New techniques in contraception: gossypol, vaccines and GnRH analogues

Proc Annu Symp Eugen Soc. 1983;19:1-18.

Abstract

PIP: Discussion focuses on 3 of the most promising lines of current contraceptive research -- gossypol, vaccines, and GnRH analogues, considering both the scientific principles behind their development and the ethical implications of their future application. 1) Chinese scientists confirmed the antispermatogenic effects of cotton seed oil in animal experiments; in 1971 the active agent was identifed as gossypol. The 1st clinical trials were initiated in 1972 and thus far more than 8000 volunteers have been treated with a variety of gossypol preparations including native gossypol, gossypol acetic acid, and gossypol formic acid. The conventional contraceptive regime involves a loading dose of 20mg/day for 60-75 days followed by a maintenance dose of 50 mg/week. An undisclosed number of pregnancies have occurred. Reversibility seems to be a major problem since around 10% of men remain infertile after the cessation of gossypol intake. Other hazards of gossypol ingestion include fatigue, gastrointestinal disorders, decreased libido, dizziness, and in 0.75% of cases hypokalaemic paralysis. The question arises as to whether it is right that 8000 Chinese men have been administered gossypol while ignorance concerning the toxicity and effectiveness of this compound prohibits its approval by any other government west of the Himalayas. 2) The development of a contraceptive vaccine would be appropriate to the needs of the Third World, the population of which will have doubled in 34 years to 6.6 billion. The advantages of vaccines are that they can be administered by paramedical personnel, they should provide a long-lasting protection against pregnancy, and they can take advantage of the service infrastructure existing in most developing countries for the administration of vaccines against disease. The zona pellucida and human chorionic gonadotropin (hCG) are not the only candidates for an antifertility vaccine but they are the most promising. A 3rd but less attractive possibility is to immunize against sperm antigens. Possibly the most feasible sperm antigen for contraceptive development is a specific lactate dehydrogenase, isozyme, LDH-X. Both gossypol and vaccines will most likely find their ultimate application in developing countries where factors such as cost, ease of administration, and duration of action are paramount. 3) Progress has also recently been made with an alternative method more oriented toward the Western market. This approach involves the chronic administration of powerful analogues of the hypothalamic releasing hormone, GnRH, modified to contain a D-aminoacid in position 6 and, in some formulations, an ethylamide group in position 10 to prolong the half-life of the agonist "in vivo." Recent clinical trials have noted some variability in the responsiveness of individuals to chronic treatment with GnRH analogues, administered in the form of a nasal spray. The optimum protocol for administering GnRH has yet to be determined.

Publication types

  • Review

MeSH terms

  • Animals
  • Blastocyst / drug effects
  • Chorionic Gonadotropin / immunology
  • Contraceptive Agents / pharmacology*
  • Female
  • Gossypol / pharmacology
  • Humans
  • Macaca
  • Male
  • Ovarian Follicle / drug effects
  • Pituitary Hormone-Releasing Hormones / pharmacology
  • Rats
  • Sperm Motility / drug effects
  • Spermatozoa / drug effects*
  • Vaccines / pharmacology
  • Zona Pellucida / immunology

Substances

  • Chorionic Gonadotropin
  • Contraceptive Agents
  • Pituitary Hormone-Releasing Hormones
  • Vaccines
  • Gossypol