Research efforts focus on male contraception
February 1, 1998
Research efforts focus on male contraception
While it may be 10 years or more before clinicians can prescribe a pill, give an injection, or insert an implant for male contraception, those on the research front say progress on a number of methods is moving that scenario within reach.
"My personal opinion is that we are moving forward faster than we have in a long time," notes Henry Gabelnick, PhD, director of the Contraceptive Research and Development (CONRAD) Program in Arlington, VA. CONRAD is working in partnership with scientists around the globe in developing numerous approaches to male contraception.
Spermatogenesis, or sperm cell formation, is an intricate process. It is initiated by the release of gonadotropin releasing hormone (GnRH) from the hypothalamus, which in turn stimulates the production of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the anterior pituitary. These hormones then travel through the bloodstream to the testes. When LH and FSH levels are manipulated, it is possible to reduce sperm count to zero (azoospermia) or to a nonfertile level (severe oligozoospermia).
Sperm production is primarily attributed to FSH, with LH chiefly responsible for male sexual characteristics through the production of testosterone. Scientists have worked with a number of compounds and delivery systems to find an approach that provides contraceptive efficacy while maintaining libido and potency.
Much research has focused on the use of testosterone enanthate (TE) to alter male hormone levels. A large multicenter trial coordinated by the World Health Organization (WHO) in Geneva, Switzerland, showed that weekly injections of TE successfully suppress sperm formation, yielding effective contraceptive protection with minimal side effects and full recovery of sperm production after stopping treatment.1
Weekly injections never were considered the best course, but Gabelnick contends the studies demonstrate their efficacy. Other methods of delivery are now being considered for the best fit. Research is focused on combining testosterone esters or other testosterone delivery systems with a progestin, such as depo-medroxyprogesterone acetate, levonorgestrel, desogestrel, and cyproterone acetate.2
Another steroid hormone approach under review involves the use of testosterone buciclate, a long-acting testosterone ester. When injected, this hormone forms a depot in the muscle, gradually releasing testosterone over three months.3 Testosterone buciclate was tested early on, but researchers encountered formulation problems, Gabelnick says. It is being reformulated, and when that process is complete, WHO, the National Institutes of Health in Bethesda, MD, and CONRAD plan additional studies, he says.
GnRH agonists and antagonists, alone or combined with testosterone, also appear to be effective in male contraception. The New York City-based Population Council is assessing the efficacy of a two-rod implant using a GnRH agonist and its own patented synthetic androgen, 7-alpha methyl-19-nortestosterone.4
Researchers in Bologna, Italy, and Seattle have studied a male oral contraceptive pill using testosterone undecanoate and cyproterone acetate, two times daily for 16 weeks. The combination effectively suppressed sperm production with no change in sexual function or behavior. Sperm production returned to normal after the men ceased taking the medication.5 The Consortium for Indus-trial Collaboration and Contraceptive Research, a program within CONRAD, is sponsoring a study of cyproterone acetate and a testosterone injectable.
The Rockefeller Foundation, a philanthropic organization in New York City, has joined Berlin, Germany-based pharmaceutical company Scher-ing AG to propel research in the interruption of epididymal functions. The centers participating in the Rockefeller Foundation/Schering network will look at the function of the epididymis. The epididymis fulfills three functions in the reproductive process, says Mahmoud Fathalla, MD, associate director of the foundation’s population sciences division: maturation of sperm cells, storage of these cells, and regulation of their transit.
Network scientists will focus on interrupting maturation of sperm cells via action on the epididymal epithelium and/or secretion. They also will explore the delivery of drugs to the epididy-mis to affect the function of the stored potentially fertilizing sperm, he says. "It is envisioned that the program will be supported for five years. The timetable for product development will be set only after the identification of promising leads. If the mission is successful, we can hope to see a novel male contraceptive pill or injection in 10 years."
Robert A. Hatcher, MD, MPH, professor of OB/GYN at Emory University in Atlanta and chairman of Contraceptive Technology Update’s editorial board, often is asked about the lack of contraceptive methods for men. His reply is straight- forward: "At the present time, as I see it, the two very best methods of contraceptives available in the world today are male methods of birth control. The vasectomy is clearly superior to tubal sterilization in a number of ways. It is safer, less expensive, and potentially more effective. Indeed, as several tests of male semen are performed, and no sperm are found in the immediate post-vasectomy period and for several years thereafter, effectiveness approaches 100%."
The condom can be used with extremely low breakage rates and has been virtually 100% effective at preventing HIV in prostitutes in Nevada,6 he notes. "Clearly, the condom is the best approach we have at the present time for the prevention of HIV and other infections," he says.
References
1. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men. Fertility and Sterility 1996; 65:821-829.
2. Klitsch M. Still waiting for the contraception revolution. Family Planning Perspectives 1995; 27:250.
3. Liskin L, Benoit E, Blackburn R. Vasectomy: New opportunities. Population Reports, Series D, No. 5. Baltimore: Johns Hopkins University, Population Information Program; March 1992.
4. Population Council. From mice to men: Creating a male hormonal contraceptive. Population Briefs 1995; 1:5.
5. Meriggiola MC, Bremner WJ, Costantino A, et al. An oral regimen of cyproterone acetate and testosterone undecanoate for spermatogenic suppression in men. Fertility and Sterility 1997; 68:844-850.
6. Albert AE, Warner DL, Hatcher RA, et al. Condom use among female commercial sex workers in Nevada’s legal brothels. Am J Public Health 1995; 85:1,514-1,520.
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