Suppression of Follicular Rupture With Meloxicam, A Cyclooxygenase-2 Inhibitor: Potential for Emergency Contraception

Abstract

The preferred treatment for emergency contraception at present is the synthetic progestogen levonorgestrel. Although this drug is widely available, women in some countries have little access to it due to restrictions imposed by conservative groups. Recent evidence has shown that levonorgestrel may have no contraceptive effect when taken after the ovulatory process has been triggered; this suggests that contraceptive failures with this drug may result from delayed administration. A number of studies have provided evidence that nonsteroidal anti-inflammatory drugs and specifically, cyclooxygenase-2 (COX-2) inhibitors, can prevent or delay follicular rupture. In a recent placebo controlled, double-blind, crossover study, daily administration of a partially selective COX-2 inhibitor, meloxicam, for 5 days at the onset of the luteinizing hormone (LH) surge significantly delayed follicular rupture. One advantage of using a COX-2 inhibitor to prevent or delay follicular rupture and inhibit the LH surge in comparison with using levonorgestrel is that COX-2 inhibition does not suppress the luteal phase. Accordingly, meloxicam should maintain the normal oscillations of ovarian steroids and preserve normal menstrual cycles. Other benefits of using COX-2 inhibitors include their accessibility over-the-counter in many countries and low cost as well as their improved safety profile with short-term treatment in women of reproductive age compared with steroid hormones. This single center, randomized, Phase I, double-blind, crossover study assessed the efficacy of meloxicam administered during the late follicular phase to prevent or delay follicular rupture when given very close to or after the LH started. The study subjects—27 healthy surgically sterilized volunteers (18―40 years old) with regular menstrual cycles—received oral doses of meloxicam 15 or 30 mg/d for 5 consecutive days starting when the leading follicle had reached 18 mm diameter. The participants underwent 3 cycles—first a drug-treatment cycle, a resting cycle, and then a second drug-treatment cycle. The primary study outcomes were the occurrence of follicular rupture, serum levels of LH, progesterone and estradiol, and the incidence of adverse events. Of the 27 volunteers, 22 completed the study. Dysfunctional ovulation occurred in 50% (11/22) of the cycles in women treated with the 15 mg/d dose and in 91 % of the cycles in women receiving the 30 mg/d dose (P = 0.0068). All women had normal progesterone levels during luteal phase; the mean maximal value was 42 ± 4.1 nmol/L for the 15 mg/d group and 46.8 ± 2.6 nmol/L for the 30 mg/d group. No changes were found in menstrual cycle length or in LH and estradiol levels. Serious adverse events were not observed. The findings of this pilot study suggest that the administration of meloxicam 30 mg/d for 5 consecutive days during the late follicular phase is effective, safe, and may be an alternative to levonorgestrel for emergency contraception.