patients with FIGO 0-3 classified fibroids (78% of 47 patients vs. 9% of 25 patients), FIGO 4 fibroids (68% of 177 patients vs. 15% of 85 patients) and FIGO 5-8 fibroids (74% of 165 patients vs. 4% of 82 patients). The same was true in terms of both primary fibroid volume and uterine volume in patients who received elagolix plus add-back therapy, compared with those who received placebo: Patients with a primary fibroid volume of less than 36.2 cm³ (74% of 189 patients vs. 15% of 92 patients) responded similarly to elagolix plus add-back therapy as did patients with a primary fibroid volume greater than 36.2 cm³ (70% of 200 patients vs. 5% of 100 patients), and there were no significant differences between the treatment response of patients with a uterine volume less than 365.5 cm³ (75% of 203 patients vs. 15% of 88 patients) and a uterine volume greater than 365.5 cm³ (70% of 192 patients vs. 5% of 108 patients).

“These really are very encouraging results and suggests that, in women with different fibroids, elagolix with add-back therapy would be an effective treatment option despite uterine and fibroid volume and location of fibroids,” said Dr. Al-Hendy.

Dr. Al-Hendy noted there are ongoing studies analyzing elagolix with add-back in women with fibroids, in women with endometriosis, and elagolix in women with polycystic ovary syndrome.

AbbVie recently submitted a new drug application to the Food and Drug Administration for elagolix based on results from these two trials. Elagolix, an oral GnRh receptor antagonist, is an FDA-approved oral medication for the management of endometriosis with associated moderate to severe pain.

This study was funded by AbbVie, and the company was involved in the study design, research, data collection, analysis and interpretation of the data, as well as the writing, reviewing and approving of the study for publication. The authors reported various relationships with industry, pharmaceutical companies, government entities, and other organizations.
 

SOURCE: Al-Hendy A et al. ASRM 2019, Abstract O-205.

PHILADELPHIA – Factors such as primary fibroid volume, fibroid stage, and uterine volume did not appear to affect the efficacy of elagolix in improving heavy menstrual bleeding associated with uterine fibroids, according to results presented at the annual meeting of the American Society for Reproductive Medicine.

Ayman Al-Hendy, MD, PhD, director of translational research at the University of Illinois at Chicago, and associates, analyzed a pooled subgroup of 790 patients from the Elaris UF-1 and UF-2 trials who received elagolix twice daily at a dose of 300 mg (199 patients), elagolix 300 mg twice daily with add-back therapy (1 mg of estradiol plus 0.5 mg of norethindrone acetate; 395 patients), and a placebo group (196 patients) for treatment of heavy menstrual bleeding. Patients were premenopausal women aged 18-51 years with more than 80 mL of menstrual blood loss per cycle. The study design included a washout period, followed by a 2.5-month to 3.5-month screening period, and patients were randomized to 6 months of treatment with placebo, elagolix alone, or elagolix with add-back therapy in a 1:1:2 ratio. Researchers evaluated whether patients had less than 80 mL of menstrual blood loss per cycle and a 50% or more reduction in menstrual blood loss per cycle by the end of the study.

In a subgroup analysis, they also analyzed primary fibroid volume, fibroid stage, and uterine volume. The median primary fibroid volume was 36.2 cm³ (range, 1.0-1,081.5 cm³). Fibroid location was classified using the International Federation of Gynecology and Obstetrics (FIGO) staging system, and researchers placed fibroids into FIGO 0-3, FIGO 4, and FIGO 5-8 groups. At baseline, characteristics between groups were similar, but the patients who received elagolix alone had a lower number of fibroids classified as FIGO 0-3 and had a greater percentage of fibroids less than 36.2 cm³. The median uterine volume was 356.5 cm³ (range, 71.6-3,347.9 cm³).

At final follow-up, 81% of patients receiving elagolix alone and 72% of patients receiving elagolix with add-back therapy responded to treatment, compared with placebo (9%).

