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Is PCOS gender neutral? …revisiting the male-equivalent hypothesis…




Results presented at the Endo annual meeting this week, suggested there is evidence for a genetically male counterpart for PCOS which excludes the ovary as the point of origin. The pathogenesis is thought to increase risk for excess weight, type 2 diabetes and cardiovascular disease. The discovery came about by using the 2018 GWAS study to create a polygenic risk score for PCOS in women and then one for 176,360 men who shared data with the UK Biobank, a large-scale biomedical database and research resource[1].


The polygenic risk score assessed associations with obesity, type 2 diabetes mellitus and male-patterned baldness. Findings showed an increase of 0.2kg/m2 in BMI for every standard deviation increase in polygenic risk score. Similarly, as the risk score increased so too did risk of type 2 diabetes and cardiovascular disease. BMI did not completely account for diabetes but did appear to mediate the relationship between cholesterol and coronary artery disease. In addition, androgens increased and levels of sex hormone-binding globulin in men decreased too. [1]


Historically, there has been a lack of consensus regarding the exact diagnostic criteria for PCOS. Back in 2007, researchers first hypothesised that PCOS could also affect men because they thought that PCOS did not begin in the ovary. Add to that the fact that the name is a misnomer and that you can have PCOS without ovarian cysts (which are in fact immature follicles), this hypothesis is not unexpected. Immature follicles on the ovaries are a downstream manifestation of the gonadotrophin/androgen and/or insulin pathway. Other factors that led them to this hypothesis included the fact that we know there is a genetic susceptibility to PCOS and that male relatives may suffer from some PCOS symptoms like Insulin Resistance, Obesity, Type 2 Diabetes Mellitus and Cardiovascular disease. [2]


Male relatives of women with PCOS who have hormonal and metabolic disturbances have also been found to have a higher prevalence of Androgenetic Alopecia (AGA) starting before the age of 35. In addition, large cohort studies have shown a higher rate of type 2 diabetes and CVD in men with AGA. [3]


A systematic review of cardiometabolic health in offspring of women with PCOS (OPCOS) aged 1 to 18 years found subtle signs of altered cardiometabolic health in OPCOS in both sexes. Although predominantly in females, combined with this new discovery, more studies are needed to examine the influence of a PCOS diagnosis on fetal development, childhood and beyond.[4]


This latest study has important implications for PCOS. Firstly, it may be time for us to revisit the name of the condition. Secondly, it is important to adopt a life-course approach to PCOS taking advantage of opportunities to prevent long term sequelae. Thirdly, we need a shift in focus from interventions which focus solely on effects of maternal health to consider paternal health on the health of PCOS offspring. Finally, the findings fortify the need to acknowledge that Hirsutism or Alopecia are far from being mere cosmetic problems but conditions that should be effectively assessed and treated.

© PCOS Vitality 2021


REFERENCES:

[1] Genetic evidence suggests men can develop PCOS-like condition | Endocrine Society, (n.d.). https://www.endocrine.org/news-and-advocacy/news-room/featured-science-from-endo-2021/genetic-evidence-suggests-men-can-develop-pcos-like-condition (accessed March 23, 2021).

[2] R. Kurzrock, P.R. Cohen, Polycystic ovary syndrome in men: Stein-Leventhal syndrome revisited, Med. Hypotheses. 68 (2007) 480–483. https://doi.org/10.1016/j.mehy.2006.03.057.

[3] R. Cannarella, R.A. Condorelli, L.M. Mongioì, S. La Vignera, A.E. Calogero, Does a male polycystic ovarian syndrome equivalent exist?, J. Endocrinol. Invest. 41 (2018) 49–57. https://doi.org/10.1007/s40618-017-0728-5.

[4] M.N. Gunning, T. Sir Petermann, N. Crisosto, B.B. van Rijn, M.A. de Wilde, J.P. Christ, C.S.P.M. Uiterwaal, W. de Jager, M.J.C. Eijkemans, A.R. Kunselman, R.S. Legro, B.C.J.M. Fauser, Cardiometabolic health in offspring of women with PCOS compared to healthy controls: a systematic review and individual participant data meta-analysis, Hum. Reprod. Update. 26 (2020) 104–118. https://doi.org/10.1093/humupd/dmz036.


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