LBMON273 Not All Men Are Created Equal

Abstract Background Clinical assessment of androgens in the diagnosis of androgen excess, hypogonadism, androgen replacement or suppressive therapy and in anti-doping practices is generally limited to a few C19 steroids. More accurate evaluations may be gained with comprehensive steroid analysis. The aim of this study was to determine all major circulating adrenal and gonadal steroids together with the adrenal C11-oxy C19 steroids. Methods Serum androgens, mineralocorticoids, glucocorticoids, progesterones and C11-oxy steroids were determined in 71 healthy men, 18-35yrs, using ultra-performance convergence-chromatography tandem mass spectrometry. Data was analysed using GraphPad Prism Version 9.3.1. Results Profiles and inter-individual steroid concentrations differed considerably. Testosterone (25.2 nM) was detected in all subjects while dehydroepiandrosterone (DHEA) was undetectable in 18% of the subjects. Comparing subjects with DHEA, 11.14 (3.178-52.73) nM and those without DHEA identified steroids differing significantly (p≤0. 001; q values ≤5%): 11-OHA4 (4. 0 ±0.3 vs 1.6±0.3 nM), 16-hydroxyprogesterone (0.7±0. 07 vs 0.3 ±0.1 nM), corticosterone (15.5±1.8 vs 3.8±1.1 nM), 11-dehydrocorticosterone (4.5±0.3 vs 2±0.5nM), cortisol, (357±21.2 vs 157.9±29.3 nM) and cortisone (57.9±2.4 vs 35.3 ±5.4 nM). Dihydrotestosterone (∼4.3 nM) and 11-hydroxytestosterone (∼0.5 nM) were detected at comparable concentrations, however, at a frequency of 25% and >90%, respectively (in both groups). 11-ketotestosterone levels were also comparable but below the limit of accurate quantification while present in ∼50% of the subjects. Epitestosterone levels were comparable (0.2±0. 02 vs 0.1±0. 03 nM), but higher in younger subjects 18-25 yrs (p<0. 05). Conclusions Analysis of gonadal and adrenal steroids indicate greater circulating steroid heterogeneity than previously thought. Data shows that the often-disregarded adrenal C11-oxy C19 steroids contributed to 16% of the androgen profile. Furthermore, given that the C19 steroids were 1.8-fold lower in men without measurable DHEA, the functional oxyandrogens, 11-ketotestosterone and 11-hydroxytestosterone, would be of particular physiological importance due to their androgenic activity. Absence of measurable DHEA showed an overall modulated adrenal steroidogenic flux in these men, evident in the attenuated glucocorticoid production. Data underscores the modulatory role of cytochrome P450 11β-hydroxylase in these individuals, potentially impacting on diagnostic testing and evaluation. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.