Patients receiving elagolix plus add-back therapy responded to treatment better than placebo, and there were no significant differences in outcomes in terms of FIGO stage: Response was as follows for patients with FIGO 0-3 classified fibroids (78% of 47 patients vs. 9% of 25 patients), FIGO 4 fibroids (68% of 177 patients vs. 15% of 85 patients) and FIGO 5-8 fibroids (74% of 165 patients vs. 4% of 82 patients). The same was true in terms of both primary fibroid volume and uterine volume in patients who received elagolix plus add-back therapy, compared with those who received placebo: Patients with a primary fibroid volume of less than 36.2 cm³ (74% of 189 patients vs. 15% of 92 patients) responded similarly to elagolix plus add-back therapy as did patients with a primary fibroid volume greater than 36.2 cm³ (70% of 200 patients vs. 5% of 100 patients), and there were no significant differences between the treatment response of patients with a uterine volume less than 365.5 cm³ (75% of 203 patients vs. 15% of 88 patients) and a uterine volume greater than 365.5 cm³ (70% of 192 patients vs. 5% of 108 patients).

“These really are very encouraging results and suggests that, in women with different fibroids, elagolix with add-back therapy would be an effective treatment option despite uterine and fibroid volume and location of fibroids,” said Dr. Al-Hendy.

Dr. Al-Hendy noted there are ongoing studies analyzing elagolix with add-back in women with fibroids, in women with endometriosis, and elagolix in women with polycystic ovary syndrome.

AbbVie recently submitted a new drug application to the Food and Drug Administration for elagolix based on results from these two trials. Elagolix, an oral GnRh receptor antagonist, is an FDA-approved oral medication for the management of endometriosis with associated moderate to severe pain.

This study was funded by AbbVie, and the company was involved in the study design, research, data collection, analysis and interpretation of the data, as well as the writing, reviewing and approving of the study for publication. The authors reported various relationships with industry, pharmaceutical companies, government entities, and other organizations.
 

SOURCE: Al-Hendy A et al. ASRM 2019, Abstract O-205.

PHILADELPHIA – Factors such as primary fibroid volume, fibroid stage, and uterine volume did not appear to affect the efficacy of elagolix in improving heavy menstrual bleeding associated with uterine fibroids, according to results presented at the annual meeting of the American Society for Reproductive Medicine.

Ayman Al-Hendy, MD, PhD, director of translational research at the University of Illinois at Chicago, and associates, analyzed a pooled subgroup of 790 patients from the Elaris UF-1 and UF-2 trials who received elagolix twice daily at a dose of 300 mg (199 patients), elagolix 300 mg twice daily with add-back therapy (1 mg of estradiol plus 0.5 mg of norethindrone acetate; 395 patients), and a placebo group (196 patients) for treatment of heavy menstrual bleeding. Patients were premenopausal women aged 18-51 years with more than 80 mL of menstrual blood loss per cycle. The study design included a washout period, followed by a 2.5-month to 3.5-month screening period, and patients were randomized to 6 months of treatment with placebo, elagolix alone, or elagolix with add-back therapy in a 1:1:2 ratio. Researchers evaluated whether patients had less than 80 mL of menstrual blood loss per cycle and a 50% or more reduction in menstrual blood loss per cycle by the end of the study.

In a subgroup analysis, they also analyzed primary fibroid volume, fibroid stage, and uterine volume. The median primary fibroid volume was 36.2 cm³ (range, 1.0-1,081.5 cm³). Fibroid location was classified using the International Federation of Gynecology and Obstetrics (FIGO) staging system, and researchers placed fibroids into FIGO 0-3, FIGO 4, and FIGO 5-8 groups. At baseline, characteristics between groups were similar, but the patients who received elagolix alone had a lower number of fibroids classified as FIGO 0-3 and had a greater percentage of fibroids less than 36.2 cm³. The median uterine volume was 356.5 cm³ (range, 71.6-3,347.9 cm³).

At final follow-up, 81% of patients receiving elagolix alone and 72% of patients receiving elagolix with add-back therapy responded to treatment, compared with placebo (9%).

