Comorbidities in women with polycystic ovary syndrome: a sibling study

BACKGROUND: Polycystic ovary syndrome (PCOS) has previously been associated with several comorbidities that may have shared genetic, epigenetic, developmental or environmental origins. We analyzed the association between PCOS and several relevant comorbidities while adjusting for early-life biological and socioeconomic conditions, also investigating the extent to which the association is affected by familial risk factors. METHODS: This total-population register-based cohort study included 857,757 singleton females (333,999 with at least one full sister) born between 1962 and 1980. PCOS and comorbidity diagnoses were measured at age 17-45 years through national hospital register data from 1997 to 2011, and complemented with information on the study subjectś early-life and social characteristics. In the main analysis, sibling fixed effects (FE) models were used to control for all factors that are shared and time-invariant among sisters, thereby testing whether PCOS and examined comorbidities are determined by unobserved familial; environmental, social or genetic factors. RESULTS: 9,321 women were diagnosed with PCOS, of whom 15% had obesity, 9% had depression, 8% had anxiety and 4% suffered from sleeping, sexual and eating disorders (SSE). Having PCOS was associated with the odds of obesity increasing nearly 6-fold (adjusted OR (aOR): 5.8 [95%CI:5.5-6.2]). This association was attenuated considerably when accounting for characteristics shared between full sisters (Sister FE: aOR: 4.5 [95% CI: 3.6-5.6]). Among the psychiatric comorbidities, depression (Sister FE: aOR: 1.4 [95% CI: 1.2-1.8]) and anxiety (Sister FE: aOR: 1.5 [95% CI: 1.2-1.8), there was a small decrease in the aORs when also controlling for factors shared between sisters. CONCLUSIONS: Having been diagnosed with PCOS is associated with an increased risk of obesity and psychiatric comorbidities and a substantial part of this risk can be attributed to factors shared between sisters. KEY MESSAGES: • PCOS is associated with an increased risk of obesity, depression and anxiety. • Among women with PCOS, 16% of the increased risk for obesity, 20% for depression and 29% for anxiety can be attributed to shared family factors between sisters.