Reproductive hormone levels predict changes in frailty status in community-dwelling older men: European Male Ageing Study prospective data

Agnieszka Swiecicka, Robert J A H Eendebak, Mark Lunt, Terence W O'Neill, György Bartfai, Felipe F Casanueva, Gianni Forti, Aleksander Giwercman, Thang S Han, Jolanta Slowikowska-Hilczer, Michael E J Lean, Neil Pendleton, Margus Punab, Dirk Vanderschueren, Ilpo T Huhtaniemi, Frederick C W Wu, Martin K Rutter, EMAS Study Group

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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: 4.3-year prospective cohort study of community-dwelling men participating in the European Male Ageing Study.

Participants: 3369 men aged 40-79 from 8 European centres.

Intervention: nil.

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, centre and smoking, the risk of worsening FI decreased with higher testosterone (T), free T and dihydrotestosterone (DHT) [% change (95%CI) in FI associated with 1SD 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 BMI, only free T remained a significant predictor of FI change. In fully adjusted models, higher LH and FSH were positively related to worsening FI only in men <60 years and higher estradiol predicted lower likelihood of improving FP [OR 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 yr might be an early marker of frailty, the role of estradiol in frailty needs further clarification.

Original languageEnglish
Pages (from-to)701-709
JournalJournal of Clinical Endocrinology and Metabolism
Issue number2
Early online date24 Nov 2017
Publication statusPublished - 2018


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