PCOS Tied to Risk for Cardiovascular Disease After Menopause

Women with polycystic ovarian syndrome (PCOS) before menopause appear to have a greater risk of stroke, heart attack, and other cardiovascular events after menopause, according to findings presented Saturday, October 17, at the virtual American Society for Reproductive Medicine (ASRM) 2020 Scientific Congress.

"We found a PCOS diagnosis prior to menopause was associated with a 64% increased risk of cardiovascular disease after menopause independent of age at enrollment, race, body mass index, and smoking status," presenter Jacob Christ, MD, a resident at the University of Washington in Seattle, told attendees. "Taken together, our results suggest that women with PCOS have more risk factors for future cardiovascular disease at baseline, and a present PCOS diagnosis prior to menopause is associated with an increased risk of cardiovascular disease after menopause."

Dr Jacob Christ

The results are important to consider in women seeking care related to fertility, according to Amanda N. Kallen, MD, an assistant professor of reproductive endocrinology and infertility at Yale Medicine in New Haven, Connecticut.

"As fertility specialists, we often see women with PCOS visit us when they are having trouble conceiving, but often [they] do not return to our care once they've built their family," said Kallen, who was not involved in the research.

"This excellent talk emphasized how critical it is for us as reproductive endocrinologists to have ongoing discussions with PCOS patients about long-term cardiovascular risks at every opportunity, and to emphasize that these risks persist long after the reproductive years have ended," Kallen told Medscape Medical News.

Identifying Women at Higher Risk

Characteristics of PCOS in adolescence are already understood, including hyperandrogenism, acne, irregular bleeding, and variable ages of menarche, Christ explained. Similarly, in women's reproductive years, PCOS is linked to abnormal uterine bleeding, hirsutism, dyslipidemia, infertility, impaired glucose tolerance, gestational diabetes, and preeclampsia.

"What is less clear is if baseline cardiometabolic dysfunction during reproductive years translates into cardiovascular disease after menopause," Christ said. "Menopausal changes may reduce risk of cardiovascular disease among PCOS women, as it is known that overall, androgen levels decline during menopause. Furthermore, ovarian aging may be delayed in PCOS women, which may be protective against cardiovascular disease."

To learn more, the researchers completed a secondary analysis of data from the Study of Women's Health Across the Nation (SWAN), a prospective cohort study. Women enrolled in the study were aged 42 to 52 years at baseline, had a uterus and at least one ovary, and menstruated within the previous 3 months. Women were considered to have PCOS if they had both biochemical hyperandrogenism and a history of irregular menses.

The researchers included participants in the secondary analysis if they had complete data on the women's baseline menstrual status and total testosterone and if the women had at least one follow-up visit after menopause. Menopause was approximated as 51 years old if not otherwise reported (or one year after study entry if age 51 at entry). At the follow-up visit, women self-reported any cardiovascular disease events since menopause.

The study's primary outcome was the first postmenopausal cardiovascular event. These included any of the following: myocardial infarction, cerebrovascular accident or stroke, angina, percutaneous coronary intervention or angioplasty, coronary artery bypass graft, congestive heart failure, carotid artery procedure, peripheral artery disease or lower extremity procedure, renal artery procedure, deep vein thrombosis, pulmonary embolism, and abdominal aortic aneurysm.

Among 1340 women included in the analysis, 174 (13%) women had PCOS and 1166 did not. The average age at screening and at menopause were not significantly different between the groups, but they did differ based on other baseline characteristics.

More women with PCOS frequently smoked cigarettes (22%) vs those without PCOS (12.7%), and women with PCOS had an average BMI of 31.3, vs 26.7 among those without PCOS. Women with PCOS also had higher systolic blood pressure (120.7 vs 115.8 mm Hg), higher total cholesterol (202 vs. 192 mg/dL), and higher fasting blood glucose (103.7 vs 89.2 mg/dL; P < .01 for all).

After controlling for age at enrollment, race, BMI, and smoking status, women with PCOS had 1.6 times greater odds of a cardiovascular event after menopause compared with women without PCOS (odds ratio [OR], 1.6; P = .029). Those with PCOS also had a significantly higher Atherosclerotic Cardiovascular Disease risk scores (P = .024), but their Framingham 10-year risk score was not significantly different from those without PCOS.

Although the findings are not necessarily surprising, the study's value particularly lay in its size, prospective data collection, and rigorous methods, said Ginny Ryan, MD, MA, professor and division chief of reproductive endocrinology and infertility at the University of Washington School of Medicine in Seattle.

Dr Ginny Ryan

"While this study's criteria used to identify subjects with PCOS selected a population with a particularly severe phenotype of PCOS and thus a higher risk population for cardiovascular disease, it is vital for women's health providers to truly understand the medium- and long-term life-threatening associations found more commonly in many with PCOS," Ryan, who attended the talk and was not involved in the research, told Medscape Medical News.

"This study emphasizes the importance of identifying PCOS premenopause, not just for the patient's immediate well-being, but also so that appropriate counseling and referral can take place to optimize primary, secondary, and tertiary prevention efforts against CVD and related morbidity and mortality," Ryan said. "Providers who focus on reproductive health and reproductive-aged women have the opportunity to play a vital role in optimizing the long-term health of their patients."

Aside from being a prospective cohort with more than two decades of follow-up, the study's other strengths included the definition of PCOS before menopause and use of multiple markers of postmenopausal cardiovascular disease, Christ said. The study's main weaknesses were the exclusion of mild PCOS, the self-reporting of cardiovascular events, and the multiple ways of defining menopause.

Kallen is a consultant for Gynaesight and a reviewer for Healthline. Christ and Ryan have disclosed no relevant financial relationships.

American Society for Reproductive Medicine (ASRM) 2020 Scientific Congress: Abstract O-35. Presented October 17, 2020.

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