Patients receiving elagolix plus add-back therapy responded to treatment better than placebo, and there were no significant differences in outcomes in terms of FIGO stage: Response was as follows for patients with FIGO 0-3 classified fibroids (78% of 47 patients vs. 9% of 25 patients), FIGO 4 fibroids (68% of 177 patients vs. 15% of 85 patients) and FIGO 5-8 fibroids (74% of 165 patients vs. 4% of 82 patients). The same was true in terms of both primary fibroid volume and uterine volume in patients who received elagolix plus add-back therapy, compared with those who received placebo: Patients with a primary fibroid volume of less than 36.2 cm³ (74% of 189 patients vs. 15% of 92 patients) responded similarly to elagolix plus add-back therapy as did patients with a primary fibroid volume greater than 36.2 cm³ (70% of 200 patients vs. 5% of 100 patients), and there were no significant differences between the treatment response of patients with a uterine volume less than 365.5 cm³ (75% of 203 patients vs. 15% of 88 patients) and a uterine volume greater than 365.5 cm³ (70% of 192 patients vs. 5% of 108 patients).

“These really are very encouraging results and suggests that, in women with different fibroids, elagolix with add-back therapy would be an effective treatment option despite uterine and fibroid volume and location of fibroids,” said Dr. Al-Hendy.

Dr. Al-Hendy noted there are ongoing studies analyzing elagolix with add-back in women with fibroids, in women with endometriosis, and elagolix in women with polycystic ovary syndrome.

AbbVie recently submitted a new drug application to the Food and Drug Administration for elagolix based on results from these two trials. Elagolix, an oral GnRh receptor antagonist, is an FDA-approved oral medication for the management of endometriosis with associated moderate to severe pain.

This study was funded by AbbVie, and the company was involved in the study design, research, data collection, analysis and interpretation of the data, as well as the writing, reviewing and approving of the study for publication. The authors reported various relationships with industry, pharmaceutical companies, government entities, and other organizations.
 

SOURCE: Al-Hendy A et al. ASRM 2019, Abstract O-205.

PHILADELPHIA – Women with ovarian torsion had a lower rate of perioperative complications when treated with conservative surgery, compared with oophorectomy, according to results from a retrospective study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The effectiveness of laparoscopy and conservative surgery has increased in recent years, but over 75% of women with ovarian torsion in the study were treated with oophorectomy and 60% underwent a laparotomy, said Rachel S. Mandelbaum, MD, of the department of obstetrics & gynecology at the University of Southern California, Los Angeles.

“We believe that conservative surgery should be performed whenever possible in young women with ovarian torsion regardless of the appearance of the ovary intraoperatively,” said Dr. Mandelbaum.

The researchers performed a retrospective, observational study of 89,801 women in the Nationwide Inpatient Sample who were younger than age 50 years, were diagnosed with ovarian torsion during Jan. 2001–Sept. 2015, and were treated with conservative surgery or oophorectomy. Patients were excluded if they had malignancy, were older than 50 years of age, or their surgery information was unavailable. The majority of patients in the study were white (46%), nonobese (91%), without comorbidities, privately insured (59%), and were seen at a large (61%) urban hospital (51% teaching; 38% nonteaching).

Dr. Mandelbaum and colleagues found 78% of patients received a cystectomy, 19% had cyst drainage, 11% had detorsion alone, and 0.5% had an oophoropexy, with less than 10% of patients having a combination of cystectomy, cyst drainage, and oophoropexy. According to a multivariable analysis, patients who were treated with conservative surgery were more likely to be young, have a high income, live in the northeastern United States, be treated with laparoscopy, and be seen at a large hospital or teaching hospital (P less than .001). Oophorectomy was more common in patients with a high number of comorbidities and in patients with morbid obesity (P less than .001).

Between 2001 and 2015, the rate of conservative surgery increased from 19% to 25% (P less than .001); however, the rate of conservative surgery by age was nearly 40% in pediatric patients up to 15 years old, while the rate of conservative surgery declined by almost half until 35 years, followed by a further decline until age 50 years, said Dr. Mandelbaum. Use of laparoscopy also increased from 31% in 2001 to 42% in 2015 (P less than .001).

