Testosterone analogs

Testosterone (5.45) is the prototypic androgen sex hormone. Testosterone is synthesized by the testes, and must be reduced to dihydrotestosterone (5.46, DHT) before it will bind to the receptor. Among highly active synthetic testosterone analogs, 7a-methyl-19-nortestosterone (5.47) and oxandrolone (5.48) have about 100 times greater activity than testosterone as androgens. 17a-Methyltestosterone (5.49) is orally active. 

Highly effective oral A, can be obtained by structural modification, e.g. methyltestosterone and mes-terolone. A. are used therapeutically, in particular to correct for deficiency symptoms following castration, hypogenitalism, impotency due to lack of hormones, climacterium, mammary carcinoma and peripheral circulatory impairment. Some synthetic testosterone analogs with a 1,2-cyclopropane ring have antiandro-genic effects. Inappropriate administration of anabolic steroids (e.g. to athletes) can lead to impotence or sterility. 

Gonadotropin releasing hormone analogs (goserelin, buserelin, leuprorelin, triptorelin) inhibit gonadotropin release and thus lower testosterone or estrogen levels. They are used to treat breast cancer and prostate cancer. 

Recently, Voogt et al. [91] have reported on the d5-pathway in steroid metabolism of Asterias rubens. These workers established the existence of the d5-pathway (Scheme 20), analogous to the pathway found in mammals this conclusion was based on the observation that radiolabeled cholesterol (1) was converted to pregnenolone (112), 17a-hydroxypregnenolone (141), and androstenediol (142). Labeled pregnenolone was converted additionally to progesterone (129). Androstenediol (142) was the main metabolite of de-hydroepiandrosterone (143), a reaction catalyzed by 17/i-hydroxysteroid dehydrogenase (17/1-HSD). The metabolic conversion of androstenedione (131) to testosterone (132) is also mediated by 17/J-HSD and is related to... 

Anti androgens GnRH analogs Steroid synthesis inhibitors f>a reductase inhibitors Testosterone receptor inhibitors... 

A second example can be found in the metabolism of the male sex steroid hormone testosterone. In addition to 7a -hydroxy- and 6a-hydroxytestosterone, CYP2A1 was also found to form A6-testosterone (136) (Fig. 4.69). Using selectively deuterated analogs (136), A6-testosterone was established as being formed in competition with 6o -hydroxytestosterone after initial hydrogen atom abstraction from C6 to form the common radical intermediate. Little, if any, A6-testosterone was found to be formed in competition with la-hydroxytestosterone after initial hydrogen abstraction from Cl. 

An exactly analogous enzymic transformation is encountered during the formation of oestrogen and androgen sex hormones, e.g. estradiol and testosterone respectively, where dehydroepiandrosterone is oxidized to androstenedione. 

In applied medicine, testosterone esters (propionate, cypionate, and enantate) and a synthetic analog, methyltestosterone, are widely used. In many tissues, testosterone s androgenic... 

The nonapeptide leuprolide is a synthetic analog of the decapeptide, gonadotropin releasing hormone, and it exceeds the activity of the natural hormone and significantly elevates the level of testosterone and dihydrotestosterone in men, and estrogen in women. It also inhibits foUicle-stimulating hormone and leutenizing hormone. 

Anabolic-androgenic steroids (AAS), which are analogs of the male hormone testosterone, are used among athletes and bodybuilders. AAS alter the hormonal systems of males and females, and induce many adverse effects. In addition to the sex-related changes, violent behavior and psychological dependence can also occur. The use of AAS in professional sports as well as in high school sports has aroused considerable attention. 

At present, pituitary hormones—and potent antagonist analogs of GnRH—are receiving increased attention. A GnRH antagonist in combination with testosterone has been shown to produce reversible azoospermia in nonhuman primates. 

There are fewer reports on other parenteral routes of administration of emulsions such as intramuscular, subcutaneous, and intraperitoneal. V Mer-in-oil and w/o/w emulsions of bleomycin, mytomycin C, and 5-Luorouracil have been administered by these routes, apparently resulting in increased regional lymphatic uptake, hence the term lymphotropic emulsions (Davis et al., 1987). Gasco et al. (1990) developed a w/o emulsion of an LHRH analog measurements of testosterone levels after intramuscular administration to rats suggested that the formulation led to prolonged release of the drug. 

Athletes engaging in androgen abuse usually obtain these drugs from various illicit but readily available sources.155 Some examples of anabolic steroids that are used by athletes are listed in Table 30-2. These agents include testosterone, synthetic analogs of testosterone, and precursors that are converted to ana-... 

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