Reproductive endocrine effects of intranasal administration of progesterone to adult female rhesus monkeys

Abstract

Adult female rhesus monkeys exhibiting normal ovulatory menstrual cycles were treated with progesterone nasal sprays. Animals in group A (n = 9) were treated with the solvent only (controls). Animals in groups B (n = 6), C (n = 17) and D (n = 7), respectively, were treated with a daily dose of 0.4, 2 and 10 μg of progesterone and the spraying was done between days 5-14 of the cycle. Ovulation was monitored by laparoscopy on day 20. The serum endocrine profile throughout the treated menstrual cycle was studied with respect to oestradiol and progesterone. Bioactive luteinizing hormone (bLH) was studied in blood samples taken on the day of the mid-cycle oestradiol peak, 2 days before, and 2 days after. The menstrual cycle was divided into two phases with respect to the mid-cycle oestradiol peak: phase I was taken to include day 1 of the cycle to the day of the oestradiol peak, and the remaining part of the menstrual cycle was considered to be phase II. The serum-endocrine profile in the controls was similar to that observed in normal ovulatory menstrual cycles. However, in the progesterone-treated groups three types of menstrual cycles were discernable on the basis of the serum endocrine profile. In the type I menstrual cycle, observed only in group C (n = 10), the mid-cycle bLH peak was abolished and the progesterone levels remained low throughout the cycle. Laparoscopy revealed these to be anovulatory cycles. In the type II menstrual cycle, seen in the 3 animals of group B, 2 animals of group C, and in all the 7 animals of group D, the mid-cycle bLH peak was abolished and the progesterone levels during phase II of the cycle were significantly lower than in the controls, indicative of poor luteal function. In the type III menstrual cycle seen in the remaining monkeys, the serum endocrine profile did not differ from that seen in the controls. Thus, the present studies indicate that the intranasal administration of progesterone shows a dose-response effect with respect to the suppression of the oestradiol induced mid-cycle surge of bLH. Suppression of the mid-cycle bLH peak resulted in anovulatory cycles or ovulatory cycles with poor luteal function.