Serum Testosterone and Non-alcoholic Fatty Liver Disease in men and Women in the US

Jeong Yoon Yim; Jinju Kim; Donghee Kim; Aijaz Ahmed


Liver International. 2018;38(11):2051-2059. 

In This Article

Abstract and Introduction


Background & Aims: Testosterone plays a role in predisposing individuals to cardiovascular and metabolic diseases, but its effects differ between men and women. We investigated the association between serum total testosterone and non-alcoholic fatty liver disease in adults in the US.

Methods: A cross-sectional analysis of data from participants in the 2011–2012 National Health and Nutrition Examination Survey was performed. Subjects with significant alcohol consumption and those with viral hepatitis were excluded. We used the highest sex-specific quartiles of serum total testosterone as references. Suspected non-alcoholic fatty liver disease was diagnosed when serum alanine aminotransferase was >30 IU/L for men and >19 IU/L for women.

Results: Of the 4758 subjects (49.4% men), the prevalence of suspected non-alcoholic fatty liver disease was inversely correlated with the sex-specific quartiles of testosterone in men and women. In a multivariate model, low total testosterone levels were associated with progressively higher odds of suspected non-alcoholic fatty liver disease in men after adjusting for age, obesity and other metabolic risk factors (P values for trends <.01). When the women were divided into 2 groups according to menopausal status, a significant correlation was observed only in the post-menopausal women (P values for trends <.01). The adjusted odds ratios for suspected non-alcoholic fatty liver disease were 1.72–1.99 in men and 2.15–2.26 in post-menopausal women (lowest quartile vs highest quartile).

Conclusions: In this nationally representative sample of adults in the US, low total testosterone levels were associated with suspected non-alcoholic fatty liver disease in men and post-menopausal women independent of known risk factors.


Over the past 30 years, non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in the United States (US).[1] NAFLD includes a spectrum of clinical syndromes ranging from non-alcoholic fatty liver to non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and cirrhosis complicated by hepatocellular carcinoma.

Accumulating evidence suggests that sex steroid hormones play important roles in predisposing individuals to cardiovascular and metabolic diseases. Oestrogen has an atheroprotective effect in women, but circulating androgen may affect men and women differently. In men, obesity and metabolic syndrome were inversely associated with serum testosterone levels.[2,3] By contrast, in women, higher total testosterone levels were associated with an increased risk of metabolic syndrome.[4,5] This association in women was investigated in detail in the setting of polycystic ovary syndrome (PCOS), which is a common condition in premenopausal women and is characterized by hyperandrogenism and chronic oligo/anovulation.

Increasing data support the association between NAFLD and serum testosterone levels.[6–10] Several cross-sectional studies have reported a relatively consistent relationship between low total testosterone levels and NAFLD in men.[6,7] In women, data from the Multi-Ethnic Study of Atherosclerosis (MESA) indicated that post-menopausal women with fatty livers had higher serum total testosterone levels than those without fatty livers, which differed from the results of another study from Greece.[7,8] Although we reported that hyperandrogenaemia may be an independent risk factor for non-obese NAFLD in premenopausal PCOS patients,[11] other studies have reported that circulating levels of androgens did not correlate with the presence of NAFLD in women with PCOS.[9,10] Likewise, a few studies examining serum testosterone levels and NAFLD have exclusively focused on post-menopausal women or PCOS patients, and the results are controversial.

In this study, we investigated the relationship between suspected NAFLD and serum total testosterone levels in both men and women in a nationally representative sample of adults in the US. Since the hormonal milieu changes after menopause, women were subdivided into premenopausal and post-menopausal groups.