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

Journal: The Journal of clinical endocrinology and metabolism 2018;103(2):701-709

PMID: 29186457

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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.

Address: 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, United Kingdom.; Arthritis Research UK Centre for Epidemiology, Faculty of Biology, Medicine, and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.; NIHR Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.; 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, CIBER de Fisiopatología Obesidad y Nutricion, 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, Lund, Sweden.; Institute of Cardiovascular Research, Royal Holloway University of London, Egham, United Kingdom.; Ashford and St. Peter's NHS Foundation Trust, Surrey, United Kingdom.; Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Lodz, Poland.; Department of Human Nutrition, University of Glasgow, Glasgow, United Kingdom.; Division of Neuroscience and Experimental Psychology, School of Biological Sciences, University of Manchester, Hope Hospital, Salford, United Kingdom.; 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, United Kingdom.; Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.; 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, United Kingdom.; Manchester Diabetes Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.

DOI: 10.1210/jc.2017-01172

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MeSH Terms: Adult, Aged, Aging, Cohort Studies, Europe, Frail Elderly, Frailty, Geriatric Assessment, Gonadal Hormones, Humans, Independent Living, Male, Middle Aged, Prognosis