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.

<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 incre...

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Main Authors: Balachandran Kumarendran, Michael W O'Reilly, Konstantinos N Manolopoulos, Konstantinos A Toulis, Krishna M Gokhale, Alice J Sitch, Chandrika N Wijeyaratne, Arri Coomarasamy, Wiebke Arlt, Krishnarajah Nirantharakumar
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-03-01
Series:PLoS Medicine
Online Access:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1002542&type=printable
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author Balachandran Kumarendran
Michael W O'Reilly
Konstantinos N Manolopoulos
Konstantinos A Toulis
Krishna M Gokhale
Alice J Sitch
Chandrika N Wijeyaratne
Arri Coomarasamy
Wiebke Arlt
Krishnarajah Nirantharakumar
author_facet Balachandran Kumarendran
Michael W O'Reilly
Konstantinos N Manolopoulos
Konstantinos A Toulis
Krishna M Gokhale
Alice J Sitch
Chandrika N Wijeyaratne
Arri Coomarasamy
Wiebke Arlt
Krishnarajah Nirantharakumar
author_sort Balachandran Kumarendran
collection DOAJ
description <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 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.<h4>Conclusions</h4>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.
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institution Kabale University
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language English
publishDate 2018-03-01
publisher Public Library of Science (PLoS)
record_format Article
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spelling doaj-art-7fc7d0d5c11047569fdb818e62aabfbf2025-08-20T03:25:45ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762018-03-01153e100254210.1371/journal.pmed.1002542Polycystic 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.Balachandran KumarendranMichael W O'ReillyKonstantinos N ManolopoulosKonstantinos A ToulisKrishna M GokhaleAlice J SitchChandrika N WijeyaratneArri CoomarasamyWiebke ArltKrishnarajah Nirantharakumar<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 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.<h4>Conclusions</h4>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.https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1002542&type=printable
spellingShingle Balachandran Kumarendran
Michael W O'Reilly
Konstantinos N Manolopoulos
Konstantinos A Toulis
Krishna M Gokhale
Alice J Sitch
Chandrika N Wijeyaratne
Arri Coomarasamy
Wiebke Arlt
Krishnarajah Nirantharakumar
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.
PLoS Medicine
title 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.
title_full 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.
title_fullStr 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.
title_full_unstemmed 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.
title_short 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.
title_sort 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
url https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1002542&type=printable
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