Effect of the menstrual cycle and oral contraceptives on cyclooxygenase-2 expression in the endometrium

To compare the expression of cyclooxygenase-2 (COX-2) and proliferation markers (Ki-67) in the endometrium of patients with ovulatory cycles with those in the endometrium of patients using oral contraceptives.

Endometrial biopsies from 104 premenopausal patients with regular ovulatory cycles (n=90) or using an oral contraceptive (n=14) were selected for this study. Using immunohistochemical methods, both COX-2 (Novocastra clone 4H12) and Ki-67 (Dako clone MIB-1) expression were determined in the endometrium during the various phases of the menstrual cycle or following the use of oral contraceptives.

COX-2 expression in the glandular epithelium was maximal during menstruation, the late proliferative phase and the early luteal phase, and minimal during the late luteal phase. However, in the surface epithelium, COX-2 expression remained strongly positive throughout the luteal phase. Ki-67 positivity increased during the proliferative phase and diminished during the luteal phase in the glands. In contraceptive users, both Ki-67 and COX-2 expression in the endometrium was low.

The increased expression of COX-2 during menstruation and at mid-cycle is eliminated by the continuous use of oral contraceptives. This may be the rationale for their therapeutic action in the treatment of dysmenorrhea and bleeding.