C. Alvin Paulsen, M.D.
Professor Emeritus, Department of Medicine
For more than two hundred years, there has been no new method for the regulation of male fertility (male contraception). We have only interrupted coitus, condoms and vasectomy as available male methods. Vasectomy is unacceptable to many individuals since it represents a potentially irreversible condition.
Since 1972 our laboratory has been involved in extending concepts derived from basic studies on the interaction between the testis and the pituitary-hypothalamic system to applications in the clinical setting, to determine whether steroid hormones might be suitable as a male contraceptive agent. We are examining the administration of testosterone for this purpose. The male hormone, testosterone, inhibits the signals from the hypothalamus and the anterior pituitary by shutting off the releasing hormones and gonadotropins. These events, in turn, diminish testicular function, which suppresses spermatogenesis to azoospermia or severe oligospermia. Additionally, Leydig cell function is inhibited so that endogenous testosterone secretion is diminished; but since we are administering male hormone, no evidence of androgen deprivation occurs.
The results of a multi-center clinical trial with testosterone enanthate were published in late 1990. This study focused on couples where the male achieved azoospermia during testosterone administration. In this 10-center trial, it was clear that weekly injections of testosterone achieved greater efficacy than condom use and approached the efficacy of the oral contraceptive agents used by women. The beauty of using testosterone is that when the injections are stopped, complete recovery of spermatogenesis occurs. Unfortunately, weekly injections of testosterone are unacceptable, except to the most highly motivated couples. Studies in other laboratories have indicated that there is a long-acting preparation that should be available to clinical investigators shortly. This would be an analog of testosterone, and a single injection would last for three months. Clearly, progress in male contraceptive development is occurring.
Finally, our laboratory maintains an interest in basic mechanisms involved in the male reproductive system. These include examining the hormonal environment associated with testosterone administration to determine why only a certain number of men achieve azoospermia and others achieve oligospermia.
Publications:
Nieschlag E, Michel E, Knuth UA, and Paulsen CA. (1985) Hormonal Suppression of spermatogenesis as an approach to male fertility regulation, in Quian Shao-Zhen and Geoffrey Waites (eds) Advances in Fertility Regulation in the Male, The Proceedings of a W.H.O. Symposium, Dec. 14-16, 1984 in Nanjing, China. Beijing, China: The People's Publishing House, pp 67-74.
Paulsen CA. (1986) Androgen-progestagen combinations, in GI Zatuchni, A Goldsmith, JM Spieler and JJ Sciarra (eds) Male Contraception: Advances and Future Prospects. Philadelphia: Harper and Row, pp 300-303.
Gui-yuan Z, Guo-zhu L, Wu FCW, Baker HWG, Xing-hai W, Soufir JC, Huhtaniemi I, Paulsen CA, Gottlieb C, Handelsman DJ, Farley TMM, and Waites GMH. (1990) Contraceptive efficacy of testosterone-induced azoospermia in normal men. Lancet 336:955-959.
Plymate SR, Paulsen CA, and McLachlan RI. (1992) Relationship of serum inhibin levels to serum follicle stimulating hormone and sperm production in normal men and men with varicoceles. Journal of Clinical Endocrinology, in press.
