Endogenous sex hormones, sex hormone-binding globulin, and muscle health: insights into sarcopenia and sarcopenic obesity from the Women's Health Initiative

Menopause. 2026 Feb 17. doi: 10.1097/GME.0000000000002734. Online ahead of print.

Abstract

Objective: The relationship between sex hormones and lean body mass in postmenopausal women is unclear. To address this, we conducted a longitudinal observational study using data from the Women's Health Initiative study.

Methods: We analyzed endogenous serum sex hormones and sex hormone-binding globulin (SHBG) at baseline in 1,565 postmenopausal women not using hormone therapy, who underwent 3 lean body mass measurements over 6 years. Sex hormone concentrations were assessed at baseline using radioimmunoassay. Lean body mass was assessed by dual-energy x-ray absorptiometry at baseline, year 3 and 6. Free estradiol and free testosterone concentrations were calculated. Each sex hormone was analyzed independently of the other hormones. Associations between sex hormones or SHBG were examined using repeated-measures linear regression for lean mass and repeated-measures logistic regression for sarcopenia/sarcopenic obesity. Regression models were adjusted for age, race/ethnicity, lifestyle, and metabolic confounders.

Results: Concentration of free testosterone in the highest quartile was associated with a 55% lower odds for sarcopenia compared with the lowest quartile (OR: 0.45; 95% CI: 0.25-0.81). Similarly, individuals with the highest concentration of free estradiol had a 54% reduced odds of sarcopenia (OR: 0.46, 95% CI: 0.28-0.76). Conversely, a higher concentration of SHBG at baseline was significantly associated with reduced total lean mass and a higher odds of sarcopenia.

Conclusion: Among postmenopausal women, higher SHBG concentrations at baseline were associated with lower lean body mass and a higher odds of sarcopenia, while higher free estradiol and free testosterone concentrations were associated with a lower odds of sarcopenia.

Keywords: Endocrinology; Postmenopause; Sarcopenia; Sarcopenic obesity; Sex hormones; Skeletal muscle; Women..