Target sites for suppressing fertility in the male.

The present status and perspectives in the control of fertility in the male have been reviewed. There are two potential sites in the male reproductive processes that can be used as targets for regulation of fertility in the male: (1) inhibition of spermatogenesis, and (2) interference with sperm maturation in the epididymis. A variety of compounds tested for their antispermatogenic action in laboratory animals have no future for the control of fertility in the human male because of a number of undesirable side effects (cf. Prasad, 1973). Progestational compounds inhibit spermatogenesis by affecting the hypothalamo-hypophysial system and result in impairment of libido. The possibility of adjustment of the minimal dose of progestational compounds required to induce suppression of spermatogenesis and reduction of plasma testosterone to a level compatible with the maintenance of normalcy of libido and potency needs to be studied. A new approach to contraception in the male involves the use of a combination of progestational compounds for suppression of spermatogenesis along with testosterone (administered through silastic capsule implants or as intramuscular injections) for maintenance of libido and accessory sex gland function. A number of such combinations have been tested clinically with some success. However, the limitations of side effects, such as weight gain, gynecomastia, and psychological complications preclude their long-term use for contraception in man. Short-term use of these combination regimens by the male for 1 year followed by use of a contraceptive method by the female may be desirable to encourage partnership in family planning. Although testosterone and other androgens suppress spermatogenesis in man, the feasibility of their use for contraception depends on the establishment of a dosage and mode of adminstration that provide antispermatogenic action without causing more general metabolic alterations. Inhibition of spermatogenesis by selective interference with the action of FSH on the Sertoli cells by active or passive immunization or by selective suppression of synthesis and release of FSH by administration of "Inhibin" offers exciting possibilities in the control of fertility in the male. Studies on the physiology of the rete testis highlight its importance as a post-tubular site of action of antifertility agents in conveying (to the epididymis) compounds interfering with epididymal functions and/or viability of spermatozoa. A new approach to the induction of functional sterility in the male by selective alteration of epididymal function by a local androgen deprivation effect has been successfully tested in clinical trials. Small doses of cyproterone acetate, administered orally, result in maintenance of libido and accessory sex gland function accompanied by a decrease in the motility of ejaculated spermatozoa and incomplete inhibition of spermatogenesis...