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Background  Age-associated decline in testosterone levels represent one of the potential mechanisms involved in the development of frailty. Although this association has been widely reported in older men, very few data are available in women. We studied the association between testosterone and frailty in women and assessed sex differences in this relationship.    Methods  We used cross-sectional data from the Toledo Study for Healthy Aging, a population-based cohort study of Spanish elderly. Frailty was defined according to Fried's approach. Multivariate odds-ratios (OR) and 95% confidence intervals (CI) associated with total (TT) and free testosterone (FT) levels were estimated using polytomous logistic regression.    Results  In women, there was a U-shaped relationship between FT levels and frailty (p for FT 2  = 0.03). In addition, very low levels of FT were observed in women with ≥4 frailty criteria (age-adjusted geometric means = 0.13 versus 0.37 in subjects with &lt;4 components, p = 0.010). The association of FT with frailty appeared confined to obese women (p-value for interaction = 0.05).In men, the risk of frailty levels linearly decreased with testosterone (adjusted OR for frailty = 2.9 (95%CI, 1.6–5.1) and 1.6 (95%CI, 1.0–2.5), for 1 SD decrease in TT and FT, respectively). TT and FT showed association with most of frailty criteria. No interaction was found with BMI.    Conclusion  There is a relationship between circulating levels of FT and frailty in older women. This relation seems to be modulated by BMI. The relevance and the nature of the association of FT levels and frailty are sex-specific, suggesting that different biological mechanisms may be involved.

Sex Differences in the Association between Serum Levels of Testosterone and Frailty in an Elderly Population: The Toledo Study for Healthy Aging