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The pattern of prostaglandins (PGs) synthesized by persistent proliferative endometrium of women with excessive menstrual bleeding (greater than 50 ml) associated with anovulatory cycles was compared to endometrium collected from women with normal menstrual blood loss (less than 50 ml). Levels of PGF2 alpha in normal and persistent proliferative endometrium were lower than the levels of PGF2 alpha found in normal secretory endometrium (P less than 0.005 for both normal and persistent proliferative endometria). When incubated with exogenous [1-14C]arachidonic acid (9.1 nmol), normal secretory endometrium synthesized more PGF2 alpha and PGE2 than did normal proliferative endometrium, but the amounts of PGF2 alpha and PGE2 released by persistent proliferative endometrium were similar to those obtained by normal secretory endometrium. These findings suggest that persistent proliferative and normal secretory endometria have the same PG synthetase activity, and that the low endogenous concentrations of PGF2 alpha in the former arise from a lack of endogenous precursor. PGF2 alpha has predominantly vasoconstricting properties, and a reduced capacity to synthesize this PG by persistent proliferative endometrium may result in excessive menstrual bleeding, as was suggested by the inverse correlation between the ratio of the endogenous concentrations of PGF2 alpha and PGE and the menstrual blood loss (r = -0.7; P less than 0.005; n = 26).

We investigated the ability of the nonpregnant human uterus to metabolize prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha) using radiolabeled substrates together with gas chromatography-mass spectrometry for the measurement of specific metabolites. Both the 15-hydroxyprostaglandin dehydrogenase and the delta 13-reductase enzymes are present in endometrium and myometrium. As shown for other tissues, the dehydrogenase is NAD+ dependent, while the delta 13-reductase requires NADPH as cofactor. PGE2 was the preferred substrate in both tissues; however, the metabolizing capacity of follicular phase myometrium was comparable with that of midluteal phase endometrium. The Km values of the dehydrogenase for PGE2 and PGF2 alpha were similar in both endometrium (1.89 X 10(-6) and 18.52 X 10(-6) mol/liter, respectively) and myometrium (2.76 X 10(-6) and 11.64 X 10(-6) mol/liter, respectively), suggesting that the same enzyme is present in both tissues although the regulation of this enzyme may differ in endometrium and myometrium.