GnRH Agonist Acts as Ovarian Protection in Chemotherapy Induced Gonadotoxicity: An Experiment Using a Rat Model

Abstract

Summary:To reduce chemotherapy induced gonadotoxicity, co-treatment with gonadotropin releasing hormone against analogue (GnRHa) was tested using rat model. Leuprorelin acetate (Leuplin) with or without cisplatin (CDDP) was given subcutaneously at a dose of 9.4 μg/ml to Wistar strain female rats. The total number of follicles was counted and the maturation of follicles was evaluated at the largest section of the ovary on the 5th and 10th day after administration. Leuplin led the ovary to a resting phase in which primordial follicle occupied 80% of all follicles in only 5 days after administration. The serum E2 level was also down by the 5th day and maintained a low level to the 10th day. In co-treatment with GnRHa and CDDP rats, the primordial follicle occupied 90% of all follicles and the total number of follicles was higher than in CDDP alone rats. This rat model verified that GnRHa co-treatment well minimized CDDP induced gonadotoxocity by desensitization of the ovary. These results were promising for the clinical application introducing GnRHa co-treatment as ovarian protection in cancer chemotherapy in young women.

Prevention of paclitaxel and cisplatin induced ovarian damage in rats by a gonadotropin-releasing hormone agonist

“…A limited number of studies prove that paclitaxel and cisplatin damage primordial follicles, which constitute the major part of ovarian reserve (5, 6). Matsuo et al (7) reported that the gonadotoxic effect of cisplatin may be prevented by a GnRH agonist, the cytotoxic effects of paclitaxel with cisplatin, on primordial and mature follicles. The role of the GnRH agonists in the prevention of cytotoxic effect of paclitaxel, alone or combined with cisplatin has been evaluated in the present experimental study for the first time in the literature.…”

Collaborative work on evaluation of ovarian toxicity 6) Two- or four-week repeated-dose studies and fertility study of cisplatin in female rats

“…As for the effects of CDDP on rat ovary, decreases in primordial follicles and Müllerian inhibiting substance, which is produced by the primordial and small ovarian follicles, were observed after a single dose of CDDP (Borovskaya et al, 2004;Yucebilgin et al, 2004;Yeh et al, 2006). Repeated dosing of CDDP during 1 or 2 estrous cycles in rats induces a decrease in the total number of follicles and large follicles are more sensitive to the toxic effects of CDDP than small follicles (Shinagawa, 1998;Matsuo et al, 2007). However, the mechanism of CDDP ovarian toxicity is not well known.…”

Protective effect of bilberry (Vaccinium myrtillus L.) on cisplatin induced ovarian damage in rat

“…Our study has demonstrated that CDDP caused significant toxicity in the ovarian tissues of rats. Matsuo et al (2007) reported that GnRH agonists are useful against chemotheraphy induced ovarian toxicity. They claimed that addition of Leuprorelin acetate protected primordial follicles from harmful effect of CDDP.…”