Overall, 20,643 patients underwent conservative surgery and 69,157 patients received an oophorectomy. Patients in the conservative surgery group were more likely to undergo a conservative surgery with a laparoscopic surgical approach (51%) than a laparotomy (41%), while patients receiving an oophorectomy were more likely to have a laparotomy (67%) than a laparoscopic surgical approach (33%). In 1,663 conservative surgeries (8%), the approach was unknown.

Postoperative complications were higher in the oophorectomy group (12%) than the conservative surgery (8%) group (odds ratio, 0.57; 95% confidence interval, 0.57-0.78; P less than .001), but there was a similar rate of venous thromboembolism (0.3% vs. 0.2%; P equals .568) and sepsis (0.3% vs. 0.3%; P equals .865) in each group.

Dr. Mandelbaum attributed the high rate of oophorectomies in the study to “differential uptake of evidence” in different areas of the United States, fear of complications from leaving an infected ovary in situ, or the surgeon’s belief that the ovary is not viable because of its color intraoperatively. “We know from animal and human studies that the intraoperative appearance of the ovary does not correlate to viability, and that 90% of black or blue ovaries regain function and subsequently appear normal on both transvaginal ultrasound or on a second look grossly,” she said. Oophorectomy rates also vary by surgeon, and gynecologists are more likely to perform conservative surgery, she added.

The researchers said they were unable to obtain data on specific surgical variables such as the size of the mass, time to surgery, intraoperative appearance, laterality, fertility wishes of the patient, and surgeon type. There were also no postdischarge data, or information on the timing of complications.

Dr. Mandelbaum reported no relevant conflicts of interest.

SOURCE: Mandelbaum RS et al. ASRM 2019. Abstract O-96.

PHILADELPHIA – Women with ovarian torsion had a lower rate of perioperative complications when treated with conservative surgery, compared with oophorectomy, according to results from a retrospective study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The effectiveness of laparoscopy and conservative surgery has increased in recent years, but over 75% of women with ovarian torsion in the study were treated with oophorectomy and 60% underwent a laparotomy, said Rachel S. Mandelbaum, MD, of the department of obstetrics & gynecology at the University of Southern California, Los Angeles.

“We believe that conservative surgery should be performed whenever possible in young women with ovarian torsion regardless of the appearance of the ovary intraoperatively,” said Dr. Mandelbaum.

The researchers performed a retrospective, observational study of 89,801 women in the Nationwide Inpatient Sample who were younger than age 50 years, were diagnosed with ovarian torsion during Jan. 2001–Sept. 2015, and were treated with conservative surgery or oophorectomy. Patients were excluded if they had malignancy, were older than 50 years of age, or their surgery information was unavailable. The majority of patients in the study were white (46%), nonobese (91%), without comorbidities, privately insured (59%), and were seen at a large (61%) urban hospital (51% teaching; 38% nonteaching).

Dr. Mandelbaum and colleagues found 78% of patients received a cystectomy, 19% had cyst drainage, 11% had detorsion alone, and 0.5% had an oophoropexy, with less than 10% of patients having a combination of cystectomy, cyst drainage, and oophoropexy. According to a multivariable analysis, patients who were treated with conservative surgery were more likely to be young, have a high income, live in the northeastern United States, be treated with laparoscopy, and be seen at a large hospital or teaching hospital (P less than .001). Oophorectomy was more common in patients with a high number of comorbidities and in patients with morbid obesity (P less than .001).

Between 2001 and 2015, the rate of conservative surgery increased from 19% to 25% (P less than .001); however, the rate of conservative surgery by age was nearly 40% in pediatric patients up to 15 years old, while the rate of conservative surgery declined by almost half until 35 years, followed by a further decline until age 50 years, said Dr. Mandelbaum. Use of laparoscopy also increased from 31% in 2001 to 42% in 2015 (P less than .001).

