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

Hum Reprod. 1998 Feb;13(2):259-67. doi: 10.1093/humrep/13.2.259.

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 136317 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Contraceptive Agents, Female / administration & dosage*
  • Corpus Luteum / anatomy & histology
  • Corpus Luteum / drug effects
  • Corpus Luteum / physiology
  • Estradiol / blood
  • Female
  • Fertility / drug effects
  • Follicle Stimulating Hormone / blood
  • Hormone Antagonists / administration & dosage*
  • Humans
  • Luteinizing Hormone / blood
  • Macaca mulatta
  • Menstrual Cycle / blood
  • Menstrual Cycle / drug effects*
  • Menstrual Cycle / physiology
  • Ovary / anatomy & histology
  • Ovary / drug effects
  • Ovary / physiology
  • Progesterone / blood
  • Progestins / antagonists & inhibitors*

Substances

  • Contraceptive Agents, Female
  • Hormone Antagonists
  • Progestins
  • Progesterone
  • Estradiol
  • Luteinizing Hormone
  • Follicle Stimulating Hormone