Our previous studies showed that treatment of female rats with large doses of
Cetrorelix, an antagonist of
luteinizing hormone-releasing hormone (
LHRH), reduces levels of serum LH,
estradiol,
progesterone, and the concentration of pituitary
LHRH receptors (
LHRH-Rs) and their
mRNA expression. Serum LH and
testosterone levels and pituitary
LHRH-R in male rats are also decreased by high doses of
Cetrorelix. This approach can be used for
therapy of
sex hormone-dependent
cancers. However, in conditions where an incomplete
hormone deprivation is indicated, lower doses of
Cetrorelix may suffice. Thus, we investigated the effect of a 30-day treatment with a low-dose depot formulation of
Cetrorelix (20-24 microg per kg per day) on the pituitary-gonadal axis of male and female rats. In both sexes, lower serum LH levels were observed on day 4 after administration. In males, LH returned to control levels by day 10, whereas in females, a rebound LH elevation occurred.
Testosterone levels in male rats were decreased up to day 20, but on day 30, the values were similar to controls. In females, serum
estradiol was reduced on day 4; however, by day 10 it returned to normal.
Progesterone levels were diminished through the entire period. Female rats showed diestrous smears during the first week of treatment and prolonged estrous periods thereafter. The weights of testes and ovaries were significantly lower, but not the weights of prostate, seminal vesicles, and uterus. Pituitary
LHRH-R
mRNA and
LHRH-R
protein levels were not significantly different from the controls. Thus, the treatment with low doses of
Cetrorelix did not seriously impair gonadal functions. The results suggest that
Cetrorelix in low doses induces only a partial pituitary-gonadal inhibition and might be indicated for treatment of
endometriosis,
leiomyomas, and
benign prostatic hyperplasia.