Walter L. Herrmann

Association of exogenous estrogen and endometrial carcinoma.

To determine the association between the incidence of endometrial cancer and the use of estrogen in menopausal and post-menopausal women, we retrospectively compared 317 patients with adenocarcinoma of the endometrium with an equal number of matched controls having other gynecologic neoplasms; 152 patients used estrogen, as compared to 54 of 317 controls. Thus, the risk of endometrial cancer was 4.5 times greater among women exposed to estrogen therapy. When estrogen use was adjusted for concomitant variables such as obesity, hypertension, diabetes, parity, referral pattern, age at diagnosis, year of diagnosis and other gynecologic neoplasms, the magnitude of the increased relative risk was associated with several of these variables, and was highest in patients without obesity and hypertension. Exogenous estrogen therapy is associated with an increased risk of endometrial carcinoma, but this increased relative risk is less apparent in patients with physiologic characteristics previously associated with an increased risk.

QUANTITATIVE PAPER CHROMATOGRAPHY OF CONJUGATED 17-KETOSTEROIDS IN PLASMA*

The determination of urinary 17-ketosteroids has limited applications in the understanding and diagnosis of the nature of endocrine disorders associated with mild hirsutism and virilism in the female, because a very large number of these patients excretes 17-ketosteroids well within the normal range. Recent experience of Finkelstein, Forchielli and Dorfman (1) suggests that in these cases the blood levels and nature of the circulating androgens may be very important. Earlier indirect evidence (2-12) and the more recent isolation and partial identification of sulfates of dehydroisoandrosterone, androsterone, and etiocholanolone by Baulieu (13) indicate that 17-ketosteroids are present in plasma mainly in the form of esters. Direct estimation of these conjugated steroids in plasma offers distinct advantages: the alteration of the steroid molecule which occurs with certain types of hydrolysis as well as possible problems of incomplete hydrolysis can be circumvented. Also, information concerning the physiological significance of the steroid conjugating mechanisms may be gained through direct qualitative and quantitative estimation of these conjugates. The present paper describes a convenient method, using quantitative paper chromatography, for the estimation of dehydroisoandrosterone and androsterone sulfates (DHIA-SO and Andro-SO4) in plasma.

Estriol in pregnancy urine and amniotic fluid

Abstract 1. 1. The clinical value of urinary estriol determinations in various complications of pregnancy is confirmed. 2. 2. Gas-liquid chromatography for this purpose seems to offer definite method advantages. 3. 3. A modified method for amniotic fluid is described. 4. 4. In 27 normal pregnancies, the estriol concentration in amniotic fluid varied from 185 μg per liter to nearly 3,000 μg per liter, with a mean value of 979 μg per liter. No correlation with fetal sex, weight, length, and placental weight could be established. 5. 5. Among 10 complicated pregnancies, 5 cases of severe Rh-isoimmunization, showed low estriol concentration (

Measurement of estriol in plasma by gas-liquid chromatography

A method for the measurement of plasma estriol in pregnancy is described, using a radioactive internal standard, acid hydrolysis, phenolic extraction, thin-layer chromatography, and separation and quantification of estriol TMS derivative by gas-liquid chromatography (GLC). Accuracy, sensitivity, specificity, and precision were found to be acceptable. Plasma estriol in normal pregnancy increased from 25xa0weeks’ gestation to term from 0.5xa0μg to 3xa0μg up to 9xa0μg to 22xa0μg per 100xa0ml. In pregnancy complicated by severe pre-eclampsia, diabetes mellitus, fetal death, and eclampsia, low values of estriol in plasma were found. No correlation was found between plasma estriol and severity of Rh disease. Increase or decrease of plasma and urinary estriol levels in pregnancy correlated well. It was demonstrated that protein precipitation caused a decrease of detectable plasma estriol by 40.3xa0±xa08.8 per cent.

Peripheral control of hormone metabolism

Abstract The presence of 5α-reductase and 20α-hydroxysteroid dehydrogenase has been demonstrated in brain from two species (rat and baboon). Under the conditions of the present experimental design, there appear to be significant differences related to sex and species but not to age. Our data, supported by observations of others, suggest a regulatory role of these enzymes in the control of feedback mechanisms.

Isolation of estrone and 11β-hydroxy estrone from a feminizing adrenal carcinoma *

Abstract This paper reports the isolation and characterization of estrone and 11β-hydroxy estrone from an adrenal carcinoma in a 25 year old male with gynecomastia. The tumor was homogenized and the extract divided into unconjugated neutral, phenolic, and conjugated fractions. The phenolic fraction was further divided into individual estrogens using paper chromatography. Characterization of estrone and 11β-hydroxy estrone was done by comparing the chromatographic behavior and functional groups before and after sodium borohydride reduction as well as acetylation with authentic reference standards. Final confirmation of the identity was obtained by infra-red analysis.

Perturbations of the human menstrual cycle by oxymetholone

The luteolytic activity of oxymetholone, and anabolic steroid, has been evaluated in 10 women. Administration early in the follicular phase of the cycle inhibited ovulation and prolonged the duration of the cycles in 2 of 3 subjects, but treatment beginning on Day 10 (3 subjects) did not prevent ovulation, although subsequent plasma progesterone concentrations were reduced. Treatment after ovulation (4 subjects) suppressed progesterone levels by 50 to 80 per cent and shortened cycle length by 6 to 8 days. Side effects were weight gain and bromosulfophthalein retention. The most likely mechanisms producing these perturbations are the inhibition of luteinizing hormone release early in the cycle and, later, inhibition of progesterone biosynthesis.

Monitoring health care

Health risk determinants in obstetrics and gynecology are readily obtainable from state birth records. This study demonstrates the manner in which these determinants may be used to assess health care delivery and monitor its progress. The over-all problem is quite complex. Some parameters are interrelated, while others are not. In addition, any specific parameter may be causally related to many different antecedents, acting singly or in combination. Hence, one must take care not to generalize about deficiencies in our health care systems and thereby propose simplistic, unworkable solutions. However, the study does clearly identify certain specific areas of risk which deserve greater attention than they have hitherto received from health care officials, physicians, and responsible citizens. We believe that the approach outlined in this paper offers a means to achieve unbiased, ongoing monitoring of health care, which may, in turn, be used in attempts to improve the delivery of health services.

The Measurement of Estriol in Urine and Amniotic Fluid by Gas-Liquid Chromatography

The excretion pattern of estriol is of special interest to the clinician. During pregnancy, urinary levels of this compound can be directly correlated with several parameters applying directly to the fetus, ranging from weight to fetal embarrassment and death. The reason for this is the active participation of the fetus in the metabolism of estriol.