Bricout, V., & Wright, F. (2004). Update on nandrolone and norsteroids: How endogenous or xenobiotic are these substances? European Journal of Applied Physiology, 92, 1-12.

"Norsteroids are xenobiotics with androgenic and anabolic properties known since as far back as the 1930s. In doping controls, the use of the banned xenobiotic norsteroids is detected in the competitor's urines by the measurement of norandrosterone (19-NA) and noretiocholanolone (19-NE), which are the main metabolites for nandrolone (NT) and most norsteroids with anabolic properties. In 1996, the IOC subcommission "Doping and Biochemistry of Sport" informed the Heads of the "IOC Accredited Laboratories" that the recommended cut-off limit for reporting an offence was to be 1-2 ng ml(-1) urine for either 19-NA or 19-NE. We will discuss how technical progress in gas chromatography coupled to high-resolution mass spectrometry permitted a dramatic increase in sensitivity with a detection limit of 1 pg ml(-1) urine, or less, and an assay limit of 20-50 pg ml(-1) urine, for either 19-NA or 19-NE. As a paradox, norsteroids have been known for decades as not only xenobiotics but also obligatory endogenous intermediates in the biosynthesis of estrogens from androgens in all species, man included. It is this biochemical observation which fed the active scientific and medical controversy initiated in 1998 over the possibly endogenous production of nandrolone and metabolites well over the new IOC's recommended cut-off limit of 2 ng ml(-1) urine. Notwithstanding the particular technical difficulties attached, we will provide data and discuss the minute endogenous levels detected and measured in man either at rest, after performance or training and compare them to the relatively high levels reported in male athlete's doping controls today. We will also discuss data on the pharmacological effects of some contraceptive therapies containing norsteroids in women".

Implication. Within the normal population, endogenous norandrosterone (19-NA) and noretiocholanolone (19-NE) occur in very small amounts, ostensibly below the WADA/IOC cut-off levels of 1-2 ng/ml in urine. However, this assumes that selected groups of unusual athletes have normal biochemistries. It is contended that such an assumption is dubious at best and false at worst. Select groups of athletes and a small number of individuals in the general population have endogenous levels of 19-NA or 19-NE that exceed anti-doping limits. In other athletes, reactions to extreme exercise, injury, medications (in women contraceptive pills), and health problems stimulate transitory elevations in those markers, rendering those individuals susceptible to positive test results purely because of their natural functioning. It is time for the medical establishment and anti-doping agencies to recognize the false application of normal-population parameters to abnormal populations.

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