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Tetrahydrogestrinone can be easily manufactured by the catalytic hydrogenation of the ethynyl group of the progestogen gestrinone ( Figure 5 ). This relatively simple synthetic step hides the thinking that probably lay behind the design of THG. Given the close homology of their receptors, there is an overlap between the activity of progestogens and androgens, especially those xenobiotic steroids that lack the C-19 methyl group, but which activity predominates depends on whether the alkyl substituent at carbon-17 is ethynyl or ethyl. Substitution of the 17?-H with an ethynyl group on nandrolone, a 19-nor anabolic steroid with some progestational activity, will result in a potent orally active progestogen, this being called norethisterone (norethindrone), a steroid that is still used in some contraceptives today. The synthetic route is described in a seminal paper by Djerassi et al. However, substitution with an ethyl group on nandrolone rather than ethynyl group results in another anabolic steroid known as norethandrolone, which also has oral activity. Gestrinone, is a pharmaceutically available progestogen that lacks the C-19 angular methyl group but has a 17?-ethynyl group, and it follows that reduction of this ethynyl group to the tetrahydro product should make THG a ‘potent’ androgen. This is indeed the case, as subsequently THG was found to be a highly potent androgen (and progestogen) in an in vitro bioassay system expressing human steroid receptors (Death et al. Despite the presence of the 17?-alkyl function, which should make the steroid resistant to first-pass metabolism, it is of interest that the instructions from BALCO Laboratories were to place a few drops of the liquid preparation under the tongue, that is, a sublingual route of administration. THG was invisible on the routine gas chromatography’mass spectrometry screen employed by the WADA-accredited laboratories and necessitated the development of a liquid chromatography’mass spectrometry/mass spectrometry (LC’MS/MS) screen for its detection; for a current and detailed review on the analysis of anabolic steroids see Kicman et al. Catalytic hydrogenation of gestrinone to form tetrahydrogestrinone (THG). An example of a catalyst is palladium on carbon (Pd/C), as described in a procedure employed by Catlin et al. Underground chemists appear also to be accessing information concerning other steroids that were synthesized several decades ago by pharmaceutical companies but were never marketed. Such steroids that have been detected until recently are norbolethone (Catlin et al. Although the extent of this activity appears to be limited, as screening procedures rely on targeting selecting ions for monitoring by mass spectrometry, unknown steroids may escape detection. 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