Women's Health

TOPLINE:

About one in six women experience symptoms of postpartum depression (PPD) 2 months after cesarean delivery, with certain obstetric factors such as emergency cesarean delivery before labor, cesarean delivery after labor induction, lack of social support in the operating room, and severe postoperative pain influencing the risk.

METHODOLOGY:

• Researchers conducted a prospective ancillary cohort study of the Tranexamic Acid for Preventing Postpartum Hemorrhage after Cesarean Delivery (TRAAP2) trial to examine the prevalence of PPD 2 months after cesarean delivery and associated risk factors.
• A total of 2793 women (median age, 33.5 years) were included who had a cesarean delivery at 34 or more weeks of gestation; they completed the Edinburgh Postnatal Depression Scale (EPDS), a self-administered questionnaire, at 2 months after delivery.
• Information about the cesarean delivery, postpartum blood loss, immediate postpartum period, psychiatric history, and memories of delivery and postoperative pain were prospectively collected.
• Medical records were used to obtain details about characteristics of patients; 5.0% had a psychiatric history (2.4% composed of depression).
• The main endpoint was a positive screening for symptoms consistent with this depression — defined as a PPD diagnosis — 2 months after caesarian delivery, with an EPDS score of 13 or higher.

TAKEAWAY:

• The prevalence of a provisional PPD diagnosis at 2 months after cesarean delivery was 16.4% (95% CI, 14.9-18.0) with an EPDS score of 13 or higher and was 23.1% (95% CI, 21.4-24.9%) with a cutoff value of 11 or higher.
• Women who had an emergency cesarean delivery before labor had a higher risk for PPD than those who had a normal cesarean delivery before labor started (adjusted odds ratio [aOR], 1.70; 95% CI, 1.15-2.50); women who had started labor after induction but then had a cesarean delivery also had a higher risk for PPD than those who had a cesarean delivery before going into labor (aOR, 1.36; 95% CI, 1.03-1.84).
• Severe pain during the postpartum stay (aOR, 1.73; 95% CI, 1.32-2.26) and bad memories of delivery (aOR, 1.67; 95% CI, 1.14-2.45) were also risk factors for PPD.
• However, women who had social support in the operating room showed a 27% lower risk for PPD (P = .02).

IN PRACTICE:

“Identifying subgroups of women at risk for PPD based on aspects of their obstetric experience could help to screen for women who might benefit from early screening and interventions,” the authors wrote.

SOURCE:

This study was led by Alizée Froeliger, MD, MPH, of the Department of Obstetrics and Gynecology at Bordeaux University Hospital in France, and was published online in American Journal of Obstetrics & Gynecology.

LIMITATIONS:

The study population was derived from a randomized controlled trial, which may have underestimated the prevalence of PPD. The use of a self-administered questionnaire for PPD screening may not have provided a definitive diagnosis. Moreover, this study did not assess the prevalence of depressive symptoms during pregnancy.

DISCLOSURES:

The TRAAP2 trial was supported by a grant from the French Ministry of Health under its Clinical Research Hospital Program. One author reported carrying out consultancy work and lecturing for Ferring Laboratories, GlaxoSmithKline, and other pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About one in six women experience symptoms of postpartum depression (PPD) 2 months after cesarean delivery, with certain obstetric factors such as emergency cesarean delivery before labor, cesarean delivery after labor induction, lack of social support in the operating room, and severe postoperative pain influencing the risk.

METHODOLOGY:

• Researchers conducted a prospective ancillary cohort study of the Tranexamic Acid for Preventing Postpartum Hemorrhage after Cesarean Delivery (TRAAP2) trial to examine the prevalence of PPD 2 months after cesarean delivery and associated risk factors.
• A total of 2793 women (median age, 33.5 years) were included who had a cesarean delivery at 34 or more weeks of gestation; they completed the Edinburgh Postnatal Depression Scale (EPDS), a self-administered questionnaire, at 2 months after delivery.
• Information about the cesarean delivery, postpartum blood loss, immediate postpartum period, psychiatric history, and memories of delivery and postoperative pain were prospectively collected.
• Medical records were used to obtain details about characteristics of patients; 5.0% had a psychiatric history (2.4% composed of depression).
• The main endpoint was a positive screening for symptoms consistent with this depression — defined as a PPD diagnosis — 2 months after caesarian delivery, with an EPDS score of 13 or higher.

TAKEAWAY:

• The prevalence of a provisional PPD diagnosis at 2 months after cesarean delivery was 16.4% (95% CI, 14.9-18.0) with an EPDS score of 13 or higher and was 23.1% (95% CI, 21.4-24.9%) with a cutoff value of 11 or higher.
• Women who had an emergency cesarean delivery before labor had a higher risk for PPD than those who had a normal cesarean delivery before labor started (adjusted odds ratio [aOR], 1.70; 95% CI, 1.15-2.50); women who had started labor after induction but then had a cesarean delivery also had a higher risk for PPD than those who had a cesarean delivery before going into labor (aOR, 1.36; 95% CI, 1.03-1.84).
• Severe pain during the postpartum stay (aOR, 1.73; 95% CI, 1.32-2.26) and bad memories of delivery (aOR, 1.67; 95% CI, 1.14-2.45) were also risk factors for PPD.
• However, women who had social support in the operating room showed a 27% lower risk for PPD (P = .02).

IN PRACTICE:

“Identifying subgroups of women at risk for PPD based on aspects of their obstetric experience could help to screen for women who might benefit from early screening and interventions,” the authors wrote.

SOURCE:

This study was led by Alizée Froeliger, MD, MPH, of the Department of Obstetrics and Gynecology at Bordeaux University Hospital in France, and was published online in American Journal of Obstetrics & Gynecology.

LIMITATIONS:

The study population was derived from a randomized controlled trial, which may have underestimated the prevalence of PPD. The use of a self-administered questionnaire for PPD screening may not have provided a definitive diagnosis. Moreover, this study did not assess the prevalence of depressive symptoms during pregnancy.

DISCLOSURES:

The TRAAP2 trial was supported by a grant from the French Ministry of Health under its Clinical Research Hospital Program. One author reported carrying out consultancy work and lecturing for Ferring Laboratories, GlaxoSmithKline, and other pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

About one in six women experience symptoms of postpartum depression (PPD) 2 months after cesarean delivery, with certain obstetric factors such as emergency cesarean delivery before labor, cesarean delivery after labor induction, lack of social support in the operating room, and severe postoperative pain influencing the risk.

METHODOLOGY:

• Researchers conducted a prospective ancillary cohort study of the Tranexamic Acid for Preventing Postpartum Hemorrhage after Cesarean Delivery (TRAAP2) trial to examine the prevalence of PPD 2 months after cesarean delivery and associated risk factors.
• A total of 2793 women (median age, 33.5 years) were included who had a cesarean delivery at 34 or more weeks of gestation; they completed the Edinburgh Postnatal Depression Scale (EPDS), a self-administered questionnaire, at 2 months after delivery.
• Information about the cesarean delivery, postpartum blood loss, immediate postpartum period, psychiatric history, and memories of delivery and postoperative pain were prospectively collected.
• Medical records were used to obtain details about characteristics of patients; 5.0% had a psychiatric history (2.4% composed of depression).
• The main endpoint was a positive screening for symptoms consistent with this depression — defined as a PPD diagnosis — 2 months after caesarian delivery, with an EPDS score of 13 or higher.

TAKEAWAY:

• The prevalence of a provisional PPD diagnosis at 2 months after cesarean delivery was 16.4% (95% CI, 14.9-18.0) with an EPDS score of 13 or higher and was 23.1% (95% CI, 21.4-24.9%) with a cutoff value of 11 or higher.
• Women who had an emergency cesarean delivery before labor had a higher risk for PPD than those who had a normal cesarean delivery before labor started (adjusted odds ratio [aOR], 1.70; 95% CI, 1.15-2.50); women who had started labor after induction but then had a cesarean delivery also had a higher risk for PPD than those who had a cesarean delivery before going into labor (aOR, 1.36; 95% CI, 1.03-1.84).
• Severe pain during the postpartum stay (aOR, 1.73; 95% CI, 1.32-2.26) and bad memories of delivery (aOR, 1.67; 95% CI, 1.14-2.45) were also risk factors for PPD.
• However, women who had social support in the operating room showed a 27% lower risk for PPD (P = .02).

IN PRACTICE:

“Identifying subgroups of women at risk for PPD based on aspects of their obstetric experience could help to screen for women who might benefit from early screening and interventions,” the authors wrote.

SOURCE:

This study was led by Alizée Froeliger, MD, MPH, of the Department of Obstetrics and Gynecology at Bordeaux University Hospital in France, and was published online in American Journal of Obstetrics & Gynecology.

LIMITATIONS:

The study population was derived from a randomized controlled trial, which may have underestimated the prevalence of PPD. The use of a self-administered questionnaire for PPD screening may not have provided a definitive diagnosis. Moreover, this study did not assess the prevalence of depressive symptoms during pregnancy.

DISCLOSURES:

The TRAAP2 trial was supported by a grant from the French Ministry of Health under its Clinical Research Hospital Program. One author reported carrying out consultancy work and lecturing for Ferring Laboratories, GlaxoSmithKline, and other pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

People with central obesity (CO), characterized by excess fat around the abdomen, are at a greater risk for pelvic organ prolapse (POP), particularly those who are younger than 60 years or without a history of hysterectomy. Also, women who have overweight but do not have CO are at greater risk.

METHODOLOGY:

• Researchers conducted a prospective cohort study to estimate the association between CO and general obesity and the risk for POP in individuals using the UK Biobank.
• A total of 251,143 participants (median age, 57 years) without preexisting POP were included, of whom 60.9% were postmenopausal and 17.2% had undergone hysterectomy before enrollment.
• Participants were followed for a median duration of 13.8 years, and POP cases were identified using International Classification of Diseases, 10th Revision (ICD-10) codes.
• Waist circumference, height, and body weight were measured at enrollment for the calculation of waist/height ratio and body mass index (BMI); CO was defined as a waist/height ratio ≥ 0.5.
• The relative risk of POP for the various combinations of waist/height ratio and BMI was evaluated against the reference group (waist/height ratio < 0.5; BMI < 25) using Cox proportional hazards models.

TAKEAWAY:

• During the follow-up period, 9781 cases of POP were identified, of which 71.2% occurred in a single pelvic compartment.
• Around 21.7% of all POP cases were attributable to CO; 2% were attributable to being overweight without CO.
• The risk for POP was 48% higher in individuals with CO regardless of BMI (hazard ratio [HR], 1.48; 95% CI, 1.41-1.56) and 23% higher in those who had overweight without CO (HR, 1.23; 95% CI, 1.14-1.34).
• The association between POP and CO was further strengthened in individuals who were younger than 60 years and those without a history of hysterectomy.

IN PRACTICE:

“We found that waist/height ratio combined with BMI could help differentiate individuals with varying risks of prolapse more accurately. Among individuals within the same BMI category, waist/height ratio can vary, with those having a higher ratio generally facing a greater risk of POP, compared with those with a normal ratio. Therefore, they should not be grouped together based solely on a single measure of obesity. In addition, this combination can help identify more individuals at high risk for POP, compared with using either alone,” the study authors wrote.
 

SOURCE:

This study was led by Keyi Si, PhD, of Tongji University in Shanghai, China, and was published online in Obstetrics & Gynecology.

