Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study

J Clin Endocrinol Metab. 2008 Jul;93(7):2737-45. doi: 10.1210/jc.2007-1972. Epub 2008 Feb 12.


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; > or = 25 to < 30 kg/m(2)) and lower TT (-5.09 nmol/liter) and FT (-53.72 pmol/liter) for BMI 30 kg/m(2) or greater (P < 0.001-0.01, referent: BMI < 25 kg/m(2)) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging / physiology*
  • Alcohol Drinking
  • Body Mass Index
  • Comorbidity
  • Cross-Sectional Studies
  • Humans
  • Hypothalamo-Hypophyseal System / physiology*
  • Luteinizing Hormone / blood
  • Male
  • Middle Aged
  • Obesity / blood
  • Risk Factors
  • Sex Hormone-Binding Globulin / analysis
  • Testis / physiology*
  • Testosterone / blood
  • Waist-Hip Ratio


  • Sex Hormone-Binding Globulin
  • Testosterone
  • Luteinizing Hormone