The mechanisms underlying excessive menstrual bleeding or menorrhagia
are not understood, In view of its potent vasoconstrictor and growth f
actor properties, endothelin has been proposed to have a potential par
acrine role in the regulation of uterine blood how and therefore could
be a factor in menorrhagia. We compared the cellular localization of
endothelin and its metabolizing enzyme, neutral endopeptidase, in endo
metrial biopsies from women with documented menorrhagia and in those w
ith a normal menstrual cycle, Menorrhagia was documented by measuremen
t 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 immunoreacti
vity was not different from the normal cycle and although neutral endo
peptidase immunostaining in stroma was similar to the secretory phase
of normal endometrium, cyclical variation was absent. The potential fo
r increased metabolism of endothelin could be an explanation for the d
ecreased endothelin immunostaining in the glandular epithelium.