Oral estrogen leads to falsely low concentrations of estradiol in a common immunoassay

Objectives: Recently, an estradiol immunoassay manufacturer (Beckman Coulter, USA) issued an “Important Product Notice” alerting clinical laboratories their assay (Access Sensitive Estradiol) was not indicated for patients undergoing exogenous estradiol treatment. The objective of this analysis was to evaluate immunoassay bias relative to liquid chromatography tandem mass spectrometry (LC-MS/MS) in transgender women and to examine the influence of unconjugated estrone on measurements. Design: Cross sectional secondary analysis. Methods: Estradiol concentrations from 89 transgender women were determined by three immunoassays (Access Sensitive Estradiol [‘New BC’] and Access Estradiol assays [‘Old BC’], Beckman Coulter; Estradiol III assay [‘Roche’], Roche Diagnostics) and LC-MS/MS. Bias was evaluated with and without adjustment for estrone concentrations. The number of participants who shifted between three estradiol concentration ranges for each immunoassay versus LC-MS/MS (>300 pg/mL, 70-300 pg/mL, and <70 pg/mL) was calculated. Results: The New BC assay had the largest magnitude overall bias (median: -34%) and was -40%, -22%, and -10%, among participants receiving tablet, patch, or injection preparations, respectively. Overall bias was -12% and +17% for the Roche and Old BC assays, respectively. When measured with the New BC assay, 18 participants shifted to a lower estradiol concentration range (versus 9 and 10 participants based on Roche or Old BC assays, respectively). Adjustment for estrone did not minimize bias. Conclusions: Immunoassay measurement of estradiol in transgender women may lead to falsely decreased concentrations that have the potential to affect management. A multi-disciplinary health care approach is needed to ensure appropriate analytical methods are available.

Blood supply to the uterus and ovaries in healthy women and patients with ovarian insufficiency

The aim of this study was to investigate the relation between ovarian blood flow, folliculogenesis and sex-steroid production during normal menstrual cycle and in women with ovarian failure. Ten healthy women and 40 patients with ovarian failure underwent hormonal assays (follicle-stimulating, luteinizing hormones, estradiol, progesterone, prolactine, testosterone) and ultrasound examination of the uterus and ovaries with color Doppler ultrasonography of the uterine and ovarian vessels on the 3 -5th, 11- 13th, 17- 19th and 21 -23rd days оf menstrual cycle. Intraovarian blood flow of the ovary carrying the predominant follicle in healthy women appeared more active than in conrdlateral ovary on the 3-5th days of the cycle. Inpatients with ovarian failure no difference was detected between the ovaries during the periods in question. Ovarian and uterine blood flow inpatients with the ovarian failure was less intensive comparingwith healthy women. Positive correlation between uterine blood flow and estradiol concentration in serum was revealed.

One-carbon metabolism during the menstrual cycle and pregnancy

Many enzymes in one-carbon metabolism (OCM) are up- or down-regulated by the sex hormones which vary diurnally and throughout the menstrual cycle. During pregnancy, estradiol and progesterone levels increase tremendously to modulate physiological changes in the reproductive system. In this work, we extend and improve an existing mathematical model of hepatic OCM to understand the dynamic metabolic changes that happen during the menstrual cycle and pregnancy due to estradiol variation. In particular, we add the polyamine drain on S-adenosyl methionine and the direct effects of estradiol on the enzymes cystathionine β-synthase (CBS), thymidylate synthase (TS), and dihydrofolate reductase (DHFR). We show that the homocysteine concentration varies inversely with estradiol concentration, discuss the fluctuations in 14 other one-carbon metabolites and velocities throughout the menstrual cycle, and draw comparisons with the literature. We then use the model to study the effects of vitamin B12, vitamin B6, and folate deficiencies and explain why homocysteine is not a good biomarker for vitamin deficiencies. Additionally, we compute homocysteine throughout pregnancy, and compare the results with experimental data. Our mathematical model explains how numerous homeostatic mechanisms in OCM function and provides new insights into how homocysteine and its deleterious effects are influenced by estradiol. The mathematical model can be used by others for further in silico experiments on changes in one-carbon metabolism during the menstrual cycle and pregnancy.

