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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.

ABSTRACT: Background: 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.

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-, 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.

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 women with PCOS. In women with PCOS-related androgen excess, systematic NAFLD screening should be considered.

SUBMITTER: Kumarendran B

PROVIDER: S-EPMC5873722 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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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.

Kumarendran Balachandran B O'Reilly Michael W MW Manolopoulos Konstantinos N KN Toulis Konstantinos A KA Gokhale Krishna M KM Sitch Alice J AJ Wijeyaratne Chandrika N CN Coomarasamy Arri A Arlt Wiebke W Nirantharakumar Krishnarajah K

PLoS medicine 20180328 3

<h4>Background</h4>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.<h4>Methods and findings</h4>We carried out a retrospective longitudinal cohort ...[more]

PMID: 29590099

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Project description:Study questionWhat is the effect of saturated fat ingestion on mononuclear cell (MNC) TNFα, IL-6 and IL-1β secretion and circulating IL-6 levels in women with polycystic ovary syndrome (PCOS)?Summary answerWomen with PCOS exhibit increases in MNC-derived TNFα, IL-6 and IL-1β secretion and circulating IL-6 following saturated fat ingestion even in the absence of obesity, and these increases are linked to metabolic aberration and androgen excess.What is known alreadyCytokine excess and metabolic aberration is often present in PCOS.Study design, size, durationA cross-sectional design was used in this study of 38 reproductive-age women.Participants/materials, setting, methodsGroups of 19 reproductive-age women with PCOS (10 lean, 9 obese) and 19 ovulatory controls (10 lean, 9 obese) participated in this study that was performed at a tertiary academic medical centre. TNFα, IL-6 and IL-1β secretion was measured from cultured MNC, and IL-6 was measured in plasma from blood sampling while fasting and 2, 3 and 5 h after saturated fat ingestion. Insulin sensitivity was determined using the Matsuda index following an oral glucose tolerance test. Androgen secretion was evaluated with blood sampling while fasting and 24, 48 and 72 h after an HCG injection.Main results and the role of chanceLean and obese women with PCOS exhibited lipid-induced incremental AUC increases in MNC-derived TNFα (489-611%), IL-6 (333-398%) and IL-1β (560-695%) secretion and in plasma IL-6 levels (426-474%), in contrast with lean control subjects. In both PCOS groups, insulin sensitivity was lower (42-49%) and androgen secretion after HCG injection was greater (63-110%) compared with control subjects. The MNC-derived TNFα, IL-6 and IL-1β and circulating IL-6 responses were inversely associated with insulin sensitivity and directly associated with fasting lipids and androgen secretion after HCG injection.Limitations, reasons for cautionThe sample size of each of the four study groups was modest following group assignment of subjects by body mass.Wider implications of the findingsThis study showcases the unique pro-inflammatory contribution of circulating MNC in the development of metabolic aberration and androgen excess in PCOS.Study funding/competing interest(s)This research was supported by grant R01 DK107605 to F.G. from the National Institutes of Health, the Indiana Clinical and Translational Sciences Institute Clinical Research Center which is funded in part by grant UL1TR002529 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award, and the Indiana University Center for Diabetes and Metabolic Diseases funded by grant P30 DK097512 from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. No conflicts of interest, financial or otherwise, are declared by the authors.Trial registration numberClinicalTrials.gov NCT01489319.

Dataset Information

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.

Publications

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.

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