Sex Hormone–Frailty Axis in Women with Cirrhosis

Endocrine disturbance and impaired physical reserve coexist in cirrhosis, but female-specific associations between circulating sex hormones and frailty remain insufficiently characterized. We examined hormone–frailty associations across menopausal categories in a clinical database of women with cirrhosis. This exploratory, single-centre, record-based cross-sectional analysis used retrospectively reviewed clinical records of 94 women with cirrhosis treated at “Sf. Apostol Andrei” Emergency County Hospital, Constanța, Romania, during January 2021–March 2025. The continuous Liver Frailty Index (LFI) was the principal outcome; handgrip strength and L3 skeletal muscle index were complementary phenotypes. Six separate linear models evaluated estradiol, follicle-stimulating hormone (FSH), luteinizing hormone, progesterone, total testosterone, and sex hormone-binding globulin, adjusting for age, recorded MELD-Na, and body mass index. HC3 heteroscedasticity-robust confidence intervals and Benjamini–Hochberg false-discovery-rate correction were used. Sensitivity analyses addressed menopausal status, exogenous hormones, inflammation, disease severity, sampling context, and severe hepatic encephalopathy (HE). There were 10 premenopausal, 11 perimenopausal, and 73 postmenopausal women. Median LFI was 3.76 (interquartile range, 3.14–4.48); 25 women (26.6%) had LFI ≥ 4.4. Estradiol was not clearly associated with LFI after adjustment: coefficient −0.022 per doubling (95% confidence interval, −0.257 to 0.214; p = 0.855). FSH was associated with higher LFI: 0.125 per 10 mIU/mL (0.042–0.208; p = 0.004; adjusted q = 0.022). The FSH estimate remained positive in postmenopausal women, but its interval crossed zero after excluding records labelled with severe HE. No hormone–muscle correlation survived correction across 18 exploratory comparisons. FSH, but not estradiol, showed an adjusted cross-sectional association with frailty. These findings do not establish causality, prognostic utility, or an indication for hormone treatment. Unresolved sampling-context and physical-assessment timing require source-record verification before clinical interpretation.