6-ketoprostaglandin-f1-alpha and Genital-Neoplasms--Female

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

C-reactive protein (CRP) is an acute phase reactant that appears to have a variety of biologic effects, including stimulation of prostaglandin production by peripheral blood monocytes. Both CRP and 6-keto prostaglandin F 1-alpha (6-keto PGF1-alpha) have been noted to be elevated in the sera of patients with malignant disease, therefore the current study was undertaken to determine whether any correlation exists between serum levels of these two substances. Thirty-five samples of sera from 16 patients undergoing treatment for primary gynecologic malignancies were tested. CRP was elevated above normal in 97% of samples and 6-keto PGF1-alpha was elevated in 91% of samples. No correlation between levels of CRP and 6-keto PGF1-alpha was identified. Serial serum samples were available for 6 patients undergoing therapy; in 5 of 6 patients CRP levels reflected the clinical disease course. There was no apparent correlation between 6-keto PGF1-alpha levels and clinical progression or regression of disease.

Topics: 6-Ketoprostaglandin F1 alpha; C-Reactive Protein; Female; Genital Neoplasms, Female; Humans

The production of the antiaggregatory and vasodilatory prostacyclin (PGI2) in patients with gynaecological tumours was studied by assaying urinary 6-keto-prostaglandin F1a (= 6-keto-PGF1a), a hydration product of PGI2), by radioimmunoassay following high performance liquid chromatography (HPLC) in 59 patients with gynaecological tumours and 12 non-tumourous control women. Urinary 6-keto-PGF1a excretion in patients with cervical cancer (28.3 +/- 3.6 pmol/mmol creatinine, mean +/- S.E., n = 12), endometrial cancer (22.8 +/- 3.7 pmol/mmol creatinine, n = 12, uterine fibroids (26.0 +/- 3.5 pmol/mmol creatinine, n = 12) benign ovarian cysts (22.4 +/- 1.8 pmol/mmol creatinine, n = 12) did not differ from that in the control women (29.9 +/- 3.6 pmol/mmol creatinine, n = 12). However, patients with ovarian cancer excreted increased amounts of 6-keto-PGF1a (55.4 +/- 10.4 pmol/mmol creatinine, n = 11, P less than 0.05), although this bore no relation to tumour histology, clinical stage or the outcome of the patients. Thus, ovarian cancer is accompanied by increased PGI2 production, perhaps in the kidneys and/or in the cancer tissue.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Epoprostenol; Female; Genital Neoplasms, Female; Humans; Middle Aged

Peripheral plasma levels of immunoreactive 6-oxo-PGF1 alpha, the stable hydrolysis product of prostacyclin, were significantly higher in female patients with tumours of the genital tract than in normal controls. In the groups with malignant tumours, these high levels declined after operation and/or radiotherapy if the tumour responded to treatment. In patients who did not respond to treatment or with tumour recurrence, levels of plasma 6-oxo-PGF1 alpha remained high or even rose further. Benign gynaecological tumours were also associated with significantly raised plasma 6-oxo-PGF1 alpha levels, and these fell to normal levels immediately on surgical removal of the tumour. Possible reasons for these alterations are described. Further investigations are warranted to see whether serial measurements of plasma 6-oxo-PGF1 alpha could be used as a prognostic index for the clinical status of patients with gynaecological tumours.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Antineoplastic Agents; Female; Follow-Up Studies; Genital Neoplasms, Female; Humans; Hysterectomy; Middle Aged; Prognosis; Prostaglandins F