Anovulation in the prevention of cytotoxic-induced follicular attrition and ovarian failure.

BACKGROUND

Gonadal failure secondary to alkylating agents may be related to ovulatory status. The objective of this investigation was to evaluate whether anovulation protected ovarian follicles during treatment with cyclophosphamide.

METHODS

Four groups (n = 20 mature female Sprague-Dawley rats per group) were studied: control (group I), 5 mg/kg/day cyclophosphamide only (group II), 5 mg/kg/day cyclophosphamide and the combination of 50 micro g ethinyl estradiol/2 mg norgestrel (group III) and 5 mg/kg/day cyclophosphamide and 2.5 micro g leuprolide acetate daily (group IV). Animals were sacrificed after 4 weeks of treatment. Follicles were classified as medium (300-450 micro m) and large (>450 micro m) per section of ovary.

RESULTS

Group II developed a significantly greater number of medium and large follicles [15.1 +/- 6.1 and 4.9 +/- 1.9 (mean +/- SD), respectively] compared with group I [7.1 +/- 2.1 and 1.0 +/- 0.7 (mean +/- SD), respectively] (P </= 0.05). Groups III and IV developed a significantly greater number of medium follicles [13.2 +/- 2.5 and 10.8 +/- 2.3 (mean +/- SD), respectively) compared with group I (P < or = 0.05). There was a trend toward a greater number of large follicles in groups III and IV when they were compared with group I. There were no differences in medium follicles in groups II, III and IV. No differences were noted in the number of large follicles between groups III and IV (2.9 +/- 1.2 and 2.3 +/- 1.0, respectively).

CONCLUSIONS

These results suggest that in the rat model, cyclophosphamide exerts a stimulatory effect on the ovary resulting in the greater development of both medium and large follicles. Anovulation conferred no protection against cyclophosphamide-induced gonadal toxicity. These data suggest that in the rat model, cyclophosphamide may result in ovarian failure by enhancing recruitment of follicles regardless of ovulatory status or hormonal milieu.