Gossypol: reasons for its failure to be accepted as a safe, reversible male antifertility drug

There have been reports that studies conducted in China confirm the efficacy of gossypol as a male antifertility drug. This paper presents the extensive investigations on formal animal toxicology and on the recovery of male fertility after cessation of gossypol use. Studies conducted by the International Organization for Chemical Sciences in Development showed that 40 of the 70 highly purified novel structural forms of gossypol were no more active than gossypol. Experiments conducted on Sprague-Dawley rats and cynomolgous monkeys confirm that either (-) or (+) gossypol is too toxic to be developed for human contraception. Among the side effects associated with the use of gossypol the most serious was hypokalemic paralysis although differences in reported incidences could be attributed to the regional differences in dietary intake of potassium and genetic predisposition. On the other hand studies that examine the risk of permanent sterility among healthy reproductive males were confirmed by two separate studies which found an incidence of 25% irreversible sterility. The failure of recovery among those who stopped gossypol use could be attributed to longer treatment greater total dose of gossypol smaller testicular volume and elevated follicle stimulating hormone concentrations. The cessation of clinical studies on gossypol because of increased risk in irreversible testicular damage and low therapeutic ratio is recommended.