Sequential regimen of the antiprogesterone RU486 and synthetic progestin for contraception

Raimo Kekkonen, R Kekkonen, Pekka Lähteenmäki, P. Lähteenmäki, T Luukkainen, Tapani Luukkainen, J Tuominen, Juhani Tuominen
Fertility and sterility · 1993 · vol. 60(4) , pp. 610–615 · doi:10.1016/s0015-0282(16)56209-8 · PMID:8405512 · W2293181083
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This paper investigated the use of a sequential regimen combining the antiprogesterone RU486 with a synthetic progestin for contraceptive purposes.

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Abstract

OBJECTIVE: To examine the effect of sequential use of the antiprogesterone RU486 and synthetic progestin on ovarian function of healthy women. DESIGN: Healthy women were given a sequential antiprogesterone-progestin treatment. Blood samples were taken twice a week during one control cycle and one to three treatment cycles; prospective analysis. SETTING: The outpatient clinic of the Helsinki City Maternity Hospital, Helsinki, Finland, and Steroid Research Laboratory, Department of Medical Chemistry, University of Helsinki, Helsinki, Finland. PATIENTS: Eleven healthy women, volunteers, 20 to 34 years of age. INTERVENTIONS: A dose of 25 mg/d of RU486 was given during cycle days 1 to 21, and synthetic progestin (5 mg of norethisterone to six and 5 mg of medroxyprogesterone acetate to five women) during cycle days 22 to 31. MAIN OUTCOME MEASURES: Serum P, E2, FSH, and LH were measured from serum samples. RESULTS: In 20 of the 24 treatment cycles analyzed the serum concentrations of P were anovulatory. In the remaining 4 cycles, P levels rose above 3 ng/mL, suggestive of ovulation. Folliculogenesis was not completely inhibited, but serum E2 profiles were subnormal and delayed. Bleeding control was satisfactory. CONCLUSIONS: Antiprogesterone RU486 hampers or delays follicular development, suggesting a possible use as an estrogen-free oral contraceptive. However, the synthetic progestins used in this regimen induced serum P rises in some cycles. The synthetic progestin provides the cycle control, but its possible effect on the reliability of the method remains to be evaluated.

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MeSH descriptors

Contraceptives, Oral Mifepristone Norethindrone Adult Drug Administration Schedule Estradiol Estradiol Female Gonadal Steroid Hormones Gonadal Steroid Hormones Gonadotropins, Pituitary Gonadotropins, Pituitary Humans Medroxyprogesterone Acetate Medroxyprogesterone Acetate Menstruation Menstruation Mifepristone Mifepristone Mifepristone

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