Role of 5areduction

Androgens, which are not reducible by the tissue-specific enzyme 5a-reductase are likely to be dissociated (see 20.2.1). Several steroidal compounds on the market with enhanced anabolic effects as well as recently described non-steroidal compounds are not 5a-reducible (e.g. anadrol, oxandrolone) (for overview Chengalvala etal. 2003).

A steroidal compound, 7a-methyl-19-nortestosterone (MENT), with selective properties was described for the development for male contraception. MENT which acts as an agonist only, differs from testosterone as it does not undergo 5a-reduction in the prostate as does testosterone (Anderson etal. 2003; Cummings et al. 1998; Sundaram et al. 1993). Therefore a dose of MENT sufficient to maintain normal androgen function in most organs will not hyper-stimulate the prostate because its action is not amplified as is that of testosterone. This compound as well as anabolic compounds described since the 50s were the first hints that androgens with different tissue specific action are possible showing tissue-specific effects in vivo. Contrary to non-steroidal compounds as well as to some steroidal compounds, MENT is aromatisable (LaMorte etal. 1994) and may address beneficial estrogenic effects of in vivo aromatized MENT.

Tissue-selective non-steroidal compounds were identified with selected anabolic effects (e.g. Hamann 1999; Yin etal. 2003a). In preclinical studies the compounds were less potent and efficacious than testosterone propionate in androgenic organs, but their anabolic activity was similar to that of testosterone propionate. It is possible to achieve with the non-steroidal compounds tissue-selective actions and generate agents with activity profiles meeting specific therapeutic needs. The compounds are of course not aromatisable to an estrogen, only the internal testosterone and androstendione serve as substrates for the aromatase enzyme. Therefore, further reduction in the amount of the internal aromatisable androgens are not desired. Unfortunately data about effects on gonadotropin synthesis are rare or have limited prediction for the situation in human.

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