Endothelin and neutral endopeptidase in the endometrium of women with menorrhagia

The mechanisms underlying excessive menstrual bleeding or menorrhagia are not understood. In view of its potent vasoconstrictor and growth factor properties, endothelin has been proposed to have a potential paracrine role in the regulation of uterine blood flow and therefore could be a factor in menorrhagia. We compared the cellular localization of endothelin and its metabolizing enzyme, neutral endopeptidase, in endometrial biopsies from women with documented menorrhagia and in those with a normal menstrual cycle. Menorrhagia was documented by measurement of menstrual blood loss, 146 +/- 141 ml (median +/- SD). Endothelin and neutral endopeptidase were localized by immunohistochemistry, and the staining intensity was graded. Their immunostaining patterns were found to differ in menorrhagia compared to the normal menstrual cycle. Endothelin was reduced in glandular epithelium in menorrhagia and did not vary cyclically, while neutral endopeptidase was increased in the glandular epithelium. In menorrhagia, stromal endothelin immunoreactivity was not different from the normal cycle and although neutral endopeptidase immunostaining in stroma was similar to the secretory phase of normal endometrium, cyclical variation was absent. The potential for increased metabolism of endothelin could be an explanation for the decreased endothelin immunostaining in the glandular epithelium.