Effect of long-term treatment of ulipristal acetate on rat ovarian tissue

Abstract Ulipristal (UPA), a selective progesterone receptor modulator, has both agonistic and antagonistic effects on progesterone receptors. UPA suppresses ovulation by inhibiting the luteinizing hormone (LH) surge from the pituitary gland; however, the direct effect of UPA on ovarian tissue remains poorly studied. In the present study, we examined the effects of UPA on the ovaries of rats. Rats were treated for 28 d with 4, 20, and 100 mg/kg UPA. UPA treatment increased the number of primordial follicles at each treatment group, with the highest number found in the 4 mg/kg group, and the number of primordial follicles decreasing with increasing dose. The number of primary and antral follicles tended to increase with increasing UPA levels. Furthermore, the decrease in primary follicle number could be attributed to the exhaustion of follicles, but the examination of proliferation markers, oxidative stress markers, and cell death markers revealed no remarkable toxic effects on ovarian tissues. These results suggest that UPA treatment promotes follicle development at each stage but inhibits ovulation by suppressing the LH surge, resulting in an increase in atretic follicles or unruptured luteinized cysts. UPA may not have toxic effects on the ovary because the expression of antioxidant genes and cell death markers was not dramatic in follicles treated with UPA. Taken together, these results suggest that UPA may not have a direct local effect on ovarian follicles. Hence, we hypothesized that prolonged UPA treatment in patients with uterine fibroids may not be harmful and may not decrease future fecundity.