norethindrone-enanthate and testosterone-enanthate

The principle of male hormonal contraception is based on the suppression of LH and FSH and the replacement of testosterone to maintain androgenicity. The goal can best be achieved by testosterone alone or by testosterone in combination with a gestagen. The five clinical trials using pregnancy rates as end points and the one trial performed by the pharmaceutical industry are reviewed here. An ongoing large multicenter trial launched by WHO and the US CONRAD Programme will decide about the future of male hormonal contraception.

Topics: Azoospermia; Clinical Trials as Topic; Contraception; Contraceptive Agents, Male; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Medroxyprogesterone Acetate; Norethindrone; Pregnancy; Pregnancy Rate; Progesterone Congeners; Progestins; Testosterone

The combination of androgens and progestogens has been shown to be a suitable male contraceptive. Previous experiments revealed that injection of a dimeric testosterone-ethynodiol ester into rats and monkeys induces azoospermia for several weeks. In order to investigate the mechanism of action, we compared the endocrine effects of a single injection of 10 mg of the dimeric ester into intact male rats with that of 6 mg of norethisterone enanthate + 6 mg of testosterone enanthate. After the injection of the dimer there was a transitory reduction of serum FSH and a strong suppression of serum LH and testosterone, of testicular testosterone and of androgen-binding protein (ABP) in the testis and epididymis for at least 8 weeks, whereas spermatogenesis was totally depressed between the 4th and 8th week. Contrary to this, the enanthates caused only a slight suppression of spermatogenesis, although serum LH, testicular testosterone and ABP were profoundly reduced. The only conspicuous difference in the endocrine pattern of both groups during the first 4 weeks was in the serum testosterone level which remained normal in the rats treated with the enanthates. The results suggest that testicular testosterone and ABP concentrations are of minor significance for an intact spermatogenesis, and that some other factors produced by Sertoli cells might be involved and possibly maintained by normal serum testosterone levels.

Topics: Androgen-Binding Protein; Animals; Ethynodiol Diacetate; Follicle Stimulating Hormone; Luteinizing Hormone; Male; Norethindrone; Rats; Rats, Inbred Strains; Spermatogenesis; Testis; Testosterone

The time- and dose-dependent effects of a dimeric ethynodiol-testosterone ester upon intact and hemi-castrated female rats were compared to those of equivalent doses of norethisterone enanthate plus testosterone enanthate. In intact rats, serum LH was markedly suppressed for at least 8 weeks after a single i.m. injection of 10 or 20 mg of the dimer which exceeded the depot-effect of the combination of the enanthates. A biphasic time-and dose-dependent effect of the dimeric ester upon ovarian and uterine weight was observed. During first 2 weeks following the injection there was a pronounced enlargement of corpora lutea and a marked enhancement of progesterone secretion, probably due to a direct stimulation by the androgens. At the same time, the uteri were markedly enlarged. During the following weeks, the ovaries became progressively smaller and showed degenerative changes, the steroid levels decreased and the uteri became atrophic. When hemi-castrated rats were injected once with 1 and 5 mg of the dimer, LH became suppressed, and the compensatory hypertrophy of the ovary was inhibited. At higher doses, the weight of the ovary and uterus was increased, and the luteal function was stimulated. The results indicate that, even though the gonadotropins are suppressed, there is possibly a direct stimulatory effect of high doses of the intact dimeric molecule upon the uterus, while the stimulation of the corpus luteum function is due to an interference of the transiently elevated testosterone level with ovarian steroid biosynthesis.

Topics: Animals; Castration; Dose-Response Relationship, Drug; Drug Implants; Estradiol; Ethynodiol Diacetate; Female; Luteinizing Hormone; Norethindrone; Organ Size; Ovary; Pituitary Gland; Progesterone; Rats; Structure-Activity Relationship; Testosterone; Thymus Gland; Time Factors