Effect of long term gossypol treatment on human testicular structure.

PIP: 16 male volunteers, ages 30-45 years, were treated with gossypol for 6-8 years, with the total amount of drug taken between 13.6-18.28 gm. Their wives never became pregnant during the treatment period. All of the volunteers except 1 are still taking 40 mg of gossypol acetic acid each week for the maintenance of infertility. Gossypol, derived from cottonseed, suppresses spermatogenesis, prevents sperm maturation, and inhibits sperm motility. In 1 case out of 5 tested, the testis completely lacked germ cells, some spermatocytes remained in 3, and 1 still had all types of germ cell intact although the number was reduced from that found in normal seminiferous tubules. These tubules we severly degenerated and their volume decreased to less than 1/2 of what is considered normal. The basic lamina of the tubules thickened and protruded into the epithelium. Sertoli cells were highly vasculolized, degenerated, and exfoliated into lumen. In some cases, the tubules became fibrotic. In the cytoplasm of the Sertoli cells, there were vacuoles of different sizes which were surrounded by or fused with lysosomes. Leydig cells changed in both number and size. It would appear that gossypol acts prior to or in conjunction with the incorporation of selenium into mitochondrial selenoprotein and that longterm treatment with gossypol affects not only the germ cells but the Sertoli and Leydig cells as well.^ieng

Antifertility treating with long term gossypol.

PIP: In the 1974-86 period, gossypol acetate was taken as an antifertility measure by 16 men. The initial dose was 20 mg/day, with a maintenance dose of 40 mg/week. Antifertility efficacy was obtained in all 16 cases. Azoospermia persisted in 1 case where the gossypol had been taken for 8 years and discontinued for the past 2 1/2 years. Symptoms experienced in the first 2 weeks of gossypol acetate administration included dizziness, anorexia, nausea, fatigue, and stomach discomfort. Results of examinations of blood and urine; functions of the heart, liver, lung, and liver; electrolytes; external genitalia; and sexual performance were all in the normal range. Measurements of semen, plasma biochemistry, and endocrine changes also were within normal limits. However, in the 9 cases in which the average value of plasma testosterone was near the lower limit of normal, the average value of follicle-stimulating hormone was higher than normal and the testosterone/luteinizing hormone ratio was unusually low. Testis biopsy indicated that long-term gossypol treatment affected both germ cells and Sertoli cells. Leydig cells also demonstrated some damage. Gossypol acetate is, in general, considered an ideal male contraceptive because of its long-term effectiveness, reversibility, and lack of severe toxic side effects.^ieng