Sense or nonsense of prohormone designing : reduced metandienone as supplement

Since the mid of the 1990s anabolic steroids are marketed as dietary supplements by labeling them as so-called ‘prohormones’. The first prohormones on the market were derived from Testosterone and Nortestosterone by oxidation or reduction at C3 or C17 yielding (19-nor)androst-4-or-5-ene-3,17-dione or-diols. Recently, products were found on the market stating to contain “17α-methyl-1,4-androstadiene-3,17-diol”. These products were analyzed for their steroid content following soxhlett extraction with n-hexane using GC-MS of the underivatized compound and its per-TMS derivative. Additionally, NMR data were recorded to confirm the structure. Differing from the label, the derived structure was confirmed as 4,l7-dimethylestra-1,3,5-trien-l7β-ol. Reproducing the reduction of the oxo—group on C3 of metandienone with lithium aluminium hydride or sodium borohydride under different conditions most likely provides the explanation: water was directly eliminated from the intermediate in a reaction called benzene-hydroxy dienol rearrangement. To characterize the biological activity of 4,17-dimethylestra-1,3,5-trien-l7β-ol it was tested in yeast androgen and estrogen receptor transactivation assays for agonistic and antagonistic effects. None of the assays resulted in any transactivation. Additionally, it was studied in a rat animal model. Orchiectomized rats were treated s.c. for 12 days with 1 mg/kg BW/day. Tissue wet weights were determined to indicate the anabolic (m. lev. ani) and androgenic (prostate) activity, which were confirming the inactivity of this substance. Verf.-Referat