LIMITATIONS:

Differences in healthcare-seeking behavior could have biased the association between obesity and risk for POP, as individuals with obesity may have been less likely to notice or report symptoms of POP. The diagnosis of POP was according to ICD-10 codes rather than physical examination, which may have affected accuracy. Other limitations included missing data on delivery mode and history of constipation.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the Science and Technology Commission of Shanghai Municipality, the Shanghai Hospital Development Center, and the Shanghai First Maternity and Infant Hospital. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

People with central obesity (CO), characterized by excess fat around the abdomen, are at a greater risk for pelvic organ prolapse (POP), particularly those who are younger than 60 years or without a history of hysterectomy. Also, women who have overweight but do not have CO are at greater risk.

METHODOLOGY:

• Researchers conducted a prospective cohort study to estimate the association between CO and general obesity and the risk for POP in individuals using the UK Biobank.
• A total of 251,143 participants (median age, 57 years) without preexisting POP were included, of whom 60.9% were postmenopausal and 17.2% had undergone hysterectomy before enrollment.
• Participants were followed for a median duration of 13.8 years, and POP cases were identified using International Classification of Diseases, 10th Revision (ICD-10) codes.
• Waist circumference, height, and body weight were measured at enrollment for the calculation of waist/height ratio and body mass index (BMI); CO was defined as a waist/height ratio ≥ 0.5.
• The relative risk of POP for the various combinations of waist/height ratio and BMI was evaluated against the reference group (waist/height ratio < 0.5; BMI < 25) using Cox proportional hazards models.

TAKEAWAY:

• During the follow-up period, 9781 cases of POP were identified, of which 71.2% occurred in a single pelvic compartment.
• Around 21.7% of all POP cases were attributable to CO; 2% were attributable to being overweight without CO.
• The risk for POP was 48% higher in individuals with CO regardless of BMI (hazard ratio [HR], 1.48; 95% CI, 1.41-1.56) and 23% higher in those who had overweight without CO (HR, 1.23; 95% CI, 1.14-1.34).
• The association between POP and CO was further strengthened in individuals who were younger than 60 years and those without a history of hysterectomy.

IN PRACTICE:

“We found that waist/height ratio combined with BMI could help differentiate individuals with varying risks of prolapse more accurately. Among individuals within the same BMI category, waist/height ratio can vary, with those having a higher ratio generally facing a greater risk of POP, compared with those with a normal ratio. Therefore, they should not be grouped together based solely on a single measure of obesity. In addition, this combination can help identify more individuals at high risk for POP, compared with using either alone,” the study authors wrote.
 

SOURCE:

This study was led by Keyi Si, PhD, of Tongji University in Shanghai, China, and was published online in Obstetrics & Gynecology.

LIMITATIONS:

Differences in healthcare-seeking behavior could have biased the association between obesity and risk for POP, as individuals with obesity may have been less likely to notice or report symptoms of POP. The diagnosis of POP was according to ICD-10 codes rather than physical examination, which may have affected accuracy. Other limitations included missing data on delivery mode and history of constipation.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the Science and Technology Commission of Shanghai Municipality, the Shanghai Hospital Development Center, and the Shanghai First Maternity and Infant Hospital. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

People with central obesity (CO), characterized by excess fat around the abdomen, are at a greater risk for pelvic organ prolapse (POP), particularly those who are younger than 60 years or without a history of hysterectomy. Also, women who have overweight but do not have CO are at greater risk.

METHODOLOGY:

• Researchers conducted a prospective cohort study to estimate the association between CO and general obesity and the risk for POP in individuals using the UK Biobank.
• A total of 251,143 participants (median age, 57 years) without preexisting POP were included, of whom 60.9% were postmenopausal and 17.2% had undergone hysterectomy before enrollment.
• Participants were followed for a median duration of 13.8 years, and POP cases were identified using International Classification of Diseases, 10th Revision (ICD-10) codes.
• Waist circumference, height, and body weight were measured at enrollment for the calculation of waist/height ratio and body mass index (BMI); CO was defined as a waist/height ratio ≥ 0.5.
• The relative risk of POP for the various combinations of waist/height ratio and BMI was evaluated against the reference group (waist/height ratio < 0.5; BMI < 25) using Cox proportional hazards models.

TAKEAWAY:

• During the follow-up period, 9781 cases of POP were identified, of which 71.2% occurred in a single pelvic compartment.
• Around 21.7% of all POP cases were attributable to CO; 2% were attributable to being overweight without CO.
• The risk for POP was 48% higher in individuals with CO regardless of BMI (hazard ratio [HR], 1.48; 95% CI, 1.41-1.56) and 23% higher in those who had overweight without CO (HR, 1.23; 95% CI, 1.14-1.34).
• The association between POP and CO was further strengthened in individuals who were younger than 60 years and those without a history of hysterectomy.

IN PRACTICE:

“We found that waist/height ratio combined with BMI could help differentiate individuals with varying risks of prolapse more accurately. Among individuals within the same BMI category, waist/height ratio can vary, with those having a higher ratio generally facing a greater risk of POP, compared with those with a normal ratio. Therefore, they should not be grouped together based solely on a single measure of obesity. In addition, this combination can help identify more individuals at high risk for POP, compared with using either alone,” the study authors wrote.
 

SOURCE:

This study was led by Keyi Si, PhD, of Tongji University in Shanghai, China, and was published online in Obstetrics & Gynecology.

LIMITATIONS:

Differences in healthcare-seeking behavior could have biased the association between obesity and risk for POP, as individuals with obesity may have been less likely to notice or report symptoms of POP. The diagnosis of POP was according to ICD-10 codes rather than physical examination, which may have affected accuracy. Other limitations included missing data on delivery mode and history of constipation.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China, the Science and Technology Commission of Shanghai Municipality, the Shanghai Hospital Development Center, and the Shanghai First Maternity and Infant Hospital. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Weight loss interventions using medication or behavioral changes can improve insulin resistance, hormonal markers, and menstrual frequency in women with polycystic ovary syndrome (PCOS), according to a new meta-analysis. Losing weight may not significantly reduce hirsutism or improve quality of life in women with the condition, however.

METHODOLOGY:

• Researchers systematically reviewed randomized controlled trials comparing weight loss interventions to usual care in women with PCOS.
• They focused on 12 studies with behavioral interventions (mainly diets with modest energy deficits), nine trials that used glucagon-like peptide 1 (GLP-1) receptor agonists, and eight studies using other weight loss medications.
• A total of 1529 participants were included in the analysis.
• The investigators synthesized the data using a random-effects meta-analysis with Knapp-Hartung adjustment to examine pooled mean differences.

TAKEAWAY:

• Menstrual frequency increased by 2.64 menses per year (95% CI, 0.65-4.63) with weight loss interventions.
• “To our knowledge, this is the first review to show a clinically significant association in improvement in menstrual frequency with weight loss interventions, an important indicator of subsequent fertility and an important outcome for women,” the researchers wrote.
• Glycemic control also improved, with a mean reduction in homeostatic model assessment of insulin resistance of 0.45 (95% CI, –0.75 to –0.15).
• Free androgen index decreased by an average of 2.03 (95% CI, –3.0 to –1.07).

IN PRACTICE:

“Clinicians may use these findings to counsel women with PCOS on the expected improvements in PCOS markers after weight loss and direct patients toward interventions,” the authors of the study wrote. “Because weight loss programs are cost-effective interventions to improve cardiometabolic risk, they may be particularly valuable for this population at elevated risk.”

SOURCE:

The study was led by Jadine Scragg, PhD, with the Nuffield Department of Primary Care Health Sciences at the University of Oxford in England. It was published online in Annals of Internal Medicine.

LIMITATIONS:

Interventions using GLP-1 agonists were dosed for glycemic control rather than weight management. The studies in the meta-analysis were relatively few and heterogeneous. Data were insufficient to assess ovulation and acne.

DISCLOSURES:

The meta-analysis was supported by grants from the National Institute for Health and Care Research School for Primary Care Research. Authors disclosed ties to Nestlé Health Science and Second Nature.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Weight loss interventions using medication or behavioral changes can improve insulin resistance, hormonal markers, and menstrual frequency in women with polycystic ovary syndrome (PCOS), according to a new meta-analysis. Losing weight may not significantly reduce hirsutism or improve quality of life in women with the condition, however.

METHODOLOGY:

• Researchers systematically reviewed randomized controlled trials comparing weight loss interventions to usual care in women with PCOS.
• They focused on 12 studies with behavioral interventions (mainly diets with modest energy deficits), nine trials that used glucagon-like peptide 1 (GLP-1) receptor agonists, and eight studies using other weight loss medications.
• A total of 1529 participants were included in the analysis.
• The investigators synthesized the data using a random-effects meta-analysis with Knapp-Hartung adjustment to examine pooled mean differences.

TAKEAWAY:

• Menstrual frequency increased by 2.64 menses per year (95% CI, 0.65-4.63) with weight loss interventions.
• “To our knowledge, this is the first review to show a clinically significant association in improvement in menstrual frequency with weight loss interventions, an important indicator of subsequent fertility and an important outcome for women,” the researchers wrote.
• Glycemic control also improved, with a mean reduction in homeostatic model assessment of insulin resistance of 0.45 (95% CI, –0.75 to –0.15).
• Free androgen index decreased by an average of 2.03 (95% CI, –3.0 to –1.07).

IN PRACTICE:

“Clinicians may use these findings to counsel women with PCOS on the expected improvements in PCOS markers after weight loss and direct patients toward interventions,” the authors of the study wrote. “Because weight loss programs are cost-effective interventions to improve cardiometabolic risk, they may be particularly valuable for this population at elevated risk.”

SOURCE:

The study was led by Jadine Scragg, PhD, with the Nuffield Department of Primary Care Health Sciences at the University of Oxford in England. It was published online in Annals of Internal Medicine.

LIMITATIONS:

Interventions using GLP-1 agonists were dosed for glycemic control rather than weight management. The studies in the meta-analysis were relatively few and heterogeneous. Data were insufficient to assess ovulation and acne.

DISCLOSURES:

The meta-analysis was supported by grants from the National Institute for Health and Care Research School for Primary Care Research. Authors disclosed ties to Nestlé Health Science and Second Nature.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Weight loss interventions using medication or behavioral changes can improve insulin resistance, hormonal markers, and menstrual frequency in women with polycystic ovary syndrome (PCOS), according to a new meta-analysis. Losing weight may not significantly reduce hirsutism or improve quality of life in women with the condition, however.

METHODOLOGY:

• Researchers systematically reviewed randomized controlled trials comparing weight loss interventions to usual care in women with PCOS.
• They focused on 12 studies with behavioral interventions (mainly diets with modest energy deficits), nine trials that used glucagon-like peptide 1 (GLP-1) receptor agonists, and eight studies using other weight loss medications.
• A total of 1529 participants were included in the analysis.
• The investigators synthesized the data using a random-effects meta-analysis with Knapp-Hartung adjustment to examine pooled mean differences.

TAKEAWAY:

• Menstrual frequency increased by 2.64 menses per year (95% CI, 0.65-4.63) with weight loss interventions.
• “To our knowledge, this is the first review to show a clinically significant association in improvement in menstrual frequency with weight loss interventions, an important indicator of subsequent fertility and an important outcome for women,” the researchers wrote.
• Glycemic control also improved, with a mean reduction in homeostatic model assessment of insulin resistance of 0.45 (95% CI, –0.75 to –0.15).
• Free androgen index decreased by an average of 2.03 (95% CI, –3.0 to –1.07).

IN PRACTICE:

“Clinicians may use these findings to counsel women with PCOS on the expected improvements in PCOS markers after weight loss and direct patients toward interventions,” the authors of the study wrote. “Because weight loss programs are cost-effective interventions to improve cardiometabolic risk, they may be particularly valuable for this population at elevated risk.”

