Chronic treatment of female rhesus monkeys with low doses of the antiprogestin ZK 137 316: establishment of a regimen that permits normal menstrual cyclicity
| Autor: | Kristof Chwalisz, Ov D. Slayden, Robert M. Brenner, Richard L. Stouffer, Mary B. Zelinski-Wooten, D L Hess |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
media_common.quotation_subject Ovary Biology Progesterone Antagonist Anovulation Menstruation Hormone Antagonists Corpus Luteum Internal medicine Contraceptive Agents Female medicine Animals Humans Ovarian follicle Menstrual Cycle Progesterone Menstrual cycle media_common Estradiol Rehabilitation Obstetrics and Gynecology Luteinizing Hormone medicine.disease Macaca mulatta Fertility medicine.anatomical_structure Endocrinology Reproductive Medicine Female Amenorrhea Follicle Stimulating Hormone Progestins medicine.symptom Corpus luteum |
| Zdroj: | Human Reproduction. 13:259-267 |
| ISSN: | 1460-2350 0268-1161 |
| DOI: | 10.1093/humrep/13.2.259 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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