Overall, 20,643 patients underwent conservative surgery and 69,157 patients received an oophorectomy. Patients in the conservative surgery group were more likely to undergo a conservative surgery with a laparoscopic surgical approach (51%) than a laparotomy (41%), while patients receiving an oophorectomy were more likely to have a laparotomy (67%) than a laparoscopic surgical approach (33%). In 1,663 conservative surgeries (8%), the approach was unknown.

Postoperative complications were higher in the oophorectomy group (12%) than the conservative surgery (8%) group (odds ratio, 0.57; 95% confidence interval, 0.57-0.78; P less than .001), but there was a similar rate of venous thromboembolism (0.3% vs. 0.2%; P equals .568) and sepsis (0.3% vs. 0.3%; P equals .865) in each group.

Dr. Mandelbaum attributed the high rate of oophorectomies in the study to “differential uptake of evidence” in different areas of the United States, fear of complications from leaving an infected ovary in situ, or the surgeon’s belief that the ovary is not viable because of its color intraoperatively. “We know from animal and human studies that the intraoperative appearance of the ovary does not correlate to viability, and that 90% of black or blue ovaries regain function and subsequently appear normal on both transvaginal ultrasound or on a second look grossly,” she said. Oophorectomy rates also vary by surgeon, and gynecologists are more likely to perform conservative surgery, she added.

The researchers said they were unable to obtain data on specific surgical variables such as the size of the mass, time to surgery, intraoperative appearance, laterality, fertility wishes of the patient, and surgeon type. There were also no postdischarge data, or information on the timing of complications.

Dr. Mandelbaum reported no relevant conflicts of interest.

SOURCE: Mandelbaum RS et al. ASRM 2019. Abstract O-96.

PHILADELPHIA – Women with ovarian torsion had a lower rate of perioperative complications when treated with conservative surgery, compared with oophorectomy, according to results from a retrospective study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The effectiveness of laparoscopy and conservative surgery has increased in recent years, but over 75% of women with ovarian torsion in the study were treated with oophorectomy and 60% underwent a laparotomy, said Rachel S. Mandelbaum, MD, of the department of obstetrics & gynecology at the University of Southern California, Los Angeles.

“We believe that conservative surgery should be performed whenever possible in young women with ovarian torsion regardless of the appearance of the ovary intraoperatively,” said Dr. Mandelbaum.

The researchers performed a retrospective, observational study of 89,801 women in the Nationwide Inpatient Sample who were younger than age 50 years, were diagnosed with ovarian torsion during Jan. 2001–Sept. 2015, and were treated with conservative surgery or oophorectomy. Patients were excluded if they had malignancy, were older than 50 years of age, or their surgery information was unavailable. The majority of patients in the study were white (46%), nonobese (91%), without comorbidities, privately insured (59%), and were seen at a large (61%) urban hospital (51% teaching; 38% nonteaching).

Dr. Mandelbaum and colleagues found 78% of patients received a cystectomy, 19% had cyst drainage, 11% had detorsion alone, and 0.5% had an oophoropexy, with less than 10% of patients having a combination of cystectomy, cyst drainage, and oophoropexy. According to a multivariable analysis, patients who were treated with conservative surgery were more likely to be young, have a high income, live in the northeastern United States, be treated with laparoscopy, and be seen at a large hospital or teaching hospital (P less than .001). Oophorectomy was more common in patients with a high number of comorbidities and in patients with morbid obesity (P less than .001).

Between 2001 and 2015, the rate of conservative surgery increased from 19% to 25% (P less than .001); however, the rate of conservative surgery by age was nearly 40% in pediatric patients up to 15 years old, while the rate of conservative surgery declined by almost half until 35 years, followed by a further decline until age 50 years, said Dr. Mandelbaum. Use of laparoscopy also increased from 31% in 2001 to 42% in 2015 (P less than .001).

Overall, 20,643 patients underwent conservative surgery and 69,157 patients received an oophorectomy. Patients in the conservative surgery group were more likely to undergo a conservative surgery with a laparoscopic surgical approach (51%) than a laparotomy (41%), while patients receiving an oophorectomy were more likely to have a laparotomy (67%) than a laparoscopic surgical approach (33%). In 1,663 conservative surgeries (8%), the approach was unknown.

