Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: The European male aging study

Abdelouahid Tajar, Gyorgy Bartfai, Felipe Casanueva, Gianni Forti, Aleksander Giwercman, Ilpo T. Huhtaniemi, Krzysztof Kula, Margus Punab, Steven Boonen, Dirk Vanderschueren, Luisa Petrone, Antonio Cilotti, Herman Borghs, Jolanta Slowikowska-Hilczer, Renata Walczak-Jedrzejowska, Frederick Wu, Alan Silman, Terence O'Neill, Joseph Finn, Philip SteerDavid Lee, Stephen Pye, Marta Ocampo, Mary Lage, George Bartfai, Imre Földesi, Imre Fejes, Paul Korrovitz, Min Jiang

Research output: Contribution to journalArticlepeer-review


Context: The cause of declining testosterone (T) in aging men and their relationships with risk factors are unclear. Objective: The objective of the study was to investigate the relationships between lifestyle and health with reproductive hormones in aging men. Design: This was a baseline cross-sectional survey on 3200 community-dwelling men aged 40-79 yr from a prospective cohort study in eight European countries. Results: Four predictors were associated with distinct modes of altered function: 1) age: lower free T (FT; -3.12 pmol/liter·yr, P <0.001) with raised LH, suggesting impaired testicular function; 2) obesity: lower total T (TT; -2.32 nmol/liter) and FT (-17.60 pmol/liter) for body mass index (BMI; ≥ 25 to <30 kg/m 2) and lower TT (-5.09 nmol/liter) and FT (-53.72 pmol/liter) for BMI 30 kg/m2 or greater (P <0.001-0.01, referent: BMI <25 kg/m2) with unchanged/decreased LH, indicating hypothalamus/pituitary dysfunction; 3) comorbidity: lower TT (-0.80 nmol/liter, P <0.01) with unchanged LH in younger men but higher LH in older men; and 4) smoking: higher SHBG (5.96 nmol/liter, P <0.001) and LH (0.77 U/liter, P <0.01) with increased TT (1.31 nmol/liter, P <0.001) but not FT, compatible with a resetting of T-LH-negative feedback due to elevated SHBG. Conclusions: Complex multiple alterations in the hypothalamic-pituitary-testicular axis function exist in aging men against a background of progressive age-related testicular impairment. These changes are differentially linked to specific risk factors. Some risk factors operate independently of but others interact with age, in contributing to the T decline. These potentially modifiable risk factors suggest possible preventative measures to maintain T during aging in men. Copyright © 2008 by The Endocrine Society.
Original languageEnglish
Pages (from-to)2737-2745
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number7
Publication statusPublished - Jul 2008


Dive into the research topics of 'Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: The European male aging study'. Together they form a unique fingerprint.

Cite this