Dan Tulchinsky

Plasma estrone, estradiol, estriol, progesterone, and 17-hydroxyprogesterone in human pregnancy: I. Normal pregnancy☆

To describe normal relationships between the various plasma unconjugated estrogens and progesterone during the second half of human pregnancy, the plasma concentrations of progesterone, 17-hydroxyprogesterone (17-OHP), and unconjugated estrone (E1), estradiol (E2), and estriol (E3) were measured in 126-310 normal women. Progesterone and unconjugated E1, E2, and E3 increased gradually throughout later pregnancy; 17-OHP increased only after the thirty-third week. At term the mean value of progesterone was 9 times higher than that 17-OHP. Throughout pregnancy the mean value of E2 was higher than that of E1 or E3. During the second half of pregnancy the ratios of progesterone to estradiol and estriol and of estradiol to estriol remained unchanged, indicating no preferential increase of plasma concentration of maternal or fetal hormones.

Plasma human chorionic gonadotropin estrone estradiol estriol progesterone and 17-alpha-hydroxyprogesterone in human pregnancy. 3. Early normal pregnancy.

Abstract The concentrations of human chorionic gonadotropin (HCG), progesterone (P), 17α-hydroxyprogesterone (17-OHP), and unconjugated estrone (E 1 ), estradiol (E 2 ), and estriol (E 3 ) were measured by radioimmunoassay in plasma of 10 patients followed from the third to the thirteenth week of pregnancy. Up to the fifth week of pregnancy, an increase in the mean plasma concentration of E 1 , E 2 , P, and 17-OHP was observed. After the fifth week of pregnancy, however, only the mean plasma concentration of E 1 and E 2 continued to increase, whereas that of 17-OHP started to decrease and that of P remained unchanged until the tenth week of pregnancy. Unconjugated E 3 became detectable (> 50 pg. per milliliter) only after the ninth week of pregnancy, after which its level continued to increase gradually. The mean HCG plasma level increased until the tenth week of pregnancy, after which it began to decline. No correlation was found between HCG and E 2 or HCG and P plasma concentrations, but good correlation was found between E 1 and E 2 levels. The mean P plasma concentrations between the third and the fifth weeks of pregnancy was about 100 times higher than that of E 2 . By the thirteenth week of pregnancy, however, the mean P / E 2 ratio had decreased sixfold, reaching a ratio similar to that observed at the second half of pregnancy. Most levels of P, E 1 , and E 2 up to the seventh week of pregnancy were in the range found during the menstrual period. During the first 7 weeks of pregnancy, the diagnosis of intrauterine pregnancy cannot be made with certainty by determination of any of these steroid hormones.

Simultaneous Measurement of Plasma Progesterone, 17-Hydroxyprogesterone and Estradiol-17B by Radioimmunoassay

Abstract Combining a simple chromatographic system on celite microcolumns with partially specific antisera as binding reagents, simultaneous radioimmunoassay of progesterone, 17-hydroxyprogesterone, and estradiol-17B could be performed on the same aliquot of plasma. These steroids have been measured in plasma samples obtained from subjects of both sexes under various conditions.

Total cortisol in amniotic fluid and fetal lung maturation.

Abstract Total Cortisol was determined by radioimmunoassay in 48 samples of amniotic fluid obtained at various stages of normal pregnancy. Before the 34th week, all cortisol levels were 40 weeks, a further increase in total amniotic-fluid cortisol was observed, and values > 120 ng per milliliter were found only in patients of this group. A good rank correlation between cortisol and lecithin/sphingomyelin ratio was found in 43 samples (r = 0.83, p 60 ng per milliliter (16 patients). Total amniotic-fluid cortisol may reflect initiation of fetal lung maturation, and may help identify pregnancies with a gestation period of over 40 weeks. (N Engl J Med 292:133–136, 1975)

Chromatographic purification of estradiol-17β for use in radio-ligand assay

Abstract Using disposable microcolumns of Celite, a rapid, simple, and reliable method of purification of estradiol-17β was obtained. This purification procedure was found adequate for detection methods such as the two radio-ligand assays described. Estradiol-17α is a possible contaminant, and, therefore, in materials containing this steroid in the free form, specificity for estradiol-17β would be lacking unless binding protein used in the detection method does not react with estradiol-17α. Other possible contaminants in this system would be exogenously administered synthetic estrogens.

On the regulation of estrogen production by cortisol and ACTH in human pregnancy at term: Memorial foundation award thesis☆

Abstract Maternal and fetal adrenals provide precursors for placental estrogens. Mechanisms of adrenal control were studied in patients undergoing elective cesarean section at term. Ten patients served as controls; six received 150 mg. of cortisol intravenously and 13 received 40 I.U. of Depo-ACTH intramuscularly. Maternal venous and cord venous and arterial plasma were analyzed for ACTH, total and unbound unconjugated cortisol, DHEA and DHEA sulfate, estrone, estradiol, and estriol. Cortisol increased maternal and—after placental transfer—fetal cortisol and subsequently estrogen precursors, and estrogens in mother and fetus. ACTH first appears to increase estrogens; four to seven hours after its injection, estrone and estradiol normalize while estriol decreases to subnormal values in mother and fetus. Interpretation of these findings is given. The data further support the hypothesis that ACTH is a regulating hormone for the fetal adrenal, although no evidence was obtained to substantiate transfer of ACTH from mother to fetus.