SOURCE:

The study was led by Jadine Scragg, PhD, with the Nuffield Department of Primary Care Health Sciences at the University of Oxford in England. It was published online in Annals of Internal Medicine.

LIMITATIONS:

Interventions using GLP-1 agonists were dosed for glycemic control rather than weight management. The studies in the meta-analysis were relatively few and heterogeneous. Data were insufficient to assess ovulation and acne.

DISCLOSURES:

The meta-analysis was supported by grants from the National Institute for Health and Care Research School for Primary Care Research. Authors disclosed ties to Nestlé Health Science and Second Nature.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In women with polycystic ovary syndrome (PCOS) and with obesity or overweight, the combination of topiramate and metformin along with a low-calorie diet can result in effective weight loss and improve androgen levels, lipid levels, and psychosocial scores, without any serious adverse events.

METHODOLOGY:

• Topiramate is often used off-label for weight loss and may be a promising option added to a metformin regimen to improve cardiometabolic and reproductive health in women with PCOS and obesity or overweight when lifestyle changes alone fall short.
• This double-blind trial conducted at Hospital de Clínicas de Porto Alegre in Porto Alegre, Brazil, evaluated the effects of adding topiramate to metformin in 61 women aged 14-40 years with PCOS and body mass index (BMI) ≥ 30 or BMI ≥ 27 with concurrent hypertension, type 2 diabetes, or dyslipidemia.
• All participants were prescribed a 20 kcal/kg diet, as well as desogestrel for contraception during the study, and either started on 850 mg metformin or continued with their existing metformin regimen.
• They were randomly assigned to receive either topiramate or placebo (25 mg for 15 days and then 50 mg at night) along with metformin, with dose adjustments based on weight loss at 3 months.
• The primary outcome was the percent change in body weight from baseline, and the secondary outcomes included changes in clinical, cardiometabolic, and hormonal parameters and psychosocial features at 3 and 6 months.

TAKEAWAY:

• Topiramate combined with metformin resulted in greater mean weight loss at 3 months (−3.4% vs −1.6%; P = .03) and 6 months (−4.5% vs −1.4%; P = .03) than placebo plus metformin.
• Both treatment groups showed improvements in androgen and lipid levels and psychosocial scores, while the levels of C-reactive protein decreased only in the topiramate plus metformin group.
• Women who experienced ≥ 3% weight loss at 6 months showed a significant improvement in hirsutism scores (change in modified Ferriman-Gallwey scores, 8.4-6.5), unlike those who experienced < 3% weight loss (change in modified Ferriman-Gallwey scores, 8.02-8.78).
• Paresthesia was more common in the topiramate plus metformin group than in the metformin plus placebo group (23.3% vs 3.2%), but no serious adverse events were reported.

IN PRACTICE:

“In the era of new effective drugs for treating obesity, topiramate with metformin can be an option for women with obesity and PCOS, considering its low cost, reports of long-term experience with this medication, and ease to use,” the authors wrote.

SOURCE:

The study was led by Lucas Bandeira Marchesan, Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The small sample size and high attrition rates were major limitations of this study. Increasing the topiramate dose at 3 months in those with < 3% weight loss did not provide additional benefit, and this study did not test for a higher topiramate dose response from the beginning, which could have potentially provided a better response to the medication. The small sample size of the study also prevented the authors from conducting a subgroup analysis.

DISCLOSURES:

The study was supported by research grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In women with polycystic ovary syndrome (PCOS) and with obesity or overweight, the combination of topiramate and metformin along with a low-calorie diet can result in effective weight loss and improve androgen levels, lipid levels, and psychosocial scores, without any serious adverse events.

METHODOLOGY:

• Topiramate is often used off-label for weight loss and may be a promising option added to a metformin regimen to improve cardiometabolic and reproductive health in women with PCOS and obesity or overweight when lifestyle changes alone fall short.
• This double-blind trial conducted at Hospital de Clínicas de Porto Alegre in Porto Alegre, Brazil, evaluated the effects of adding topiramate to metformin in 61 women aged 14-40 years with PCOS and body mass index (BMI) ≥ 30 or BMI ≥ 27 with concurrent hypertension, type 2 diabetes, or dyslipidemia.
• All participants were prescribed a 20 kcal/kg diet, as well as desogestrel for contraception during the study, and either started on 850 mg metformin or continued with their existing metformin regimen.
• They were randomly assigned to receive either topiramate or placebo (25 mg for 15 days and then 50 mg at night) along with metformin, with dose adjustments based on weight loss at 3 months.
• The primary outcome was the percent change in body weight from baseline, and the secondary outcomes included changes in clinical, cardiometabolic, and hormonal parameters and psychosocial features at 3 and 6 months.

TAKEAWAY:

• Topiramate combined with metformin resulted in greater mean weight loss at 3 months (−3.4% vs −1.6%; P = .03) and 6 months (−4.5% vs −1.4%; P = .03) than placebo plus metformin.
• Both treatment groups showed improvements in androgen and lipid levels and psychosocial scores, while the levels of C-reactive protein decreased only in the topiramate plus metformin group.
• Women who experienced ≥ 3% weight loss at 6 months showed a significant improvement in hirsutism scores (change in modified Ferriman-Gallwey scores, 8.4-6.5), unlike those who experienced < 3% weight loss (change in modified Ferriman-Gallwey scores, 8.02-8.78).
• Paresthesia was more common in the topiramate plus metformin group than in the metformin plus placebo group (23.3% vs 3.2%), but no serious adverse events were reported.

IN PRACTICE:

“In the era of new effective drugs for treating obesity, topiramate with metformin can be an option for women with obesity and PCOS, considering its low cost, reports of long-term experience with this medication, and ease to use,” the authors wrote.

SOURCE:

The study was led by Lucas Bandeira Marchesan, Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The small sample size and high attrition rates were major limitations of this study. Increasing the topiramate dose at 3 months in those with < 3% weight loss did not provide additional benefit, and this study did not test for a higher topiramate dose response from the beginning, which could have potentially provided a better response to the medication. The small sample size of the study also prevented the authors from conducting a subgroup analysis.

DISCLOSURES:

The study was supported by research grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In women with polycystic ovary syndrome (PCOS) and with obesity or overweight, the combination of topiramate and metformin along with a low-calorie diet can result in effective weight loss and improve androgen levels, lipid levels, and psychosocial scores, without any serious adverse events.

METHODOLOGY:

• Topiramate is often used off-label for weight loss and may be a promising option added to a metformin regimen to improve cardiometabolic and reproductive health in women with PCOS and obesity or overweight when lifestyle changes alone fall short.
• This double-blind trial conducted at Hospital de Clínicas de Porto Alegre in Porto Alegre, Brazil, evaluated the effects of adding topiramate to metformin in 61 women aged 14-40 years with PCOS and body mass index (BMI) ≥ 30 or BMI ≥ 27 with concurrent hypertension, type 2 diabetes, or dyslipidemia.
• All participants were prescribed a 20 kcal/kg diet, as well as desogestrel for contraception during the study, and either started on 850 mg metformin or continued with their existing metformin regimen.
• They were randomly assigned to receive either topiramate or placebo (25 mg for 15 days and then 50 mg at night) along with metformin, with dose adjustments based on weight loss at 3 months.
• The primary outcome was the percent change in body weight from baseline, and the secondary outcomes included changes in clinical, cardiometabolic, and hormonal parameters and psychosocial features at 3 and 6 months.

TAKEAWAY:

• Topiramate combined with metformin resulted in greater mean weight loss at 3 months (−3.4% vs −1.6%; P = .03) and 6 months (−4.5% vs −1.4%; P = .03) than placebo plus metformin.
• Both treatment groups showed improvements in androgen and lipid levels and psychosocial scores, while the levels of C-reactive protein decreased only in the topiramate plus metformin group.
• Women who experienced ≥ 3% weight loss at 6 months showed a significant improvement in hirsutism scores (change in modified Ferriman-Gallwey scores, 8.4-6.5), unlike those who experienced < 3% weight loss (change in modified Ferriman-Gallwey scores, 8.02-8.78).
• Paresthesia was more common in the topiramate plus metformin group than in the metformin plus placebo group (23.3% vs 3.2%), but no serious adverse events were reported.

IN PRACTICE:

“In the era of new effective drugs for treating obesity, topiramate with metformin can be an option for women with obesity and PCOS, considering its low cost, reports of long-term experience with this medication, and ease to use,” the authors wrote.

SOURCE:

The study was led by Lucas Bandeira Marchesan, Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The small sample size and high attrition rates were major limitations of this study. Increasing the topiramate dose at 3 months in those with < 3% weight loss did not provide additional benefit, and this study did not test for a higher topiramate dose response from the beginning, which could have potentially provided a better response to the medication. The small sample size of the study also prevented the authors from conducting a subgroup analysis.

DISCLOSURES:

The study was supported by research grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Vaccination against human papilloma virus (HPV), a group of more than 200 viruses infecting at least 50% of sexually active people over their lifetimes, has proved more than 90% effective for preventing several diseases caused by high-risk HPV types. 

Gardasil 4: 2006 

It started in 2006 with the approval of Human Papillomavirus Quadrivalent, types 6, 11, 16, and 18 (Gardasil 4). Merck’s vaccine began to lower rates of cervical cancer, a major global killer of women.

“It’s fair to say the vaccine has been an American and a global public health success story in reducing rates of cervical cancer,” Paula M. Cuccaro, PhD, assistant professor of health promotion and behavioral sciences at University of Texas School of Public Health, Houston, said in an interview.

How does a common virus trigger such a lethal gynecologic malignancy? “It knocks out two important cancer suppressor genes in cells,” explained Christina Annunziata,MD, PhD, a medical oncologist and senior vice president of extramural discovery science for the American Cancer Society. HPV oncoproteins are encoded by the E6 and E7 genes. As in other DNA tumor viruses, the E6 and E7 proteins functionally inactivate the tumor suppressor proteins p53 and pRB, respectively.
 

US Prevalence

Despite screening and vaccination, cervical cancer is still very much around. This year, 13,820 new cases of invasive cervical cancer will be diagnosed in the United States, and approximately 4360 women will die of it, according to the American Cancer Society. Even before the advent of Gardasil 4, incidence rates had already decreased by more than half from the mid-1970s to the mid-2000s, thanks largely to Pap smear screening programs for treatable premalignant lesions. “The US rate had dropped to about 20 per 100,000 women even before Gardasil 4,” said Annunziata. “After the introduction of the first vaccine, it decreased to 7 per 100,000, a decrease of about 30%, but it remains plateaued now at about the same level.”

Although the past decade has seen rates generally stabilize, there have been some changes in different age groups. In women ages 30-44, rates increased 1.7% each year from 2012 to 2019, while rates declined 11% each year for women ages 20-24— probably reflecting the impact of the first wave of prevention from Gardasil 4.

In one 2021 population-based study of US cancer registry data from 1999 to 2017, rates of both cervical squamous cell carcinoma and adenocarcinoma dropped. The largest declines occurred in females 15-20 years old, the age group most likely to be vaccinated against HPV but not typically screened, suggesting a vaccine-related effect.
 

Gardasil 9: 2014

With the 2014 approval of the vaccine’s second iteration, Gardasil 9, which replaced Gardasil 4 and targeted 9 HPV strains, immunization has taken broader aim. The strains covered by Gardasil 9 protect against oropharyngeal and other head and neck cancers — as well as penile, anal, vulvar, and vaginal malignancies and premalignancies, and genital warts in both sexes ages 9-45. 

