High-free androgen index is associated with increased risk of non-alcoholic fatty liver disease in women with polycystic ovary syndrome, independent of obesity and insulin resistance

Cai, Jialin; Wu, Chuanlong; Zhang, Y; Wang, Yue-Ying; Xu, Wangyang; Lin, Tzu-Chun; Li, S X; Wang, L H; Zheng, Jiali; Sun, Yun; Liu, W; Tao, Ting

doi:10.1038/ijo.2017.116

Cited by 61 publications

(46 citation statements)

References 38 publications

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“…174 These associations have been observed in other studies. [175][176][177] Our group has carried out a cohort study utilising a large primary care database in the United Kingdom, including 63,000 women with PCOS and 121,000 matched controls, revealing that the risk of NAFLD was significantly increased in women with PCOS, even in women with a normal BMI (hazard ratio = 2.23, 95% CI 1.86-2.66, p < 0.001). 178 Androgen excess (high testosterone, low SHBG) was found to be a contributing risk factor for the development of NAFLD in PCOS in this study.…”

Section: Livermentioning

confidence: 99%

Implicating androgen excess in propagating metabolic disease in polycystic ovary syndrome

Kempegowda

Melson

Manolopoulos

et al. 2020

Therapeutic Advances in Endocrinology

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Polycystic ovary syndrome (PCOS) has been traditionally perceived as a reproductive disorder due to its most common presentation with menstrual dysfunction and infertility. However, it is now clear that women with PCOS are at increased risk of metabolic dysfunction, from impaired glucose tolerance and type 2 diabetes mellitus to nonalcoholic fatty liver disease and cardiovascular disease. PCOS is characterised by androgen excess, with cross-sectional data showing that hyperandrogenism is directly complicit in the development of metabolic complications. Recent studies have also shown that C11-oxy C19 androgens are emerging to be clinically and biochemically significant in PCOS, thus emphasising the importance of understanding the impact of both classic and C11-oxy C19 androgens on women’s health. Here we discuss androgen metabolism in the context of PCOS, and dissect the role played by androgens in the development of metabolic disease through their effects on metabolic target tissues in women.

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Section: Livermentioning

confidence: 99%

Implicating androgen excess in propagating metabolic disease in polycystic ovary syndrome

Kempegowda

Melson

Manolopoulos

et al. 2020

Therapeutic Advances in Endocrinology

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“…Similarly, 2 small cross-sectional studies found significant associations between NAFLD and PCOS [ 14 , 15 ]. Following the publication of some preliminary evidence [ 16 ], 2 recent studies and a very recent meta-analysis have implicated androgen excess as a potentially BMI-independent risk factor for NAFLD in PCOS [ 17 – 19 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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BackgroundAndrogen 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 findingsWe 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.ConclusionsWe 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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“…P olycystic ovary syndrome (PCOS) is an endocrine disorder affecting approximately 5-16% of women in reproductive age and is characterized by at least two of the following conditions: hyperandrogenism (clinical or biochemical), irregular menstrual cycle, and presence of ovarian cysts (1,2). PCOS directly affects body composition and anthropometric indices, as well as endocrine, metabolic, and cardiovascular system parameters (1)(2)(3)(4)(5). Central obesity is also a prevalent characteristic because of hyperandrogenism and insulin resistance (IR), which act in vicious feedback mechanisms (6,7).…”

Section: Introductionmentioning

confidence: 99%

“…Central obesity is also a prevalent characteristic because of hyperandrogenism and insulin resistance (IR), which act in vicious feedback mechanisms (6,7). However, abdominal fat may go undetected in women of normal weight who exhibit an apparently lean PCOS (6,7), predisposing them to risk factors for chronic diseases, such as metabolic syndrome and arterial hypertension (1,(4)(5). The prevalence of metabolic syndrome among individuals with PCOS is 12.6%, which is almost seven times higher than that in healthy women with a higher body mass index (BMI) (8).…”

Section: Introductionmentioning

confidence: 99%

Association of measures of central fat accumulation indices with body fat distribution and metabolic, hormonal, and inflammatory parameters in women with polycystic ovary syndrome

Ribeiro¹,

Kogure²,

Lopes³

et al. 2019

Archives of Endocrinology and Metabolism

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Objective: To investigate the associations among visceral adiposity index (VAI), lipid accumulation product (LAP), body fat percentage (%), and android/gynoid ratio (A/G ratio) in women with polycystic ovary syndrome (PCOS) and verify if the parameters representative of visceral obesity correlate with and exhibit the same frequency as body composition variables; anthropometric indices; and metabolic, hormonal, and inflammatory parameters. Subjects and methods: This was a cross-sectional study that included 94 women with PCOS. Hormonal, metabolic, and inflammatory parameters were analyzed in all women. Free androgen index (FAI) and homeostasis model assessment (HOMA-IR), as well as LAP, VAI, and anthropometric indices, were calculated. The regions of interest (ROIs) in body composition and body composition indices were evaluated using a dual X-ray absorptiometry (DXA). Overall, 32 variables were selected as markers of body fat distribution. Results: Among the 32 markers evaluated, 29 correlated with LAP, whereas 25 correlated with VAI, 19 with body fat (%), and 30 with A/G ratio. Additionally, some markers correlated with the four adiposity indices evaluated: ROIs, except for total mass and leg fat (%); body composition (body mass index, waist circumference, and hip circumference) indices; fasting insulin; and C-reactive protein. Conclusion: LAP and VAI may be sensitive measures for screening and preventing metabolic syndrome and insulin resistance in PCOS, with LAP being more sensitive than VAI, and the A/G ratio may be more sensitive than body fat percentage.

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High-free androgen index is associated with increased risk of non-alcoholic fatty liver disease in women with polycystic ovary syndrome, independent of obesity and insulin resistance

Cited by 61 publications

References 38 publications

Implicating androgen excess in propagating metabolic disease in polycystic ovary syndrome

Implicating androgen excess in propagating metabolic disease in polycystic ovary syndrome

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

Association of measures of central fat accumulation indices with body fat distribution and metabolic, hormonal, and inflammatory parameters in women with polycystic ovary syndrome

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