Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder, affecting up to 1 in 5 women of child-bearing age and characterized by irregular ovulation, features of hyperandrogenism, and polycystic ovaries (1, 2). Moreover, incidence of PCOS has been increasing worldwide along with the epidemics of obesity and type 2 diabetes (T2D). The ovarian dysfunction characterizing PCOS makes it a leading cause of infertility, which is also impacted by higher rates of obesity, insulin resistance, gestational and T2D, and hypertension (2). Additionally, there are important race/ethnic variations to consider in PCOS manifestations (2). The diversity in PCOS phenotypes often leads to delayed diagnosis, making early intervention and prevention challenging.
Overweight or obese body mass index (BMI) are common in women with PCOS, with prevalence as high as 80% (1). Obesity in PCOS may also be secondary to insulin resistance and hyperinsulinemia leading to downstream increased availability of free androgens, visceral fat accumulation, and central obesity (1). Rapid weight gain in adolescence can be secondary to PCOS and should trigger screening for PCOS with other concerning symptoms. Obesity is also an important risk factor for hypertension and hypertensive disorders in pregnancy (3).
Hypertension in PCOS is thought to develop from several proposed mechanisms: (1) activation of the renin-angiotensin system from hyperaldosteronism, (2) insulin resistance and compensatory hyperinsulinemia, (3) hyperandrogenism, (4) activation of the sympathetic nervous system, and (5) reduction in the production of nitric oxide (1). PCOS has been associated with an approximately 2-fold increased risk of cardiovascular disease (CVD) (1). Cardiometabolic risk factors such as hypertension are important mediators of future CVD among women with PCOS. However, whether the relationship between PCOS and hypertension is independent of obesity has been difficult to establish.
The study by Joham et al, published in the June 2021 issue of the Journal of Clinical Endocrinology and Metabolism (4), offers some clarity by examining these associations prospectively with both adjustments for BMI and stratification by BMI groups. Using the Australian Longitudinal Study on Women’s Health, the authors followed a population of 8223 women of reproductive age (mean age 25 years), with 8.3% self-reporting PCOS at baseline. Of these, 18.5% developed incident hypertension over the 15-year follow-up period. The key findings were 3-fold. First, PCOS was independently associated with a 37% greater risk of incident hypertension (hazard ratio 1.37 [95% CI, 1.14-1.65]), even after adjustment including age, BMI, and concomitant T2D. Second, when the population was stratified by BMI, the incidence of hypertension was higher among women with PCOS (compared with women without PCOS) across all weight categories. Nevertheless, obesity modified this relationship with the incidence rate difference (between women with and without PCOS) being nearly 4-fold higher among women with obesity (≥30 kg/m2) than those of healthy weight (18.5-24.9 kg/m2). This suggests obesity further compounds risk attributable to PCOS, making it an important focus for screening and intervention. Third, the authors found a population attributable fraction of 5%, meaning a half million hypertension cases in Australia might have been averted if PCOS could be prevented or cured. The population attributable fraction is an important population-level statistic describing the proportional of incident hypertension attributable to PCOS to help guide policy and interventions directed toward this group.
This current study does have some limitations; given the observational nature, residual confounding cannot be excluded, and both PCOS and hypertension were self-reported (4). Nevertheless, it represents one of the largest prospective evaluations of the relationship between PCOS and hypertension and confirms other prior cross-sectional and case control studies (5, 6). A prior study from Brazil had found a high prevalence of hypertension (defined as blood pressure [BP] ≥ 130/80 mmHg) among women with PCOS (65%), that was significantly greater than matched control women (41%) (5). Complimentary to this current Australian study, a retrospective cohort in Taiwan also found that young women with PCOS had greater risk of incident hypertension than controls (adjusted hazard ratio 1.62 [1.48-1.76]) (7). This association was magnified among women with additional comorbidities of diabetes and dyslipidemia up to 9-fold, suggesting multiplicative risk (7). Additional support for the higher risk for hypertension with PCOS comes from a meta-analysis by Amiri et al (6). In that study, women with PCOS of reproductive age were found to have a relative risk of hypertension 1.7-fold (1.43-2.07) higher than control women of similar ages. However, the relative risk of prevalent hypertension in menopausal or older women with PCOS was similar to controls, suggesting that PCOS is a less important risk factor for hypertension after menopause (6).
Current guidelines recommend that all women with PCOS get yearly BP screening, although more frequent measures would be prudent in women with concurrent obesity, hyperlipidemia, or diabetes (2). It is important that women with PCOS are counseled on healthy diet, regular physical exercise, and maintenance of a normal BMI to decrease the risk of incident hypertension. However, beyond healthy lifestyle (recommended for all women), it is not clear what additional interventions, such as pharmacotherapy, could reduce PCOS-related hypertension risk, and more research is needed.
Oral contraceptives are frequently used in management of PCOS, yet even contemporary low-dose combined estrogen/progestin oral contraceptives can increase BP up to 8/6 mmHg (8). Clomiphene is also associated with elevations in BP. Combined hormonal contraceptives are discouraged among women with hypertension (BP ≥ 140/90 mmHg) in the absence of other suitable options and should be avoided altogether in women with BP ≥160/100 mmHg (8). Conversely, progestin-only pills and depot medroxyprogesterone acetate do not have significant BP effects. These are important considerations when considering treatment for PCOS, since combined oral contraceptives are often used to manage hyperandrogenism and irregular menstrual cycles and clomiphene for infertility (2).
Treatment in women with PCOS has largely focused on the menstrual irregularity, infertility, acne, and hirsutism aspects. Less attention has been placed on longer-term PCOS risks such as incident hypertension and CVD, and many women with PCOS are unaware of these associations, resulting in missed opportunities for prevention. More research should be directed toward the development of novel interventions that target the biological pathways responsible for insulin resistance, hypertension, and dyslipidemia in PCOS to reduce the substantial morbidity conferred by this syndrome.
In conclusion, hypertension is common among women with PCOS and may represent an important mediator for subsequent CVD risk. Further research on lifestyle interventions is needed in this high-risk, and yet profoundly understudied population of younger women.
Acknowledgments
Financial Support: Dr Michos is supported by the Amato Fund in Women’s Cardiovascular Health at Johns Hopkins School of Medicine. Dr Kovell is supported in part by a Physician Development Pilot Grant at the University of Massachusetts. Dr Juraschek is supported by National Institute of Health (NIH)/National Heart Lung Blood Institute (NHLBI) K23HL135273.
Glossary
Abbreviations
- BMI
body mass index
- BP
blood pressure
- CVD
cardiovascular disease
- PCOS
polycystic ovary syndrome
- T2D
type 2 diabetes
Additional Information
Disclosures: None of the authors report any disclosures.
Data Availability
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
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Data Availability Statement
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.