Gossypol

The discovery by the Chinese scientists of gossypol as a male fertility regulating agent constitutes a major lead in male contraception. Gossypol is a polyphenolic compound present in the seed of the glandular variety of the cotton plant. Most of the basic and clinical studies in China and in other countries more recently, have been carried out with gossypol or gossypol acetic acid. Species differences and strain differences among rats have been reported in the antifertility action of gossypol. The damage to the testis seems to be specific, affecting the cell types of the seminiferous epithelium. The pharmacokinetics and toxicology of gossypol show species differences. Nearly 8800 men were treated in China with gossypol/gossypol acetic acid, 20 mg/day for 60–70 days, followed generally, by a maintenance dose of 60 mg/week; azoospermia or sperm counts < 4 mn/ml were seen in 2–3 months in over 99% of treated subjects. Recovery of sperm counts after cessation of treatment appears to be related to the length of treatment and degree of effects on the testis. Chances of recovery appear to be (a) greater in subjects who have not achieved azoospermia, and (b) gready reduced with longer duration of treatment of over 2 years. The primary side effect is hypokalemia and hypokalemic paralysis, occurring in 0.75% of treated subjects in China. This appears to show regional differences and may be related to dietary intake of potassium. No changes in serum potassium occurred in Brazilian men treated with gossypol. Though gossypol has been used extensively in clinical trials in China, a number of concerns have been expressed on the safety of the compound, particularly with reference to hypokalemia, toxicity and reversibility. It is necessary to re‐evaluate the safety of gossypol to permit Drug Regulatory agencies to consider its use for male fertility regulation. A scheme for the assessment of safety of gossypol is outlined. Gossypol represents the only approach which appears to have a reasonable chance to reach large‐scale clinical testing before the end of this decade.