Methods and findings: We carried out a retrospective longitudinal cohort study utilizing a large primary care database in the United Kingdom, evaluating NAFLD rates in 63,120 women with PCOS and 121,064 age-, BMI- and location-matched control women registered from January 2000 to May 2016. In two independent cohorts, we also determined the rate of NAFLD in women with a measurement of serum testosterone (n=71,061) and sex hormone-binding globulin (SHBG; n=49,625). We used multivariate Cox models to estimate Hazard Ratio (HR) for NAFLD and found that women with PCOS had an increased rate of NAFLD (HR=2·23, 95%CI 1·86-2·66, p<0.001), also after adjusting for BMI or dysglycemia. Serum testosterone >3.0 nmol/L was associated with an increase in NAFLD (HR=2.30, 95%CI 1.16-4.53, p=0.017 for 3-3.49 nmol/L and HR=2·40, 95%CI 1·24-4·66, p=0.009 for >3.5 nmol/L). Mirroring this finding, SHBG <30 nmol/L was associated with increased NAFLD hazard (HR=4.75, 95%CI 2.44-9.25, p<0.001 for 20-29.99 nmol/L and HR=4·98, 95%CI 2·45-10·11, p<0.001 for <20 nmol/L). Limitations include its retrospective nature, absence of detailed information on criteria used to diagnosis PCOS and NAFLD, and the absence of data on laboratory assays used to measure serum androgens.
Conclusions: We found that women with PCOS have an increased rate of NAFLD. In addition to increased BMI and dysglycemia, androgen excess contributes to the development of NAFLD in PCOS. In women with PCOS-related androgen excess, systematic NAFLD screening should be considered.