Genetic data show evidence for ‘male PCOS,’ with cardiometabolic consequences
Genetic risk factors for polycystic ovary syndrome can act independently of ovarian function, causing cardiometabolic dysfunction and hyperandrogenism through biological pathways common to both men and women, according to a speaker.
An analysis of UK Biobank data suggests there is evidence for a genetically defined male counterpart for PCOS, with an ovarian-independent pathogenesis that can increase risk for excess weight, type 2 diabetes and cardiovascular disease, Jia Zhu, MD, an endocrinology fellow at Boston Children’s Hospital, said during a virtual presentation at the ENDO annual meeting.
“Our study shows that men can develop characteristics of PCOS, a common reproductive disorder that, by definition, affects only women,” Zhu told Healio. “By taking genetic factors that contribute to risk for PCOS in women and examining them in men, we found that these genetic risk factors are associated with increased risk for obesity, type 2 diabetes, CVD and male-pattern baldness. Thus, some of the mechanisms leading to features of PCOS do not act primarily through the ovaries, but rather through pathways present in both women and men.”
Zhu and colleagues used findings from a 2018 genome-wide association study to optimize a polygenic risk score for PCOS in women. Researchers then used the optimized polygenic risk score to calculate a PCOS polygenic risk score for 176,360 men who shared data with the UK Biobank, a large-scale biomedical database and research resource, and assessed associations between the risk score, cardiometabolic outcomes (obesity, type 2 diabetes and CVD) and male-pattern baldness.
Among the men, researchers observed a BMI increase of 0.2 kg/m² for every standard deviation increase in the PCOS polygenic risk score. Similarly, researchers observed a 9% increase in odds for obesity per 1 standard deviation increase in polygenic risk score.
Looking at cardiometabolic outcomes, researchers found that, as polygenic risk score increased, HbA1c and triglyceride levels increased, whereas HDL cholesterol decreased. The risk for type 2 diabetes and CVD also increased as polygenic risk score increased. In causal mediation analysis, researchers found that BMI partially, but not completely, mediated the relationship between HbA1c, type 2 diabetes and polygenic risk score. However, BMI appeared to completely mediate the relationship between polygenic risk score and HDL cholesterol, triglyceride levels and coronary artery disease, Zhu said.
Additionally, as polygenic risk score increased, free androgen index increased and levels of sex hormone-binding globulin in men decreased.
“Although the name ‘polycystic ovary syndrome’ implies that the ovaries play a central role in the disorder, PCOS may not always be primarily a disorder of the female reproductive system,” Zhu told Healio. “Our findings shed light on the significant and often lifelong associated metabolic conditions — obesity, type 2 diabetes, CVD — that affect women long beyond the reproductive years and that can also affect men who carry genetic risk factors for PCOS. Future studies on the mechanisms and treatment targets of the metabolic dysfunction associated with PCOS may benefit both men and women.”