The association of sex steroid hormone concentrations with non-alcoholic fatty liver disease and liver enzymes in US men

Hong Phan; Aline Richard; Mariana Lazo; William G Nelson; Samuel R Denmeade; John Groopman; Norma Kanarek; Elizabeth A Platz; Sabine Rohrmann

doi:10.1111/liv.14652

The association of sex steroid hormone concentrations with non-alcoholic fatty liver disease and liver enzymes in US men

Liver Int. 2021 Feb;41(2):300-310. doi: 10.1111/liv.14652.

Authors

Hong Phan¹, Aline Richard², Mariana Lazo^{3

4

5}, William G Nelson^{6

7

8}, Samuel R Denmeade⁷, John Groopman^{7

8}, Norma Kanarek^{7

8}, Elizabeth A Platz^{3

5

6

7}, Sabine Rohrmann²

Affiliations

¹ Medical Faculty, University of Zurich, Zurich, Switzerland.
² Division of Chronic Disease Epidemiology; Epidemiology, Biostatistics and Prevention Institute, University Zürich, Zurich, Switzerland.
³ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁴ Department of Medicine, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, MD, USA.
⁶ Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷ Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
⁸ Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Abstract

Background & aims: This study aimed to analyse the association of sex hormone levels with liver enzyme levels and non-alcoholic fatty liver disease (NAFLD) in a nationally representative sample of men.

Methods: A total of 919 men from the US National Health and Nutrition Examination Study (NHANES) III were included in this cross-sectional analysis of data from 1988 to 1991. We used existing data on serum total and free testosterone, total and free estradiol, androstanediol glucuronide (AAG) and sex steroid-binding globulin (SHBG), and estimated their associations with aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and NAFLD, as determined using ultrasound, after adjusting for possible confounders including age, race, smoking, alcohol, physical activity, waist circumference and steroid hormones.

Results: Lower total testosterone (TT) and higher free estradiol were associated with higher odds of NAFLD after adjusting for confounders including the other sex hormones. Lower TT was associated with higher odds of elevated AST, but not ALT. Free testosterone, total estradiol, SHBG and AAG were not associated with NAFLD or liver enzymes.

Conclusions: This study supports an inverse association between TT concentration and NAFLD in men independent of other sex hormones (SHBG, AAG and estradiol) and known risk factors, such as obesity, age and lifestyle. Exploration of whether TT might be a non-invasive marker for NAFLD diagnosis is warranted.

Keywords: estradiol; hepatic steatosis; non-alcoholic fatty liver disease; sex hormone-binding globulin; testosterone.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Cross-Sectional Studies
Gonadal Steroid Hormones
Humans
Male
Non-alcoholic Fatty Liver Disease* / epidemiology
Nutrition Surveys
Testosterone

Substances

Gonadal Steroid Hormones
Testosterone

Grants and funding

P30 CA006973/CA/NCI NIH HHS/United States