Development of and recovery from secondary hypogonadism in aging men: Prospective results from the EMAS

Giulia Rastrelli, Emma L. Carter, Tomas Ahern, Joseph D. Finn, Leen Antonio, Terence W. O'Neill, Gyorgy Bartfai, Felipe F. Casanueva, Gianni Forti, Brian Keevil, Mario Maggi, Aleksander Giwercman, Thang S. Han, Ilpo T. Huhtaniemi, Krzysztof Kula, Michael E.J. Lean, Neil Pendleton, Margus Punab, Dirk Vanderschueren, Frederick C.W. Wu Prof MdC. Pott, E. Wouters, M. Nilsson, M. Del Mar Fernandez, M. Jedrzejowska, H. M. Tabo, A. Heredi, C. Moseley

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Abstract

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/m2; 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.

Original languageEnglish
Pages (from-to)3172-3182
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number8
DOIs
Publication statusPublished - Aug 1 2015

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Rastrelli, G., Carter, E. L., Ahern, T., Finn, J. D., Antonio, L., O'Neill, T. W., Bartfai, G., Casanueva, F. F., Forti, G., Keevil, B., Maggi, M., Giwercman, A., Han, T. S., Huhtaniemi, I. T., Kula, K., Lean, M. E. J., Pendleton, N., Punab, M., Vanderschueren, D., ... Moseley, C. (2015). Development of and recovery from secondary hypogonadism in aging men: Prospective results from the EMAS. Journal of Clinical Endocrinology and Metabolism, 100(8), 3172-3182. https://doi.org/10.1210/jc.2015-1571