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Development of and Recovery from Secondary Hypogonadism in Aging Men: Prospective Results from the EMAS
Giulia Rastrelli1, Emma L Carter1, Tomas Ahern1
1Sexual Medicine and Andrology Unit (G.R., G.F., M.M.), Department of Experimental Clinical and Biomedical Sciences, University of Florence, 50139 Florence, Italy; Andrology Research Unit (E.L.C., T.A., J.D.F., F.C.W.W.), Centre for Endocrinology and Diabetes, Institute of Human Development, The University of Manchester, Manchester M13 9WL, United Kingdom; Department of Andrology and Endocrinology (L.A., D.V.), Katholieke Universiteit Leuven, B 3000 Leuven, Belgium; Arthritis Research UK Centre for Epidemiology (T.W.O.), Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester and National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit, Central Manchester National Health Service Foundation Trust, Manchester M13 9WL, United Kingdom; Department of Obstetrics, Gynaecology, and Andrology (G.B.), Albert Szent-György Medical University, H6725 Szeged, Hungary; Department of Medicine (F.F.C.), Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago, Centro de Investigación Biomedical en Red de Fisiopatología Obesidad y Nutricion (CB06/03), Instituto Salud Carlos III, 15076 Santiago de Compostela, Spain; Department of Clinical Biochemistry (B.K.), Istituto Nazionale Biostrutture e Biosistemi (M.M.), Consorzio Interuniversitario, 00136 Rome, Italy; University Hospital of South Manchester, Manchester M13 9WL, United Kingdom; Reproductive Medicine Centre (A.G.), Malmö University Hospital, University of Lund, SE-205 02 Malmö, Sweden; Department of Endocrinology (T.S.H.), Ashford and St Peter's National Health Service Trust, Surrey KT16 0PZ, United Kingdom; Department of Surgery and Cancer (I.T.H.), Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, United Kingdom; Department of Andrology and Reproductive Endocrinology (K.K.), Medical University of Łódź, 90-419 Łódź, Poland; Depar
Context:
Secondary hypogonadism is common in aging men; its natural history and predisposing factors are unclear.
Objectives:
The objectives were 1) to identify factors that predispose eugonadal men (T ≥ 10.5 nmol/L) to develop biochemical secondary hypogonadism (T < 10.5 nmol/L; LH ≤ 9.4 U/L) and secondary hypogonadal men to recover to eugonadism; and 2) to characterize clinical features associated with these transitions.
Design:
The study was designed as a prospective observational general population cohort survey.
Setting:
The setting was clinical research centers.
Participants:
The participants were 3369 community-dwelling men aged 40-79 years in eight European centers.
Intervention:
Interventions included observational follow-up of 4.3 years.
Main Outcome Measure:
Subjects were categorized according to change/no change in biochemical gonadal status during follow-up as follows: persistent eugonadal (n = 1909), incident secondary hypogonadal (n = 140), persistent secondary hypogonadal (n = 123), and recovered from secondary hypogonadism to eugonadism (n = 96). Baseline predictors and changes in clinical features associated with incident secondary hypogonadism and recovery from secondary hypogonadism were analyzed by regression models.
Results:
The incidence of secondary hypogonadism was 155.9/10 000/year, whereas 42.9% of men with secondary hypogonadism recovered to eugonadism. Incident secondary hypogonadism was predicted by obesity (body mass index ≥ 30 kg/m(2); odds ratio [OR] = 2.86 [95% confidence interval, 1.67; 4.90]; P < .0001), weight gain (OR = 1.79 [1.15; 2.80]; P = .011), and increased waist circumference (OR = 1.73 [1.07; 2.81], P = .026; and OR = 2.64 [1.66; 4.21], P < .0001, for waist circumference 94-102 and ≥102 cm, respectively). Incident secondary hypogonadal men experienced new/worsening sexual symptoms (low libido, erectile dysfunction, and infrequent spontaneous erections). Recovery from secondary hypogonadism was predicted by nonobesity (OR = 2.28 [1.21; 4.31]; P = .011), weight loss (OR = 2.24 [1.04; 4.85]; P = .042), normal waist circumference (OR = 1.93 [1.01; 3.70]; P = .048), younger age (< 60 y; OR = 2.32 [1.12; 4.82]; P = .024), and higher education (OR = 2.11 [1.05; 4.26]; P = .037), but symptoms did not show significant concurrent improvement.
Conclusion:
Obesity-related metabolic and lifestyle factors predispose older men to the development of secondary hypogonadism, which is frequently reversible with weight loss.
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