Endocrine Abstracts

Introduction: Even in healthy men, androgen levels start decreasing from early adulthood and these decreases are more pronounced in men with an increasing body mass index (BMI). It is, however, unclear to what extent changes in other indices of body composition and metabolic health are associated with changes in sex steroid exposure in healthy men over time.

Objective: Investigating longitudinal changes in body composition and metabolic health in relation to sex steroid levels in young adult men.

Methods: Longitudinal, population-based, observational study: 999 healthy men aged 24-46 years of whom 691 were re-evaluated after 12 +/- 2 years. Serum sex hormone binding globulin (SHBG) and insulin levels were measured using immuno-assay, glucose by hexokinase method, testosterone (T) using LC-MS/MS, free T (cFT) and homeostasis model for insulin resistance (HOMA-IR) calculated. Body composition was determined using DXA (Hologic) at the whole body minus head. Fat (FM%) and lean mass (LM%) percentages were calculated. Linear mixed models were used for statistical analyses. All models were adjusted for baseline age.

Results: Baseline age was 34±6 years. Mean BMI increased by 4.7% (25.1 kg/m²vs 26.3 kg/m²). Mean T levels decreased by 14.2% (20.8 nmol/l vs. 17.8 nmol/l), cFT by 19.1% (392 pmol/l vs. 317 pmol/l) and SHBG increased by 3.0% (39.8 nmol/l vs. 41.0 nmol/l) (all P < 0.001). FM% increased by 1.2% (19.6% vs 21.6%; P < 0.001), especially at the trunk (8.1 kg vs 9.6 kg; P < 0.001). LM% decreased by 1.8% (77.3% vs 75.4%; P < 0.001). HOMA-IR increased from 1.7 to 2.2 (P < 0.001). At baseline, total T, cFT and SHBG were inversely associated with truncal fat, FM% and HOMA-IR and positively associated with LM% (all P < 0.001). Longitudinally, changes in sex steroids were not associated with changes in either FM% and LM%. However, changes in total T, cFT and SHBG were inversely associated with changes in truncal fat and HOMA-IR (all P < 0.018).

Conclusion: In this population of healthy young men, adiposity and insulin resistance increased while LM% decreased over a period of 12 years. We found that a stronger decline in both total and free T levels was associated with stronger increases in truncal adiposity and insulin resistance. Whether our findings suggest a direct role of sex steroids as determinants of metabolic state, result from residual confounding or are mediated by the intriguing relationship between SHBG levels and metabolic health remains to be established. Moreover, the possibility of a reverse causality between androgen levels and metabolic state should be taken into account.