Effects of Letrozole on Reproductive Organs of Male Rats of Different Ages

Aim: Study of the reproductive organs at long-term administration of letrozole, the steroid aromatase inhibitor, followed by its withdrawal in young male rats and ones with age-related involution of reproductive organs.

Materials and Methods: The trials were conducted on Wistar rats aged 5 months to 15 months, who were gavaged with letrozole every other day at a rate of 1 mg/kg b. w for 3 months and then 2 months after it was stopped. Immunoassays were used to determine the levels of testosterone and estradiol in the blood plasma. The concentrations of spermatozoa in epididymal washes were measured. The testicles and accessory sexual glands were weighed, and the gonads and ventral prostate morphology were investigated. The results of the study were compared with those of control animals of corresponding age.

Results: The ratio of testosterone to estradiol in the blood plasma of aged rats increased as a result of letrozole treatment. The average amount of spermatozoa in the epididymis increased by 28%. The histological analysis demonstrated that Leydig cells were functionally activated, with considerable delays in involutive changes in their number and shape. Some of the Leydig cells showed symptoms of functional depletion. When compared to control rats, letrozole increased the relative weights of the coagulation gland by 40 percent, seminal vesicles by 31 percent, and the ventral prostate by 33 percent. There were no signs of difference between letrozole-treated and control animals two months following letrozole cessation. The effects of letrozole were nearly undetectable in young rats.

Conclusions: Letrozole administration to male rats with age-related involution of the reproductive system increases testosterone/estradiol ratio in blood plasma, the spermatozoa content in epididymises and the weights of androgen-dependent accessory sexual glands. This is followed by a slowing of age-related morphological changes in the gonad and prostate gland. The effects of letrozole on reproduction are reversible.