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

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.

To determine associations between male reproductive hormones and prospective changes in frailty status.

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

3369 men aged 40-79 from 8 European centres.


Frailty status was determined using frailty index (FI n=2278) and frailty phenotype (FP, n=1980).

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)].

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.

The Journal of clinical endocrinology and metabolism. 2017 Nov 24 [Epub ahead of print]

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

Andrology Research Unit, Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Arthritis Research UK Centre for Epidemiology, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester & NIHR Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK., Department of Obstetrics, Gynaecology and Andrology, Albert Szent-Györgyi Medical University, Szeged, Hungary., Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago (CHUS); CIBER de Fisiopatología Obesidad y Nutricion (CB06/03), Instituto Salud Carlos III; Santiago de Compostela, Spain., Sexual Medicine and Andrology Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy., Reproductive Medicine Centre, Malmö University Hospital, University of Lund, Sweden., Institute of Cardiovascular Research, Royal Holloway University of London (ICR2UL) and Ashford and St Peter's NHS Foundation Trust, Surrey, UK., Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Lodz, Poland., Department of Human Nutrition, University of Glasgow, Glasgow, UK., Division of Neuroscience and Experimental Psychology, School of Biological Sciences, University of Manchester, Hope Hospital, Salford, UK., Andrology Unit, United Laboratories of Tartu University Clinics, Tartu, Estonia., Department of Andrology and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium., Department of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, UK, and Department of Physiology, Institute of Biomedicine, University of Turku, Finland.