Adrenal and gonadal contributions to urinary excretion and plasma concentration of epitestosterone in men - effect of adrenal stimulation and implications for detection of testosterone abuse

OBJECTIVE The ratio of urinary testosterone (T) to epitestosterone (EpiT) i s used to detect T abuse in sport. Also, plasma or urinary concentrations o f EpiT have been measured to assess testicular steroidogenesis during hormo nal male contraception. Further investigations are required to evaluate the relative contributions of the testis and adrenal to EpiT production. To th is purpose, we have compared basal urinary EpiT glucuronide and plasma EpiT and the response to synthetic adrenocorticotrophic hormone (ACTH) stimulat ion between eugonadal and hypogonadal men. DESIGN AND SUBJECTS The basal urinary excretion rate of EpiT glucuronide wa s determined in 34 eugonadal men. Six men, clinically diagnosed as hypogona dal, and 6 out of the 34 eugonadal men previously described, received an in tramuscular injection of synthetic ACTH depot(1 mg) at 0800 h on two consec utive days. Blood samples were collected prior to and then at 1.5, 8, 24, 2 5.5, 32 and 48 h with respect to the first administration (0 h). 24-h urine specimens were collected from 0800 h on days 1 and 2 (baseline) and 3 and 4 (stimulation). MEASUREMENTS Plasma EpiT, T and cortisol were measured by RIA and urinary E piT and T, following glucuronide hydrolysis, by gas chromatography-mass spe ctrometry (extract combines aglycones with a minor amount of urinary free s teroids). RESULTS Basal excretion rates of EpiT glucuronide in eugonadal men (range:6 2-751 nmol/24 h) were considerably greater than in hypogonadal men (range: 3-34nmol/24 h). Mean basal plasma EpiT in eugonadal men (1.32 +/- 0.08 nmol /l) were greater than in hypogonadal men (0.68 +/- 0.04 nmol/l). In each gr oup, synthetic ACTH stimulation increased plasma cortisol 4-fold. In eugona dal men, plasma and urinary EpiT were unchanged whereas plasma and urinary T glucuronide decreased in response to ACTH. In hypogonadal patients, ACTH increased plasma and urinary EpiT while plasma T remained unchanged. CONCLUSION The testes are the major source of epitestosterone, the adrenal contribution being relatively modest. Following adrenal stimulation, urinar y epitestosterone glucuronide increases considerably in hypogonadal men but this increase is masked in eugonadal men because testicular production is probably suppressed by the ACTH-induced rise in cortisol. Activation of the adrenal cortex results in no change or only a small decrease in the urinar y T/EpiT ratio in eugonadal men.