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  • Title: Interference with ovulation by sequential treatment with the antiprogesterone RU486 and synthetic progestin.
    Author: Kekkonen R, Alfthan H, Haukkamaa M, Heikinheimo O, Luukkainen T, Lähteenmäki P.
    Journal: Fertil Steril; 1990 Apr; 53(4):747-50. PubMed ID: 2108063.
    Abstract:
    Seven healthy women were treated with the antiprogesterone RU486, 25 mg/d, on days 1 to 14 of the follicular phase of the menstrual cycle, followed by the synthetic progestin NET in the luteal phase of the cycle. Venous blood samples were collected twice per week. Serum E2, P, and RU486 concentrations were determined by RIAs, and FSH and LH by immunofluorometric assays. Ultrasonography was used to measure the sizes of the follicles. Serum concentrations of FSH and LH were not suppressed during the treatment. Ovulation was apparently suppressed during RU486 treatment according to E2 and P concentrations and ultrasonography findings. During NET treatment, some evidence of ovulation and follicle growth were found during the first treatment periods. During the third treatment cycle, there was no evidence of ovulation (n = 2). Estradiol concentrations were sufficient to stimulate normal proliferative growth of the endometrium during the treatment. Control of bleeding was good. The exact mechanism of action of RU486 on steroid synthesis and ovulation is not clear, but it appears to act at the ovarian level. The evidence indicates that sequential RU486/progestin treatment could be developed to result in suppression of follicular growth and ovulation. In Finland, physicians at the outpatient clinic at the Helsinki City Maternity Hospital followed 7 26-38 year old women who took 25 mg RU-486/day during days 1-14 (follicular phase) and 5 mg of norethindrone/day (NET) during days 15-24 (luteal phase) for 1 menstrual cycle or for 3 menstrual cycles to investigate the possibility of sequential use of an antiprogesterone and progestin as an oral contraceptive. They used ultrasonography to monitor follicular growth and obtained blood samples 2 times/week to do radioimmunoassays and immunofluorometric assays to measure estradiol, progesterone, RU-486, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels. They took endometrial biopsies at the end of RU-486 treatment (days 12- 13) and during NET treatment (days 21-22). Before RU-486/NET treatment the physicians performed various tests during a control cycle. RU-486 treatment did not alter FSH or LH levels. Progesterone and estradiol levels and ultrasonography indicated, however, that RU-486 did suppress ovulation. Ovulation and follicle growth did occur during NET treatment, yet during the third cycle no one ovulated. Bleeding control was adequate. It appeared that the mechanism of action of RU-486 on steroid synthesis and ovulation occurred at the ovarian level. Even though RU-486 at least partially inhibited estradiol synthesis, sufficient estradiol remained to stimulate normal proliferative growth of the endometrium. None of the women experienced steroidal side effects from the treatment. These findings indicated that further development of sequential RU-486/progestin treatment could suppress follicular growth and ovulation.
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