Tamoxifen-induced light and electron microscopic changes in the rat testicular morphology and serum hormonal profile of reproductive hormones.

The effects of oral administration of tamoxifen at doses of 40 and 200 micrograms/kg/day on testicular histology, testicular ultrastructure and serum hormonal profile were studied. The drug was administered to adult male rats over a period of 90 days and the effect was assessed at 10-day intervals. The morphometry, microscopic structures of the testis, including ultrastructure and daily sperm production rate, were evaluated. The hormone profiles of luteinizing hormone (LH), follice-stimulating hormone (FSH), testosterone, and estradiol were studied. The testes from treated animals showed disorganization of tubular elements with increased intercellular space. At day 50, the changes were extensive including presence of phagosomes. Morphometric studies showed a reduction in the spermatid and spermatozoan population (69.3%) with no changes in tubular diameter. The mean Leydig cell area was significantly lowered at day 50, at both doses. The daily sperm production rate was reduced as compared with controls. An array of degenerative changes were revealed by ultrastructural studies. The changes were extensive at day 50 at both doses. The characteristic features were lost in most of the cells with phagolysosomes becoming abundant. The cytoplasm of the cells was dense with poorly defined cytoplasmic organelles. Circulating LH levels were not modified at the 40 micrograms/kg/day dose but at 200 micrograms/kg/day, LH levels were significantly decreased. Initial transitory rise in FSH was seen with both doses. Both doses of tamoxifen decreased testosterone levels. Changes in the circulating estradiol levels were inconsistent, and no apparent relationship between dose and days of treatment was observed. Thus, this study supports our thesis of tamoxifen as a potential male contraceptive agent.