CHRONIC TREATMENT OF FEMALE RHESUS-MONKEYS WITH LOW-DOSES OF THE ANTIPROGESTIN ZK-137-316 - ESTABLISHMENT OF A REGIMEN THAT PERMITS NORMAL MENSTRUAL CYCLICITY

Large doses of antiprogestin typically disrupt menstrual cyclicity, A chronic low-dose regimen of the potent new antiprogestin ZK 137 316, w hich permits continued menstrual cyclicity but alters gonadal-reproduc tive 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 invo lving 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 sub sequent progesterone production, were absent in C-3 and C-5, Ovarian c yclicity was accompanied by timely menstruation in the vehicle and 0.0 1 mg/kg groups, By C-3, half the animals in the 0.03 mg/kg group and a ll animals in the 0.1 mg/kg group were amenorrhoeic, A corpus luteum w as 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 13 6 317 permitted normal menstrual cyclicity in macaques, While the dail y administration of 0.03 mg/kg ZK 136 317 allowed ovarian cyclicity, m enstruation was disrupted in some animals, Increasing the dose to 0.1 mg/kg antagonized pituitary function and resulted in anovulation and a menorrhoea, A chronic low-dose regimen of the antiprogestin ZK 137 316 , which permits normal ovarian/menstrual cyclicity, has potential as a contraceptive in women.