Tulchinsky, D., Hobel, C. J., Yeager, E., & Marshall, J. R. (1972). Plasma estrone, estradiol, estriol, progesterone, and 17-hydroxyprogesterone in human pregnancy. I. Normal pregnancy. American journal of obstetrics and gynecology, 112(8), 1095-1100. https://doi.org/10.1016/0002-9378(72)90185-8
Tulchinsky D, Hobel CJ, Yeager E, Marshall JR. Plasma estrone, estradiol, estriol, progesterone, and 17-hydroxyprogesterone in human pregnancy. I. Normal pregnancy. Am J Obstet Gynecol. 1972;112(8):1095-1100. doi:10.1016/0002-9378(72)90185-8
Tulchinsky, D., et al. "Plasma estrone, estradiol, estriol, progesterone, and 17-hydroxyprogesterone in human pregnancy. I. Normal pregnancy." American journal of obstetrics and gynecology, vol. 112, no. 8, 1972, pp. 1095-1100.
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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.
Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism and chronic anovulation. Although the etiology of PCOS is unknown, perturbations of gonadotropin secretion are one of the hallmarks of this disorder. In normal menstrual physiology, the monotropic rise of plasma follicle-stimulating hormone (FSH) during the luteal-follicular transition is critical for follicular development and subsequent ovulation. One of the mechanisms by which FSH is differentially synthesized involves the luteal slowing of gonadotropin-releasing hormone (GnRH) pulse frequency by ovarian steroids. In PCOS, plasma leutinizing hormone (LH) is commonly increased, FSH is typically in the lower follicular range, and LH (and by inference GnRH) pulse frequency is persistently rapid at approximately one LH pulse per hour. The etiology of the neuroendocrine abnormalities in PCOS remain unclear; however, recent studies have revealed decreased sensitivity of the GnRH pulse generator to inhibition by ovarian steroids, particularly progesterone. This abnormality is reversed by the androgen receptor antagonist flutamide, suggesting that elevated androgen levels may alter the sensitivity of the hypothalamic GnRH pulse generator to steroid inhibition and lead to enhanced LH secretion. As such, women with PCOS require higher levels of progesterone to slow the frequency of GnRH pulse secretion, resulting in inadequate FSH synthesis and persistent LH stimulation of ovarian androgens. The decreased sensitivity of the GnRH pulse generator may help to explain the genesis of PCOS during puberty. In normal early puberty, sleep-entrained increases in LH stimulate ovarian steroids, which subsequently suppress LH frequency and amplitude during the subsequent day. In hyperandrogenemic girls destined to develop PCOS, this nocturnal increase in ovarian steroids may not be adequate to suppress the GnRH pulse generator, leading to a persistently rapid LH pulse frequency, impaired FSH production, and inadequate follicular development.
The primary objective of this prospective study was to test whether preterm birth prevention education plus increased clinic visits and selected prophylactic interventions reduce preterm birth. Eight West Los Angeles prenatal county clinics, comparable with respect to selected demographics, were randomized to be either experimental or control clinics. High-risk patients in all clinics were identified with a risk scoring system derived from a similar population. High-risk patients (N = 1774) in experimental clinics were offered a program of education and more frequent visits and were randomized to receive various secondary intervention protocols in addition to the basic interventions of education and more frequent visits. Control clinic patients (N = 880) received standard county care. Preterm birth rates were 19% lower among the experimental high-risk patients (7.4% vs 9.1%), and differences were significant (p < 0.05) when preterm risk was taken into account. There was no evidence to suggest that the secondary interventions provided added benefit over the primary intervention protocol of preterm birth prevention education and increased visits. The 19% reduction in preterm birth rate observed in the experimental clinics suggest an overall program benefit from a protocol that offered education, more frequent visits, and greater attention given to patients while the selected interventions were applied.
The premenstrual syndrome (PMS) has been proposed to result from excessive exposure to and/or withdrawal of brain opioid activity during the luteal phase. Because hypothalamic opioids are believed to modulate GnRH secretion, in part under the influence of ovarian steroids, we performed longitudinal studies of gonadotropin and ovarian steroid secretion across ovulatory, symptomatic cycles of 17 PMS patients and 8 normal volunteers. Pulsatile LH secretion was measured every 10 min for 8 hr at times when central opioid activity was expected to be low (early follicular phase), high (mid-luteal phase; ML), and declining (late luteal phase). In both subject groups, a cycle-phase effect was observed for LH pulse frequency (p = < 0.001) and amplitude (p = 0.002), and for the transverse mean concentrations of LH (p = 0.05), FSH (p < = 0.001), estradiol (E2) (p = < 0.001) and progesterone (P) (p = < 0.001). ML P secretion in PMS patients was pulsatile, and mean concentrations (over 30-60 min) were similar to those of normal controls. The changes in pulsatile LH secretion across the cycle were not different in the PMS patients compared to the normal women, though mean FSH in the ML phase was higher in the PMS group (p = < 0.05). The similar changes in luteal LH pulse frequency fail to provide evidence that GnRH secretion is impaired, thus challenging the view that the neuroregulation of the menstrual cycle in women with PMS is markedly altered.
Reproductive function in humans changes markedly during life and is usually divided into four stages. During the initial stage, which begins early in fetal life and ends in infancy, gonadotropins and gonadal steroids are secreted at levels similar to those seen in early and mid-adolescence. In the second stage, which lasts from infancy through the first decade of life, reproductive function first regresses and then becomes quiescent. Puberty, the third stage, is heralded by a nocturnal increase in the secretion of gonadotropins and sex steroids. This nocturnal predominance gradually diminishes and disappears during the fourth stage — adulthood. In men, . . .
