SUN-678 Age-related Decline In Serum Testosterone And Relationship To Adiposity: Implications For TRT

Abstract Disclosure: K.E. Friedl: None. G.C. Chin: None. D.P. Looney: None. A.W. Potter: None. Age-related decline in serum testosterone (T) has been used as justification for T replacement therapy (TRT) in men, with the expectation that treatment slows osteoporosis and sarcopenia and helps to maintain mental health and vigor. Requests for TRT by active duty members have markedly increased in recent years. Widely circulated opinions among soldiers suggest that exogenous androgens are vital to sustaining health and performance of men involved in high stress and physically demanding missions and as they age beyond their 30s. On the other hand, liberal administration of T to relatively young men in the military is a risk to behavioral health, reducing autonomy through interactions with the dopaminergic system (“the steroids made me do it”). Further, acute declines in circulating T may actually be physiologically adaptive responses to high stress bioenergetic challenges, where survival functions such as resistance to disease could be compromised by a TRT intervention. The nonmedical use of androgens is prohibited in the US but TRT can be prescribed for hypogonadism defined as repeated serum T concentrations <0.3 mg/dL and consistent signs or symptoms. We examined the age-related decline in T and associated modifiable factors such as increasing adiposity that might be offset through weight management and physical training instead of TRT. We examined the prevalence of hypogonadism (serum T concentrations <0.3 mg/dL) across age (age 20-60) and relationship to adiposity using a nationally representative sample of men from the publicly available NHANES data. Testosterone demonstrated a gradual and weakly correlated (r2=0.02) decline with age (20-60 years). Sex hormone binding globulin (SHBG) gradually increased with age. Rates of hypogonadism (defined as T<0.3 mg/dL) were similar across all age groups but higher for >30y men than <30y. Free T (fT) calculated from T, SHBG, and albumin concentrations followed the T levels. Percent body fat (%BF) and visceral adipose tissue (VAT) obtained by DXA, increased with age and had a strong inverse curvilinear relationship to T, while the relationship between T and fat-free mass was weak. The subsample of men with T<0.3 mg/dL had higher %BF and VAT, and lower FFM index, than the rest of the men and this was consistent across age groups by decade. T and body fat are associated through several mechanisms, where T administration increases lipolysis in intraabdominal adipocytes, and adipocytes increase T metabolism with aromatase enzyme conversion to estradiol. Thus, the strong relationship between circulating T concentration and adiposity has plausible mechanistic explanations for causality in both directions. We conclude that managing body composition is a first line intervention to hypogonadism but T administration to men age > 30y with increased adiposity might also be effective in reducing VAT and consequent metabolic health risks. Presentation: Sunday, July 13, 2025