It may be years, however, before the impact of the newer polyvalent formulation is felt. “While the first vaccine has been successful against the prevalent strains of HPV linked to cervical cancer, it’s a little early to call it for the newer vaccine since oropharyngeal cancers tend to develop later in older men,” Cuccaro said. “But the types of HPV linked to mouth and throat cancers and covered by the newer vaccines are much less prevalent in those who are vaccinated. The strains not covered in the vaccine you see are equally present in the vaccinated and non-vaccinated.”

Angela L. Myers, MD, MPH, division director of infectious diseases and medical director of the Center for Wellbeing at Children’s Mercy in Kansas City, Missouri, added, “Unlike for cervical cancer, there are no screening programs for oropharyngeal lesions, so you have to wait to see rates until actual cancer develops.”

A 2023 review reported that HPV vaccination reduced levels of oropharyngeal HPV positivity in men, strengthening the case for pangender immunization. 

And in a recent phase 3 doubled-blind trial, GARDASIL 9 reduced the incidence of anogenital persistent infection caused by nine types of HPV compared with a placebo. 
 

Increasing Uptake

The current public health aim is to have 80% of young people in the targeted age group vaccinated with two doses. Today, uptake among those 9-26 years old stands at about 78% of girls and 75% of boys for the first dose, said Annunziata. “But it’s only about 61% for the two doses in the current series, and we want to improve that.” 

Some parents may still harbor fears that immunizing teens and tweens — both the American Academy of Pediatrics and the American Cancer Society recommend immunization at age 9 — will open the door to precocious sexual activity. 

“But overall, uptake in tweens and young teens has increased because the messaging has changed,” said Myers, with the rationale now focusing on cancer prevention not sexual-infection prophylaxis. “This is similar to the hepatitis B vaccine, which used to be given to young adults and is now given to newborns to prevent cancer.” 

Cuccaro added that a proactive presentation by healthcare professionals has a significant effect on vaccine uptake and increases the odds of vaccination ninefold. “Providers should take a presumptive approach and avoid just offering the vaccine as an option. It should be included with regular childhood vaccinations,” she said. “And the advantage of starting early at age 9 is that you can spread the doses out across other regular childhood vaccinations, whereas if you start at age 11, you need to add the HPV vaccine to three other vaccines that are given at that time.” 

After age 15, three doses are necessary. “Providers should stress to parents that it’s most effective when given before young people become sexually active and exposed to HPV,” Cuccaro said. And Myers stressed that despite the vaccine’s effectiveness, routine screening for cervical premalignancies is still important. 

Despite increasing coverage, vaccination rates have some distance to go before the public health target of at least 80% uptake of the series in the targeted age group, Cuccaro cautioned.

On the global stage, barriers to immunization remain, but the World Health Organization has endorsed a campaign to eradicate cervical cancer through HPV vaccination. It has predicted that the 21st century may be the last to experience HPV-associated cancers, currently responsible for more than 300,000 annual deaths worldwide.
 

A Brief History of HPV Vaccines

• 1951. Cervical cancer patient Henrietta Lacks’ rapidly dividing cervical cells are collected by George Otto Gey at Johns Hopkins Hospital. They create the first immortal cell line (HeLa) used to study cancers and vaccines worldwide.
• 1976. Harald zur Hausen suggests that genital wart-associated HPV, not herpes simplex, is the probable cause of cervical cancer.
• 1983. HPV is confirmed as a cause of cancer.
• 1991. The first HPV vaccine is developed.
• 2002. Proof of principle and protective efficacy for the monovalent HPV 16 are shown.
• 2006. Merck’s Gardasil 4 (HPV 4) is FDA approved in girls ages 9-26 for protection against strains 6, 11, 16, and 18 — the cause of more than 70% of cervical cancer cases.
• 2009. Approval of Gardasil 4 is expanded to boys ages 9-26 for the prevention of genital warts.
• 2009. The FDA approves GlaxoSmithKline’s Cervarix (HPV 16 and 18) for girls and young women. The vaccine was withdrawn from the US market in 2016 following the success of Gardasil 9 but is used abroad for HPV cancer prevention.
• 2014. The 9-valent recombinant vaccine Gardasil 9 is FDA approved for protection against several low-risk, wart-causing HPV strains as well as the high-risk cancer strains targeted by HPV 4.
• 2018. The FDA expands approval to include females and males 27-45 years old.
• 2020. The FDA extends approval of Gardasil 9 to include prevention not only of cervical cancer but also, vaginal, vulvar, anal, oropharyngeal, and other head and neck cancers.

Annunziata, Cuccaro, and Myers had no competing interests to declare.
 

A version of this article appeared on Medscape.com.

Vaccination against human papilloma virus (HPV), a group of more than 200 viruses infecting at least 50% of sexually active people over their lifetimes, has proved more than 90% effective for preventing several diseases caused by high-risk HPV types. 

Gardasil 4: 2006 

It started in 2006 with the approval of Human Papillomavirus Quadrivalent, types 6, 11, 16, and 18 (Gardasil 4). Merck’s vaccine began to lower rates of cervical cancer, a major global killer of women.

“It’s fair to say the vaccine has been an American and a global public health success story in reducing rates of cervical cancer,” Paula M. Cuccaro, PhD, assistant professor of health promotion and behavioral sciences at University of Texas School of Public Health, Houston, said in an interview.

How does a common virus trigger such a lethal gynecologic malignancy? “It knocks out two important cancer suppressor genes in cells,” explained Christina Annunziata,MD, PhD, a medical oncologist and senior vice president of extramural discovery science for the American Cancer Society. HPV oncoproteins are encoded by the E6 and E7 genes. As in other DNA tumor viruses, the E6 and E7 proteins functionally inactivate the tumor suppressor proteins p53 and pRB, respectively.
 

US Prevalence

Despite screening and vaccination, cervical cancer is still very much around. This year, 13,820 new cases of invasive cervical cancer will be diagnosed in the United States, and approximately 4360 women will die of it, according to the American Cancer Society. Even before the advent of Gardasil 4, incidence rates had already decreased by more than half from the mid-1970s to the mid-2000s, thanks largely to Pap smear screening programs for treatable premalignant lesions. “The US rate had dropped to about 20 per 100,000 women even before Gardasil 4,” said Annunziata. “After the introduction of the first vaccine, it decreased to 7 per 100,000, a decrease of about 30%, but it remains plateaued now at about the same level.”

Although the past decade has seen rates generally stabilize, there have been some changes in different age groups. In women ages 30-44, rates increased 1.7% each year from 2012 to 2019, while rates declined 11% each year for women ages 20-24— probably reflecting the impact of the first wave of prevention from Gardasil 4.

In one 2021 population-based study of US cancer registry data from 1999 to 2017, rates of both cervical squamous cell carcinoma and adenocarcinoma dropped. The largest declines occurred in females 15-20 years old, the age group most likely to be vaccinated against HPV but not typically screened, suggesting a vaccine-related effect.
 

Gardasil 9: 2014

With the 2014 approval of the vaccine’s second iteration, Gardasil 9, which replaced Gardasil 4 and targeted 9 HPV strains, immunization has taken broader aim. The strains covered by Gardasil 9 protect against oropharyngeal and other head and neck cancers — as well as penile, anal, vulvar, and vaginal malignancies and premalignancies, and genital warts in both sexes ages 9-45. 

It may be years, however, before the impact of the newer polyvalent formulation is felt. “While the first vaccine has been successful against the prevalent strains of HPV linked to cervical cancer, it’s a little early to call it for the newer vaccine since oropharyngeal cancers tend to develop later in older men,” Cuccaro said. “But the types of HPV linked to mouth and throat cancers and covered by the newer vaccines are much less prevalent in those who are vaccinated. The strains not covered in the vaccine you see are equally present in the vaccinated and non-vaccinated.”

Angela L. Myers, MD, MPH, division director of infectious diseases and medical director of the Center for Wellbeing at Children’s Mercy in Kansas City, Missouri, added, “Unlike for cervical cancer, there are no screening programs for oropharyngeal lesions, so you have to wait to see rates until actual cancer develops.”

A 2023 review reported that HPV vaccination reduced levels of oropharyngeal HPV positivity in men, strengthening the case for pangender immunization. 

And in a recent phase 3 doubled-blind trial, GARDASIL 9 reduced the incidence of anogenital persistent infection caused by nine types of HPV compared with a placebo. 
 

Increasing Uptake

The current public health aim is to have 80% of young people in the targeted age group vaccinated with two doses. Today, uptake among those 9-26 years old stands at about 78% of girls and 75% of boys for the first dose, said Annunziata. “But it’s only about 61% for the two doses in the current series, and we want to improve that.” 

Some parents may still harbor fears that immunizing teens and tweens — both the American Academy of Pediatrics and the American Cancer Society recommend immunization at age 9 — will open the door to precocious sexual activity. 

“But overall, uptake in tweens and young teens has increased because the messaging has changed,” said Myers, with the rationale now focusing on cancer prevention not sexual-infection prophylaxis. “This is similar to the hepatitis B vaccine, which used to be given to young adults and is now given to newborns to prevent cancer.” 

Cuccaro added that a proactive presentation by healthcare professionals has a significant effect on vaccine uptake and increases the odds of vaccination ninefold. “Providers should take a presumptive approach and avoid just offering the vaccine as an option. It should be included with regular childhood vaccinations,” she said. “And the advantage of starting early at age 9 is that you can spread the doses out across other regular childhood vaccinations, whereas if you start at age 11, you need to add the HPV vaccine to three other vaccines that are given at that time.” 

After age 15, three doses are necessary. “Providers should stress to parents that it’s most effective when given before young people become sexually active and exposed to HPV,” Cuccaro said. And Myers stressed that despite the vaccine’s effectiveness, routine screening for cervical premalignancies is still important. 

Despite increasing coverage, vaccination rates have some distance to go before the public health target of at least 80% uptake of the series in the targeted age group, Cuccaro cautioned.

On the global stage, barriers to immunization remain, but the World Health Organization has endorsed a campaign to eradicate cervical cancer through HPV vaccination. It has predicted that the 21st century may be the last to experience HPV-associated cancers, currently responsible for more than 300,000 annual deaths worldwide.
 

A Brief History of HPV Vaccines

• 1951. Cervical cancer patient Henrietta Lacks’ rapidly dividing cervical cells are collected by George Otto Gey at Johns Hopkins Hospital. They create the first immortal cell line (HeLa) used to study cancers and vaccines worldwide.
• 1976. Harald zur Hausen suggests that genital wart-associated HPV, not herpes simplex, is the probable cause of cervical cancer.
• 1983. HPV is confirmed as a cause of cancer.
• 1991. The first HPV vaccine is developed.
• 2002. Proof of principle and protective efficacy for the monovalent HPV 16 are shown.
• 2006. Merck’s Gardasil 4 (HPV 4) is FDA approved in girls ages 9-26 for protection against strains 6, 11, 16, and 18 — the cause of more than 70% of cervical cancer cases.
• 2009. Approval of Gardasil 4 is expanded to boys ages 9-26 for the prevention of genital warts.
• 2009. The FDA approves GlaxoSmithKline’s Cervarix (HPV 16 and 18) for girls and young women. The vaccine was withdrawn from the US market in 2016 following the success of Gardasil 9 but is used abroad for HPV cancer prevention.
• 2014. The 9-valent recombinant vaccine Gardasil 9 is FDA approved for protection against several low-risk, wart-causing HPV strains as well as the high-risk cancer strains targeted by HPV 4.
• 2018. The FDA expands approval to include females and males 27-45 years old.
• 2020. The FDA extends approval of Gardasil 9 to include prevention not only of cervical cancer but also, vaginal, vulvar, anal, oropharyngeal, and other head and neck cancers.

