The use of testosterone as a male contraceptive

Abstract

Testosterone functions as a contraceptive by suppressing secretion of the pituitary gonadotropins luteinizing hormone and follicle stimulating hormone. Low levels of these hormones decrease endogenous testosterone secretion from the testis and deprive developing sperm of the signals required for normal maturation. Interference with sperm maturation causes a decline in sperm production and can lead to reversible infertility in men, raising the possibility that testosterone could be utilized in a commercially available contraceptive. To this end, testosterone has been studied alone and in combination with either gonadotropin releasing hormone analogues or progestins in efforts to improve its contraceptive efficacy. In this chapter, we will review efforts to use testosterone to create a safe, convenient, efficacious contraceptive method for men.

PIP: This article reviews efforts promoting the use of testosterone (TE) as a safe, convenient and an efficacious contraceptive method for men. In order to assess the efficacy of a potential male contraceptive, it is important to determine what level of sperm inhibition is necessary to achieve infertility. In efforts to improve its contraceptive efficacy, the following contraceptive trials have been studied: TE alone; TE and gonadotropin releasing hormone (GnRH) analogues; and TE and progestins. TE requires weekly injections, which is a significant drawback. Thus, longer-acting esters, such as 19-nortestosterone and its derivative 7-alpha-methyl-19-nortestosterone, have been evaluated as potential substitutes for TE. Moreover, several advances have been made in understanding estrogen activity at the molecular level. This article concludes that TE is useful as contraceptive in human males; combinations with GnRH antagonists improve the efficacy of TE, although impractical for widespread use; and TE with progestins may also be promising. Furthermore, recent insights into the molecular regulation of transcription by estrogen receptors may point to the existence of a similar complexity in the androgen receptor and may provide new avenues for the generation of a male hormonally-derived contraceptive. A better understanding of the molecular regulation of spermatogenesis will clearly increase the chances of successfully manipulating these systems to create an easily usable, long-term contraceptive for men and to complement the success of the estrogen-progestin pill for women.