The effects of an lh-rh antagonist ([N-Ac-D-Trp 1,3,D-p-Cl-Phe 2,D-Phe 6,D-Ala 10]-LH-RH) during the preovulatory period of the rhesus monkey

Seven regularly cycling rhesus monkeys ( Macaca mulatta ) were used in this experiment. The animals were followed during two consecutive cycles. During the first cycle (control), the animals did not receive any treatment and the date of ovulation was determined by using daily total serum estrogens and serial laparoscopies. In the second cycle, the animals received 1 mg daily of [N-Ac-D-Trp 1,3, D-p-Cl-Phe 2,D-Phe 6,D-Ala 10]-LH-RH by intramuscular injection from days 10 to 14. The date of ovulation was determined by using the same methodology as the control cycle. Blood samples were drawn daily from day 8 of the cycle until the onset of menses, and the serum was used to measure total estrogens, progesterone and LH. A significant delay of the preovulatory LH peak and ovulation occurred in 5 of the 7 animals resulting in a proportional increase in cycle length as compared to the control cycle. No changes in cycle length or date of LH peak occurred in the other 2 animals. One of them did not present signs of ovulation as determined by laparoscopy (no recognizable stigma or corpus luteum). Progesterone production and length of the luteal phase were not affected by the treatment

The effects of chronic administration of LH-RH agonists and antagonists on the menstrual cycle and endometrium of the rhesus monkey

Regularly cycling rhesus monkeys ( Macaca mulatta) were used to study the effects of prolonged administration of LH-RH analogs on the menstrual cycle and the endometrium. According to the treatment, animals were divided into: Group 1, vehicle; Group 2, LH-RH agonist (D-Trp 6 LH-RH, 20μg/ day); and Group 3, LH-RH antagonist ([N-Ac-D-Trp 1,3, D-p-Cl-Phe 2, D-Arg 6, D-Ala 10]-LH-RH, 200μg/day) for 90 days. Follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E 2) and progesterone (P) were measured every second day until thirty days past the discontinuation of drug administration. Endometrial biopsies were obtained on days 10, 40, 90 and 120 and processed for histologic exam and determination of estrogen (E) and progesterone receptors. Animals of Group 1 presented regular cycles, while those in Groups 2 and 3 remained anovulatory throughout the treatment. Animals of Group 2 presented different degrees of endometrial hyperplasia during treatment and animals of Group 3 showed either resting or atrophic endometrium. Administration of LH-RH agonist produced a marked increase in E and P endometrial receptors and the antagonist produced a decrease in P receptors. In both instances, reversal of the effects on the menstrual cycle and in the endometrium was observed 30 days after discontinuation of drug administration

Administration of agonistic and antagonistic analogues of LH-RH induce anovulation in Macaca fasicularis

This study was designed to compare the effects of [N-Ac-D-Trp 1,3, D-p-Cl-Phe 2, D-Phe 6, D-Ala 10] (A-LH-RH), an inhibitory analogue, and D-Trp 6-LH-RH, an agonist of LH-RH, administered to normally cycling cynomologous monkeys. Animals were divided into three groups (n = 5 each), each group receiving one of the following daily during the first 25 days of the menstrual cycle: 1) 20 μg of D-Trp 6-LH-RH daily. 2) 1 mg of A-LH-RH, and 3) vehicle. Ovulation was established by serial laparoscopies and serum estradiol measurement. Controls presented normal cycles, as evidenced by ovulation day, luteal phase length and hormone levels. Ovulation was completely inhibited during drug administration in all animals of groups 1 and 2. Luteal phase length of all monkeys that ovulated was normal. The present data, therefore, not only show evidence for a consistent anovulatory effect of agonistic and antagonistic analogues of LH-RH in non-human primates, but also open a new approach for non-steroidal contraception