Postoperative complications were higher in the oophorectomy group (12%) than the conservative surgery (8%) group (odds ratio, 0.57; 95% confidence interval, 0.57-0.78; P less than .001), but there was a similar rate of venous thromboembolism (0.3% vs. 0.2%; P equals .568) and sepsis (0.3% vs. 0.3%; P equals .865) in each group.

Dr. Mandelbaum attributed the high rate of oophorectomies in the study to “differential uptake of evidence” in different areas of the United States, fear of complications from leaving an infected ovary in situ, or the surgeon’s belief that the ovary is not viable because of its color intraoperatively. “We know from animal and human studies that the intraoperative appearance of the ovary does not correlate to viability, and that 90% of black or blue ovaries regain function and subsequently appear normal on both transvaginal ultrasound or on a second look grossly,” she said. Oophorectomy rates also vary by surgeon, and gynecologists are more likely to perform conservative surgery, she added.

The researchers said they were unable to obtain data on specific surgical variables such as the size of the mass, time to surgery, intraoperative appearance, laterality, fertility wishes of the patient, and surgeon type. There were also no postdischarge data, or information on the timing of complications.

Dr. Mandelbaum reported no relevant conflicts of interest.

SOURCE: Mandelbaum RS et al. ASRM 2019. Abstract O-96.

The REPLENISH trial evaluated the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4) approved by the US Food and Drug Administration in October 2018 as Bijuva (TherapeuticsMD) for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. In separate subanalyses presented at the annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019), researchers examined E2/P4’s ability to address VMS according to age and body mass index (BMI), ability to address sleep, and appropriate dosing in smokers versus nonsmokers.

REPLENISH

The REPLENISH trial was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the safety and efficacy of E2/P4 for the treatment of VMS in 1,835 postmenopausal women aged 40 to 65 years with a uterus. Women with moderate to severe VMS (≥7/day or ≥50/week) were randomly assigned to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo.¹

E2/P4 and VMS according to age and BMI

Percent changes in the weekly frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12 versus placebo were analyzed by age (<55 and ≥55 years) and BMI in the study participants.¹ The BMI subgroups had similar baseline VMS, but women in the younger age group had higher baseline frequency of moderate to severe VMS than women in the older age group.

Age. The percent changes in VMS frequency from baseline for women treated with E2/P4 were similar at weeks 4 and 12 between age groups. While subgroup analyses were not powered for statistical significance, significant differences were observed between E2/P4 dosages and placebo at week 12. For VMS severity, the percent changes from baseline for women treated with E2/P4 ranged from 16% to 22% at week 4 and 24% to 51% for either age group at week 12.

BMI. When analyzed by BMI, larger percent reductions from baseline in VMS frequency and severity were observed with E2/P4 dosaging versus placebo, with some groups meeting statistical significance at both weeks 4 and 12.

The authors concluded that their subgroup analyses show a consistency of efficacy for VMS frequency and severity among the different age group and BMI populations of women treated with E2/P4.

E2/P4 and sleep outcomes

Participants in the REPLENISH trial took 2 surveys related to sleep—the Medical Outcomes Study (MOS)-Sleep, a 12-item questionnaire measuring 6 sleep dimensions, and the Menopause-specific Quality of Life (MENQOL), which included a “difficulty sleeping” item.² Except for women treated with E2/P4 0.25/50 at week 12, women receiving E2/P4 reported significantly better change in the MOS-Sleep total, as well as better ratings on sleep problems and disturbance subscales, than women treated with placebo at week 12 and months 6 and 12. The incidence of somnolence was low with E2/P4 treatment. In addition, sleep mediation models showed that E2/P4 improved MOS-sleep disturbances indirectly through improvements in VMS. The study authors concluded that women taking E2/P4 for moderate to severe VMS may experience improved sleep.

