Testosterone is Associated With Nonalcoholic Steatohepatitis and Fibrosis in Premenopausal Women With NAFLD
Higher testosterone contributes to imaging-confirmed nonalcoholic fatty liver disease (NAFLD) in women, but whether testosterone influences their disease severity is unknown. The association of free testosterone (free T) with nonalcoholic steatohepatitis (NASH) was determined in pre-menopausal women...
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Veröffentlicht in: | Clinical gastroenterology and hepatology 2021-06, Vol.19 (6), p.1267-1274.e1 |
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container_title | Clinical gastroenterology and hepatology |
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creator | Sarkar, Monika A. Suzuki, Ayako Abdelmalek, Manal F. Yates, Katherine P. Wilson, Laura A. Bass, Nathan M. Gill, Ryan Cedars, Marcelle Terrault, Norah |
description | Higher testosterone contributes to imaging-confirmed nonalcoholic fatty liver disease (NAFLD) in women, but whether testosterone influences their disease severity is unknown.
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.
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 |
doi_str_mv | 10.1016/j.cgh.2020.09.045 |
format | Article |
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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.
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).
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.</description><identifier>ISSN: 1542-3565</identifier><identifier>EISSN: 1542-7714</identifier><identifier>DOI: 10.1016/j.cgh.2020.09.045</identifier><identifier>PMID: 33010412</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Abdominal Adiposity ; Adult ; Androgens ; Female ; Fibrosis ; Hepatic Inflammation ; Humans ; Liver - pathology ; Liver Cirrhosis - pathology ; Non-alcoholic Fatty Liver Disease - complications ; Non-alcoholic Fatty Liver Disease - pathology ; Nonalcoholic Fatty Liver Disease ; Obesity, Abdominal ; Sex Hormones ; Testosterone</subject><ispartof>Clinical gastroenterology and hepatology, 2021-06, Vol.19 (6), p.1267-1274.e1</ispartof><rights>2021 AGA Institute</rights><rights>Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-f632bb31558b523a21df7873c00b7469f035a144f660bca93a364552e7004bf43</citedby><cites>FETCH-LOGICAL-c396t-f632bb31558b523a21df7873c00b7469f035a144f660bca93a364552e7004bf43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1542356520313756$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33010412$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sarkar, Monika A.</creatorcontrib><creatorcontrib>Suzuki, Ayako</creatorcontrib><creatorcontrib>Abdelmalek, Manal F.</creatorcontrib><creatorcontrib>Yates, Katherine P.</creatorcontrib><creatorcontrib>Wilson, Laura A.</creatorcontrib><creatorcontrib>Bass, Nathan M.</creatorcontrib><creatorcontrib>Gill, Ryan</creatorcontrib><creatorcontrib>Cedars, Marcelle</creatorcontrib><creatorcontrib>Terrault, Norah</creatorcontrib><creatorcontrib>NASH Clinical Research Network</creatorcontrib><title>Testosterone is Associated With Nonalcoholic Steatohepatitis and Fibrosis in Premenopausal Women With NAFLD</title><title>Clinical gastroenterology and hepatology</title><addtitle>Clin Gastroenterol Hepatol</addtitle><description>Higher testosterone contributes to imaging-confirmed nonalcoholic fatty liver disease (NAFLD) in women, but whether testosterone influences their disease severity is unknown.
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.
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).
