Oral administration of the cyclooxygenase-2 (COX-2) inhibitor meloxicam blocks ovulation in non-human primates when administered to simulate emergency contraception

Abstract

BACKGROUND: Prostaglandins produced via cyclooxygenase-2 (COX-2) within the periovulatory follicle are required for successful ovulation. Inhibition of follicular prostaglandin synthesis prevents timely follicle rupture and oocyte release. This study was conducted to determine if a 5-day course of oral administration of the COX-2 inhibitor meloxicam can prevent ovulation while maintaining normal menstrual cycles in non-human primates. METHODS: Adult female cynomolgus monkeys were studied in each of four sequential menstrual cycles. In Cycle 1, a serum sample was obtained each day and assayed for estradiol, progesterone and luteinizing hormone; first menses was also noted to establish parameters of a normal menstrual cycle for each animal. In Cycle 2, meloxicam was administered orally once each day for 5 days beginning at either mid follicular (n = 4), late follicular (n = 4) or periovulatory (n = 4) phase of the menstrual cycle; daily serum samples and menses were assessed as for Cycle 1. In Cycle 3, the follicle-bearing ovary was removed 2 days after the expected day of ovulation (n = 3-4/treatment group). In Cycle 4, monkeys received the 5-day courses of oral meloxicam as in Cycle 2 (n = 3-4/treatment group), and the remaining ovary was removed. Ovaries were examined for the presence of an oocyte within the follicle. RESULTS: Monkeys had the expected levels of changing reproductive hormones during Cycle 1. Meloxicam treatment in Cycle 2 did not alter hormone levels or the luteal phase length. Follicles of ovaries removed during Cycle 3 did not contain oocytes, indicating successful ovulation. Follicles did contain oocytes after meloxicam treatment beginning in the mid follicular (67%), late follicular (100%) or periovulatory (50%) phase of Cycle 4, indicating failure of ovulation. CONCLUSIONS: A 5-day course of oral meloxicam administered around the time of ovulation reduced the rate of oocyte release without alteration of reproductive hormones or menstrual cycle length. Meloxicam may be effective as an emergency contraceptive in women.