Cardiovascular disease risk in women with hyperandrogenism, oligomenorrhea/menstrual irregularity or polycystic ovaries (components of polycystic ovary syndrome): a systematic review and meta-analysis.

Aims: Prior meta-analyses indicate polycystic ovary syndrome (PCOS) is associated with cardiovascular diseases (CVDs), but have high statistical heterogeneity, likely because PCOS is a heterogenous syndrome diagnosed by having any two of the three components: hyperandrogenism, oligomenorrhea/menstrual irregularity or polycystic ovaries. Several studies report higher risk of CVDs from individual PCOS components, but a comprehensive assessment of how each component contributes to CVD risk is lacking. This study aims to assess CVD risk for women with one of the PCOS components. Methods and results: A systematic review and meta-analysis of observational studies was conducted. PubMed, Scopus, and Web of Science were searched without restrictions in July 2022. Studies meeting inclusion criteria examined the association between PCOS components and risk of a CVD. Two reviewers independently assessed abstracts and full-text articles, and extracted data from eligible studies. Where appropriate, relative risk (RR) and 95% confidence interval (CI) were estimated by random-effects meta-analysis. Statistical heterogeneity was assessed using the I² statistic. Twenty-three studies, including 346 486 women, were identified. Oligo-amenorrhea/menstrual irregularity was associated with overall CVD (RR = 1.29, 95%CI = 1.09–1.53), coronary heart disease (CHD) (RR = 1.22, 95%CI = 1.06–1.41), and myocardial infarction (MI) (RR = 1.37, 95%CI = 1.01–1.88) but not cerebrovascular disease. These results were broadly consistent even after further adjustment for obesity. There was mixed evidence for the role of hyperandrogenism in CVDs. No studies examined polycystic ovaries as an independent exposure for CVD risk. Conclusion: Oligo-amenorrhea/menstrual irregularity is associated with greater risk of overall CVD, CHD, and MI. More research is needed to assess the risks associated with hyperandrogenism or polycystic ovaries. Lay Summary: Polycystic ovary syndrome (PCOS) is associated with a higher risk of cardiovascular disease (CVD). It is unclear how risk of CVD varies with the different components of PCOS and whether risk occurs independently of obesity. In this systematic review of 346 486 women, we found that irregular, infrequent or absent periods were associated with a higher risk of CVD, coronary heart disease, and myocardial infarction, with this association occurring independently of obesity. There was mixed evidence of a higher risk of CVDs with hyperandrogenism and no studies evaluated polycystic ovaries as a lone risk factor. The clear association between irregular, infrequent or absent periods and certain CVDs could inform how cardiometabolic screening and risk management may be tailored to specific PCOS phenotypes. Future research could focus on the influence of polycystic ovaries and different manifestations of hyperandrogenism on CVD risk. Graphical abstract [ABSTRACT FROM AUTHOR]