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 - Funding Information:
Funding This work was supported by a K23 from the National Institutes of Diabetes and Digestive and Kidney Diseases (DK111944 to MAS). The NASH CRN is supported by the National Institutes of Diabetes and Digestive and Kidney Diseases.The authors thank the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) investigators and the Ancillary Studies Committee for providing clinical samples and relevant data from the Nonalcoholic Fatty Liver Disease Database, Nonalcoholic Fatty Liver Disease Adult Database 2, PIVENS trial, and FLINT trial. Sex hormones measurements were supported by the National Institutes of Health, Award P51OD011106 to the Wisconsin National Primate Research Center, University of Wisconsin-Madison. Monika A. Sarkar (Conceptualization: Lead; Formal analysis: Lead; Funding acquisition: Lead; Methodology: Supporting; Writing – original draft: Lead), Ayako Suzuki (Methodology: Supporting; Writing – review & editing: Supporting), Manal F. Abdelmalek (Methodology: Supporting; Writing – review & editing: Supporting), Katherine P. Yates (Data curation: Equal; Methodology: Supporting; Writing – review & editing: Supporting), Laura A. Wilson (Data curation: Equal; Methodology: Supporting; Writing – review & editing: Supporting), Nathan Bass (Methodology: Supporting; Writing – review & editing: Supporting), Ryan Gill (Writing – review & editing: Supporting), Marcelle Cedars (Methodology: Supporting; Writing – review & editing: Supporting), Norah Terrault (Conceptualization: Supporting; Methodology: Supporting; Writing – review & editing: Supporting)
Funding Information:
Funding This work was supported by a K23 from the National Institutes of Diabetes and Digestive and Kidney Diseases (DK111944 to MAS). The NASH CRN is supported by the National Institutes of Diabetes and Digestive and Kidney Diseases.
Funding Information:
The authors thank the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) investigators and the Ancillary Studies Committee for providing clinical samples and relevant data from the Nonalcoholic Fatty Liver Disease Database, Nonalcoholic Fatty Liver Disease Adult Database 2, PIVENS trial, and FLINT trial. Sex hormones measurements were supported by the National Institutes of Health , Award P51OD011106 to the Wisconsin National Primate Research Center, University of Wisconsin-Madison.
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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UR - http://www.scopus.com/inward/citedby.url?scp=85103703408&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2020.09.045
DO - 10.1016/j.cgh.2020.09.045
M3 - Article
C2 - 33010412
AN - SCOPUS:85103703408
VL - 19
SP - 1267-1274.e1
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
SN - 1542-3565
IS - 6
ER -