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Abstract Details
Testosterone is Associated With Nonalcoholic Steatohepatitis and Fibrosis in Premenopausal Women With NAFLD
Clin Gastroenterol Hepatol. 2021 Jun;19(6):1267-1274.e1. doi: 10.1016/j.cgh.2020.09.045.Epub 2020 Oct 1.
Monika A Sarkar1, Ayako Suzuki2, Manal F Abdelmalek2, Katherine P Yates3, Laura A Wilson3, Nathan M Bass4, Ryan Gill5, Marcelle Cedars6, Norah Terrault7, NASH Clinical Research Network
Author information
1Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, California. Electronic address: monika.sarkar@ucsf.edu.
2Division of Gastroenterology and Hepatology, Duke University, Durham, North Carolina.
3Department of Epidemiology and Biostatistics, Johns Hopkins University, Baltimore, Maryland.
4Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, California.
5Department of Pathology, University of California, San Francisco, San Francisco, California.
6Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of California, San Francisco, San Francisco, California.
7Division of Gastroenterology and Hepatology, University of Southern California, Los Angeles, California.
Abstract
Background & aims: Higher testosterone contributes to imaging-confirmed nonalcoholic fatty liver disease (NAFLD) in women, but whether testosterone influences their disease severity is unknown.
Methods: The association of free testosterone (free T) with nonalcoholic steatohepatitis (NASH) was determined in pre-menopausal women with biopsy-confirmed NAFLD (n = 207). Interaction testing was performed for age and free T given decline in testosterone with age, and association of aging with NASH. Regression models adjusted for abdominal adiposity, diabetes, and dyslipidemia.
Results: Median age was 35 yrs (interquartile range, 29-41); 73% were white, 25% Hispanic; 32% had diabetes, 93% abdominal adiposity, and 95% dyslipidemia. 69% had NASH, 67% any fibrosis, and 15% advanced fibrosis. Higher free T levels were associated with NAFLD severity in younger women (interaction P value <.02). In the youngest age quartile, free T was independently associated with NASH (odds ratio [OR], 2.3; 95% CI, 1.2-4.4), NASH fibrosis (OR, 2.1; 95% CI, 1.1-3.8), and higher fibrosis stage (OR, 1.9; 95% CI, 1.1-3.4), P value .02. In these women, the proportion with NASH steadily rose from 27% to 88%, and with NASH fibrosis rose from 27% to 81%, with higher free T quartiles (P < .01). Free T was additionally associated with abdominal adiposity among all pre-menopausal women (OR, 2.2; 95% CI, 1.2-4.1: P = .02).
Conclusions: In young women with NAFLD, higher testosterone levels conferred a 2-fold higher risk of NASH and NASH fibrosis, and increased risk of abdominal adiposity, supporting a potential mechanistic link of abdominal fat on testosterone-associated liver injury. Testosterone may represent an early risk factor for NASH progression in young women, prior to their onset of more dominant, age-related metabolic risk factors.