Smoking and E2/P4 dosage

Among postmenopausal women, smoking has been shown to reduce the efficacy of hormone therapy.³ Researchers found that nonsmokers (never or past smokers) may benefit more from a lower E2/P4 dosage than current smokers (<15 cigarettes per day).⁴ (Women smoking ≥15 cigarettes per day or any e-cigarettes were excluded from REPLENISH). Compared with nonsmokers taking placebo, nonsmokers taking any dosage of E2/P4 had a significant and clinically meaningful reduction in VMS frequency and severity beginning at week 4 and maintained through week 12 (except for the E2/P4 dosage of 0.5/50 at week 4 for severity). By contrast, current smokers in any E2/P4 group had no significant VMS improvements from baseline to weeks 4 and 12 compared with placebo, and proportions of smokers who did measure some response to treatment (at both ≥50% and ≥75% levels) were not different from placebo at weeks 4 and 12. In addition, current smokers had significantly lower median levels of systemic estradiol and estrone concentrations with all E2/P4 treatment groups than did nonsmokers, despite both groups having similar estradiol and estrone concentrations at baseline.

The REPLENISH trial evaluated the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4) approved by the US Food and Drug Administration in October 2018 as Bijuva (TherapeuticsMD) for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. In separate subanalyses presented at the annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019), researchers examined E2/P4’s ability to address VMS according to age and body mass index (BMI), ability to address sleep, and appropriate dosing in smokers versus nonsmokers.

REPLENISH

The REPLENISH trial was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the safety and efficacy of E2/P4 for the treatment of VMS in 1,835 postmenopausal women aged 40 to 65 years with a uterus. Women with moderate to severe VMS (≥7/day or ≥50/week) were randomly assigned to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo.¹

E2/P4 and VMS according to age and BMI

Percent changes in the weekly frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12 versus placebo were analyzed by age (<55 and ≥55 years) and BMI in the study participants.¹ The BMI subgroups had similar baseline VMS, but women in the younger age group had higher baseline frequency of moderate to severe VMS than women in the older age group.

Age. The percent changes in VMS frequency from baseline for women treated with E2/P4 were similar at weeks 4 and 12 between age groups. While subgroup analyses were not powered for statistical significance, significant differences were observed between E2/P4 dosages and placebo at week 12. For VMS severity, the percent changes from baseline for women treated with E2/P4 ranged from 16% to 22% at week 4 and 24% to 51% for either age group at week 12.

BMI. When analyzed by BMI, larger percent reductions from baseline in VMS frequency and severity were observed with E2/P4 dosaging versus placebo, with some groups meeting statistical significance at both weeks 4 and 12.

The authors concluded that their subgroup analyses show a consistency of efficacy for VMS frequency and severity among the different age group and BMI populations of women treated with E2/P4.

E2/P4 and sleep outcomes

Participants in the REPLENISH trial took 2 surveys related to sleep—the Medical Outcomes Study (MOS)-Sleep, a 12-item questionnaire measuring 6 sleep dimensions, and the Menopause-specific Quality of Life (MENQOL), which included a “difficulty sleeping” item.² Except for women treated with E2/P4 0.25/50 at week 12, women receiving E2/P4 reported significantly better change in the MOS-Sleep total, as well as better ratings on sleep problems and disturbance subscales, than women treated with placebo at week 12 and months 6 and 12. The incidence of somnolence was low with E2/P4 treatment. In addition, sleep mediation models showed that E2/P4 improved MOS-sleep disturbances indirectly through improvements in VMS. The study authors concluded that women taking E2/P4 for moderate to severe VMS may experience improved sleep.

Smoking and E2/P4 dosage

Among postmenopausal women, smoking has been shown to reduce the efficacy of hormone therapy.³ Researchers found that nonsmokers (never or past smokers) may benefit more from a lower E2/P4 dosage than current smokers (<15 cigarettes per day).⁴ (Women smoking ≥15 cigarettes per day or any e-cigarettes were excluded from REPLENISH). Compared with nonsmokers taking placebo, nonsmokers taking any dosage of E2/P4 had a significant and clinically meaningful reduction in VMS frequency and severity beginning at week 4 and maintained through week 12 (except for the E2/P4 dosage of 0.5/50 at week 4 for severity). By contrast, current smokers in any E2/P4 group had no significant VMS improvements from baseline to weeks 4 and 12 compared with placebo, and proportions of smokers who did measure some response to treatment (at both ≥50% and ≥75% levels) were not different from placebo at weeks 4 and 12. In addition, current smokers had significantly lower median levels of systemic estradiol and estrone concentrations with all E2/P4 treatment groups than did nonsmokers, despite both groups having similar estradiol and estrone concentrations at baseline.

