Antiandrogens
There are three possibilities to reduce the effects of testosterone and dihydrotestosterone: either to reduce their production, or to inhibit the transformation of testosterone into dihydrotestosterone, or to inhibit their effects.
Decrease of the production of testosterone
Testosterone secretion can be decreased:
- by inhibiting the secretion of LH by the administration of gonadorelin, GnRH, in a continuous way ( See “hypothalamic Hormone: gonadorelin”. ) or by GnRH antagonists
- by inhibiting testosterone synthesis in testes. Among the inhibitors, one can quote ketoconazole, antifungal which, in large doses, inhibits testosterone synthesis.
Inhibition of conversion of testosterone into dihydrotestosterone: 5-alpha-reductase inhibitors
The inhibition of 5-alpha-steroid-reductase, present in certain organs such as prostate or skin, prevents the transformation of testosterone into dihydrotestosterone.
Finasteride is an inhibitor of 5-alpha-reductase, particularly type 2, present in the male urogenital tract. By selectively inhibiting the transformation of testosterone into dihydrotestosterone, it leaves the effect of testosterone on muscular force and libido intact , and reduces that of the dihydrotestosterone.
Finasteride is indicated in the treatment of benign prostate hypertrophy but its beneficial effects appear only after a few months of treatment. Gynecomastia is frequently observed in men treated by finasteride.
Dutasteride inhibits the two types of 5-alpha-reductase and is used for the treatment of benign prostatic hyperplasia.
Finasteride, tablet with 1 mg, is used for the treatment of the male alopecia. During clinical trials, finasteride was well tolerated. It is nevertheless a hormonal inhibitor whose use in alopecia depends on the importance that one grants to this mark of ageing. The treatment must be continued; if not the loss of hair begins again.
Notice
Extracts from vegetable origin, from bark of Pygeum Africanum, also called African prune, and from fruit of Serenoa repens also called American dwarf palm or saw palmetto have some anti-androgenic and anti-edematous effects on the level of the prostate. They reduce the functional symptoms of benign prostatic hyperplasia (pollakiuria, dysuria, nocturia) by various mechanisms not well known.
Androgens antagonists
Estrogens and progesterone have a low anti-androgenic effect, but there are more powerful antagonists like cyproterone, flutamide, nilutamide and bicalutamide.
Cyproterone
Cyproterone is a synthetic derivative of progesterone having anti-androgenic and progestogen effects.
- It inhibits the effects of dihydrotestosterone competitively for binding to the cytoplasmic receptor.
- It decreases testosterone biosynthesis by decreasing the release of pituitary gonadotropins.
- It has a progestational effect not used in therapeutics because of its anti-androgenic effect, administered to animals during gestation, it disturbs in a dose-dependant manner the sexual differentiation of the male fetus.
Cyproterone, 50 mg presentation, is used for the treatment of major hirsutism in women, and for the palliative treatment of prostate cancer. It is used to prevent the male sexual deviances of certain offenders. When given to men, it inhibits spermatogenesis and causes infertility and often gynecomastia.
Cyproterone, 2 mg, combined to ethinyl-estradiol, is used in women for the treatment of acne and symptoms related to a testosterone excess. It has moreover a contraceptive effect.
The use of cyproterone during pregnancy is contra-indicated because in particular of the risk of feminization of the male fetus. However, it does not seem that malformations were observed in children whose mothers were taking low doses of cyproterone during the first trimester of pregnancy.
It can cause hepatitis as an adverse effect.
Flutamide
Flutamide is a nonsteroidal anti-androgen which probably acts after transformation into 2-hydroxyflutamide.
Flutamide inhibits the binding of testosterone to its cytoplasmic and nuclear receptors. It inhibits the inhibiting effect of testosterone on LH secretion whose secretion increases considerably, and consequently that of testosterone. In patients treated by flutamide, there is an increase of LH and testosterone levels.
The therapeutic use of the flutamide is metastastatic prostate cancer for which it is often combined with an inhibitor of gonadotropin secretion. Its principal adverse effect is hepatitis.
Nilutamide
Nilutamide has properties similar to those of flutamide and the same therapeutic uses.
Among his adverse effects one can quote, on the one hand, disorders of accommodation to darkness and vision of colours, and on the other hand, an Antabuse-like effect (reactions after alcohol intake).
Bicalutamide
Bicalutamide (Casodex*) is a more recent nonsteroidal anti-androgen which has the same therapeutic use as the preceding products but with less hepatotoxicity.
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