Induction of delayed follicular rupture in the human by the selective COX-2 inhibitor rofecoxib: a randomized double-blind study

BACKGROUND: The aims of the present study were to examine whether periovula tory administration of a cyclooxygenase (COX)-2 inhibitor affects human ovu lation and endocrine parameters. METHODS: Thirteen healthy women, 30-40 yea rs of age, without hormonal treatment and with regular menstrual cycles (27 -34 days), were given the selective COX-2 inhibitor rofecoxib (n = 6) or pl acebo (n = 7) in a random double-blind fashion. In an initial control cycle , serial hormonal analyses, detection of a measurable mid-cycle urine LH pe ak and transvaginal ultrasound scans were performed to confirm normal ovula tory and endocrinological cyclic patterns, in ail participating women. Duri ng the subsequent treatment cycle, serial ultrasound scans were performed. When the dominant follicle reached 14-16 mm in diameter, 25 mg rofecoxib or placebo was taken orally, once daily for 9 consecutive days, during which follicle size was monitored daily by ultrasound scans and serial hormone an alyses were performed. RESULTS: Four of the six women who received rofecoxi b demonstrated delayed follicle rupture, > 48 h after the LH peak, when com pared with the placebo group, who all had follicular rupture > 36 h after t he detected LH peak. No differences in peripheral serum concentrations of p rogesterone, oestradiol, LH and FSH were observed between placebo and rofec oxib groups, when analysed at specified time intervals. CONCLUSIONS: This s tudy suggests that selective COX-2 inhibition has a negative, local effect on human ovulation, resulting in delayed follicular rupture, without affect ing peripheral hormonal cyclicity.