Eicosanoids in primary dysmenorrhea, endometriosis and menstrual migraine

Abstract

This paper summarizes what has been learned over the years about the role of eicosanoids in the pathogenesis of primary dysmenorrhea, endometriosis and menstrual migraine. The role of prostaglandins (PGs) in the pathogenesis of primary dysmenorrhea is inferred from four main observations: firstly, the clinical symptoms of primary dysmenorrhea are similar to those induced by the administration of PGF_2α and PGE₂ for the induction of labour; secondly, the increased production of PGs by the endometrium during the luteal and menstrual phases of ovulatory cycles is consistent with the occurrence of primary dysmenorrhea mainly in ovulatory cycles; thirdly, the concentrations of PGF_2α and PGE₂ in the endometrium and menstrual fluid of dysmenorrheic women are significantly higher than in controls; fourthly, certain PG inhibitors have been proved to be effective in the treatment of dysmenorrhea. The change in PG production can explain the major symptoms of primary dysmenorrhea, including the increased uterine contractility, uterine ischemia and the lowering of the pain threshold to chemical and physical stimuli in the pelvic nerve terminals. Moreover, recent experimental data suggest that leukotrienes (LTs) might be among the alternative pathogenetic causes of primary dysmenorrhea. The data which support a relationship between eicosanoids and endometriosis are as follows: endometriotic tissue produces PGs; the peritoneal fluid concentration of PGF2α increases significantly after the induction of endometriosis in laboratory animals; the concentration of PGs in peritoneal fluid of some patients with endometriosis is greater than in controls and, finally, the number and activation of pelvic macrophages which are able to synthesize eicosanoids increase in patients with endometriosis. Possible roles for eicosanoids in the pathogenesis of infertility and secondary dysmenorrhea induced by endometriosis have been suggested. Eicosanoids are probably also involved in the pathogenesis of menstrual migraine. Different types of PGs might play a role both in the initial vasoconstriction during the prodromal phase of migraine and in the vasodilation and sensitization to pain typical of the pain phase.