Annunziata, Cuccaro, and Myers had no competing interests to declare.
 

A version of this article appeared on Medscape.com.

Vaccination against human papilloma virus (HPV), a group of more than 200 viruses infecting at least 50% of sexually active people over their lifetimes, has proved more than 90% effective for preventing several diseases caused by high-risk HPV types. 

Gardasil 4: 2006 

It started in 2006 with the approval of Human Papillomavirus Quadrivalent, types 6, 11, 16, and 18 (Gardasil 4). Merck’s vaccine began to lower rates of cervical cancer, a major global killer of women.

“It’s fair to say the vaccine has been an American and a global public health success story in reducing rates of cervical cancer,” Paula M. Cuccaro, PhD, assistant professor of health promotion and behavioral sciences at University of Texas School of Public Health, Houston, said in an interview.

How does a common virus trigger such a lethal gynecologic malignancy? “It knocks out two important cancer suppressor genes in cells,” explained Christina Annunziata,MD, PhD, a medical oncologist and senior vice president of extramural discovery science for the American Cancer Society. HPV oncoproteins are encoded by the E6 and E7 genes. As in other DNA tumor viruses, the E6 and E7 proteins functionally inactivate the tumor suppressor proteins p53 and pRB, respectively.
 

US Prevalence

Despite screening and vaccination, cervical cancer is still very much around. This year, 13,820 new cases of invasive cervical cancer will be diagnosed in the United States, and approximately 4360 women will die of it, according to the American Cancer Society. Even before the advent of Gardasil 4, incidence rates had already decreased by more than half from the mid-1970s to the mid-2000s, thanks largely to Pap smear screening programs for treatable premalignant lesions. “The US rate had dropped to about 20 per 100,000 women even before Gardasil 4,” said Annunziata. “After the introduction of the first vaccine, it decreased to 7 per 100,000, a decrease of about 30%, but it remains plateaued now at about the same level.”

Although the past decade has seen rates generally stabilize, there have been some changes in different age groups. In women ages 30-44, rates increased 1.7% each year from 2012 to 2019, while rates declined 11% each year for women ages 20-24— probably reflecting the impact of the first wave of prevention from Gardasil 4.

In one 2021 population-based study of US cancer registry data from 1999 to 2017, rates of both cervical squamous cell carcinoma and adenocarcinoma dropped. The largest declines occurred in females 15-20 years old, the age group most likely to be vaccinated against HPV but not typically screened, suggesting a vaccine-related effect.
 

Gardasil 9: 2014

With the 2014 approval of the vaccine’s second iteration, Gardasil 9, which replaced Gardasil 4 and targeted 9 HPV strains, immunization has taken broader aim. The strains covered by Gardasil 9 protect against oropharyngeal and other head and neck cancers — as well as penile, anal, vulvar, and vaginal malignancies and premalignancies, and genital warts in both sexes ages 9-45. 

It may be years, however, before the impact of the newer polyvalent formulation is felt. “While the first vaccine has been successful against the prevalent strains of HPV linked to cervical cancer, it’s a little early to call it for the newer vaccine since oropharyngeal cancers tend to develop later in older men,” Cuccaro said. “But the types of HPV linked to mouth and throat cancers and covered by the newer vaccines are much less prevalent in those who are vaccinated. The strains not covered in the vaccine you see are equally present in the vaccinated and non-vaccinated.”

Angela L. Myers, MD, MPH, division director of infectious diseases and medical director of the Center for Wellbeing at Children’s Mercy in Kansas City, Missouri, added, “Unlike for cervical cancer, there are no screening programs for oropharyngeal lesions, so you have to wait to see rates until actual cancer develops.”

A 2023 review reported that HPV vaccination reduced levels of oropharyngeal HPV positivity in men, strengthening the case for pangender immunization. 

And in a recent phase 3 doubled-blind trial, GARDASIL 9 reduced the incidence of anogenital persistent infection caused by nine types of HPV compared with a placebo. 
 

Increasing Uptake

The current public health aim is to have 80% of young people in the targeted age group vaccinated with two doses. Today, uptake among those 9-26 years old stands at about 78% of girls and 75% of boys for the first dose, said Annunziata. “But it’s only about 61% for the two doses in the current series, and we want to improve that.” 

Some parents may still harbor fears that immunizing teens and tweens — both the American Academy of Pediatrics and the American Cancer Society recommend immunization at age 9 — will open the door to precocious sexual activity. 

“But overall, uptake in tweens and young teens has increased because the messaging has changed,” said Myers, with the rationale now focusing on cancer prevention not sexual-infection prophylaxis. “This is similar to the hepatitis B vaccine, which used to be given to young adults and is now given to newborns to prevent cancer.” 

Cuccaro added that a proactive presentation by healthcare professionals has a significant effect on vaccine uptake and increases the odds of vaccination ninefold. “Providers should take a presumptive approach and avoid just offering the vaccine as an option. It should be included with regular childhood vaccinations,” she said. “And the advantage of starting early at age 9 is that you can spread the doses out across other regular childhood vaccinations, whereas if you start at age 11, you need to add the HPV vaccine to three other vaccines that are given at that time.” 

After age 15, three doses are necessary. “Providers should stress to parents that it’s most effective when given before young people become sexually active and exposed to HPV,” Cuccaro said. And Myers stressed that despite the vaccine’s effectiveness, routine screening for cervical premalignancies is still important. 

Despite increasing coverage, vaccination rates have some distance to go before the public health target of at least 80% uptake of the series in the targeted age group, Cuccaro cautioned.

On the global stage, barriers to immunization remain, but the World Health Organization has endorsed a campaign to eradicate cervical cancer through HPV vaccination. It has predicted that the 21st century may be the last to experience HPV-associated cancers, currently responsible for more than 300,000 annual deaths worldwide.
 

A Brief History of HPV Vaccines

• 1951. Cervical cancer patient Henrietta Lacks’ rapidly dividing cervical cells are collected by George Otto Gey at Johns Hopkins Hospital. They create the first immortal cell line (HeLa) used to study cancers and vaccines worldwide.
• 1976. Harald zur Hausen suggests that genital wart-associated HPV, not herpes simplex, is the probable cause of cervical cancer.
• 1983. HPV is confirmed as a cause of cancer.
• 1991. The first HPV vaccine is developed.
• 2002. Proof of principle and protective efficacy for the monovalent HPV 16 are shown.
• 2006. Merck’s Gardasil 4 (HPV 4) is FDA approved in girls ages 9-26 for protection against strains 6, 11, 16, and 18 — the cause of more than 70% of cervical cancer cases.
• 2009. Approval of Gardasil 4 is expanded to boys ages 9-26 for the prevention of genital warts.
• 2009. The FDA approves GlaxoSmithKline’s Cervarix (HPV 16 and 18) for girls and young women. The vaccine was withdrawn from the US market in 2016 following the success of Gardasil 9 but is used abroad for HPV cancer prevention.
• 2014. The 9-valent recombinant vaccine Gardasil 9 is FDA approved for protection against several low-risk, wart-causing HPV strains as well as the high-risk cancer strains targeted by HPV 4.
• 2018. The FDA expands approval to include females and males 27-45 years old.
• 2020. The FDA extends approval of Gardasil 9 to include prevention not only of cervical cancer but also, vaginal, vulvar, anal, oropharyngeal, and other head and neck cancers.

Annunziata, Cuccaro, and Myers had no competing interests to declare.
 

A version of this article appeared on Medscape.com.

While primary care physicians are generally comfortable prescribing vaginal estrogen therapy for recurrent urinary tract infections (UTIs), other nonantibiotic prophylactic options remain significantly underutilized, according to new research that highlights a crucial gap in antibiotic stewardship practices among primary care physicians.

UTIs are the most common bacterial infection in women of all ages, and an estimated 30%-40% of women will experience reinfection within 6 months. Recurrent UTI is typically defined as two or more infections within 6 months or a greater number of infections within a year, according to the American Academy of Family Physicians.

Antibiotics are the first line of defense in preventing and treating recurrent UTIs, but repeated and prolonged use could lead to antibiotic resistance.

Researchers at the University of North Carolina surveyed 40 primary care physicians at one academic medical center and found that 96% of primary care physicians prescribe vaginal estrogen therapy for recurrent UTI prevention, with 58% doing so “often.” Estrogen deficiency and urinary retention are strong contributors to infection.

However, 78% of physicians surveyed said they had never prescribed methenamine hippurate, and 85% said they had never prescribed D-mannose.

Physicians with specialized training in menopausal care felt more at ease prescribing vaginal estrogen therapy to patients with complex medical histories, such as those with a family history of breast cancer or endometrial cancer. This suggests that enhanced education could play a vital role in increasing comfort levels among general practitioners, said Lauren Tholemeier, MD, a urogynecology fellow at the University of North Carolina at Chapel Hill.

“Primary care physicians are the front line of managing patients with recurrent UTI,” said Tholemeier.

“There’s an opportunity for further education on, and even awareness of, methenamine hippurate and D-mannose as an option that has data behind it and can be included as a tool” for patient care, she said.

Indeed, physicians who saw six or more recurrent patients with UTI each month were more likely to prescribe methenamine hippurate, the study found, suggesting that familiarity with recurrent UTI cases can lead to greater confidence in employing alternative prophylactic strategies.

Tholemeier presented her research at the American Urogynecologic Society’s PFD Week in Washington, DC.

Expanding physician knowledge and utilization of all available nonantibiotic therapies can help them better care for patients who don’t necessarily have access to a subspecialist, Tholemeier said.

According to the American Urogynecologic Society’s best practice guidelines, there is limited evidence supporting routine use of D-mannose to prevent recurrent UTI. Methenamine hippurate, however, may be effective for short-term UTI prevention, according to the group.

By broadening the use of vaginal estrogen therapy, methenamine hippurate, and D-mannose, primary care physicians can help reduce reliance on antibiotics for recurrent UTI prevention — a practice that may contribute to growing antibiotic resistance, said Tholemeier.

“The end goal isn’t going to be to say that we should never prescribe antibiotics for UTI infection,” said Tholemeier, adding that, in some cases, physicians can consider using these other medications in conjunction with antibiotics.

“But it’s knowing they [clinicians] have some other options in their toolbox,” she said.

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

While primary care physicians are generally comfortable prescribing vaginal estrogen therapy for recurrent urinary tract infections (UTIs), other nonantibiotic prophylactic options remain significantly underutilized, according to new research that highlights a crucial gap in antibiotic stewardship practices among primary care physicians.

UTIs are the most common bacterial infection in women of all ages, and an estimated 30%-40% of women will experience reinfection within 6 months. Recurrent UTI is typically defined as two or more infections within 6 months or a greater number of infections within a year, according to the American Academy of Family Physicians.

Antibiotics are the first line of defense in preventing and treating recurrent UTIs, but repeated and prolonged use could lead to antibiotic resistance.

Researchers at the University of North Carolina surveyed 40 primary care physicians at one academic medical center and found that 96% of primary care physicians prescribe vaginal estrogen therapy for recurrent UTI prevention, with 58% doing so “often.” Estrogen deficiency and urinary retention are strong contributors to infection.

However, 78% of physicians surveyed said they had never prescribed methenamine hippurate, and 85% said they had never prescribed D-mannose.

