6-ketoprostaglandin-f1-alpha and Menorrhagia

The gynecologic and obstetric implications of the smooth muscle-relaxing, antiaggregatory prostacyclin and its endogenous antagonist, thromboxane A2, are reviewed. In addition to the vascular wall and circulating platelets, which are primary sources for prostacyclin and thromboxane A2, respectively, reproductive tissues produce great amounts of these prostanoids, evidently for the regulation of the vascular tone and/or vascular platelet interaction. Several gynecologic and obstetric disorders are characterized by abnormalities in prostacyclin and/or thromboxane A2. In primary menorrhagia the uterine release of prostacyclin is increased, and consequently menstrual blood loss can be reduced with various prostaglandin synthesis inhibitors. Prostacyclin relaxes the nonpregnant myometrium in vitro and may also do so in vivo, although intravenous infusion of prostacyclin has no effect upon the uterine contractility in nonpregnant or pregnant subjects. Patients with pelvic endometriosis may have increased levels of prostacyclin and thromboxane A2 metabolites in the peritoneal fluid. The prostacyclin/thromboxane A2 balance shifts to thromboxane A2 dominance in patients with gynecologic cancer. During pregnancy the production of prostacyclin and thromboxane A2 increases in the mother and fetoplacental tissue. Preeclampsia and other chronic placental insufficiency syndromes are accompanied by prostacyclin deficiency in the mother and in fetomaternal tissues and by an overproduction of thromboxane A2, at least in the placenta. These changes may account for the vasoconstriction and platelet hyperactivity, which are pathognomonic for hypertensive pregnancies. By directing the prostacyclin/thromboxane A2 balance to prostacyclin dominance (by dietary manipulation, administration of prostacyclin and/or its analogues, drugs with prostacyclin-stimulating and/or thromboxane A2-inhibiting action), it may be possible to prevent and/or treat hypertensive pregnancy complications in the future.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Ascitic Fluid; Endometriosis; Epoprostenol; Estrogens; Female; Genital Diseases, Female; Genital Neoplasms, Female; Humans; Hypertension; Menorrhagia; Platelet Aggregation; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Progestins; Thromboxane A2; Thromboxane B2; Thromboxanes; Uterine Contraction; Vasoconstriction

The endometrial concentration of 6-keto-PGF1 alpha and TXB2 were measured by RIA in women with Tcu-IUD induced menorrhagia (MBL greater than 80 ml) and in levonorgestrel-IUD users with oligomenorrhea or amenorrhea. Non-IUD users with normal menses (MBL less than 80 ml) were chosen as control. It was found that the Tcu-IUD group showed a significantly higher 6-keto-PGF1 alpha concentration than the other two groups (P less than 0.01). Conversely, the TXB2 concentration of levonorgestrel-IUD group was significantly higher than that of the other groups (P less than 0.05). As a result, the 6-keto-PGF1 alpha/TXB2 ratio was much higher in Tcu-IUD group (P less than 0.01). Our results indicated that the unbalance of PGI2/TXA2 ratio may be the direct cause of the IUD-induced menorrhagia.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Endometrium; Epoprostenol; Female; Humans; Intrauterine Devices; Intrauterine Devices, Copper; Intrauterine Devices, Medicated; Levonorgestrel; Menorrhagia; Oligomenorrhea; Thromboxane B2

43 samples of endometrium from IUD users with excessive uterine bleeding (MBL 80 ml), normal menstrual blood loss (MBL 80 ml), and non-IUD users with normal menstrual blood loss (80 ml) have been studied. Concentration of 6-keto-PGF1alpha, a metabolite of prostacyclin (PGI2), was determined by radioimmunoassay. It was found that the concentration of 6-keto-PGF1alpha of patients with IUD-induced excessive uterine bleeding was significantly higher than that of IUD users with MBL 80 ml (p 0.05) and of non-IUD users (p,0.01). But the difference between IUD users with normal menstruation and the controls was of no statistical significance (p0.05). The results also indicated a positive correlation between the amount of MBL and 6-keto-PGF1alpha concentration in the endometria of IUD users (r=0.439; p0.05). The measurements of both tissue plasminogen activation (t-PA_ and 6-keto-PGF1alpha concentrations from samples of 28 cases showed a weak positive correlation between t-PA and 6-keto-PGF1alpha (r=0.459; p0.05). Further study is necessary to evaluate the significance of this result. These studies prove that the increased 6-keto-PGF1alpha is an important factor in the existence of excessive uterine bleeding in IUD users.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Endometrium; Epoprostenol; Female; Humans; Intrauterine Devices; Menorrhagia; Tissue Plasminogen Activator

The synthesis of prostanoids from arachidonic acid incubated with endometrium alone or together with myometrium was studied in women with excessive menstrual blood-loss (range 57--186 ml, median 86 ml). Production of prostaglandins F2 alpha, E2, and D2 was similar to that observed for the endometrium of women with normal periods (range 5--50 ml; median 11 ml). However, the endometrium from women with excessive menstrual blood-loss was more effective than endometrium from women with normal menstrual blood-loss at enhancing the production by a control preparation of myometrium of 6-oxo-prostaglandin F1 alpha, the stable metabolite of prostacyclin. The ability of the uterus to generate prostacyclin, a prostaglandin known to inhibit platelet aggregation and stimulate vasodilatation, may influence the degree and duration of menstrual bleeding.

Topics: 6-Ketoprostaglandin F1 alpha; Endometrium; Epoprostenol; Female; Humans; Menorrhagia; Myometrium; Platelet Aggregation; Prostaglandins; Prostaglandins D; Prostaglandins E; Prostaglandins F; Vasodilation