Fetal programming by sodium saccharin and damage on male offspring reproductive

Male infertility is responsible for 20-70% of infertility in couples. We investigated the effects of fetal programming with sodium saccharin consumption in testis structure and function and in male offspring fertility. Feed intake and efficiency, organ and fat weight, quantification and expression of AR and PCNA proteins, sperm count and hormonal dosages were performed. Changes in consumption were found in the final weeks of the experiment. Decreases in the expression and quantification of AR and PCNA, tubular diameter and luminal volume, and increase in epithelial and interstitial relative volumes were observed. Lower sperm count and transit and lower estradiol concentration were also found. The consumption of sodium saccharin by the dams programmed the male offspring affecting the HPG axis with alterations in Sertoli cell proliferation, AR expression and quantification, and sperm count. We hypothesize that these changes may be due to the reduction of estradiol that caused the loosening of the tight junctions of the blood-testis-barrier (BTB), causing cell losses during spermatogenesis, also reflecting, under the decrease in tubular diameter with an increase in epithelial volume and consequent decrease in luminal volume. Sodium saccharin programming directly affected the reproductive parameters of male offspring and adult fertility.

Phoenixin as a New Target in the Development of Strategies for Endometriosis Diagnosis and Treatment

Small integral membrane protein 20/phoenixin (SMIM20/PNX) and its receptor GPR173 (G Protein-Coupled Receptor 173) play a role in the regulation of the hypothalamic–pituitary–gonadal axis (HPG). The aim of the study was to determine PNX, FSH, LH, and 17β-estradiol association in women with endometriosis, and the expression of SMIM20/PNX signaling via GPR173. Serum PNX, FSH, LH, and 17β-estradiol concentrations were measured by enzyme and electrochemiluminescence immunoassay. SMIM20/PNX and GPR173 expression in the eutopic and ectopic endometrium was assessed by qPCR and immunohistochemistry. Reduced PNX level, increased LH/FSH ratio and elevated 17β-estradiol concentration were found in patients with endometriosis. No differences in SMIM20 expression were observed between the studied endometria. GPR173 expression was lower in ectopic than in eutopic endometria. SMIM20 expression was mainly restricted to stroma. GPR173 was detected in some eutopic and ectopic stromal cells and in eutopic glandular epithelial cells. Discriminant analysis indicates the diagnostic relevance of PNX and LH/FSH ratio in patients with endometriosis. In women with endometriosis, reduced PNX levels and GPR173 expression may be responsible for HPG axis dysregulation. These new insights may contribute to a better understanding of the pathophysiology of endometriosis and provide the basis for a new strategy for diagnosis and treatment of endometriosis.

PSXV-18 Dynamics of steroid hormones in young fine harness horses during the preparatory period of the race-course training

The aim of the study was to determine the dynamics of steroid hormones (pg /ml) in 2-year-old mares and stallions. During preparatory training, at rest, stallions and mares had similar testosterone levels (0,98±0,745-0,82±0,013), estradiol (21.18±5.05–22.50±3.01) and cortisol (90.17±2.11–83.26±2.48), respectively. In response to submaximal power, stallions and mares expend their reserves uneconomically, expressed in an increase of testosterone (9.54±0.353 – 19.59±1.85) and cortisol (203.07±8.70 -245.57±18.60). The estradiol in stallions fell 27% to 16,68±3,01, and in mares increased by 9% (24.50±0,89). At the end of the preparatory period, stallions showed increase in testosterone by 13 (to 13.47±2,21), cortisol 1.5 times (139,12 ±of 12.97), a fall in estradiol levels 5.3 times (to 4.00± 1,72). The content of testosterone in mares increased by 8.6 times (to 7.09±0.97), cortisol by 2.2 times (to 185.24±3.78), and estradiol fell by 6.8 times (to 3.30±0.84). The swing movement at the end of the preparatory period caused a significantly (P ≥ 0.999) less increase in testosterone in stallions (up to 2.63±0.42) and mares (9.39±3.09) in contrast to the previous period. The cortisol content in stallions increased by 88% (to 381.5±17.3), in mares by 384% (to 711.80±47.50). Estradiol concentration decreased 10-fold in stallions (to 1.40±0.576; P ≥ 0.999), and 3.5-fold (to 6.94±0.829; P ≥ 0.999) in mares. Conclusion: the training is sufficient for adaptation of stallions to the racetrack. For mares, the duration of the preparatory training is not sufficient.

