Relaxin stimulates expression of vascular endothelial growth factor in normal human endometrial cells in vitro and is associated with menometrorrhagia in women

Although the role of the reproductive hormone, relaxin, in rodents is well documented, its potential contribution to human reproduction is less well d efined. In this study, we examine the effects of relaxin on human endometri al cells in vitro and describe the clinical effects of relaxin on menstrual how in women. In cultured endometrial cells, relaxin specifically induces the expression of an angiogenic agent, vascular endothelial growth factor ( VEGF). cAMP is implicated as a second messenger involved in VEGF stimulatio n. VEGF expression is temporally regulated in the endometrium, and our resu lts suggest that relaxin, which is secreted by the corpus luteum and is pre sent in the endometrium during the menstrual cycle and pregnancy, may be in volved in regulating endometrial VEGF expression. Relaxin was recently test ed in a clinical trial for efficacy in the treatment of progressive systemi c sclerosis, and was administered at levels up to 10 times higher than that measured during pregnancy. The most frequent relaxin-related adverse event reported during the course of the study was the onset of menometrorrhagia, defined in this study as heavier-than-usual or irregular menstrual bleedin g. The intensification of menstrual flow observed in these patients is cons istent with the hypothesis that relaxin mediates neovascularization of the endometrial lining.