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Even though only 12’14% of androstenedione is converted peripherally to testosterone (Horton and Tait, 1966; Bardin and Lipsett, 1967), this amount accounts for about half the circulating testosterone in the women. As the peripheral contribution to blood testosterone is far greater in the young adult women than the men, ingestion of modest amounts of androstenedione, DHEA or androstenediol (the natural steroid or the ? 4 analogue) is likely to significantly raise circulating testosterone. There are modest-to-large increases in circulating testosterone following androstenedione administration to women (Leder et al. Women who chronically administer large doses of weaker androgens that can be converted to more potent steroids would be expected to suffer from virilizing effects. In 2004, the FDA (Food and Drug Administration), as part of its public health mission, sent warning letters to 23 companies in the United States requesting them to cease distributing androstenedione as dietary supplements (FDA, 2004). Designer anabolic steroids are considered as ones that are manufactured specifically to circumvent doping tests in human sport, and, therefore, for obvious reasons, they are supplied in a clandestine fashion. There are few examples to draw on. Classified documents (Franke and Berendonk, 1997) saved after the collapse of the German Democratic Republic revealed that, since 1983, a pharmaceutical company had produced preparations of epitestosterone propionate exclusively for the governmental doping programme. Epitestosterone, an epimer of testosterone, is a steroid with no anabolic activity but its administration with testosterone simultaneously or sequentially enables an athlete to manipulate the test for testosterone administration if the test is based solely on determination of the urinary testosterone/epitestosterone (T/E) ratio. Recently, a company in California called BALCO (Bay Area Laboratory Co-operative; Burlingame, CA, USA) attracted much media attention due to the high profile of the athletes involved, not least because of the supply of a transdermal preparation coded as ‘The Cream’ containing testosterone and epitestosterone, as well as a sublingual preparation of a new anabolic steroid coded as ‘The Clear’, which was identified from the contents of a spent syringe as tetrahydrogestrinone (THG) by the WADA-accredited laboratory within the University of California, Los Angeles (UCLA) (Catlin et al. 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, buy caberlin 0.25 mg antiestrogens cabaser. 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. 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