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Elevated free and bioavailable testosterone linked to non-alcoholic fatty liver disease risk in postmenopausal women

Elevated free and bioavailable testosterone linked to non-alcoholic fatty liver disease risk in post…
Photo by Navy Medicine / Unsplash
Key Takeaway
Note free and bioavailable testosterone associate with non-alcoholic fatty liver disease risk in postmenopausal women.

This prospective cohort study included 1,705 postmenopausal women in a community-based setting. Researchers assessed serum total testosterone, free testosterone, and bioavailable testosterone levels against non-alcoholic fatty liver disease progression over 5,269 person-years.

Higher concentrations and percentages of free testosterone and bioavailable testosterone were associated with increased risk of non-alcoholic fatty liver disease development. The odds ratio for free testosterone quartile 4 versus quartile 1 was 2.35 (95% CI 1.44-3.84). Bioavailable testosterone quartile 4 versus quartile 1 showed an odds ratio of 1.95 (95% CI 1.21-3.14). Total testosterone showed no significant association.

Conversely, higher free testosterone and bioavailable testosterone levels were associated with decreased probability of non-alcoholic fatty liver disease regression. The odds ratio for free testosterone quartile 4 versus quartile 1 was 0.56 (95% CI 0.33-0.95). Bioavailable testosterone quartile 4 versus quartile 1 had an odds ratio of 0.54 (95% CI 0.31-0.91). Adverse events and tolerability were not reported.

Limitations include the need for further studies in diverse populations and with longer follow-up periods. Findings need verification to determine broader implications. Free testosterone and bioavailable testosterone could be potential biomarkers for predicting non-alcoholic fatty liver disease progression. Associations were observed without explicit claims of causality.

Study Details

Study typeCohort
EvidenceLevel 3
PublishedApr 2026
View Original Abstract ↓
BackgroundSex steroid hormones may play vital roles in predisposing individuals to metabolic diseases. However, relationship between testosterone and progression of non-alcoholic fatty liver disease (NAFLD) in postmenopausal women remains unclear. Therefore, we conducted a community-based prospective cohort study, to investigate the associations between NAFLD progression and serum testosterone, as well as its fractions, in postmenopausal women.MethodsA total of 1,705 postmenopausal women were included and analyzed after 5,269 person-years of follow-up. Serum total testosterone (TT) was measured by chemiluminescent immunoassay; concentrations and percentages (%) of free testosterone (cFT) and bioavailable testosterone (BioT) were calculated. Their relationships with NAFLD development or regression were investigated using logistic regression.ResultsBaseline concentrations and percentages of cFT and BioT, rather than TT levels, were significantly higher in non-NAFLD postmenopausal women who developed NAFLD after follow-up than in those who did not, while prominently lower in women with NAFLD regression than in those who had sustained NAFLD. Moreover, both higher concentrations and percentages of cFT and BioT were associated with the increased risk of NAFLD development; the fully adjusted ORs (95% CIs) for Q4 vs. Q1 of cFT were 2.35 (1.44–3.84) and 4.58 (2.67–7.86), and for BioT were 1.95 (1.21–3.14) and 3.13 (1.87–5.24). Meanwhile, they were associated with the decreased probability of NAFLD regression, the fully adjusted ORs (95% CIs) of cFT were 0.56 (0.33–0.95) and 0.23 (0.12–0.42), of BioT were 0.54 (0.31–0.91) and 0.22 (0.12–0.40). However, no significant association between TT levels and NAFLD progression was observed.ConclusionsSerum concentrations and percentages of cFT and BioT are associated with the progression of NAFLD among postmenopausal women; they could be potential biomarkers for predicting NAFLD progression. Further studies in diverse populations and with a longer follow-up period are needed to verify whether our findings have broader implications.
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