Urinary nandrolone metabolites of endogenous origin in man: A confirmationby output regulation under human chorionic gonadotropin stimulation

19-Nortestosterone (nandrolone) is an anabolic steroid compound widely used as a doping agent by athletes. The analysis of its urinary metabolites, 19 -norandrosterone (NA) and 19-noretiacholanolone (NE) glucuronides, allows t he detection of surreptitious administration of nandrolone in sport. A thre shold concentration at 2 mug/L urinary nandrolone metabolites is advocated by the International Olympic Committee for the detection of doping, but som e controversy concerning the validity of this threshold arose hom the demon stration of endogenous production of nandrolone in mammals, including human s. The regulation of human nandrolone production and its contribution in vi vo to the process of aromatization remain unknown. In the present study 10 healthy men were successively submitted to insulinic stress and gonadal sti mulation by hCG administration. Urinary NA and NE concentrations were quant ified by gas chromatography-mass spectrometry. NA was detected in basal uri ne samples from all subjects, with a mean urinary excretion rate (UER) of 3 .17 +/- 0.35 ng/h, whereas NE was detected in 4 of 10 (UER range, 0.8-4.7 n g/h). Insulinic hypoglycemia did not significantly modify mean NA UER despi te random intraindividual variations between timed urine collections. After hCG administration, NA UER increased by 250% (P < 0.01) and estradiol (E-2 ) UER by 260% (P < 0.001). The maximum NA concentration obtained aff er sti mulation was 0.43 mug/L. NA UER, plasma E-2, and E-2/T ratio peaked on day 1 after hcG administration, whereas plasma T peaked later on day 3. NA UER correlated with plasma E-2 (r = 0.61; P < 0.001) and E-2/T (r = 0.51; P < 0 .001), but not with plasma T. in conclusion, insulinic stress did not signi ficantly alter nandrolone metabolism, whereas the effect of hCG was a stimu lation of NA excretion in all subjects, which constitutes strong support fo r the endogenous origin of low basal NA excretion. The comparative kinetics of NA UER, plasma E-2, and E-2/T ratio suggest a contribution of the aroma tase process to nandrolone biosynthesis in man.