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.
Lindberg BS et al., 1974·Acta Obstet Gynecol Scand
Plasma progesterone levels were estimated by competitive protein binding in 815 samples from healthy pregnant women with uncomplicated pregnancies. This series includes 32 patients who were followed serially throughout pregnancy. The mean level increased from 47 ng/ml in week 22 to 148 ng/ml in week 41. The spread was large. Individual patients showed very large variations between two consecutive weeks.
Diurnal variations were examined in 7 patients and short-time variations during one hour in 5 patients. Large but non-systematic variations were found in most cases. The maximal difference between values observed over a 24-hour-period was 123 ng/ml and during one hour 150 ng/ml.
Plasma progesterone levels were studied in 87 cases of toxemia of pregnancy, 6 cases of hypertension, 54 cases of Rh-immunization, 37 cases of diabetes and 5 cases of fetal growth retardation of unknown origin. The results indicate that no constant changes occur in plasma progesterone levels in these groups or in cases of impending fetal death.
As the normal limits are very wide, the intraindividual variations large, and the progesterone values in high risk pregnancies are inconclusive, plasma progesterone estimates during the latter part of pregnancy seem to be of limited value.
During human pregnancy large amounts of progesterone are produced by the placenta (1, 14). The production rate during the third trimester lies between 200 and 300 mg/day (9). Part of the progesterone produced is metabolized to pregnanediol and excreted in the urine as the 3-glucuronidate (16). The percentage of conversion to pregnanediol seems to vary with the stage of gestation and is influenced by pathological alterations in risk pregnancies (2, 5).
Large day to day variations in the urinary pregnanediol levels have been found. It is thus hardly surprising that the clinical value of serial determinations of urinary pregnanediol in late pregnancy has been limited.
Recently useful methods for the assay of progesterone in plasma have been developed and applied to physiological and clinical studies. A number of reports dealing with the prognostic value of progesterone determinations in complicated pregnancies have been published (8, 12, 17). The number of cases investigated is, however, small and the results are, in many respects, inconclusive. The aim of the present investigation was to determine the normal limits during the latter half of uncomplicated pregnancies, circadian and short-time variations, and to evaluate the prognostic value of progesterone determinations in plasma in high risk pregnancies.
17 beta-Estradiol (E2) and progesterone (P) concentrations in blood and in the myometrium of human pregnancy at term (n=33) and in a few samples (n=5) around midterm of pregnancy were determined. E2 concentration in the myometrium (per g wet wt) at midterm was lower than the concentration in the plasma (per ml) so that the myometrium to plasma (My:Pl) ratio was 0.7. Relative to plasma concentration, the myometrial E2 increased little from midterm to term so that My:Pl was only 0.2 at term. Although P concentration in the myometrium was much greater than that in the plasma at midterm, My:Pl ratio being 2.2, it was lower than that in plasma at term so that My:Pl ratio was only 0.6. A fairly good correlation between plasma steroids and the myometrial steroids was observed at midterm but was distorted at term, probably due to saturation of the tissue-binding capacity. Steroid concentrations determined on the basis of protein showed a good correlation to the values expressed on the basis of wet weight. Whereas myometrial E2 concentration was significantly influenced by the distance from placenta, P concentration was not.
Plasma levels of progesterone* were measured during normal human pregnancy by a sensitive and rapid competitive protein binding technique. During the first half of gestation 440 determinations in 321 women and in the second half of gestation, 209 determinations in 160 women were performed.
The average plasma level of progesterone in the 5th week of gestation was 24.8 ± 7.3 (s) ng/ml which is above the normal range of the luteal plateau of the menstrual cycle (10–20 ng/ml). Between the 5th and the 9th week of gestation the plasma concentration decreased significantly. From the 9th to the 32nd week of gestation the plasma level of progesterone increased from 16.7 ± 7.4 (s) to 125.2 ± 37.9 (s) ng/ml. During the last 8 weeks of gestation the plasma levels of progesterone did not show any significant rise. One woman was followed up from the day of ovulation to the 8th week of gestation. An increase in progesterone levels was observed about 10 days after ovulation. Morning samples of progesterone, which were taken before the 20th week of gestation, when the woman was still in bed, were found to be somewhat higher than levels found during the remainder of the day.
Progesterone concentrations in a few abnormal pregnancies are also reported.
PMID 5025870 5025870 DOI 10.1016/0002-9378(72)90185-8 10.1016/0002-9378(72)90185-8 Tulchinsky et al. 1972, Tulchinsky 1972
Cite this article
Tulchinsky, D., Hobel, C. J., Yeager, E., & Marshall, J. R. (1972). Plasma estrone, estradiol, estriol, progesterone, and 17-hydroxyprogesterone in human pregnancy. I. Normal pregnancy. American journal of obstetrics and gynecology, 112(8), 1095-1100. https://doi.org/10.1016/0002-9378(72)90185-8
Tulchinsky D, Hobel CJ, Yeager E, Marshall JR. Plasma estrone, estradiol, estriol, progesterone, and 17-hydroxyprogesterone in human pregnancy. I. Normal pregnancy. Am J Obstet Gynecol. 1972;112(8):1095-1100. doi:10.1016/0002-9378(72)90185-8
Tulchinsky, D., et al. "Plasma estrone, estradiol, estriol, progesterone, and 17-hydroxyprogesterone in human pregnancy. I. Normal pregnancy." American journal of obstetrics and gynecology, vol. 112, no. 8, 1972, pp. 1095-1100.
