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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.

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  • Authors+Show Affiliations

    ,

    Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom. Department of Public Health, Faculty of Medicine, University of Kelaniya, Kelaniya, Sri Lanka.

    ,

    Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom. Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, United Kingdom.

    ,

    Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom. Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, United Kingdom.

    ,

    Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom.

    ,

    Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom.

    ,

    Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom.

    ,

    Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.

    ,

    Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom. Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, United Kingdom.

    ,

    Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom. Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, United Kingdom.

    Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom. Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom. Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, United Kingdom.

    Source

    PLoS medicine 15:3 2018 03 pg e1002542

    MeSH

    Adolescent
    Adult
    Androgens
    Body Mass Index
    Diabetes Mellitus, Type 2
    Female
    Humans
    Insulin Resistance
    Longitudinal Studies
    Male
    Middle Aged
    Multivariate Analysis
    Non-alcoholic Fatty Liver Disease
    Polycystic Ovary Syndrome
    Prevalence
    Proportional Hazards Models
    Retrospective Studies
    Risk Factors
    United Kingdom
    Young Adult

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    29590099

    Citation

    Kumarendran, Balachandran, et al. "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, vol. 15, no. 3, 2018, pp. e1002542.
    Kumarendran B, O'Reilly MW, Manolopoulos KN, et al. 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 Med. 2018;15(3):e1002542.
    Kumarendran, B., O'Reilly, M. W., Manolopoulos, K. N., Toulis, K. A., Gokhale, K. M., Sitch, A. J., ... Nirantharakumar, K. (2018). 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, 15(3), pp. e1002542. doi:10.1371/journal.pmed.1002542.
    Kumarendran B, et al. 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 Med. 2018;15(3):e1002542. PubMed PMID: 29590099.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - 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. AU - Kumarendran,Balachandran, AU - O'Reilly,Michael W, AU - Manolopoulos,Konstantinos N, AU - Toulis,Konstantinos A, AU - Gokhale,Krishna M, AU - Sitch,Alice J, AU - Wijeyaratne,Chandrika N, AU - Coomarasamy,Arri, AU - Arlt,Wiebke, AU - Nirantharakumar,Krishnarajah, Y1 - 2018/03/28/ PY - 2017/09/12/received PY - 2018/02/21/accepted PY - 2018/3/29/entrez PY - 2018/3/29/pubmed PY - 2019/1/31/medline SP - e1002542 EP - e1002542 JF - PLoS medicine JO - PLoS Med. VL - 15 IS - 3 N2 - 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. SN - 1549-1676 UR - https://www.unboundmedicine.com/medline/citation/29590099/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_ L2 - http://dx.plos.org/10.1371/journal.pmed.1002542 DB - PRIME DP - Unbound Medicine ER -