Male contraception: clinical trials.

Current research in the chemical and hormonal disruption of the male reproductive system is reviewed. The authors suggest that it is possible to induce azoospermia and oligospermia in 70-100% of normal men. The most promising compounds are danazol and depo-medroxyprogesterone acetate. Studies of danazol administered with methyltestosterone orally decreased sperm counts significantly and as effectively as intramuscular administrations of danazol and testosterone enanthate 200 mg/month. Drug related effects included decreases in levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) and smaller decreases in serum testosterone levels. Some patients experienced weight gain and increased acne 2 cases of gynecomastia were reported. Full recovery occurred within 13-63 weeks after discontinuation. Administration of 200 mg depo-medroxyprogesterone acetate and 250 mg testosterone cypionate/month appears to be the most practical and effective form of chemical contraception for men. Azoospermia was achieved in 56% of the study group within 6-15 weeks oligospermia was present in all other group members. Full recovery was reported in 14-60 weeks and minimal side effects (weight gain and transient gynecomastia) developed. Administration of testosterone enanthate using several regimens was not as effective and impractical due to the necessity of administration every 7 to 10 days to achieve maximum suppression of spermatogenesis. Studies with cyproterone acetate 5 mg 10 mg or 20 mg/day showed varying degrees of oligospermia. The compound inhibits gonadotrophin secretion and decreases levels of serum testosterone. Conflicting data were available on the impairment of sperm migration through midcycle cervical mucus. No serious adverse drug related effects were reported. Indications of acceptability from these studies are promising. A low dropout rate (11-25% at 1 year) was reported for monthly injection or monthly injection plus daily oral doses. This is comparable to the dropout rate among oral contraceptive users 32%. Doses that would achieve azoospermia in 70% of normal men are presumed to have unacceptable levels of toxicity. The failure rate associated with oligospermia is unknown. 1 study reported 7 pregnancies from the study group of 300 men over 6 months. Other chemicals that are presently in the animal study or clinical trial stage include the administration of LH-releasing hormone (LHRH) which suppresses spermatogenesis but needs to be accompanied with androgen replacement. Inhibin decreases sperm production but not androgen production as does gossypol. Further testing to determine reversibility and the side effects associated with gossypol is needed. Several compounds (alpha-chlorohydrin amino-chlorohydrin and chlorinated sugars) that alter epididymal function are being tested. Minimal adverse genetic effects are associated with interference at this site. The suspected mechanism of action of these compounds is interference with normal glucose metabolic pathways within the epididymis. Serious systemic toxic effects are evident with these compounds.