Hypothalamic-Pituitary-Testicular Axis Disruptions in Older Men Are Differentially Linked to Age and Modifiable Risk Factors: The European Male Aging Study

TLDR

The cause of declining testosterone in aging men and its links to risk factors remains unclear. The study aimed to examine how lifestyle and health factors relate to reproductive hormones in aging men. The authors conducted a baseline cross‑sectional survey of 3,200 men aged 40–79 from eight European countries. Age, obesity, comorbidity, and smoking were each linked to distinct patterns of altered testosterone, LH, and SHBG, revealing progressive testicular impairment and hypothalamic‑pituitary dysfunction and highlighting modifiable risk factors that could help maintain testosterone levels in aging men.

Abstract

Abstract 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/m2) 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.