SAT-010 Adrenal Androgen Synthesis in Aging Men

Abstract

Background: The testes are the major source of androgens in men. The adrenal glands are important sources of sex-steroids and precursors during fetal life and adrenarche. The major adrenal C ₁₉ steroids, dehydroepiandrosterone and its sulfate (DHEA and DHEAS), peak in the 20s and then decline progressively with aging in both men and women. Testosterone (T) and androstenedione (A4), which are produced by both the adrenal glands and the gonads, also decline with aging. In contrast, we have recently shown that the adrenal-derived 11-oxygenated C ₁₉ (11oxyC19) steroids do not decline in aging women. While ovarian estrogen synthesis ceases abruptly by the 6 ^th decade of life in most women, T production from the male testis declines gradually with aging. The adrenal contribution to the pool of circulating androgens and the trajectory of 11oxyC19 steroid production in aging men is not well understood. Objective: To assess the production of adrenal androgens in adult men, across a wide range of ages. Patients and methods: Morning serum was obtained from 107 men, age 20-92 years, during routine outpatient evaluations. Patients with severe comorbidities and those taking hormonal therapy were excluded. We quantified 17 steroids by liquid chromatography-tandem mass spectrometry, including A4, T, 4 steroid sulfates, and the 11oxyC19 steroids; 11β-hydroxyandrostenedione, 11β-hydroxytestosterone, 11-ketoandrostenedione and 11-ketotestosterone. The nonparametric Mann-Whitney U test was used for comparison of steroids between young and old men. Pearson’s correlation test was used to assess the relationship between steroids and age. Results: DHEAS, androstenediol-3-sulfate (AdiolS), pregnenolone sulfate (PregS) and 17-hydroxypregnenlone sulfate (17OHPregS), A4, and T were significantly lower in men older (N=55) vs. younger (N=52) than 60 years ( p=0.04 for T, and p<0.001 for all others). Conversely, all four 11oxyC19 steroids were similar between men younger and older than 60 years. DHEAS, AdiolS, PregS and 17OHPregS showed an inverse correlation with age ( r=-0.7, -0.6, -0.4 and -0.5, respectively, p<0.0001 for all), and A4 and T also declined modestly with age ( r=-0.4 and -0.2, respectively, p<0.01). In contrast, none of the 11oxyC19 steroids were associated with age ( p>0.05). Conclusion: Unlike the traditional adrenal androgen precursor DHEAS, the 11oxyC19 steroids do not decline with aging in men. Consequently, the relative contribution of the adrenal gland to the pool of circulating androgens increases in aging men as gonadal function declines. The potential for adrenal-derived 11oxyC19 androgens to mitigate the physiologic consequences of the age-related T decline in men deserves study.