Physicians with specialized training in menopausal care felt more at ease prescribing vaginal estrogen therapy to patients with complex medical histories, such as those with a family history of breast cancer or endometrial cancer. This suggests that enhanced education could play a vital role in increasing comfort levels among general practitioners, said Lauren Tholemeier, MD, a urogynecology fellow at the University of North Carolina at Chapel Hill.

“Primary care physicians are the front line of managing patients with recurrent UTI,” said Tholemeier.

“There’s an opportunity for further education on, and even awareness of, methenamine hippurate and D-mannose as an option that has data behind it and can be included as a tool” for patient care, she said.

Indeed, physicians who saw six or more recurrent patients with UTI each month were more likely to prescribe methenamine hippurate, the study found, suggesting that familiarity with recurrent UTI cases can lead to greater confidence in employing alternative prophylactic strategies.

Tholemeier presented her research at the American Urogynecologic Society’s PFD Week in Washington, DC.

Expanding physician knowledge and utilization of all available nonantibiotic therapies can help them better care for patients who don’t necessarily have access to a subspecialist, Tholemeier said.

According to the American Urogynecologic Society’s best practice guidelines, there is limited evidence supporting routine use of D-mannose to prevent recurrent UTI. Methenamine hippurate, however, may be effective for short-term UTI prevention, according to the group.

By broadening the use of vaginal estrogen therapy, methenamine hippurate, and D-mannose, primary care physicians can help reduce reliance on antibiotics for recurrent UTI prevention — a practice that may contribute to growing antibiotic resistance, said Tholemeier.

“The end goal isn’t going to be to say that we should never prescribe antibiotics for UTI infection,” said Tholemeier, adding that, in some cases, physicians can consider using these other medications in conjunction with antibiotics.

“But it’s knowing they [clinicians] have some other options in their toolbox,” she said.

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

While primary care physicians are generally comfortable prescribing vaginal estrogen therapy for recurrent urinary tract infections (UTIs), other nonantibiotic prophylactic options remain significantly underutilized, according to new research that highlights a crucial gap in antibiotic stewardship practices among primary care physicians.

UTIs are the most common bacterial infection in women of all ages, and an estimated 30%-40% of women will experience reinfection within 6 months. Recurrent UTI is typically defined as two or more infections within 6 months or a greater number of infections within a year, according to the American Academy of Family Physicians.

Antibiotics are the first line of defense in preventing and treating recurrent UTIs, but repeated and prolonged use could lead to antibiotic resistance.

Researchers at the University of North Carolina surveyed 40 primary care physicians at one academic medical center and found that 96% of primary care physicians prescribe vaginal estrogen therapy for recurrent UTI prevention, with 58% doing so “often.” Estrogen deficiency and urinary retention are strong contributors to infection.

However, 78% of physicians surveyed said they had never prescribed methenamine hippurate, and 85% said they had never prescribed D-mannose.

Physicians with specialized training in menopausal care felt more at ease prescribing vaginal estrogen therapy to patients with complex medical histories, such as those with a family history of breast cancer or endometrial cancer. This suggests that enhanced education could play a vital role in increasing comfort levels among general practitioners, said Lauren Tholemeier, MD, a urogynecology fellow at the University of North Carolina at Chapel Hill.

“Primary care physicians are the front line of managing patients with recurrent UTI,” said Tholemeier.

“There’s an opportunity for further education on, and even awareness of, methenamine hippurate and D-mannose as an option that has data behind it and can be included as a tool” for patient care, she said.

Indeed, physicians who saw six or more recurrent patients with UTI each month were more likely to prescribe methenamine hippurate, the study found, suggesting that familiarity with recurrent UTI cases can lead to greater confidence in employing alternative prophylactic strategies.

Tholemeier presented her research at the American Urogynecologic Society’s PFD Week in Washington, DC.

Expanding physician knowledge and utilization of all available nonantibiotic therapies can help them better care for patients who don’t necessarily have access to a subspecialist, Tholemeier said.

According to the American Urogynecologic Society’s best practice guidelines, there is limited evidence supporting routine use of D-mannose to prevent recurrent UTI. Methenamine hippurate, however, may be effective for short-term UTI prevention, according to the group.

By broadening the use of vaginal estrogen therapy, methenamine hippurate, and D-mannose, primary care physicians can help reduce reliance on antibiotics for recurrent UTI prevention — a practice that may contribute to growing antibiotic resistance, said Tholemeier.

“The end goal isn’t going to be to say that we should never prescribe antibiotics for UTI infection,” said Tholemeier, adding that, in some cases, physicians can consider using these other medications in conjunction with antibiotics.

“But it’s knowing they [clinicians] have some other options in their toolbox,” she said.

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

TOPLINE:

Children of mothers who had obesity or eating disorders before or during pregnancy may face higher risks for neurodevelopmental and psychiatric disorders.

METHODOLOGY:

• Researchers conducted a population-based cohort study to investigate the association of maternal eating disorders and high prepregnancy body mass index (BMI) with psychiatric disorder and neurodevelopmental diagnoses in offspring.
• They used Finnish national registers to assess all live births from 2004 through 2014, with follow-up until 2021.
• Data of 392,098 mothers (mean age, 30.15 years) and 649,956 offspring (48.86% girls) were included.
• Maternal eating disorders and prepregnancy BMI were the main exposures, with 1.60% of mothers having a history of eating disorders; 5.89% were underweight and 53.13% had obesity.
• Diagnoses of children were identified and grouped by ICD-10 codes of mental, behavioral, and neurodevelopmental disorders, mood disorders, anxiety disorders, sleep disorders, attention-deficit/hyperactivity disorder, and conduct disorders, among several others.

TAKEAWAY:

• From birth until 7-17 years of age, 16.43% of offspring were diagnosed with a neurodevelopmental or psychiatric disorder.
• Maternal eating disorders were associated with psychiatric disorders in the offspring, with the largest effect sizes observed for sleep disorders (hazard ratio [HR], 2.36) and social functioning and tic disorders (HR, 2.18; P < .001 for both).
• The offspring of mothers with severe prepregnancy obesity had a more than twofold increased risk for intellectual disabilities (HR, 2.04; 95% CI, 1.83-2.28); being underweight before pregnancy was also linked to many psychiatric disorders in offspring.
• The occurrence of adverse birth outcomes along with maternal eating disorders or high BMI further increased the risk for neurodevelopmental and psychiatric disorders in the offspring.

IN PRACTICE:

“The findings underline the risk of offspring mental illness associated with maternal eating disorders and prepregnancy BMI and suggest the need to consider these exposures clinically to help prevent offspring mental illness,” the authors wrote.

SOURCE:

This study was led by Ida A.K. Nilsson, PhD, of the Department of Molecular Medicine and Surgery at the Karolinska Institutet in Stockholm, Sweden, and was published online in JAMA Network Open.

LIMITATIONS:

A limitation of the study was the relatively short follow-up time, which restricted the inclusion of late-onset psychiatric disorder diagnoses, such as schizophrenia spectrum disorders. Paternal data and genetic information, which may have influenced the interpretation of the data, were not available. Another potential bias was that mothers with eating disorders may have been more perceptive to their child’s eating behavior, leading to greater access to care and diagnosis for these children.

DISCLOSURES:

This work was supported by the Swedish Research Council, the regional agreement on medical training and clinical research between Region Stockholm and the Karolinska Institutet, the Swedish Brain Foundation, and other sources. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Children of mothers who had obesity or eating disorders before or during pregnancy may face higher risks for neurodevelopmental and psychiatric disorders.

METHODOLOGY:

• Researchers conducted a population-based cohort study to investigate the association of maternal eating disorders and high prepregnancy body mass index (BMI) with psychiatric disorder and neurodevelopmental diagnoses in offspring.
• They used Finnish national registers to assess all live births from 2004 through 2014, with follow-up until 2021.
• Data of 392,098 mothers (mean age, 30.15 years) and 649,956 offspring (48.86% girls) were included.
• Maternal eating disorders and prepregnancy BMI were the main exposures, with 1.60% of mothers having a history of eating disorders; 5.89% were underweight and 53.13% had obesity.
• Diagnoses of children were identified and grouped by ICD-10 codes of mental, behavioral, and neurodevelopmental disorders, mood disorders, anxiety disorders, sleep disorders, attention-deficit/hyperactivity disorder, and conduct disorders, among several others.

TAKEAWAY:

• From birth until 7-17 years of age, 16.43% of offspring were diagnosed with a neurodevelopmental or psychiatric disorder.
• Maternal eating disorders were associated with psychiatric disorders in the offspring, with the largest effect sizes observed for sleep disorders (hazard ratio [HR], 2.36) and social functioning and tic disorders (HR, 2.18; P < .001 for both).
• The offspring of mothers with severe prepregnancy obesity had a more than twofold increased risk for intellectual disabilities (HR, 2.04; 95% CI, 1.83-2.28); being underweight before pregnancy was also linked to many psychiatric disorders in offspring.
• The occurrence of adverse birth outcomes along with maternal eating disorders or high BMI further increased the risk for neurodevelopmental and psychiatric disorders in the offspring.

IN PRACTICE:

“The findings underline the risk of offspring mental illness associated with maternal eating disorders and prepregnancy BMI and suggest the need to consider these exposures clinically to help prevent offspring mental illness,” the authors wrote.

SOURCE:

This study was led by Ida A.K. Nilsson, PhD, of the Department of Molecular Medicine and Surgery at the Karolinska Institutet in Stockholm, Sweden, and was published online in JAMA Network Open.

LIMITATIONS:

A limitation of the study was the relatively short follow-up time, which restricted the inclusion of late-onset psychiatric disorder diagnoses, such as schizophrenia spectrum disorders. Paternal data and genetic information, which may have influenced the interpretation of the data, were not available. Another potential bias was that mothers with eating disorders may have been more perceptive to their child’s eating behavior, leading to greater access to care and diagnosis for these children.

DISCLOSURES:

This work was supported by the Swedish Research Council, the regional agreement on medical training and clinical research between Region Stockholm and the Karolinska Institutet, the Swedish Brain Foundation, and other sources. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Children of mothers who had obesity or eating disorders before or during pregnancy may face higher risks for neurodevelopmental and psychiatric disorders.

METHODOLOGY:

• Researchers conducted a population-based cohort study to investigate the association of maternal eating disorders and high prepregnancy body mass index (BMI) with psychiatric disorder and neurodevelopmental diagnoses in offspring.
• They used Finnish national registers to assess all live births from 2004 through 2014, with follow-up until 2021.
• Data of 392,098 mothers (mean age, 30.15 years) and 649,956 offspring (48.86% girls) were included.
• Maternal eating disorders and prepregnancy BMI were the main exposures, with 1.60% of mothers having a history of eating disorders; 5.89% were underweight and 53.13% had obesity.
• Diagnoses of children were identified and grouped by ICD-10 codes of mental, behavioral, and neurodevelopmental disorders, mood disorders, anxiety disorders, sleep disorders, attention-deficit/hyperactivity disorder, and conduct disorders, among several others.

TAKEAWAY:

• From birth until 7-17 years of age, 16.43% of offspring were diagnosed with a neurodevelopmental or psychiatric disorder.
• Maternal eating disorders were associated with psychiatric disorders in the offspring, with the largest effect sizes observed for sleep disorders (hazard ratio [HR], 2.36) and social functioning and tic disorders (HR, 2.18; P < .001 for both).
• The offspring of mothers with severe prepregnancy obesity had a more than twofold increased risk for intellectual disabilities (HR, 2.04; 95% CI, 1.83-2.28); being underweight before pregnancy was also linked to many psychiatric disorders in offspring.
• The occurrence of adverse birth outcomes along with maternal eating disorders or high BMI further increased the risk for neurodevelopmental and psychiatric disorders in the offspring.

