Cardiovascular Events in Polycystic Ovary Syndrome: Is the Debate Settled for Good?

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is a complex disease characterized by both reproductive and metabolic disorders. Multiple studies have shown that women with PCOS are at increased risk of obesity, impaired glucose tolerance, diabetes, dyslipidemia, hypertension, and metabolic syndrome, among other cardiovascular and metabolic abnormalities (1, 2). Despite the overwhelming evidence of increased incidence of cardiovascular risk factors (CVRFs) in women with PCOS, the critical question that has been lingering in the field for decades has been whether such an increase in CVRFs does indeed translate into an increased rate of cardiovascular events. There is no doubt that CVRFs lead to an increased incidence of cardiovascular events in the general population. However, clarity as to whether this positive association between increased CVRFs and cardiovascular events holds true for women with PCOS has remained elusive. There are 2 main questions raised by such uncertainty. First, if the increase in CVRFs in women with PCOS does not translate into an increase in cardiovascular events, why should we care about CVRFs in those patients in the clinical setting? Second, if women with PCOS do not have an increased incidence of cardiovascular events despite having an increase of CVRFs, would it be possible to speculate that they have a “protective factor(s)” that overcomes the increase in CVRFs? Furthermore, would it be possible to use such “protective factor(s)” to treat other patient populations with increased CVRFs?

Previous studies addressing the question if women with PCOS have increased incidence of cardiovascular events have been inconclusive and contradictory. A study of a cohort of ~11 000 women with PCOS matched with ~55 000 control women from Northern California showed no difference in the incidence of coronary heart disease, cerebrovascular disease, or peripheral vascular disease (3). Another study of a Danish cohort of ~20 000 women with PCOS matched 1:3 with control women showed mixed results; while women with PCOS had an increase in the incidence of stroke and thrombosis, there were no differences in cardiovascular disease, myocardial infarction, or transitory cerebral ischemia (4). Moreover, a series of recent meta-analyses have also shown contradictory results. Some meta-analyses have shown that women with PCOS have increased incidence of cardiovascular events, either as a composite outcome (5) or individual outcomes such as myocardial infarction, ischemic heart disease, or stroke (6). However, another recent meta-analysis showed that women with PCOS have an increased incidence of cerebrovascular events but not coronary ones (7). Those mixed and contradictory results are undoubtedly a call for a more definitive and conclusive answer.

Berni and colleagues (8) took that call, and in this issue of The Journal of Clinical Endocrinology & Metabolism, elegantly answer the critical question whether women with PCOS have an increased incidence of cardiovascular events. Mining a massive database of more than 880 primary care practices in England, they identified ~175 000 women with a diagnosis of PCOS who were matched by age, body mass index, and primary care practice to a similar number of non-PCOS control women. The primary outcome was the time to major adverse cardiovascular event (MACE), a composite endpoint incorporating myocardial infarction, stroke, angina, vascularization, and cardiovascular mortality. Secondary endpoints were the individual MACE endpoints. The study findings clearly showed that women with PCOS have an increased MACE with a remarkable adjusted hazard ratio of 1.26 (95% CI, 1.13-1.41; P < 0.001).

Moreover, individual endpoints such as myocardial infarction, angina, and revascularization were also significantly increased in women with PCOS. However, stroke incidence rate did not differ with PCOS diagnosis status. These exciting findings clearly show that women with PCOS have indeed increased incidence of cardiovascular events. Moreover, those results strongly suggest that CVRFs should be followed up in women with PCOS as they are predictive of cardiovascular events in this, as in other, patient populations. Furthermore, CVRFs assessment in women with PCOS would surely translate into better clinical outcomes and decreased morbidity in these patients.

The study from Berni and colleagues (8) is probably not the definitive answer to their original question, as there are no final answers in science. However, the astonishing number of women with PCOS analyzed gives unprecedented strength to this study. We hope that this outstanding report will prompt further studies with even larger numbers of subjects and longer follow-up periods. Moreover, it would be exciting to confirm if the current findings also apply to PCOS populations from other ethnicities, geographical locations, age ranges, and comorbidities. Diagnosis and treatment of women with PCOS has lagged compared with other diseases. Berni and colleagues’ study (8) and expected future studies are critical to improve the clinical management and quality of life of patients with PCOS.

Glossary

Abbreviations

CVRF

cardiovascular risk factor

MACE

major adverse cardiovascular event

PCOS

polycystic ovary syndrome

Additional Information

Disclosures: The authors have stated explicitly that there are no conflicts of interest in connection with this article.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.