Low Serum Testosterone Concentrations Predict Incident Frailty in Men with HIV

CONTEXT: Older men with HIV (MWH) experience a higher burden of frailty than age-matched men without HIV, but the biological mechanisms underlying this vulnerability are not completely understood. Testosterone (T) deficiency may contribute to frailty through effects on muscle mass and physical function. OBJECTIVE: To evaluate the associations of free (T), total T, and sex hormone-binding globulin (SHBG) with incident frailty among men with HIV. DESIGN: Prospective cohort study. SETTING: The MACS/WIHS Combined Cohort Study. PARTICIPANTS: 306 non-frail MWH (129 robust, 177 prefrail) with longitudinal frailty assessments. MAIN OUTCOME MEASURES: Incident frailty defined using the Fried frailty phenotype. METHODS: Free T, Total T and SHBG were measured, with free T assessed by equilibrium dialysis. Marginal structural models were used to estimate associations with frailty outcomes while accounting for time and related covariates. RESULTS: Over a mean follow-up of 9.0 years, low free T (<54 pg/mL) and low total T (<300 ng/dL) were associated with higher risk of incident frailty compared with higher concentrations (HR: 2.49, 95%CI:1.21-5.11; HR: 3.31, 95%CI: 1.26-8.68, respectively). SHBG concentrations were not consistently associated with frailty outcomes. CONCLUSIONS: Low T levels predict incident frailty in men with HIV. Assessment of androgen status may help identify men at increased frailty risk. Further investigations are warranted to assess the role of T therapy in frailty prevention.