Does meloxicam increase the incidence of anovulation induced by single administration of levonorgestrel in emergency contraception? A pilot study.
BACKGROUND
Levonorgestrel (LNG) consistently prevents follicular rupture only when it is given before the onset of the ovulatory stimulus. As locally synthesized prostaglandin (PG) plays a crucial role in follicular rupture and cyclooxygenase-2 (cox-2) catalyses the final step of PG synthesis, we reasoned that adding a cox-2 inhibitor to LNG would prevent follicular rupture even after the ovulatory process had been triggered by the gonadotrophin surge.


METHODS
Forty-one women were divided into two groups. One was treated when the size of the leading follicle was 15-17 mm (n=10) and the other when it was >or=18 mm (n=31). Each woman contributed with one cycle treated with LNG 1.5 mg single dose plus placebo and another treated with LNG + meloxicam (Melox) 15 mg, in a randomized order. Serial blood sampling for the assay of LH and follicular monitoring by transvaginal ultrasound were performed before and after treatment.


RESULTS
Follicular rupture failed to occur within the 5-day period that followed treatment in 50 and 70% of cycles treated with LNG + Placebo and LNG + Melox, respectively, in the 15-17 mm group (P=0.15) and in 16 and 39% of cycles treated with LNG + Placebo and LNG + Melox, respectively, in the >or=18 mm group (P < 0.052). The overall proportion of cycles with no follicular rupture or ovulatory dysfunction increased significantly by the addition of Melox to LNG (66 versus 88%, P < 0.012; n=41-matched pairs).


CONCLUSIONS
The trend towards increased incidence of no follicular rupture when Melox was combined with LNG suggests that the addition of a cox-2 inhibitor has the potential to improve the contraceptive efficacy of LNG by a pre-fertilization effect.
Massai
M R
MR
Instituto Chileno de Medicina Reproductiva (ICMER), Santiago, Chile. rmassai@icmer.org
Forcelledo
M L
ML
Brache
V
V
Tejada
A S
AS
Salvatierra
A M
AM
Reyes
M V
MV
Alvarez
F
F
Faúndes
A
A
Croxatto
H B
HB
D000293:Adolescent; D000328:Adult; D000858:Anovulation / Q000139:chemically induced*; D002677:Chile; D003283:Contraceptives, Postcoital, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004293:Dominican Republic; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000494:pharmacology*; D000077239:Meloxicam; D006080:Ovarian Follicle / Q000187:drug effects / Q000502:physiology; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D003283:Contraceptives, Postcoital, Synthetic; D052246:Cyclooxygenase 2 Inhibitors; D013843:Thiazines; D013844:Thiazoles; D016912:Levonorgestrel; D000077239:Meloxicam