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Test

ICA Symposium - Male Contraception: Hormonal Aspects

This symposium was sponsored by WHO. The three speakers followed a connecting theme: the progress in the development of hormonal means of suppressing sperm production in men of reproductive age and the likely efficacy and safety of such methods. The background and motivation for the studies reported derived from two large WHO trials which had established the high contraceptive efficacy of a putative hormonal method for men based on androgen treatment. Fred Wu (UK) presented data to support the concept that a combination of progestin with relatively low dose androgen supplementation might reduce the risk of androgen-related side effects while direct actions of some progestins on the testis may increase the suppression of spermatogenesis. Recent studies on oral levonorgestrel or desorgestrel combined with testosterone enanthate intramuscularly, while producing both rapid and complete sperm suppression, still retained undesirable suppression of HDL-cholesterol, although without serious adverse reactions. Studies to define the ideal drug combination are continuing in several centers, some with the support of the pharmaceutical industry. Dr. Wu reviewed studies with the anti-androgen cyproterone acetate and with 19-nortestosterone alone or in combination with DMPA. He drew attention to the higher rate of sperm suppression achieved in Chinese and Indonesian men compared with Caucasian men, a feature which is encouraging the development of appropriate hormonal regimens for male contraception by developing country clinicians.

Herman Behre (Germany) first reviewed progress in the development of long-acting testosterone esters to replace testosterone enanthate (TE) for intramuscular application both to hypogonadal men and in contraception. He compared the pharmacokinetic profiles of testosterone buciclate (TB), a WHO-NICHD developed drug, and a new formulation of testosterone undecanoate (TU) in tea seed oil, first prepared in China. TB had the longest half-life (29.5 days) but was not yet available for general use; the half-life of TU was intermediate (20.9 days) between TB and TE (4.5 days). Dr. Behre then reviewed the studies to explore the efficacy of GnRH analogues in sperm suppression and the search for the ideal dose and timing for male contraception when combined with androgen. The most recent studies suggest that a loading dose of a GnRH antagonist to initiate sperm suppression followed by low doses to maintain the effect could be the most effective and economical. Depot and oral preparations of GnRH antagonists are being developed which, when combined with the new androgen esters TB or TU, provide promising leads to effective, safe, and reversible male contraception.

The third speaker, Zhang Gui-Yuan (China) discussed the three principal areas of male contraceptive research being undertaken in China. By comparing the endocrine responses in Chinese hypogonadal men to intramuscular injections of the tea seed oil formulation of TU with TE, it was concluded that the duration of action and half-life of TU were much longer than TE and that TU was promising for development as a clinically applicable androgen for Chinese men. Several new male antifertility diterpene epoxide compounds have been isolated from root extracts of the plant Tripterygium wilfšrdii which, when given to rats by mouth, cause reversible infertility by an action on epididymal sperm, without alterations in either gonadotropin or testosterone levels. By selection and appropriate toxicological testing it was hoped that one might be developed as a post-testicular contraceptive drug. Finally, Dr. Zhang reviewed a ten-center study to evaluate the efficacy, incidence of complications and reversibility of three methods of vas occlusion: no-scalpel vasectomy; injection of sclerosing agent; and injection of a polymerizing polyurethane of medical grade. It was concluded that no-scalpel vasectomy is the method of choice.

Geoffrey Waites, Switzerland