Potential Risks of CVD in Women with Polycystic Ovary Syndrome

Andrea Dunaif, MD

In a presentation at The Metabolic Institute of America’s (TMIOA) 2021 Heart in Diabetes sessions in New York, NY , Andrea Dunaif, MD, Professor of Medicine in the Department of Medicine and new Chief of the Hilda and J. Lester Gabrilove Division of Endocrinology, Diabetes and Bone Disease for the Mount Sinai Health System, spoke of and the “ongoing controversy” regarding the potential increased risk for cardiovascular disease in women with polycystic ovary syndrome (PCOS).

Dunaif briefly defined PCOS as a “constellation of hormonal abnormalities” of unknown etiology. The condition had been categorized by neuroendocrine and reproductive changes, increased ovarian and adrenal testosterone production, hormonal imbalances, metabolic disorders, and obesity.

“Tremendous advance have been made in the past 10 years on elucidating causal pathways through genetic pathways,” Dunaid said.

Androgen production, granulose cell function, and age in menopause were considered some of the causal pathways.

The causality of insulin resistance had also been proven in studies that showed the genes that cause resistance and increased body mass index also contributed to PCOS.

Dunaif cited the Rotterdamn Criteria, diagnostic criteria developed in recent years that focused on key clinical features such as hyperandrogenism, ovulatory dysfunction, and poor metabolic outcomes.

“These are the women that have profound insulin resistance, and there’s pretty good data that they’re about, independent of obesity, at 4-fold increased risk of type 2 diabetes with a significantly younger age of onset,” Dunaif said.

She added that younger women with PCOS who have developed type 2 diabetes due to the disease were likely at marked cardiovascular disease risk.

Despite ongoing discussions of the potential cardiovascular risk associated with the disorder, little data exists on the subject.

“Unfortunately, there have been no long-term respective cohort studies to an age which women start having increased events to answer this question,” Dunaif said. “So, we’re left with other types of data.”

An increased risk of cardiovascular disease was recorded in an early Scandanavian study involving 18,112 patients with PCOS, but the data focused solely on younger female patient populations.

A similar cohort study in Denmark, which offered a more robust definition of PCOS, observed the long-term health trajectory of older women with the disease and also found an increased risk of cardiovascular disease.

Additionally, a nearly 2-decade old Nurses’ Health study found that women with irregular menstrual cycles found a 1.5 increased risk for cardiovascular events. Though incomplete, Dunaif considered it to be the best data on the subject of PCOS and cardiovascular health.

Aside from the limited studies, Mandelian Randomization has been a key component in the study of PCOS and the potential link to cardiovascular risk.

Mandelian Randomization uses genetic variants that are correlated with exposure to PCOS, such as body mass index, to determine a causal relationship. However, much of the data requires corroboration.

Overall, though women with PCOS have not been studied to an age when cardiovascular events are considered common, Dunaif noted that the risk of type 2 diabetes by 4-fold, and the disease was linked to several traditional and emerging CVD risk factors.

At the end of the presentation, Dunfaid added that menses continue to act as a “vital sign” for cardiovascular disease, and urged patients and clinicians to incorporate the test.

“Menses that (patients are) either skipping or cycle lengths greater than 40 days are associated with increased risk across a lifespan for type 2 diabetes, and even more concerning, with premature mortality,” Dunaif said. “So, 1 simple question and you can really help your patients.”