A luteinizing hormone-releasing hormone agonist for the prevention of chemotherapy-induced ovarian follicular loss in rats

Abstract

In an attempt to prevent chemotherapy-induced ovarian follicular loss, [D-Leu6, des-Gly10-NH2]-luteinizing hormone-releasing hormone ethylamide (LHRHa) was given subcutaneously to Sprague-Dawley cycling female rats in two daily doses of 2.5 micrograms starting 2 days prior to and concomitant with cyclophosphamide (CTX) (5 mg/kg/day for 21 days). Four groups of female cycling rats (10 in each) received either no treatment, CTX alone, CTX + LHRHa, or LHRHa alone. One ovary from each animal was serially sectioned, stained, and examined for the number and size of follicles. CTX produced a significant reduction in the total number of follicles. The pool of growing follicles (medium to large, greater than 30 microns in diameter) appeared to be vulnerable to the cytotoxic effect of CTX. LHRHa resulted in a significant reduction in the number of medium-to-large follicles and an increase in the number of small follicles. When given in combination with CTX, LHRHa significantly further reduced the number of medium-to-large follicles, significantly increased the number of small follicles, and resulted in an increase in the total number of follicles. Chronic LHRHa treatment resulted in functional deprivation of follicles from gonadotropins, thus halting the process of recruitment from the quiescent pool of primordial follicles into the CTX sensitive pool and thereby preserving the functional potential of the ovary.