The role of prostaglandins and allied substances in uterine haemostasis

Abstract

This review addresses itself to summarizing the more recent studies published on the bioconversion of arachidonic acid in the human endo- and myometrium during the normal menstrual cycle and in women with increased menstrual blood loss. The data indicate an increased ability of the endo- and myometrium from women with menorrhagia to produce prostaglandins with vasodilator and platelet anti-aggregatory properties, viz., prostacyclin and prostaglandin E2. The data on prostaglandin production in endometria of IUD wearers is reviewed and discussed in relation to present knowledge on morphological findings in IUD-influenced endometrium.

PIP: This review covers eicosanoid metabolism in human uterine tissues, in normal menstrual cycles, menorrhagia, and IUD contraception. Since measuring tissue level of prostaglandins (PGs) leads to artifacts, recent studies have involved tissue culture, superfusion and histochemistry, to analyze arachidonic acid metabolism, in endometrium, its tissues, and myometrium. First, it was established that Pgf2alpha and PGE2 are the primary PGs elaborated by human endometrium. The enzyme that produces Pgf2alpha, cyclooxygenase, is located primarily in the glandular endothelium. Pgf2alpha is under estrogen receptor control. Progesterone reduces Pgf2alpha and antiprogestogens increase it. In normal menstrual cycles, both PGs are highest in late luteal phase. In women with menorrhagia, defined as menstrual blood loss over 90 ml, the Pgf2alpha:PGE2 ratio is abnormally low, a reasonable finding since Pgf2alpha is vasoconstrictive, and PGE2 is a vasodilator. Another vasodilator PG, prostacyclin or PGI2, may be abnormally high in women with excessive bleeding. Some experiments on endometrium and myometrium, cultured apart and together, suggest that there may be flow of substrates of the PG pathways such that less Pgf2alpha is available in this condition. Using radiolabelled arachidonic acid, researchers concluded that the Pgf2alpha pathway may be saturated because of substrate being incorporated into excess triglycerides, leading to alternative PG release. Another theory proposes that PG antagonist drugs which block menstrual pain may also lower synthesis of leukotrienes, an eicosanoid that causes vasoconstriction as well as inflammation and pain. There have been no studies comparable to the tissue culture work cited above concerning IUDs. Some explorations of leukocyte PG metabolism and the effects of copper are relevant to the conclusions about PGE2 as a vasodilator. There could also be an alteration of locally produced thromboxanes and prostacyclins on blood clotting in IUD wearers.