Spermatogenesis is predominantly regulated by pituitary gonadotropins. LH influences gamete production via stimulation of Leydig cells, resulting in high intratesticular testosterone concentrations, while FSH exerts its effects on Sertoli cells. Theoretically azoospermia can be achieved by suppression of gonadotropins, whereby, however, a severe decrease in androgen production would also occur. Since testosterone is required for normal male sexual function, maintenance of secondary sex characteristics, bone and protein metabolism as well as for gender identity, androgens must be an integral part of any male contraceptive method acting via suppression of gonadotropins. Although testosterone esters alone (testosterone-propionate, oenanthate, or cypionate) lead to azoospermia in a certain proportion of men, effectiveness is increased when they are combined with other antigonadotropic substances such as gestagens. Among different combinations tested testosterone oenanthate and depot medroxy-progesterone acetate were used most frequently. Instead of gestagens other steroids such as danazol and cyproterone acetate have been tested but azoospermia, the final goal of these investigations, has never been achieved in all participants. Results from non-human primates indicate that substitution with available testosterone esters may by itself maintain spermatogenesis due to high serum levels after injection. Better results with 19-nortestosterone-hexyl-oxyphenyl-propionate seem to support this hypothesis. In the future, it is likely that testosterone ester with smooth pharmacokinetic profiles or microencapsulated testosterone in combination with gestagens or with GnRH analogues will lead to a male contraceptive method based on endocrine means.
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