Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database

• Published in: PLoS medicine Vol. 15; no. 3; p. e1002542
• Main Authors: Kumarendran, Balachandran, O’Reilly, Michael W., Manolopoulos, Konstantinos N., Toulis, Konstantinos A., Gokhale, Krishna M., Sitch, Alice J., Wijeyaratne, Chandrika N., Coomarasamy, Arri, Arlt, Wiebke, Nirantharakumar, Krishnarajah
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.03.2018; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Analysis; Androgens; Androgens - blood; Biology and Life Sciences; Body mass; Body Mass Index; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - epidemiology; Fatty liver; Female; Globulins; Health risk assessment; Health risks; Humans; Insulin Resistance; Liver; Liver diseases; Longitudinal Studies; Male; Medicine and Health Sciences; Metabolic disorders; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - complications; Non-alcoholic Fatty Liver Disease - epidemiology; Polycystic ovary syndrome; Polycystic Ovary Syndrome - blood; Polycystic Ovary Syndrome - complications; Polycystic Ovary Syndrome - epidemiology; Prevalence; Proportional Hazards Models; Retrospective Studies; Risk Factors; Testosterone; United Kingdom; Women's health; Young Adult; United Kingdom; United Kingdom > UK; Sri Lanka
• ISSN: 1549-1676; 1549-1277; 1549-1676
• DOI: 10.1371/journal.pmed.1002542

Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), which affects 10% of women and represents a lifelong metabolic disorder, with increased risk of type 2 diabetes, hypertension, and cardiovascular events. Previous studies have suggested an increased risk of nonalcoholic fatty liver disease (NAFLD) in individuals with PCOS and implicated androgen excess as a potential driver. 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-, body mass index (BMI)-, and location-matched control women registered from January 2000 to May 2016. In 2 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 the 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 of this study include its retrospective nature, absence of detailed information on criteria used to diagnosis PCOS and NAFLD, and absence of data on laboratory assays used to measure serum androgens. 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 women with PCOS. In women with PCOS-related androgen excess, systematic NAFLD screening should be considered.