Common PCOS treatments do not increase, decrease metabolic syndrome risk

Key takeaways:

• Low-dose birth control pills did not change the prevalence of metabolic syndrome among women with polycystic ovary syndrome.
• Metabolic syndrome prevalence did not decrease for women with PCOS assigned metformin.

DENVER — For women with polycystic ovary syndrome and overweight or obesity, neither oral contraceptive pills nor metformin altered the characteristic markers of metabolic syndrome, either alone or in combination, researchers reported.

Combined oral contraceptive pills are first-line treatment for PCOS and effectively manage hyperandrogenism and menstrual irregularity, though their effects on CVD risk factors such as glucose, lipids and insulin resistance are mixed, Anuja Dokras, MD, MHCI, PhD, professor of obstetrics and gynecology at the Hospital of the University of Pennsylvania and director of the Penn Polycystic Ovary Syndrome Center, said during a presentation at the ASRM Scientific Congress & Expo. Metformin, a first-line treatment for type 2 diabetes, is also commonly prescribed for women with PCOS; however, in head-to-head studies, metformin is inferior for the management of PCOS symptoms, Dokras said.

“In PCOS, [metformin] is used to manage weight and decrease CVD risk, so we are not sure if there is a specific population that would benefit from the use of metformin,” Dokras said. “This has led to varying practice among physicians and great frustration among patients.”

For the COMET-PCOS study, researchers analyzed data from 240 women with hyperandrogenic PCOS and a BMI of 25 kg/m² or higher. The mean age of women was 29.5 years; mean BMI was 35.6 kg/m and 24% of participants identified as Black. Researchers randomly assigned women to continuous oral contraceptive pills for 6 months (20 ug ethinyl estradiol/0.15mg desogestrel; n = 79), extended-release metformin (2,000 mg per day; n = 81) or combination oral contraceptive pills plus metformin (n = 80). All participants also received nutrition counseling.

The primary outcome was prevalence of metabolic syndrome at the end of the 24-week study period. Secondary outcomes included changes in the individual components of metabolic syndrome and features of PCOS.

“We hypothesized that the oral contraceptive pills, based on our studies and the literature, might increase risk for metabolic syndrome by impacting one or more of these individual biomarkers, metformin would decrease the risk for metabolic syndrome and perhaps the combination might be the most effective treatment to manage both PCOS symptoms as well as CVD risk,” Dokras said.

At baseline, prevalence of metabolic syndrome was 30.4%, 30.9% and 31.3% across the oral contraceptive pill, metformin and combination groups, respectively. At 24 weeks, there was no difference in metabolic syndrome prevalence across the three arms (P = .36), with a prevalence of 27.1% in the oral contraceptive arm, 26.2% in the metformin arm and 27.06% in the combined arm.

The OR for metabolic syndrome was 0.97 for the oral contraceptive group (95% CI, 0.63-1.5), 0.78 for the metformin group (95% CI, 0.44-1.38) and 0.83 for the combination group (95% CI, 0.46-1.48).

Results of oral glucose tolerance tests were also similar across the three groups.

Researchers observed a decrease in waist circumference among participants in the oral contraceptive pill group and an increase in triglyceride and fasting glucose levels, though the changes did not effect metabolic syndrome prevalence, Dokras said.

For women assigned metformin, researchers observed changes in waist circumference and blood pressure that similarly did not affect metabolic syndrome prevalence.

For women in the combination therapy group, researchers observed only a change in HDL cholesterol.

Dokras said only a change in BP was significant between the oral contraceptive and metformin groups when assessing between-group difference for individual components (P = .04); however, there were no differences in metabolic syndrome.

“The results are reassuring that low-dose oral contraceptive pills can be used for comprehensive management of the higher-risk PCOS phenotype, as we did not observe a significant change in the prevalence of metabolic syndrome,” Dokras said. “The results also suggest that we may have to reevaluate current practice because our study does not support the use of metformin alone as a preventive therapy for all patients with a BMI of 25 kg/m² or higher. This is because we found no decrease in prevalence of metabolic syndrome and metformin alone is less effective in managing PCOS symptoms.”

Dokras added that the COMET-PCOS data also do not support prescribing metformin in addition to oral contraceptive pills for patients at risk for CVD, as metformin limited additive effect and was associated with a high prevalence of gastrointestinal adverse events.