Cardiovascular Risk Factors and Subclinical Atherosclerosis in Middle Aged Women With a History of Polycystic Ovary Syndrome

The final menstrual period defines menopause and signifies depletion of ovarian follicular reserve and endogenous estradiol. Diminished estradiol underscores postmenopausal increases in chronic health conditions of non-reproductive tissues namely the vascular, skeletal, and central nervous systems. Polycystic ovary syndrome (PCOS) is a prevalent disorder associated with an increased risk for type 2 diabetes and an adverse cardiovascular disease (CVD) risk profile evident at younger ages. It is well established that the risk of CVD increases among women following menopause. However, no definitive studies exist demonstrating increased cardiovascular morbidity or mortality among older women with a history of PCOS. Further, the association between menopause and CVD risk factors has not been fully explored in women with a history of PCOS. Women with PCOS report less menstrual cycle irregularity across time that may reflect varying degrees of ovarian function that in turn may augment CVD risk factors. We evaluated the hypotheses that menopause and lifetime menstrual cycle irregularity would have a modifying effect on CVD risk factors and markers of subclinical atherosclerosis in 152 women with PCOS and 169 normal reproductive controls ages 35 to 67 years. We found that the typical reproductive presentation and the adverse lipid profile observed in younger PCOS women was not as apparent in older PCOS cases compared to controls. Twenty-five percent of menopausal cases, however had type 2 diabetes. Coronary artery calcification (CAC) was greater in cases compared to controls and increased with age. PCOS cases reporting the greatest menstrual irregularity across time had higher total and free testosterone levels and greater CAC compared to cases with more frequent cycles. Our studies support the importance of diabetes prevention in aging women with a history of PCOS to reduce risk for early cardiovascular disease. Further, women with PCOS who present with the greater cycle irregularity may be more likely to have cardiovascular consequences. Relevance to Public Health: Because preventing PCOS is unlikely, interventions focused on promoting healthy aging among women with a history of the condition represents an important undertaking that will temper long-term health burden and improve quality of life