Contraception--a look forward, Part II: Mifepristone and gossypol.

Part II of this series examines two compounds that are or have been in use in countries other than the United States. Mifepristone (RU486) is the first of the clinically useful progesterone antagonists; it competes with progesterone for receptors in the uterus, ovary, and pituitary gland. When taken by women in the follicular phase, it might be capable of inhibiting folliculogenesis while still allowing endometrial proliferation for normal menstrual cycling. When the drug is taken in the late luteal phase, endometrial shedding can usually be induced even after nidation. Mifepristone could thus serve as an emergency postcoital agent. In principle, it could also be used as a monthly emmenagogue, but clinical trials have been unsuccessful due to disruption of the following cycle's length. Shorter-acting antiprogesterones now under development may overcome this difficulty. Political constraints ultimately may be more limiting than pharmacological ones. Gossypol is a Chinese cottonseed derivative, which, taken orally, inhibits spermatogenesis in men. Its efficacy is very high, but use is presently limited by two adverse effects: occasional symptomatic hypokalemia and a 10 percent chance of irreversibility of aspermia. Current research is directed at understanding and overcoming these obstacles.