PhD defence C. (Cindy) Meun

Summary:

Polycystic ovary syndrome (PCOS) is associated with cardiometabolic disturbances which might increase the risk for cardiovascular disease (CVD) later in life. The exact pathogenesis of PCOS is far from fully understood. We aimed to identify genetic variants associated with PCOS by performing a GWAS meta-analysis. Moreover, we assessed the cardiometabolic profile and risk for CVD later in life.

We conducted a fixed-effect, inverse weighted-variance meta-analysis from 10.074 PCOS cases and 103.164 controls. We identified three novel loci, and replicated 11 previously reported loci and a similar genetic architecture for all diagnostic criteria. The data provide the first genetic evidence for a male phenotype of PCOS and a causal link to depression.

We assessed middle-aged women with PCOS, and compared them to age-matched controls. We observed a moderately unfavorable cardiometabolic profile in women with PCOS. We found no evidence for increased CVD risk or more severe atherosclerosis. 
Furthermore, we assessed the prevalence and severity of subclinical coronary and intracranial calcification in asymptomatic women with PCOS aged >45 and compared them to age and ethnicity matched controls. Subclinical coronary artery calcification was comparable to age and ethnicity matched controls.
Finally, we studied the association of high serum androgen levels, with prevalent atherosclerosis and incident CVD in postmenopausal women. We studied women with a mean age of 70 years and average time since menopause of 20 years. Postmenopausal high androgen levels were not associated with an elevated risk for CVD. Cardiovascular health in women with PCOS might be better than was previously anticipated.