Low‐dose antiprogestin treatment prevents pregnancy in rhesus monkeys and is reversible after 1 year of treatment

• Published in: Human reproduction (Oxford) 2003-01, Vol.18 (1), p.69-76
• Main Authors: Borman, S.M., Schwinof, K.M., Niemeyer, C., Chwalisz, K., Stouffer, R.L., Zelinski‐Wooten, M.B.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Contraceptive Agents, Female - administration & dosage; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fertility - drug effects; Genital system. Reproduction; Hormone Antagonists - administration & dosage; Injections, Intramuscular; Keywords: antiprogestin/contraception/pregnancy/reversibility/ZK 137 316; Male; Medical sciences; Menstrual Cycle - drug effects; Pharmacology. Drug treatments; Pregnancy; Pregnancy Rate; Progestins - antagonists & inhibitors; Steroids - administration & dosage
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/deg014

BACKGROUND: Administration of low doses of an antiprogestin to rhesus monkeys permits ovarian/menstrual cyclicity, suppresses endometrial proliferation and prevents pregnancy without adverse or toxic side‐effects after 5–6 months of daily treatment. The purpose of this study was to test the reversibility with respect to restoration of fertility after 1 year of low‐dose antiprogestin treatment. METHODS: This experiment included a daily 1 year vehicle‐ or antiprogestin‐treatment interval followed by a 9 month post‐treatment interval for adult, female rhesus monkeys (n = 5/group) of proven fertility and exhibiting regular menstrual cycles. Co‐habitation occurred with a male of proven fertility and vaginal swabs were taken to identify the presence of sperm during the treatment (antiprogestin females) and post‐treatment intervals (vehicle and antiprogestin females). RESULTS: Mating and vaginal sperm were evident in all antiprogestin females during, and, in both groups, after treatment. Based on ultrasonography, none of the antiprogestin‐treated females became pregnant during the treatment interval. However, upon cessation of treatment, pregnancy rates were similar between antiprogestin‐treated (3/5) relative to vehicle‐treated (4/5) females with live, healthy infants born in both groups. There were no differences between groups in fetal measurements, gestation lengths, live birth rates and infant weights. CONCLUSIONS: The reversal of the anti‐fertility effects of chronic, low‐dose antiprogestin treatment supports the clinical feasibility of potent and selective antiprogestins as potential contraceptives for women.