Clinical variants and etiopathogenesis of cerebral circulation impairment in women of reproductive period

In women of reproductive period all variants of cerebral circulation impairment can be seen, but more often initial manifestations of cerebral circulation impairment and transient manifestations have place. It was found a direct relationship between estradiol concentration decrease, sexual glands functions disturbance and increase of lipid contents in blood and lipoprotein atherogenic fractions.

Relationships Between Reproductive Hormones And Maternal Pregnancy Physiology In Women Conceiving With Or Without In Vitro Fertilization

We evaluated maternal pregnancy adaptations and their relationships with circulating hormones in women who conceived with or without in-vitro fertilization (IVF). Pregnancies were grouped by corpus luteal (CL) number: 1- CL with physiological plasma relaxin concentration (PRLN; spontaneous pregnancies); 0-CL without circulating RLN (programmed cycles); >1-CL with elevated PRLN (ovarian stimulation). Major findings: declines in plasma osmolality (Posm) and sodium concentration (PNa+) were comparable in the 1- and 0-CL cohorts, correlated with plasma estradiol and progesterone concentrations, but not PRLN; gestational declines in plasma uric acid concentration (PUA) were attenuated after IVF especially programmed cycles, partly due to subdued increases of renal UA clearance; PRLN and cardiac output (CO) were inversely correlated when plasma estradiol concentration was below ~2.5ng/ml, but positively correlated above ~2.5ng/ml. Unexpectedly, PRLN and plasma sFLT1 (PsFLT1) were directly correlated. Though PsFLT1 and CO were not significantly associated, CO was positively correlated with plasma PLGF concentration after the first trimester, particularly in women who conceived with 0-CL. Major conclusions: (1) circulating RLN was unnecessary for gestational falls in Posm and PNa+; (2) PRLN and CO were inversely correlated during early gestation suggesting PRLN in the lower range may have contributed to systemic vasodilation, while at higher PRLN, relaxin influence became self-limiting; (3) evidence for cooperativity between RLN and estradiol on gestational changes in CO was observed; (4) after the first trimester in women who conceived without a CL, plasma PLGF concentration was associated with recovery of CO, which was impaired during the first trimester in this cohort.

The Potential Uses of Curcumin and PMSG Hormones to Increase Egg Production of Muscovy Ducks through Increasing Estradiol Concentrations and Shortening Laying Rest Period

The aim of this research was to study the effects of curcumin administration, injection of PMSG hormone, and the combination of curcumin supplementation and PMSG injection on the physiological parameters and performance of female Muscovy ducks. The objects of this research were 40 young female Muscovy ducks, aged 24 weeks, subjected to treatments: control (P1), curcumin supplementation at a dose of 24 mg/100 g feed (P2), intramuscular injection of PMSG hormone at a dose of 0.015 mL/hen (P3), and the combination of curcumin and PMSG (P4). The results showed that the treatment gave nonsignificant improvements in Muscovy duck performances, including feed consumption, egg production, and the day of laying period and molting period. Treatment gave a significant increase in serum estradiol concentration at molting period after treatment. This study concluded that the treatment provides no significant improvement in the performance of female Muscovy ducks because the genetic diversity of Indonesian ducks remains high.