TY - JOUR
T1 - Testosterone is Associated With Nonalcoholic Steatohepatitis and Fibrosis in Premenopausal Women With NAFLD
AU - NASH CLINICAL RESEARCH NETWORK
AU - Sarkar, Monika A.
AU - Suzuki, Ayako
AU - Abdelmalek, Manal F.
AU - Yates, Katherine P.
AU - Wilson, Laura A.
AU - Bass, Nathan M.
AU - Gill, Ryan
AU - Cedars, Marcelle
AU - Terrault, Norah
N1 - Publisher Copyright:
© 2021 AGA Institute
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - Abdominal Adiposity
KW - Androgens
KW - Hepatic Inflammation
KW - Nonalcoholic Fatty Liver Disease
KW - Sex Hormones
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U2 - 10.1016/j.cgh.2020.09.045
DO - 10.1016/j.cgh.2020.09.045
M3 - Article
C2 - 33010412
AN - SCOPUS:85103703408
SN - 1542-3565
VL - 19
SP - 1267-1274.e1
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 6
ER -