The protective effects of hormonal suppression by a gonadotropin-releasing hormone agonist or an oral contraceptive on the decreased ovarian reserve in female rats exposed to isotretinoin

OBJECTIVE: The objective of our study was to evaluate whether ovarian sup-pression by two different hormonal methods may spare the ovary the cytotoxic effects of isotretinoin in a rat model. MATERIALS AND METHODS: Four groups (n=8 Sprague-Dawley albino rats per group) were studied: control (Group I), 7.5 mg/kg/day isotretinoin (Group II), isotretinoin plus the com-bination of 0.030 mg ethinyl estradiol/0.15 mg levonorgestrel (combined oral contraceptive, COC), and isotretinoin plus 100 mu g (microgram) leuprolide acetate (GnRHa) (Group III and IV, respectively). Four rats from each group were de-capitated on the 30(th) day of treatment, and the remaining rats were decapitated on the 30(th) day of untreated follow-up. Serum anti-Mullerian hormone (AMH) concentrations, healthy and atretic follicle numbers, and apoptotic activity of follicles in oophorectomy specimens were compared between the groups.RESULTS: There were no significant differences in AMH levels among the study groups before, immediately after (first month), and one month after their last medication (second month) (p=0.08, 0.47, and 0.08, respectively). At the end of the first month, the control group had a higher median count of healthy primordial follicles com-pared to the study groups: 13.5 (8-22), 5.5 (3-11), 6 (2-13), and 1 (0-1) in control, isotretinoin, isotretinoin+COC, and isotretinoin+GnRHa groups, respectively (p=0.02). However, there was no statistically significant difference in the number of healthy primordial follicles between the groups one month after the last medication (p=0.33). The median atretic antral follicle counts in the first month were 2 (1-4), 3.5 (1-4), 0 (0-2), and 0 (0-0) in the control, isotretinoin, isotretinoin+COC, and isotretinoin+GnRHa groups, respectively (p=0.02). Otherwise, there were no significant differences in other types of follicles among the control and treated groups (p>0.05). There was also no statistical difference between the groups regarding immunostaining intensity for active caspase-3 evaluated in the first or second month of treatment (p=0.8 and 0.2, respectively).CONCLUSIONS: Our results show that GnRH agonists or COC have no protective effects on ovarian reserve when co-administered with isotretinoin in the rat model.