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Human Reproduction, Vol.25, No.2 pp. 368–373, 2010 Advanced Access publication on November 19, 2009 doi:10.1093/humrep/dep392

ORIGINAL ARTICLE Fertility control

Suppression of follicular rupture with meloxicam, a cyclooxygenase-2 inhibitor: potential for emergency contraception
´ ´ Cristian Jesam 1,4, Ana Marıa Salvatierra1, Jill L. Schwartz 2, and Horacio B. Croxatto 3
1 ´ InstitutoChileno de Medicina Reproductiva (ICMER), Jose Victorino Lastarria 29, Apt. 101, Santiago, Chile 2CONRAD/Eastern Virginia Medical School, Arlington, Virginia 3Universidad de Santiago, Santiago, Chile 4

Downloaded from at Pontificia Universidad Cat?lica de Chile on August 27, 2010

Correspondence address. Tel: þ56-2-633-5887; Fax: þ56-2-633-6204;

background: There is evidence that cyclooxygenase-2 (COX-2) inhibitors can prevent or delay follicular rupture. COX-2 inhibitors, such as meloxicam, may offer advantages over emergency contraception with levonorgestrel, such as extending the therapeutic window for up to 24 h. We assessed the effect of meloxicam administered in the late follicular phase upon ovulation in women. materialsand methods: This was a single center, double blind, crossover study designed to assess the effects in 27 eligible
women (18 –40 years old, surgically sterilized with regular menstrual cycles) of meloxicam, 15 or 30 mg/day, administered orally for five consecutive days during the late follicular phase, starting when the leading follicle reached 18 mm diameter. Volunteers underwent two treatmentcycles separated by one resting cycle, with randomization to dose sequence. Main outcomes were follicular rupture; serum LH, progesterone and estradiol (E2) levels; and incidence of adverse events.

results: Twenty-two volunteers completed the study. There were no differences between meloxicam doses in menstrual cycle
length. Dysfunctional ovulation was observed in 11/22 (50%) cycles treated with15 mg/day and 20/22 (90.9%) cycles with 30 mg/day (P ¼ 0.0068). All women had normal luteal phase progesterone levels; mean maximal values + SEM were 42 + 4.1 and 46.8 + 2.6 nmol/l for 15 and 30 mg/day groups, respectively. There were no serious adverse events, and no changes in LH and E2 levels or in cycle length.

conclusions: Meloxicam 30 mg given for five consecutive days in the latefollicular phase is safe, effective and may be an alternative form of emergency contraception.
Key words: cyclooxygenase-2 inhibitors / meloxicam / emergency contraception / delayed follicular rupture / dysfunctional ovulation

Currently, the synthetic progestogen levonorgestrel (LNG) is the preferred treatment for emergency contraception (EC –LNG) and is widely available; however, womenhave limited access in some countries because of barriers imposed by conservative groups. Recent evidence suggests that EC–LNG prevents pregnancy when administered prior to the LH surge but has no contraceptive effect if taken once the ovulatory process has been triggered (Croxatto et al., 2004; Novikova et al., 2007). As such, contraceptive failures reported with EC –LNG may be a result ofadministration too late to disrupt the ovulatory process. Prevention or delay of follicular rupture with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been described

previously (Athanasiou et al., 1996; Pall et al., 2001; Bata et al., 2006). The production of prostaglandins, mediated by the activation of the enzyme cyclooxygenase-2 (COX-2) during the ovulatory process, plays animportant role in follicular development and rupture (Richards, 2001). A recent study published by Bata et al. (2006) demonstrates that daily administration of meloxicam, a partially selective COX-2 inhibitor, in a dose of 30 mg daily for 5 days at the onset of the LH surge was associated with a significant 5 days delay of follicular rupture as compared with placebo. Another report from our group has...