Hypertension and dyslipidemia in women with PCOS: a population-based multiregister study in Sweden

What is the impact of PCOS and the hyperandrogenic (HA) PCOS phenotype on the risk of developing hypertension and dyslipidemia?

PCOS is an independent risk factor for the development of hypertension and dyslipidemia, with the risk being higher among women with the HA PCOS phenotype.

PCOS is an established risk factor for insulin resistance and the metabolic syndrome. However, prospective data regarding the risk of hypertension and dyslipidemia in population-based cohorts of women with PCOS are limited.

This nationwide multiregister-based cohort study included a total of 297 215 women with PCOS and matched controls followed for up to 20 years. Data were retrieved from the Swedish Patient Register, the Prescribed Drug Register, the Medical Birth Register, the Cause of Death Register, the Total Population Register, and the Education Register.

Study participants resided in Sweden and were born between 1950 and 1999. The median age at study entry was 28 years. Women with a diagnosis of PCOS, androgen excess, or anovulatory infertility recorded in the Swedish Patient Register between 1 January 1997 and 31 December 2016 constituted the study population (n = 50 969). For each woman with PCOS, five controls matched by birth year and municipality were randomly selected from the Total Population Register (n = 246 246). The primary outcomes were incident hypertension and dyslipidemia after PCOS diagnosis, defined by International Classification of Diseases-10 codes and/or filled prescriptions for antihypertensive or lipid-lowering medications, respectively. Women with PCOS were further classified as hyperandrogenic (HA) if they had been diagnosed with androgen excess or had a filled prescription for anti-androgenic drugs in the Prescribed Drug Register; otherwise, they were classified as normoandrogenic (NA). Cox regression analyses were performed, adjusted for birth period, country of birth, and education. Overweight and obesity were accounted for in separate models using either BMI or an obesity ICD-10 diagnosis.

Women with PCOS had a higher risk of developing hypertension compared with non-PCOS women [adjusted Hazard Ratio (aHR) 2.25 (95% CI: 2.13-2.39), adjusted for obesity]. Those with the HA-PCOS phenotype had more than 5-fold increased risk [aHR 5.51 (95% CI: 4.97-6.10)]. Similarly, PCOS was associated with a higher risk of dyslipidemia [aHR 3.05 (95% CI: 2.69-3.46), adjusted for obesity], and women with the HA phenotype exhibited a more than 7-fold increased risk [aHR 7.82 (95% CI: 6.34-9.64)].

Inclusion of the most severe cases of PCOS could have led to an overestimation of risk estimates. Information on BMI was only available among parous women. The study comprised mainly women with Nordic origin and should be replicated in cohorts with other ethnicities.

Women with PCOS, especially those with the HA phenotype, face a substantially increased long-term risk of hypertension and dyslipidemia, highlighting the need for early cardiovascular risk assessment and preventive strategies in this population. The findings underscore that PCOS is not only a reproductive disorder but also a significant cardiovascular risk factor, warranting tailored prevention and management strategies.

The study was funded by the Family Planning Fund, Uppsala, and the Selanders Fund, Uppsala University (grant number 464251850). Furthermore, E.E. has a part-time research position funded by Uppsala University Hospital (grant number ALF 937815). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. E.E. has received lecture fees from Merck AB, none in any way related to this manuscript. The rest of the authors declare no conflicts of interest.

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