Abstract
CONTEXT: Clinical sequelae of androgen deficiency share common features with frailty. Evidence supporting the role of androgens in the development of frailty is limited and conflicting. OBJECTIVE: To determine associations between male reproductive hormones and prospective changes in frailty status. DESIGN/SETTING: A 4.3-year prospective cohort study of community-dwelling men participating in the European Male Ageing Study. PARTICIPANTS: A total of 3369 men aged 40 to 79 from eight European centers. INTERVENTION: None. MAIN OUTCOME MEASURE: Frailty status was determined using frailty index (FI; n = 2278) and frailty phenotype (FP; n = 1980). RESULTS: After adjusting for baseline frailty, age, center, and smoking, the risk of worsening FI decreased with higher testosterone (T), free T, and dihydrotestosterone (DHT) [percentage change (95% confidence interval) in FI associated with 1 standard deviation higher hormone level: -3.0 (-5.9, -1.0) for total T; -3.9 (-6.8, -2.0) for free T; and -3.9 (-6.8, -2.0) for DHT]. After further adjustment for body mass index, only free T remained a significant predictor of FI change. In fully adjusted models, higher luteinizing hormone and follicle-stimulating hormone were positively related to worsening FI only in men <60 years, and higher estradiol predicted lower likelihood of improving FP [odds ratio: 0.68 (0.52, 0.88)]. CONCLUSIONS: These prospective data support the hypothesis that higher androgen levels may protect elderly men from worsening frailty. However, the causal nature of these relationships requires further investigation. Whereas raised gonadotropins in men <60 years might be an early marker of frailty, the role of estradiol in frailty needs further clarification.