Chronic treatment of female rhesus monkeys with low doses of the antiprogestin ZK 137 316: Establishment of a regimen that permits normal menstrual cyclicity

M. B. Zelinski-Wooten, O. D. Slayden, K. Chwalisz, D. L. Hess, R. M. Brenner, R. L. Stouffer

    Research output: Contribution to journalArticle

    43 Scopus citations

    Abstract

    Large doses of antiprogestin typically disrupt menstrual cyclicity. A chronic low-dose regimen of the potent new antiprogestin ZK 137 316, which permits continued menstrual cyclicity but alters gonadal-reproductive tract activity, was established. Rhesus monkeys received vehicle (n = 6) or 0.01 (n = 8), 0.03 (n = 8) or 0.1 (n = 5) mg ZK 137 316/kg body weight daily for five menstrual cycles (C-1 to C-5). Oestradiol, progesterone and gonadotrophin profiles were normal during cycles involving vehicle and 0.01 and 0.03 mg ZK 137 316/kg body weight. In the 0.1 mg/kg group, mid-cycle oestradiol and gonadotrophin surges, and subsequent progesterone production, were absent in C-3 and C-5. Ovarian cyclicity was accompanied by timely menstruation in the vehicle and 0.01 mg/kg groups. By C-3, half the animals in the 0.03 mg/kg group and all animals in the 0.1 mg/kg group were amenorrhoeic. A corpus luteum was noted during the mid-luteal phase of C-5 in the vehicle, 0.01 mg/kg and 0.03 mg/kg groups. Large antral and cystic follicles were evident in the 0.1 mg/kg group. Thus, a daily treatment with 0.01 mg/kg ZK 136 317 permitted normal menstrual cyclicity in macaques. While the daily administration of 0.03 mg/kg ZK 136 317 allowed ovarian cyclicity, menstruation was disrupted in some animals. Increasing the dose to 0.1 mg/kg antagonized pituitary function and resulted in anovulation and amenorrhoea. A chronic low-dose regimen of the antiprogestin ZK 137 316, which permits normal ovarian/menstrual cyclicity, has potential as a contraceptive in women.

    Original languageEnglish (US)
    Pages (from-to)259-267
    Number of pages9
    JournalHuman Reproduction
    Volume13
    Issue number2
    DOIs
    StatePublished - Jan 1 1998

    Keywords

    • Antiprogestin
    • Menstrual cycle
    • Ovary
    • Steroids
    • ZK 137 316

    ASJC Scopus subject areas

    • Reproductive Medicine
    • Obstetrics and Gynecology

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