The REPLENISH trial evaluated the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4) approved by the US Food and Drug Administration in October 2018 as Bijuva (TherapeuticsMD) for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. In separate subanalyses presented at the annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019), researchers examined E2/P4’s ability to address VMS according to age and body mass index (BMI), ability to address sleep, and appropriate dosing in smokers versus nonsmokers.

REPLENISH

The REPLENISH trial was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the safety and efficacy of E2/P4 for the treatment of VMS in 1,835 postmenopausal women aged 40 to 65 years with a uterus. Women with moderate to severe VMS (≥7/day or ≥50/week) were randomly assigned to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo.¹

E2/P4 and VMS according to age and BMI

Percent changes in the weekly frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12 versus placebo were analyzed by age (<55 and ≥55 years) and BMI in the study participants.¹ The BMI subgroups had similar baseline VMS, but women in the younger age group had higher baseline frequency of moderate to severe VMS than women in the older age group.

Age. The percent changes in VMS frequency from baseline for women treated with E2/P4 were similar at weeks 4 and 12 between age groups. While subgroup analyses were not powered for statistical significance, significant differences were observed between E2/P4 dosages and placebo at week 12. For VMS severity, the percent changes from baseline for women treated with E2/P4 ranged from 16% to 22% at week 4 and 24% to 51% for either age group at week 12.

BMI. When analyzed by BMI, larger percent reductions from baseline in VMS frequency and severity were observed with E2/P4 dosaging versus placebo, with some groups meeting statistical significance at both weeks 4 and 12.

The authors concluded that their subgroup analyses show a consistency of efficacy for VMS frequency and severity among the different age group and BMI populations of women treated with E2/P4.

E2/P4 and sleep outcomes

Participants in the REPLENISH trial took 2 surveys related to sleep—the Medical Outcomes Study (MOS)-Sleep, a 12-item questionnaire measuring 6 sleep dimensions, and the Menopause-specific Quality of Life (MENQOL), which included a “difficulty sleeping” item.² Except for women treated with E2/P4 0.25/50 at week 12, women receiving E2/P4 reported significantly better change in the MOS-Sleep total, as well as better ratings on sleep problems and disturbance subscales, than women treated with placebo at week 12 and months 6 and 12. The incidence of somnolence was low with E2/P4 treatment. In addition, sleep mediation models showed that E2/P4 improved MOS-sleep disturbances indirectly through improvements in VMS. The study authors concluded that women taking E2/P4 for moderate to severe VMS may experience improved sleep.

Smoking and E2/P4 dosage

Among postmenopausal women, smoking has been shown to reduce the efficacy of hormone therapy.³ Researchers found that nonsmokers (never or past smokers) may benefit more from a lower E2/P4 dosage than current smokers (<15 cigarettes per day).⁴ (Women smoking ≥15 cigarettes per day or any e-cigarettes were excluded from REPLENISH). Compared with nonsmokers taking placebo, nonsmokers taking any dosage of E2/P4 had a significant and clinically meaningful reduction in VMS frequency and severity beginning at week 4 and maintained through week 12 (except for the E2/P4 dosage of 0.5/50 at week 4 for severity). By contrast, current smokers in any E2/P4 group had no significant VMS improvements from baseline to weeks 4 and 12 compared with placebo, and proportions of smokers who did measure some response to treatment (at both ≥50% and ≥75% levels) were not different from placebo at weeks 4 and 12. In addition, current smokers had significantly lower median levels of systemic estradiol and estrone concentrations with all E2/P4 treatment groups than did nonsmokers, despite both groups having similar estradiol and estrone concentrations at baseline.