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

Abstract

Following clinical trials conducted in China in the 1970s, gossypol was proposed as a drug for male contraceptive use. This review summarizes the extensive investigations on formal animal toxicology and on the recovery of fertility in men after stopping gossypol treatment which led to the decision by the Special Programme of Research, Development and Research Training in Human Reproduction (HRP) at the World Health Organization (WHO), that gossypol would not be acceptable as an antifertility drug. It is concluded that the assessment of gossypol reinforces the mandatory requirement that future contraceptive drugs must be developed by the established routes of appropriate animal toxicology and phased clinical studies.

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

“…Other 11␤-HSD2 inhibitors, with varying degrees of selectivity, have been identified. Gossypol, a natural phenol isolated from cotton seeds and originally proposed as a male contraceptive, inhibits 11␤-HSD2 (116), conceivably accounting for the hypokalemic paralysis it can cause (739). Synthetic endocrine disrupters, including some phthalate derivatives widely used in plasticisers and solvents, organotins used in agriculture, and alkylphenols used as industrial surfactants, also inhibit 11␤-HSD2 (424), although the importance of this is uncertain.…”

Epididymis-Specific Pathologic Disorders in Rats Exposed to Gossypol from Weaning Through Puberty

“…For a long time gossypol was just considered a toxic residue in the processing of products derived from cotton (Abou-Donia, 1976). In spite of the controversies in relation to its collateral effects and mechanism of action (Waites et al, 1998), gossypol has been considered a candidate to become the base for the production of an oral male contraceptive (Udoh et al, 1992). The use of gossypol as a contraceptive was suggested initially in the 1950s, when high rates of infertility were registered in several areas of China.…”

Control of Spermatogenesis in Primate and Prospect of Male Contraception

“…Because of these side-effects, the clinical trial stopped and the related research funding from the nation and abroad was cut off, and the studies on gossypol for male contraception was interrupted from the middle of 1980s [48,64].…”