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      Second trimester maternal serum progesterone and estradiol concentrations with live and demised fetuses: Secondary analysis results from a randomized controlled trial

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          Abstract

          Objective

          To provide data on maternal levels of estradiol and progesterone in the second trimester of pregnancy with a live foetus and those complicated by a spontaneous foetal demise.

          Methods

          Within a randomised trial to assess efficacy of mifepristone in termination following foetal demise from 14 to 28 weeks of gestation, we measured progesterone and estradiol levels in trial patients and in women undergoing termination with a live foetus. Women admitted to King Edward Memorial Hospital (Western Australia) from 2013 to 2016 were considered for eligibility and enroled. Scatter plots with 95% confidence intervals were generated for hormone levels by gestation. Generalised linear models were used to estimate mean values of estradiol and progesterone, accounting for maternal age, gestation and parity.

          Results

          Overall, women with a foetal demise had lower estradiol levels compared to women with a live foetus, (mean difference of 10 460 pmol/L). With a live foetus, higher levels of estradiol were observed with increasing gestations: with a mean of 17 010 pmol/L at 14 ≤ 17 weeks, 31 180 pmol/L at 23–28 weeks and similarly progesterone with a mean of 113 nmol/L at 14 ≤ 17 weeks and 183 nmol/L at 23–28 weeks. Progesterone levels in women with foetal demise were 37 nmol/L higher than women in the live foetus group. In all women, each unit increase in parity was associated with a decrease of 10nmol/l of progesterone (95% confidence interval: 4–16, p = 0.001).

          Conclusions

          Estradiol and progesterone levels in the second trimester vary between pregnant women with a live and demised foetus.

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          Most cited references11

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          Hormone concentrations throughout uncomplicated pregnancies: a longitudinal study

          Background Evidence suggests that the hormonal milieu of pregnancy is an important determinant of subsequent cancer and other chronic diseases in both the mother and the offspring. Many of the existing maternity and birth cohorts include specimens drawn only once during pregnancy. How well a single blood specimen collected during a pregnancy characterizes exposure to these hormones throughout gestation, and also in subsequent pregnancies, is not well understood. Methods We used serial serum samples from 71 pregnant women (25 primiparous, 25 multiparous, and 21 with two consecutive pregnancies) with natural, complication-free pregnancies and a healthy offspring at term who participated in a population-based screening trial for congenital infections in Finland between January 1st, 1988 and June 30, 1989 and provided a blood sample in each trimester. Results Hormone levels were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimester (e.g., estradiol, rT1 vs. T2 = 0.51 and rT2 vs. T3 = 0.60, p < 0.01; rT1 vs. T3 = 0.32, p < 0.05). Concentrations of sRANKL remained stable throughout gestation, whereas estradiol, estrone, progesterone, testosterone, prolactin, and osteoprotegerin increased throughout pregnancy. First trimester hormone concentrations explained less of the variation in the third trimester on their own than second trimester hormone levels (e.g. estradiol R2 T1  = 16 % and R2 T2 = 42 %). Addition of maternal (e.g., smoking) and/or child characteristics (e.g., sex) improved the accuracy of the 3rd trimester estimates for some of the hormones. Conclusions One hormone measurement in early pregnancy, in conjunction with maternal and fetal characteristics, permits estimation of 3rd trimester hormone concentrations. Therefore, single hormone measurements available from maternity cohorts are suitable to quantify hormone exposure during pregnancy. To our knowledge, we provide the first data on correlations between hormone concentrations both across trimesters of a single pregnancy, as well as between two subsequent pregnancies. Electronic supplementary material The online version of this article (doi:10.1186/s12884-016-0937-5) contains supplementary material, which is available to authorized users.
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            Longitudinal assessment of changes in reproductive hormones during normal pregnancy.

            The concentrations of hormones measured in serum from maternal blood change dramatically during pregnancy. While the relative contributions of sex steroids shift from maternal ovaries and adrenals to the fetoplacental unit, other maternal tissues such as pituitary and liver respond to increasing concentrations of estrogen and secrete increasing amounts of prolactin and sex-hormone-binding globulin. To determine longitudinal changes in circulating maternal hormones, we collected blood from 60 women on three occasions during their pregnancies. We observed a 1.7-fold increase in testosterone concentration in serum; concentrations of sex-hormone-binding globulin in serum rose 5.6-fold. The major increase (6.8-fold) in estradiol in serum occurred within the first 16 weeks, followed by a further 4.8-fold increase by term. Mean concentrations of progesterone, 17-hydroxyprogesterone, and androstenedione in serum increased 11.9-, 3-, and 1.3-fold, respectively, whereas concentrations of dehydroepiandrosterone sulfate (DHEAS) fell by 50%. Mean serum prolactin concentrations increased 3.8-fold during the first trimester and by a similar amount during the final 24 weeks of pregnancy. We used these data, obtained from a cohort of women with uncomplicated pregnancies, to construct reference intervals for hormones in maternal serum.
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              Steroid hormone levels in pregnancy and 1 year postpartum using isotope dilution tandem mass spectrometry.

              To establish normal, trimester-specific reference intervals for serum 17beta-estradiol, progesterone (P), 17alpha-hydroxyprogesterone, cortisol, 11-deoxycortisol, androstenedione, DHEA, and DHEAS, measured simultaneously using isotope dilution tandem mass spectrometry. Sequential cohort study. Healthy women undergoing a normal pregnancy (age, 25-38 years; mean, 30 years) attending a prenatal well clinic at gestation weeks 12, 22, and 32 and approximately 1 year postpartum. Trimester-specific reference intervals of endogenous steroid hormones analyzed using an isotope dilution tandem mass spectrometer equipped with an atmospheric pressure photoionization source with deuterium-labeled internal standards. Serum estradiol, P, 17alpha-hydroxyprogesterone, and 11-deoxycortisol increased throughout pregnancy; cortisol increased up to the second trimester and then remained steady, while androstenedione increased by 80 percent by gestation week 12, then remained constant. Serum DHEA-S decreased by 50% by the third trimester. Trimester-specific reference intervals are reported for eight serum steroids. The ratios of individual serum hormone concentrations during pregnancy relative to their 1-year postpartum concentrations illustrate the expected normal trends of changes in hormone concentrations during pregnancy.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Reproductive, Female and Child Health
                Repro Female Child Health
                Wiley
                2768-7228
                2768-7228
                March 2024
                March 03 2024
                March 2024
                : 3
                : 1
                Affiliations
                [1 ] The Division of Obstetrics and Gynaecology The University of Western Australia Perth Western Australia Australia
                [2 ] King Edward Memorial Hospital Perth Western Australia Australia
                [3 ] School of Public Health University of Queensland Brisbane Queensland Australia
                [4 ] Office of the Chief Nurse and Midwife, Department of Health Northern Territory Government Perth Western Australia Australia
                Article
                10.1002/rfc2.77
                1ea6e18a-5c3e-46d6-86ca-6ef37f62be9c
                © 2024

                http://creativecommons.org/licenses/by/4.0/

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