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BACKGROUND: The presence of urinary excretion products of human chorionic gonadotropin (hCG) has been proposed as a tumor marker. To ascertain the clinical value in gynecologic cancers, the authors studied 612 nonpregnant women. METHODS: Three different assays in four clinical groups were compared: no disease, benign disease, malignant disease, and complete remission of previously treated malignant disease. The assays were for the urinary beta-core, "total" beta-hCG, and free alpha-subunit. RESULTS: Measurement of the alpha-subunit was of no obvious clinical value. In some patients with benign disease, hCG metabolites were elevated. In the 141 patients with active gynecologic malignancy the sensitivity of the total beta-hCG assay was 47% and that of the beta-core assay was 36%. The specificities were 80.3% and 90.4%, respectively. Advanced cancers generally had higher levels of total beta-hCG and beta-core. Squamous cell and poorly differentiated cervical tumors had higher levels of total beta-hCG than did adenocarcinomas and well-differentiated cervical tumors. Invasive, serous, endometrioid, and germ cell ovarian tumors had higher total beta-hCG, beta-core, and alpha-subunit levels than did borderline, mucinous, and clear cell ovarian tumors. Six of 16 patients with disease in complete remission had elevated levels. CONCLUSION: The excretion of hCG and its metabolic fragments is a common event in gynecologic cancer, but sensitivity and specificity are low, and there is little consistent relationship between tumor stage and histologic type.

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Progesterone and its urinary metabolite pregnanediol-3 alpha-glucuronide (PDG) are generally lower in women with abnormal pregnancies compared to those with normal intrauterine gestations. We evaluated the ability of random urinary PDG measurements determined by enzyme immunoassay (EIA) to differentiate normal from abnormal pregnancies. Patients with first-trimester vaginal bleeding (n = 104) were evaluated. Eventual outcomes indicated 39 women had viable intrauterine pregnancies (IUPs), 54 had spontaneous abortions (SABs) and 11 had ectopic pregnancies (EPs). Urinary PDG was significantly lower in SAB and EP compared to IUP patients. However, a wide range of values in IUP patients was noted (3.2-93.3 micrograms/ml), due to varying degrees of patient hydration at presentation. Hence, random measures of urinary PDG demonstrated poor specificity (32.8%) in correctly differentiating normal from abnormal gestations, thus limiting its clinical usefulness.

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There is no simple and rapid test available to predict the outcome of an early pregnancy complicated by vaginal bleeding. In this prospective study, 15 women with normal pregnancies collected a weekly urine sample between 6 and 13 weeks' gestation. A single random urine sample was obtained from 15 women with bleeding who continued to carry their child and 50 women who proceeded to have a spontaneous abortion (SAB). Pregnandiol-3-glucuronide (PDG) was determined with the use of enzyme-multiplied immunoassay technique (EMIT) and estrone conjugates (E1C) were measured by radioimmunoassay (RIA). The ratios of these metabolites to creatinine (C) were calculated. PDG/C ratios in normal women rose gradually from 6 weeks on. All women with bleeding during a normal pregnancy had ratios in the normal range, but 94% of women with a SAB had ratios below the normal range. The E1C/C ratio remained unchanged from 6 to 11 weeks and then rose rapidly. Until 11 weeks, there was no clear separation between the E1C/C ratios of the women with a SAB and the women with bleeding who continued their pregnancies. The prognosis of threatened abortion can be made by a urinary PDG/C ratio but not by an E1C/C ratio. EMIT is simple and quick and uses technology present in many laboratories.

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A reference range for urinary oestrogen excretion between 28 and 40 weeks has been produced by analysis of 18 870 estimations. The data were transformed logarithmically to give a Gaussian distribution on which parametric analysis was performed: non-parametric analysis was carried out on the untransformed data: the results of both analyses were compatible. Multiple pregnancies tended to have levels above the 50th centile, light-for-dates fetuses below the 50th centile. Antepartum haemorrhage showed no difference from the general reference range. Intrauterine death was preceded by a level below the 5th centile if the estimation was carried out less than one week before the fetus died.

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A total of 1,607 urinary estriol determinations were performed in 447 patients with normal and complicated pregnancies. In general, the test provided reliable information concerning fetal status, particularly in pregnancies complicated by toxemia, diabetes, and postmaturity. When measured consecutively, a drop of 50% or more in estriol level usually should be considered a significant index of fetal distress. Limitations of the test and several compensatory measures aimed at minimizing inaccuracy are discussed.

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Estriol excreation was studied in 216 normal and 61 pathologic pregnancies. The 95% fiducial limits of the normal excretion of estriol, within which 95% out of 100 future determinations in normal pregnancies are expected to fall, were established. The estriol curve in normal pregnancy in this study agrees well in its general shape with those presented by previous investigators who used different chemical methods of determination. The estriol values in pathologic pregnancies with preeclampsia. intrauterine fetal death and antepartum hemorrage have been analyzed. The clinical significance of estriol determinations during pregnancy was discussed.

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In 51 patients with antepartum haemorrhage, 24-hour urinary oestriol was measured continuously until delivery. A total of 765 24-hour urinary oestriol measurements was obtained and there were two stillbirths, one neonatal death and three cases of intrauterine growth retardation in this group of patients. It was felt that none of the fetal deaths would have been prevented by obstetrical treatment based on 24-hour urinary oestriol measurements and that these have little practical value in the management of patients with antepartum haemorrhage.

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PIP: The excretion of uterine estrogens was examined in 61 women: 20 with functional bleedings during climacterium, 15 with uterine myoma, 16 with cerivcal carcinomas, and 10 with ovarian carcinomas. Results showed that there were considerable individual variations in estrogen excretion and anunvanlanced relationship of the fractions with estriol prevailing in all the groups. There was no significant difference in the amounts of estrogen excreted by women with funcional bleedings and those found in women with uterine myoma. Those women with cervical carcinoma did show considerably lower excretions than those of the other groups. The lowest level of excretion was found in those women with ovarian carcinoma. THese examinations did illustrate the considerable disturbances in the biosynthesis of estrogens in the ovaries of afflicted patients. The more advanced the condition, the more prominent the disturbances were, with imbalance of estriol prevailing.^ieng

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