Steroid hormone levels in pregnancy and 1 year postpartum using isotope dilution tandem mass spectrometry

Abstract

Objective-To establish normal, trimester-specific reference intervals for serum 17β-estradiol, progesterone (P), 17α-hydroxyprogesterone, cortisol, 11-deoxycortisol, androstenedione, DHEA, and DHEAS, measured simultaneously using isotope dilution tandem mass spectrometry. Design-Sequential cohort study.Patient(s)-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.Main Outcome Measure(s)-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.Result(s)-Serum estradiol, P, 17α-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. Normal pregnancy depends on pronounced adaptations in pregnancy-related hormone concentrations, characterized by elevated levels of several circulating steroid hormones, which normally increase with the progression of pregnancy (1-6). Endogenous steroid hormone exposure during pregnancy has been of interest in studies of duration of gestation, fetal size, twin pregnancies, control of labor, nausea and vomiting in pregnancy, pregnancyinduced hypertension, and other disease states (5-9). The studies have generally produced weak and inconsistent findings because the hormone levels were either not available or lacked specificity or because surrogate measures of exposure to altered steroid hormone levels were often used to estimate these hormones. Conclusion(s)- NIH Public AccessSteroid hormones are derived from cholesterol. Binding proteins facilitate their transport and increase their half-life but limit their entry into target cells, thereby regulating their biological activity. Binding proteins make precise determination of serum steroid hormone concentrations difficult by interfering with different steroid hormones immunoassays (IAs). Furthermore, the lack of specificity of IAs due to cross reactivity with structurally related molecules is a well-known phenomenon (10-12).In contrast, isotope dilution liquid chromatography-tandem mass spectrometry (LC/MS/MS) is a specific detection method that allows the quantification of the analyte of interest. It also allows for a simpler approach to sample preparation without employing lengthy and timeconsuming extraction and sample derivatization steps. This has been reported in a previous publication, and steroid hormone analysis using isotope dilution LC/MS/MS was compared with the analysis of the same samples using IA techniques (14). Generally, tandem mass spectrometry provides lower values than IA, no doubt because of improved specificity.The reasons for the improved specificity in our tandem mass sp...

Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ Tregs in human second trimester pregnancy is induced by progesterone and 17β-estradiol

“…It should be noted that reliable information about local progesterone and 17β-estradiol concentrations is scarce. Importantly, hormone concentrations corresponding to serum levels (33,34) caused slight but statistically not consistently significant changes that followed the very pronounced effects seen at higher concentrations. Expression of estrogen and progesterone receptors have been identified in various immune cells (35,36) but to our knowledge, only receptors for estrogen have been confirmed on Tregs (24).…”

“…Recently, Tregs and levels of 17β-estradiol, but not progesterone, were shown to correlate during the menstrual cycle (41). However, as both 17β-estradiol and progesterone increase dramatically during pregnancy (33) and the effects of 17β-estradiol seem to be concentration-dependent (42), the influence of these hormones might well be different during pregnancy. Our study suggests that even though both progesterone and 17β-estradiol have important and well documented immune modulating effects on pregnancy (43,44) , these do not seem to be mediated via the promotion of Tregs.…”

IMMULITE® 2000 age and sex-specific reference intervals for alpha fetoprotein, homocysteine, insulin, insulin-like growth factor-1, insulin-like growth factor binding protein-3, C-peptide, immunoglobulin E and intact parathyroid hormone

“…Pediatric reference intervals for many analytes can vary significantly by both sex and age from those found in adults, and are of great importance in differentiating between the "healthy" and the "diseased" populations [1][2][3][4][5][6][7]. Reference intervals for alpha fetoprotein (AFP), homocysteine (HCS), insulin, insulin-like growth factor-1(IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), C-peptide, immunoglobulin E (IgE) and intact parathyroid hormone (i-PTH) are currently unavailable on the IMMULITE 2000® analyzer (Siemens, Los Angeles, CA).…”

Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: A nested case–referent study

“…41 In general, the steroid hormone levels reported here remained within the clinically normal range of early pregnancy and were consistent with previous studies, which have evaluated serum levels of steroid hormones during the first trimester of pregnancy. 42,43 Indeed, steroid hormones are fairly robust, as shown by our validation study on the effect of long-term storage on serum steroid hormone levels. 43 The measured hormone levels did not exceed the interassay variations observed in the laboratory and determined by the enzyme-immunological tests.…”

“…However, trimester-specific reference intervals for several hormones are difficult to establish due to lack of specificity in enzyme immunoassay techniques. 42 For instance, the kit insert suggests that huge estradiol and estrone mid-cycle ranges between 416 and 1,399 pmol/L and between 62 and 715 pg/mL, with outliers included.…”