Luteinizing Hormone-Releasing Hormone Agonist Inhibits Cyclophosphamide-Induced Ovarian Follicular Depletion in Rhesus Monkeys1

Abstract

Several investigators have demonstrated that LHRH agonists (LHRHa) inhibit ovarian follicular depletion induced by chemotherapeutic agents in rodents. It is not clear whether or not the same effects occur in primates. Six adult female rhesus monkeys underwent unilateral ovariectomy and were divided into two groups that received monthly injections of either Lupron depot (LHRHa) or placebo vehicle. Both groups received cyclophosphamide (CTX) injections. Weekly blood samples were assayed for FSH, estradiol and progesterone. Mean serum FSH levels significantly increased in the CTX group and significantly decreased in the LHRHa+CTX group. At the end of treatment, the remaining ovary was removed and serially sectioned, and ovarian follicle number and size were analyzed. CTX resulted in a significant reduction of nonprimordial follicles < 50 microns in diameter. The rate of loss of primordial follicles was expressed as a percentage of the original follicle count. During the treatment period, 64.6 +/- 2.8% of the total primordial follicles were lost in the CTX group compared to only 28.9 +/- 9.1% in the LHRHa+CTX group (p < 0.05). The percentage rate of decline per day was 0.120 +/- 0.012 for the CTX group compared to 0.057 +/- 0.019 (p < 0.05) for the LHRHa+CTX group. The findings indicate that LHRHa can protect the ovary against CTX-induced damage in rhesus monkeys.