IN PRACTICE:

“The findings underline the risk of offspring mental illness associated with maternal eating disorders and prepregnancy BMI and suggest the need to consider these exposures clinically to help prevent offspring mental illness,” the authors wrote.

SOURCE:

This study was led by Ida A.K. Nilsson, PhD, of the Department of Molecular Medicine and Surgery at the Karolinska Institutet in Stockholm, Sweden, and was published online in JAMA Network Open.

LIMITATIONS:

A limitation of the study was the relatively short follow-up time, which restricted the inclusion of late-onset psychiatric disorder diagnoses, such as schizophrenia spectrum disorders. Paternal data and genetic information, which may have influenced the interpretation of the data, were not available. Another potential bias was that mothers with eating disorders may have been more perceptive to their child’s eating behavior, leading to greater access to care and diagnosis for these children.

DISCLOSURES:

This work was supported by the Swedish Research Council, the regional agreement on medical training and clinical research between Region Stockholm and the Karolinska Institutet, the Swedish Brain Foundation, and other sources. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

When it comes to managing urinary tract infections (UTIs), patients often turn to over-the-counter (OTC) products in search of quick relief. However, recent research suggests some products promise more than they can deliver and can vary widely in price and ingredients. For primary care clinicians, understanding these differences could make all the difference in offering effective, cost-conscious advice to patients.

Researchers from the University of Wisconsin analyzed OTC products marketed for urinary tract health in three major US drugstores and found significant price variations and a wide array of active ingredients.

Their study, presented at the American Urogynecologic Society’s PFD Week conference, found that the price of OTC products fluctuates dramatically. Phenazopyridine hydrochloride, commonly used for UTI symptom relief, ranged from $0.17 to $0.83 per tablet, the study found. Methenamine/sodium salicylate combinations, which are marketed for UTI prevention, varied from $0.13 to $0.33 per tablet. Cranberry supplements — often touted for their preventive benefits — showed the most extreme price range, from as low as $0.07 to as high as $1.00 per serving.

The study also looked into the ingredients, which were categorized into five main groups: Phenazopyridine hydrochloride, methenamine/sodium salicylate, cranberry supplements, D-mannose, and cranberry/D-mannose combinations.

These ingredients vary not only in price but also in the strength of scientific evidence supporting their use.

The researchers concluded:

• Phenazopyridine hydrochloride offers effective symptom relief but is not a UTI treatment.
• Methenamine/sodium salicylate shows potential for preventing recurrent UTIs in certain patients.
• Cranberry supplements have limited evidence for preventing UTIs, with no proof they treat infections.
• D-mannose has shown promise for short-term use in preventing recurrent UTIs, though more research is needed to weigh its effectiveness in the long run.

“No OTC product within its respective category is superior to another,” said Ushma J. Patel, MD, a fellow in Urogynecology and Reconstructive Pelvic Surgery at the University of Wisconsin School of Medicine and Public Health, Madison, and lead author of the study.

Patel and her coresearcher also found that many products are falsely marketed as treatments for UTI.

“The products in each type of category are for symptom relief or UTI prevention — not treatment,” said Patel. “These products within the categories described are interchangeable, and consumers should make cost-effective choices as no product is superior to another within its respective category.”

This presents the opportunity for clinicians to guide individuals to pick the right products while explaining that symptom relief doesn’t necessarily mean an infection is being treated, Patel said.

Indeed, Patel proposed that clinicians utilize a summary table created from their findings to offer patients vetted information about OTC UTI products.

And, while OTC products can provide benefits, they should not replace proper medical evaluation and treatment of UTIs.

“If patients are experiencing ongoing symptoms or develop new-onset symptoms despite trialing an over-the-counter product, they should contact a healthcare provider,” said Patel. “OTC products can provide symptom relief until patients are able to see a healthcare provider.”

The researchers reported no relevant disclosures.

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

When it comes to managing urinary tract infections (UTIs), patients often turn to over-the-counter (OTC) products in search of quick relief. However, recent research suggests some products promise more than they can deliver and can vary widely in price and ingredients. For primary care clinicians, understanding these differences could make all the difference in offering effective, cost-conscious advice to patients.

Researchers from the University of Wisconsin analyzed OTC products marketed for urinary tract health in three major US drugstores and found significant price variations and a wide array of active ingredients.

Their study, presented at the American Urogynecologic Society’s PFD Week conference, found that the price of OTC products fluctuates dramatically. Phenazopyridine hydrochloride, commonly used for UTI symptom relief, ranged from $0.17 to $0.83 per tablet, the study found. Methenamine/sodium salicylate combinations, which are marketed for UTI prevention, varied from $0.13 to $0.33 per tablet. Cranberry supplements — often touted for their preventive benefits — showed the most extreme price range, from as low as $0.07 to as high as $1.00 per serving.

The study also looked into the ingredients, which were categorized into five main groups: Phenazopyridine hydrochloride, methenamine/sodium salicylate, cranberry supplements, D-mannose, and cranberry/D-mannose combinations.

These ingredients vary not only in price but also in the strength of scientific evidence supporting their use.

The researchers concluded:

• Phenazopyridine hydrochloride offers effective symptom relief but is not a UTI treatment.
• Methenamine/sodium salicylate shows potential for preventing recurrent UTIs in certain patients.
• Cranberry supplements have limited evidence for preventing UTIs, with no proof they treat infections.
• D-mannose has shown promise for short-term use in preventing recurrent UTIs, though more research is needed to weigh its effectiveness in the long run.

“No OTC product within its respective category is superior to another,” said Ushma J. Patel, MD, a fellow in Urogynecology and Reconstructive Pelvic Surgery at the University of Wisconsin School of Medicine and Public Health, Madison, and lead author of the study.

Patel and her coresearcher also found that many products are falsely marketed as treatments for UTI.

“The products in each type of category are for symptom relief or UTI prevention — not treatment,” said Patel. “These products within the categories described are interchangeable, and consumers should make cost-effective choices as no product is superior to another within its respective category.”

This presents the opportunity for clinicians to guide individuals to pick the right products while explaining that symptom relief doesn’t necessarily mean an infection is being treated, Patel said.

Indeed, Patel proposed that clinicians utilize a summary table created from their findings to offer patients vetted information about OTC UTI products.

And, while OTC products can provide benefits, they should not replace proper medical evaluation and treatment of UTIs.

“If patients are experiencing ongoing symptoms or develop new-onset symptoms despite trialing an over-the-counter product, they should contact a healthcare provider,” said Patel. “OTC products can provide symptom relief until patients are able to see a healthcare provider.”

The researchers reported no relevant disclosures.

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

When it comes to managing urinary tract infections (UTIs), patients often turn to over-the-counter (OTC) products in search of quick relief. However, recent research suggests some products promise more than they can deliver and can vary widely in price and ingredients. For primary care clinicians, understanding these differences could make all the difference in offering effective, cost-conscious advice to patients.

Researchers from the University of Wisconsin analyzed OTC products marketed for urinary tract health in three major US drugstores and found significant price variations and a wide array of active ingredients.

Their study, presented at the American Urogynecologic Society’s PFD Week conference, found that the price of OTC products fluctuates dramatically. Phenazopyridine hydrochloride, commonly used for UTI symptom relief, ranged from $0.17 to $0.83 per tablet, the study found. Methenamine/sodium salicylate combinations, which are marketed for UTI prevention, varied from $0.13 to $0.33 per tablet. Cranberry supplements — often touted for their preventive benefits — showed the most extreme price range, from as low as $0.07 to as high as $1.00 per serving.

The study also looked into the ingredients, which were categorized into five main groups: Phenazopyridine hydrochloride, methenamine/sodium salicylate, cranberry supplements, D-mannose, and cranberry/D-mannose combinations.

These ingredients vary not only in price but also in the strength of scientific evidence supporting their use.

The researchers concluded:

• Phenazopyridine hydrochloride offers effective symptom relief but is not a UTI treatment.
• Methenamine/sodium salicylate shows potential for preventing recurrent UTIs in certain patients.
• Cranberry supplements have limited evidence for preventing UTIs, with no proof they treat infections.
• D-mannose has shown promise for short-term use in preventing recurrent UTIs, though more research is needed to weigh its effectiveness in the long run.

“No OTC product within its respective category is superior to another,” said Ushma J. Patel, MD, a fellow in Urogynecology and Reconstructive Pelvic Surgery at the University of Wisconsin School of Medicine and Public Health, Madison, and lead author of the study.

Patel and her coresearcher also found that many products are falsely marketed as treatments for UTI.

“The products in each type of category are for symptom relief or UTI prevention — not treatment,” said Patel. “These products within the categories described are interchangeable, and consumers should make cost-effective choices as no product is superior to another within its respective category.”

This presents the opportunity for clinicians to guide individuals to pick the right products while explaining that symptom relief doesn’t necessarily mean an infection is being treated, Patel said.

Indeed, Patel proposed that clinicians utilize a summary table created from their findings to offer patients vetted information about OTC UTI products.

And, while OTC products can provide benefits, they should not replace proper medical evaluation and treatment of UTIs.

“If patients are experiencing ongoing symptoms or develop new-onset symptoms despite trialing an over-the-counter product, they should contact a healthcare provider,” said Patel. “OTC products can provide symptom relief until patients are able to see a healthcare provider.”

The researchers reported no relevant disclosures.

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

The Food and Drug Administration (FDA) has approved Orlynvah, a new oral treatment for uncomplicated urinary tract infections (UTIs) in women who have limited options for effective antibiotic therapy.

Uncomplicated UTIs are bladder infections that typically affect women who don’t have other issues like kidney disease or urinary tract abnormalities. These infections are common, affecting around half of all women at least once in their lives.

Treating UTIs can be difficult when standard antibiotics don’t work well, often because of antibiotic resistance or certain health conditions. Orlynvah offers a promising new option by combining two drugs, sulopenem etzadroxil and probenecid, in one oral tablet. This combination helps keep the antibiotic in the body longer, making it work better, especially against bacteria that resist traditional treatments. Orlynvah is specifically approved to target infections from bacteria like Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, which can be harder to treat.

Marjorie Golden, MD, an infectious disease specialist at Yale New Haven Hospital in Connecticut, described Orlynvah as a much-needed alternative for women struggling with difficult-to-treat UTIs. 

“Orlynvah has the potential to be an important treatment option for those who need it,” she said in a news release from Iterum Therapeutics, the drug’s maker.

The FDA approved Orlynvah based on two large clinical trials involving over 3,800 women. In these studies, Orlynvah worked as well as or better than antibiotics like ciprofloxacin and Augmentin. It was generally well-tolerated, though common side effects included diarrhea, nausea, yeast infections, and headaches.

The FDA advises people to discuss their medical history with their doctor before taking Orlynvah, especially if they have conditions like gout, kidney stones, or allergies to other antibiotics.

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

The Food and Drug Administration (FDA) has approved Orlynvah, a new oral treatment for uncomplicated urinary tract infections (UTIs) in women who have limited options for effective antibiotic therapy.

Uncomplicated UTIs are bladder infections that typically affect women who don’t have other issues like kidney disease or urinary tract abnormalities. These infections are common, affecting around half of all women at least once in their lives.

Treating UTIs can be difficult when standard antibiotics don’t work well, often because of antibiotic resistance or certain health conditions. Orlynvah offers a promising new option by combining two drugs, sulopenem etzadroxil and probenecid, in one oral tablet. This combination helps keep the antibiotic in the body longer, making it work better, especially against bacteria that resist traditional treatments. Orlynvah is specifically approved to target infections from bacteria like Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, which can be harder to treat.