Abnormal Adrenal Responses to Adrenocorticotropic Hormone in Hyperandrogenic Women

The plasma concentrations of testosterone (T), dehydroepiandrosterone (D), androstenedione (A), pregnenolone (delta 5P), progesterone (P), 17-hydroxypregnenolone (17-delta 5P), 17-hydroxyprogesterone (17-P), 11-deoxycortisol (S), and cortisol (F) were measured before, and 30 and 60 minutes after, a bolus intravenous injection of 25 units of adrenocorticotropic hormone (ACTH) in nine normal women and in fifteen patients with a variety of manifestations of androgen excess. Patients with androgen excess demonstrated significantly higher mean baseline levels of T, D, A, delta 5P, 17-delta 5P, and 17-P. After a bolus intravenous injection of 25 units of ACTH, higher-than-normal increments were noted for the following steroids: delta 5P (one patient), 17-delta 5P (one patient), D (two patients), P (one patients), 17-P (two patients), and S (two patients). Following ACTH injections, the ratios of increments in plasma steroid pairs were computed to estimate the efficiency of several adrenal enzymes, and evidence suggesting partial deficiency of 3 beta-hydroxysteroid dehydrogenase delta 4-5 isomerase (five patients) and 11 beta-hydroxylase (five patients) was found. In addition, 6 of the 15 patients with androgen excess exhibited an abnormally high increment in D relative to the increment in F. The data show that apparent abnormalities in adrenal steroid biosynthesis are a frequent occurrence in patients with hyperandrogenism.

Hormones in human pregnancy. IV. Plasma progesterone.

The plasma concentration of progesterone (P) has been measured by radioimmunoassay in maternal peripheral vein (M.P.V.) at early pregnancy and in M.P.V. umbilical artery (U.A.) and umbilical vein (U.V.) at term pregnancy. In early preganacy marked hour-to-hour fluctuation of plasma progesterone was noted. At term pregnancy plasma P levels of U.V. were higher than those of U.A. and the umbilical venous arterial differences of plasma P did not differ between male and femal fetuses. Administration of hydrocortisone and ACTH to patients scheduled to undergo cesarean section had no effect on M.P.V., U.A., and U.V. plasma P concentration. On the basis of the differences between U.V. and U.A. plasma P concentrations and reported umbilical flow it was estimated that the secretion rate of P into the fetal circulation is approximately 23 mg. per 24 hr. and would amount to approximately 10 per cent of the reported total daily production rate of P at term pregnancy. The fraction of P which is unbound to the plasma proteins was estimeated by equilibrium dialysis at 37 degrees C. The per cent unbound P in M.P.V. plasma of pregnant patients at term was not different from that of nonpregnant patients but was 40 per cent lower than that in umbilical cord plasma (P LESS THAN 0.01), and the ratio between the concentrations of unbound P and estradiol in M.P.V. increased as pregnancy progressed. Plasma P in re-eclamptic patients who subsequently sustained intrauterine fetal death had no value in assessing placental function.

Endometrial hyperplasia in women on cyclic or continuous estrogen regimens.

Twenty-five symptomatic postmenopausal women with an intact uterus were assigned in random double-blind fashion to receive 0.625 mg of conjugated estrogens on either a cyclic (3 weeks on, 1 week off) or continuous (daily) basis. The incidence of endometrial hyperplasia as demonstrated by screening biopsies at 6 and 12 months of therapy was 4.5 per 100 woman-months in the cyclic group and 3.7 per 100 woman-months in the continuous group (a difference not statistically significant). Thus, in this study, cyclic therapy was found to offer no advantage over continuous therapy. In our opinion, the rate of hyperplasia development in both groups unacceptably high, and efforts must be directed at reducing its incidence primarily.

Vaginal Absorption of Estrone and 17β-Estradiol

In order to study estrogen absorption from the vagina, 0.5 mg of unconjugated estrone (E1) or 17beta-estradiol (E2) was administered vaginally to 10 postmenopausal patients. A 29-fold increase in plasma E2 and a 4-fold increase in plasma E1 concentrations were observed 1 hour following the vaginal deposition of 0.5 mg of E2. Maximal decreases of 25% and 37% in plasma levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), respectively, were observed at 5 hours following treatment. One hour after vaginal administration of 0.5 mg of E1, a 24-fold increase in plasma E1 and a 3.7-fold increase in E2 were observed. These increases were associated with a 30% decrease in plasma FSH and LH. These data indicate that the vaginal administration of E2 or E1 may be used to achieve physiologic blood levels of these estrogens. They further suggest that vaginal estrogens not be used in patients in whom systemic estrogen therapy is contraindicated.