Male contraception: current status and future prospects

Wu, F.C.

Clinical Endocrinology 29(4): 443-465

1988


ISSN/ISBN: 0300-0664
PMID: 3075164
DOI: 10.1111/j.1365-2265.1988.tb02894.x
Document Number: 264651
Modern research in male contraception is focusing on 4 areas: 1) hormonal control of spermatogenesis, the complex processes of spermiogenesis in the testis where the spermatogonia stem cells mitotically divide into spermatocytes, which meiotically divide into nondividing spermatids, which become the spermatozoa; 2) direct (nonhormonal) inhibition of spermatogenesis; 3) the suppression of sperm maturation in the epididymis; and 4) the immunological suppression of fertility through the identification of an antisperm antibody. Hormonal suppression of spermatogenesis requires depression of testosterone levels in the testis, either by direct inhibition of the Leydig cells or by inhibition of the hypothalamic production of luteinizing hormone-releasing hormone, which induces the pituitary secretion of luteinizing hormone, which induces the secretion of testosterone. Testosterone suppression in the testis must be accompanied by exogenous androgen supplements or there will be loss of libido and potency. Preparations under investigation in the hormonal suppression of spermatogenesis include monthly injections of 200 mg depot medroxyprogesterone acetate with 200 mg testosterone enanthate; danazol with testosterone enanthate; anabolic steroids, such as 19-NT-hydroxyphenylpropionate; cyproterone acetate, an antiandrogen with progestational effects; and luteinizing hormone-releasing hormone agonists, which down-regulate pituitary receptors, or luteinizing hormone-releasing hormone antagonists, which competitively block receptor activation. None of these preparations have yet struck a balance where they can completely but reversibly block spermatogenesis at doses which do not have toxic or feminizing effects. 3 nonhormonal agents which suppress sperm production are gossypol, extract of Trypterigium wilfordii, and tolnidamine. Gossypol, an extract of cottonseed oil, has been widely studied in China and has been found 99% effective in producing azoospermia or severe oligospermia. However, it is extremely toxic, damages cells in the seminiferous epithelium, and causes hypokalemia. Over time, its effects become irreversible, and its mutagenicity and teratogenicity are not known. Agents which suppress sperm maturation in the epididymis act after cell division is complete and hence are not mutagenic, but they are extremely toxic. Alpha-chlorohydrin and 6-chloro-6 deoxysugars act by inhibiting the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase with the result that sperm cannot metabolize sugar. The sulfonamide compound, sulfasalazine, disrupts sperm motility by a mechanism not yet known. The development of a contraceptive vaccine relies on the identification of the antigenic determinants on sperm surface. Even if such a vaccine could be developed, there remains the problem of reversibility. None of the methods now being studied have demonstrated that they can reliably prevent unwanted pregnancy, and none have been around long enough for their longterm side effects to be known.

Document emailed within 0-6 h
Secure & encrypted payments