Marjorie Golden, MD, an infectious disease specialist at Yale New Haven Hospital in Connecticut, described Orlynvah as a much-needed alternative for women struggling with difficult-to-treat UTIs. 

“Orlynvah has the potential to be an important treatment option for those who need it,” she said in a news release from Iterum Therapeutics, the drug’s maker.

The FDA approved Orlynvah based on two large clinical trials involving over 3,800 women. In these studies, Orlynvah worked as well as or better than antibiotics like ciprofloxacin and Augmentin. It was generally well-tolerated, though common side effects included diarrhea, nausea, yeast infections, and headaches.

The FDA advises people to discuss their medical history with their doctor before taking Orlynvah, especially if they have conditions like gout, kidney stones, or allergies to other antibiotics.

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

The Food and Drug Administration (FDA) has approved Orlynvah, a new oral treatment for uncomplicated urinary tract infections (UTIs) in women who have limited options for effective antibiotic therapy.

Uncomplicated UTIs are bladder infections that typically affect women who don’t have other issues like kidney disease or urinary tract abnormalities. These infections are common, affecting around half of all women at least once in their lives.

Treating UTIs can be difficult when standard antibiotics don’t work well, often because of antibiotic resistance or certain health conditions. Orlynvah offers a promising new option by combining two drugs, sulopenem etzadroxil and probenecid, in one oral tablet. This combination helps keep the antibiotic in the body longer, making it work better, especially against bacteria that resist traditional treatments. Orlynvah is specifically approved to target infections from bacteria like Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, which can be harder to treat.

Marjorie Golden, MD, an infectious disease specialist at Yale New Haven Hospital in Connecticut, described Orlynvah as a much-needed alternative for women struggling with difficult-to-treat UTIs. 

“Orlynvah has the potential to be an important treatment option for those who need it,” she said in a news release from Iterum Therapeutics, the drug’s maker.

The FDA approved Orlynvah based on two large clinical trials involving over 3,800 women. In these studies, Orlynvah worked as well as or better than antibiotics like ciprofloxacin and Augmentin. It was generally well-tolerated, though common side effects included diarrhea, nausea, yeast infections, and headaches.

The FDA advises people to discuss their medical history with their doctor before taking Orlynvah, especially if they have conditions like gout, kidney stones, or allergies to other antibiotics.

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

Efforts to curb overdiagnosis of thyroid cancer have made a difference in the United States and South Korea, but these countries still have high rates of excess treatment of indolent lesions, according to a recently published global study.

The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.

Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.

Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.

Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.

“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”

Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.

This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.

Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.

“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
 

Persisting Problem

Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.

The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”

“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.

In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.

If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.

In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.

“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.

“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.

The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.

“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.

In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.

Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
 

New Thinking on Thyroid Cancer

There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.

“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”

The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.

Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.

“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.

Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.

“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.

Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.

“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”

Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.

“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”

This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.

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

Efforts to curb overdiagnosis of thyroid cancer have made a difference in the United States and South Korea, but these countries still have high rates of excess treatment of indolent lesions, according to a recently published global study.

The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.

Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.

Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.

Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.

“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”

Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.

This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.

Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.

“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
 

Persisting Problem

Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.

The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”

“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.

In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.

If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.

In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.

“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.

“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.

The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.

“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.

In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.

Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
 

New Thinking on Thyroid Cancer

There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.

“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”

The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.

Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.

“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.

Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.

“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.

Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.

“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”

Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.

“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”

This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.

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

Efforts to curb overdiagnosis of thyroid cancer have made a difference in the United States and South Korea, but these countries still have high rates of excess treatment of indolent lesions, according to a recently published global study.

The proportion of thyroid cancer cases attributable to overdiagnosis globally was higher in women (78%) than in men (68%), with this rate varying substantially across countries, wrote Mengmeng Li, PhD, of the Sun Yat-sen University Cancer Center, Guangzhou, China, and coauthors in an October paper in The Lancet Diabetes & Endocrinology.

Overdiagnosis refers to the diagnosis of lesions that would not cause symptoms and that would not progress, if left alone.

Increased testing for thyroid cancer, fueled in large part by the expansion of imaging technologies and progressively more intense and disorganized scrutiny of the thyroid, led many people to be treated for often indolent lesions, exposing them to potential side effects as well as financial and emotional distress.

Li and coauthors estimate that more than 1.7 million people might have been overdiagnosed between 2013 and 2017 in 63 countries.

“Overdiagnosis clearly emerged in some high-resource countries with private-based health systems in which access to healthcare overrules regulatory controls (eg, in the USA) and in some high-quality public health systems with easy and broad access to thyroid gland diagnostic examinations (eg, in Canada),” Li and coauthors wrote. “Conversely, thyroid cancer is less commonly diagnosed in those countries in which access to diagnosis is guided by strong regulatory rules (eg, in Nordic countries).”

Their study drew from almost 40 years of research, including the latest available data from the World Health Organization’s International Agency for Research on Cancer’s (IARC’s) Global Cancer Observatory. Li and coauthors examined patterns in the time trends of thyroid cancer, mortality data, and trends in diagnosis of thyroid cancer before testing became common in many nations.

This approach is needed in estimating overdiagnosis, where it’s not possible to see what’s happening on a case-by-case level, Salvatore Vaccarella, PhD, a scientist at IARC’s Cancer Surveillance Branch, said in an interview.

Researchers can’t tell whether an individual’s detected early-stage cancers would have remained indolent for years or eventually would have put their life at risk, he said. Instead, the patterns emerge through larger studies of the reported cases of cancer like thyroid tumors and then looking at separate datasets on mortality.

“We can only see that as a big phenomenon when we look at population-based data,” Vaccarella said.
 

Persisting Problem

Recognition of the harms of overdiagnosis has resulted in some reduction of the incidence of thyroid cancer in the United States, Li and coauthors wrote. After adjusting for age, incidence has fallen from 19 per 100,000 women in 2013 to 16 per 100,000 women in 2017. The proportion of thyroid cancer attributed to overdiagnosis has dropped from 76% to 68% in the country.

The paper adds to the evidence suggesting that the rise in screening has not changed mortality rates for thyroid cancer. For example, Li and coauthors reported seeing “a small decrease in thyroid cancer mortality rates over time in some European countries, but this decline (less than 1 per 100,000 women) is marginal compared with the increases in incidence (reaching around 100 per 100,000 women).”

“Moreover, previous data show that the downward mortality trends had begun before the wide use of ultrasonography for early detection and that period and birth cohort effects have been declining, probably due to treatment advances and reduced prevalence of risk factors, such as the reduction in iodine deficiency,” they wrote.

In an interview, Amanda Davis, MD, of AnMed, a nonprofit health system based in Anderson, South Carolina, said the new paper from Li and Vaccarella provides further evidence for a cautious approach to thyroid nodules given concerns about overdiagnosis.

If early detection of cancer via discovery of thyroid nodules actually helped patients, mortality rates would have dropped with expansion of screening and the resulting diagnoses, said Davis, who is an associate program director at AnMed’s family medicine residency program and affiliate professor at the Medical University of South Carolina, Charleston.

In many cases, people learn they have thyroid lesions after being tested for other conditions such as ultrasound done on carotid arteries to check for stroke risk. The most common form of thyroid cancer is the papillary form. Papillary thyroid cancer tends to be slow growing, carries a low risk for distant metastasis, and in many cases poses little risk. Some small (< 1 cm) papillary thyroid cancers can be monitored with active surveillance as opposed to thyroid lobectomy.

“So just finding more nodules incidentally or through screening ultrasound and even finding more papillary cancers via these methods does not make people healthier or decrease mortality,” Davis said.

“So just finding more things and even finding more papillary cancers does not increase our ability to treat people and keep them alive longer,” Davis said.

The 5-year survival rate for thyroid cancer overall is 98.1% and varies from 99.9% for localized disease to 55.3% for distant disease, the US Preventive Services Task Force (USPSTF) said in a 2017 publication in JAMA. The task force that year gave a “D” rating on screening of asymptomatic people for thyroid cancer. That means there’s moderate certainty that screening for thyroid cancer in asymptomatic persons results in harms that outweigh the benefits. The decision to give this “D” rating meant this screening is not recommended. That’s still the panel’s view.

“You can think of it as a “D” for ‘don’t screen for thyroid cancer,’ ” in people who present no symptoms of this illness, John Wong, MD, the vice chair of the USPSTF, said in an interview.

In primary care, the challenge is assessing thyroid nodules detected when people undergo testing for another reason, such as an ultrasound of the carotid artery to check for stroke risk.

Thyroid nodules can be detected by ultrasonography in up to 68% of the general population, reported a study in American Family Physician. Nodules with suspicious features or ≥ 1 cm require fine needle aspiration. The Bethesda System for Reporting Thyroid Cytopathology can be used to classify samples, with molecular testing applied to guide treatment when fine needle aspiration yields an indeterminate result.
 

New Thinking on Thyroid Cancer

There’s been a shift in recent years in the approach to how physicians should proceed if certain kinds of thyroid cancer are detected, Cari M. Kitahara, PhD, of the National Cancer Institute noted in a comment accompanying the Li paper.

“Clinicians need to be judicious in the use of thyroid ultrasonography, the diagnostic follow-up of incidentally detected thyroid nodules, and determining the optimal course of treatment,” Kitahara wrote. “For low-risk and incidentally detected tumors, strong consideration should be given to less intensive treatment options (eg, lobectomy, delayed treatment, and active surveillance).”

The American Thyroid Association guidelines encourage de-escalation of treatment for low-risk papillary thyroid carcinoma up to 4 cm.

Physicians often need to make clear to patients how a diagnosis of low-risk papillary thyroid cancer differs from other oncology diagnoses, R. Michael Tuttle, MD, of Memorial Sloan Kettering Cancer Center, New York City, said in an interview.

“I’ll frequently say that everything you’ve ever learned about cancer, you need to forget,” Tuttle said.

Some patients will mistakenly think any cancer diagnosis is a likely death sentence, meaning they should rush to get aggressive treatment. Tuttle has been a leader for many years in efforts in advancing active surveillance as an option for certain people with low-risk thyroid cancer.

“I often start my consultation by saying: ‘We’re going to choose between two right answers here. One right answer is watching right. One right answer is going to surgery,’ ” Tuttle said.

Patients with low-risk thyroid cancer tend to fall into two camps, with maximalists likely to seek quick treatment and minimalists more inclined for surveillance if that’s an option for them, Tuttle said. As opinions have shifted within the medical community about approaches to low-risk thyroid cancer, there’s also been some growing awareness among the public about thyroid overdiagnosis.

“Ten or 15 years ago, people thought we were crazy” to consider active surveillance as an option for low-risk thyroid cancers,” Tuttle said. “Now we have swung, at least in some of the public opinion, to this recognition that every little speck of cancer doesn’t need to be immediately taken out of your body.”

Some patients express regret about having learned that they have low-risk thyroid cancer, Tuttle said.

“Over the last 5 years, it’s not uncommon for patients to ask me, ‘Is this one of those that needs to be treated now, or is this one of those that we wish we would have never found?’ Or people will say, ‘My doctor talked me into an ultrasound, I didn’t want it’ or ‘I had a car wreck, and I found this nodule and I wished I had never found it.’ ”

This study from Li and coauthors was funded by the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, the Young Talents Program of Sun Yat-sen University Cancer Center, the Italian Association for Cancer Research, and the Italian Ministry of Health. Davis and Tuttle had no relevant financial disclosures.

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