Gossypol and hypokalaemia

Abstract

One major side effect of administration of gossypol as a male fertility regulating agent is the occurrence of hypokalaemic paralysis. We have reviewed the common causes of hypokalaemia in clinical practice and previous studies of gossypol—induced hypokalaemia in animals and man. The available evidences suggest that gossypol induced renal leakage of potassium. The most likely mechanism is a direct toxic effect of gossypol on the renal tubules. Gossypol has been used by Chinese scientists since 1970 as a male method for fertility regulation (1–5). The antifertility efficacy as determined by sperm concentration (below 4 million/ml) was over 99%. Full recovery of spermatogenesis occurred in 73.7% of the volunteers. The common side effects reported include fatigue, gastrointestinal symptoms, decreased libido and potency, dizziness, and dryness of mouth. However the most serious side effect of administration of gossypol is hypokalaemic paralysis reported in 66 out of 8806 volunteers, i.e. 0.75% (3–5). The clinical syndrome is that of hypokalaemia: fatigue, muscle weakness followed by flaccid paralysis. Recovery is prompt and complete after potassium (K) repletion. However, 2 patients have been reported to have chronic persistent hypokalaemia after cessation of gossypol treatment (5, 6). In one small-scale study of 12 Brazilian men, Coutinho (7) reported similar antifertility efficacy but serum K and biochemistry remained normal throughout the 12-month study. In this brief review, we will discuss some of the common causes of hypokalaemia in clinical practice, in particular hypokalaemic periodic paralysis and previous studies of gossypol-induced hypokalaemia in Chinese men. Such an inspection may shed light as to the basis for the gossypol-induced hypokalaemia.