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.</description><subject>Abdominal Adiposity</subject><subject>Adult</subject><subject>Androgens</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Hepatic Inflammation</subject><subject>Humans</subject><subject>Liver - pathology</subject><subject>Liver Cirrhosis - pathology</subject><subject>Non-alcoholic Fatty Liver Disease - complications</subject><subject>Non-alcoholic Fatty Liver Disease - pathology</subject><subject>Nonalcoholic Fatty Liver Disease</subject><subject>Obesity, Abdominal</subject><subject>Sex Hormones</subject><subject>Testosterone</subject><issn>1542-3565</issn><issn>1542-7714</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1rGzEQhkVJqJO0P6CXsMdcvB19e-nJJHVTMEkgKT4KrXY2lrteuZIc6L-vgt0cc5oZeOaF9yHkC4WaAlVfN7V7XtcMGNTQ1CDkB3JGpWBTrak4Oe5cKjkh5yltAFgjGv2RTDgHCoKyM_L7CVMOKWMMI1Y-VfOUgvM2Y1etfF5Xd2G0gwvrMHhXPWa0OaxxZ7PPBbZjVy18G0Mqhx-rh4hbHMPO7pMdqlUoxzFlvljefCKnvR0Sfj7OC_Jr8f3p-na6vP_x83q-nDreqDztFWdty6mUs1Yybhntej3T3AG0WqimBy4tFaJXClpnG265ElIy1ACi7QW_IFeH3F0Mf_aln9n65HAY7IhhnwwTYiZAayULSg-oKx1SxN7sot_a-NdQMK-OzcYUx-bVsYHGFMfl5_IYv2-32L19_JdagG8HAEvJF4_RJOdxdNj5iC6bLvh34v8BdIqMHA</recordid><startdate>202106</startdate><enddate>202106</enddate><creator>Sarkar, Monika A.</creator><creator>Suzuki, Ayako</creator><creator>Abdelmalek, Manal F.</creator><creator>Yates, Katherine P.</creator><creator>Wilson, Laura A.</creator><creator>Bass, Nathan M.</creator><creator>Gill, Ryan</creator><creator>Cedars, Marcelle</creator><creator>Terrault, Norah</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202106</creationdate><title>Testosterone is Associated With Nonalcoholic Steatohepatitis and Fibrosis in Premenopausal Women With NAFLD</title><author>Sarkar, Monika A. ; Suzuki, Ayako ; Abdelmalek, Manal F. ; Yates, Katherine P. ; Wilson, Laura A. ; Bass, Nathan M. ; Gill, Ryan ; Cedars, Marcelle ; Terrault, Norah</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-f632bb31558b523a21df7873c00b7469f035a144f660bca93a364552e7004bf43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Abdominal Adiposity</topic><topic>Adult</topic><topic>Androgens</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Hepatic Inflammation</topic><topic>Humans</topic><topic>Liver - pathology</topic><topic>Liver Cirrhosis - pathology</topic><topic>Non-alcoholic Fatty Liver Disease - complications</topic><topic>Non-alcoholic Fatty Liver Disease - pathology</topic><topic>Nonalcoholic Fatty Liver Disease</topic><topic>Obesity, Abdominal</topic><topic>Sex Hormones</topic><topic>Testosterone</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sarkar, Monika A.</creatorcontrib><creatorcontrib>Suzuki, Ayako</creatorcontrib><creatorcontrib>Abdelmalek, Manal F.</creatorcontrib><creatorcontrib>Yates, Katherine P.</creatorcontrib><creatorcontrib>Wilson, Laura A.</creatorcontrib><creatorcontrib>Bass, Nathan M.</creatorcontrib><creatorcontrib>Gill, Ryan</creatorcontrib><creatorcontrib>Cedars, Marcelle</creatorcontrib><creatorcontrib>Terrault, Norah</creatorcontrib><creatorcontrib>NASH Clinical Research Network</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical gastroenterology and hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sarkar, Monika A.</au><au>Suzuki, Ayako</au><au>Abdelmalek, Manal F.</au><au>Yates, Katherine P.</au><au>Wilson, Laura A.</au><au>Bass, Nathan M.</au><au>Gill, Ryan</au><au>Cedars, Marcelle</au><au>Terrault, Norah</au><aucorp>NASH Clinical Research Network</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Testosterone is Associated With Nonalcoholic Steatohepatitis and Fibrosis in Premenopausal Women With NAFLD</atitle><jtitle>Clinical gastroenterology and hepatology</jtitle><addtitle>Clin Gastroenterol Hepatol</addtitle><date>2021-06</date><risdate>2021</risdate><volume>19</volume><issue>6</issue><spage>1267</spage><epage>1274.e1</epage><pages>1267-1274.e1</pages><issn>1542-3565</issn><eissn>1542-7714</eissn><abstract>Higher testosterone contributes to imaging-confirmed nonalcoholic fatty liver disease (NAFLD) in women, but whether testosterone influences their disease severity is unknown.
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.
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).
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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33010412</pmid><doi>10.1016/j.cgh.2020.09.045</doi><oa>free_for_read</oa></addata></record> |
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subjects | Abdominal Adiposity Adult Androgens Female Fibrosis Hepatic Inflammation Humans Liver - pathology Liver Cirrhosis - pathology Non-alcoholic Fatty Liver Disease - complications Non-alcoholic Fatty Liver Disease - pathology Nonalcoholic Fatty Liver Disease Obesity, Abdominal Sex Hormones Testosterone |
title | Testosterone is Associated With Nonalcoholic Steatohepatitis and Fibrosis in Premenopausal Women With NAFLD |
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