Family planning remains an important challenge for sexually active men and women. For women, a wide array of options has been made available to prevent pregnancies, including oral contraceptive pills, transdermal patches, subcutaneous implants, injectables that may be administered every month or as infrequently as every three months, inrrauterine systems, vaginal rings, intravaginal spermicides, and female condoms. Recent surveys, however, have indicated that men would be willing to share family planning responsibilities, including the use of newly developed methods. Yet, the only approved and available methods of male contraception are using condoms and surgical vasectomy. It is clear to many interested parties that the development of new contraceptives should include a male focus. In fact, real progress has occurred in the past few years, with the most advanced and promising methods currently in development relying on the suppression of spermatogenesis via the exogenous administration of hormones. This post will describe the recent state-of-the-art progress in male hormonal contraception.
Condoms offer dual protection against pregnancy and sexually transmitted infections. The failure rate of condom users is about 12%. Although condoms are recommended for use in casual sexual encounters and in environments where sexually transmitted infections are prevalent, they may not be acceptable to all couples in stable relationships. Further, while nonlatex condoms are preferred by subjects in comparison studies of the efficacy of latex and nonlatex condoms, the breakage rate is higher with nonlatex condoms, although the contraceptive efficacy appears to be similar. (For further information on sexually transmitted diseases, see site)
The morbidity of surgical vas occlusion has decreased with the introduction of the no-scalpel vasectomy technique. Theoretically, vas occlusion is very effective, with a low failure rate of less than 1%. Recent prospective studies, however, have showed that the failure rate may be much higher, indicating that couples should receive appropriate counseling. The success of vas occlusion depends on the competence of the operator as well as on the method. Fascial interposition appears to result in lower failure rate. Cauterizing one of the vasal ends has also ensured effectiveness. Although percutaneous intravasal injection of occlusive substances and the placement of stents have both been tried, these methods have not shown advantages over standard methods and often have high failure rates. It is important to note that after vasectomy, the spermatozoa are not emptied instantaneously from the male accessory glands and the ejaculatory systems. Men are advised to use another method of contraception until 20 ejaculations or 12 weeks have elapsed since the vasectomy date. A recent prospective study, however, has indicated that a greater number of ejaculations or more time is required for the spermatozoa to be fully cleared from the accessory glands and the ejaculatory system.
Vasectomy is offered as an irreversible method. Although reanastomosis of the two cut ends is possible and is associated with high rates of spermatozoa reappearance, pregnancy rates remain much lower — presumably because of the development of antisperm antibodies associated with vas occlusion. (For further information on vasectomy and vasectomy reversal, see site)
Nonhormonal Male Contraception
Gossypol, a derivative from cottonseed oil, has been found to be a very effective oral contraceptive in China. Because of its direct action on germ cells, however, men treated with gossypol may sustain irreversible infertility. In some men, gossypol also led to hypokalemic paralysis. A second compound derived from the root of Tripterygium wilfordii and aptly named “triptolide” was initially thought to reduce sperm motility via direct actions on the epididymis; however, long-term studies in rodents have showed that triptolide has toxic effects on the germinal epithelium with the potential to cause irreversible infertility as well.
Lonidamine is a nonsteroidal antispermatogenic agent with direct effects on the germinal epithelium. An analog of lonidamine has been studied that also works on the germinal epithelium, but without the toxic effects of lonidamine on the kidney and liver. These agents are currently being tested in animal models.
Most recently, alkylated imino sugars were reported to have contraceptive activity in mice. When these imino sugars were administered orally in mice, epididymal sperm were discovered to have abnormal heads, acrosome reaction was blocked, and sperm motility was reduced. These mice became infertile three weeks after dosing was initiated, implicating an effect on mature sperm via interference with the biosynthesis of glucosylceramide-based sphingolipids.
There has also been research to identify possible novel targets in spermiogenesis and sperm maturation in the epididymis. These protein targets, including receptors, ligands, enzymes, and ion channels, are excellent targets for drug development. The functional roles of these targets can be tested in knockout or knock-in mouse models. Although many laboratory discoveries have since been made, these potential targets will not be available for clinical testing for the next 10 to 20 years.
The currently available male-controlled methods of contraception consisting of condoms and vasectomies are not acceptable to many couples. Male hormonal contraceptive methods may be the most promising for men and women in stable relationships who desire