Serum Estradiol Concentrations Research Articles

SAT413 Feminising Gender Affirming Hormone Therapy Prolongs QTc Interval

Abstract Disclosure: L. Angus: Speaker; Self; Kirin Brewery. T. Lin: None. S. Leemaqz: None. M. Grossmann: None. J.D. Zajac: None. A.S. Cheung: None. Background: In trans people using feminising hormone therapy there is an increased risk of cardiovascular events including conduction disorders. It is known that the QTc interval is longer in cisgender women of reproductive age than cisgender men, attributed to factors including serum sex steroid concentrations. Androgen deprivation therapy in men with prostate cancer is associated with prolongation of the QTc interval, but the effects of feminising hormone therapy in trans women are unclear. Methods: We measured the automated QTc interval from a 12-lead electrocardiogram at baseline and 6 months in trans women newly commencing feminising hormone therapy. Sex steroid concentrations were measured by LCMS. Participants were part of a randomised controlled double-blind trial of spironolactone 100mg daily versus cyproterone acetate 12.5mg daily in transgender women commencing estradiol for feminisation (ANZCTR 12620000339954) and this was a prespecified secondary outcome. Statistical analysis was performed using a linear mixed effects model looking at the effects of treatment over time. Results: Sixty-three participants were randomised and 55 participants completed the trial and were included in analysis (spironolactone group n=27, cyproterone acetate group n=28). Baseline group characteristics were comparable. Overall, the QTc interval increased by 18ms (95% CI 14 - 23 ms; p<0.001) at 6 months compared to baseline, but there was no between group difference (p=0.23). One participant had a QTc interval above 450ms. The mean serum total testosterone concentrations were similar between groups at baseline (spironolactone group 16.9 (13.5 - 20.3) nmol/L vs cyproterone acetate group 18.0 (15.0 - 21.0) nmol/L, p=0.60) but higher in the spironolactone group 4.3 (2.0 - 6.5) nmol/L than the cyproterone acetate group 1.5 (0.0 - 2.9) nmol/L, p<0.05 at 6 months. The mean serum estradiol and serum potassium concentrations were similar between groups at baseline and 6 months. Conclusions: Feminising hormone therapy with estradiol and either spironolactone or cyproterone acetate in trans women is associated with prolongation of the QTc interval over a six-month period. Further research is required to investigate the incidence of cardiac arrhythmia in this population. Presentation: Saturday, June 17, 2023

The Association of Reproductive Hormones During the Menstrual Period with Primary Dysmenorrhea.

This study aimed to investigate the association of reproductive hormones with primary dysmenorrhea in Chinese women. A case-control study was conducted and patients with primary dysmenorrhea and non-dysmenorrhea participants were recruited. Oxytocin, PGF2α, vasopressin, estriol and estradiol were respectively measured in plasma collected three to five days after menstruation. Restricted cubic spline and multiple logistic regression models were adopted to analyze the association between hormones and primary dysmenorrhea. There were 604 participants enrolled in our study including 300 patients with primary dysmenorrhea. After adjustment for the potential confounders, oxytocin levels (Q3: OR (95% CI) = 0.50 (0.27~0.95) (p=0.035); Q4: 0.34 (0.17~0.66) (p=0.001)) and PGF2α levels (Q3: 0.45 (0.24~0.87) (p=0.017); Q4: 0.43 (0.22~0.84) (p=0.013)) were respectively associated with an decreased risk of primary dysmenorrhea, but estradiol (Q2: 2.18 (1.13~4.19) (p=0.020); Q3: 2.17 (1.12~4.19) (p=0.022)) and vasopressin (Q3: 2.88 (1.48~5.63) (p=0.002); Q4: 3.20 (1.65~6.22) (p<0.001)) with an increased risk of primary dysmenorrhea, respectively. Among patients with primary dysmenorrhea, the higher estriol level was associated with higher frequent dysmenorrhea (Q2: 3.12 (1.32~7.34) (p=0.009); Q3: 4.97 (2.08~11.85) (p<0.001)) and always dysmenorrhea (Q2: 2.51 (1.03~6.11) (p=0.041); Q3: 3.10 (1.25~7.73) (p=0.015)). Similarly, high estriol levels were associated with the higher degree of pain significantly only when hormone levels were at a high level (Q3: 2.06 (1.03~4.18) (p=0.043)). Higher serum vasopressin and estradiol concentrations as well as lower oxytocin and PGF2α levels were associated with higher risk of primary dysmenorrhea. Estrogen showed a reverse U-shape association on the frequency and degree of pain among patients with primary dysmenorrhea.

Hormone imbalance of fetoplacental complex as a factor of premature birth

Despite the sufficient study of the pathogenetic factors of preterm birth, there is currently no consensus on the peculiarities of the pathogenesis of disorders of the functional state of the fetoplacental complex in this complication of pregnancy, no unified methodological approaches to early diagnosis have been developed, and there are no standards for the examination and treatment of pregnant women with detected disorders.The purpose of the work. To investigate the level of FPC hormones in pregnant women at risk of preterm birth.Materials and methods. The main group consisted of pregnant women with signs of placental dysfunction and a history of miscarriage (50 women). The control group consisted of 50 healthy pregnant women. Determination of hormones (progesterone, estradiol, placental lactogen) was carried out by the method of solid-phase enzyme immunoassay. The research was performed on an enzyme-linked immunosorbent assay according to the instructions for the specified sets of reagents.Results. The content of the hormones estradiol, progesterone and placental lactogen during pregnancy was determined to study the changes in the placental system hormonal function of pregnant women with a threat of premature birth. The concentration of estradiol in the blood serum of pregnant women of the main group was below the norm during the entire pregnancy period. It leads to a decrease in estrogens and progesterone synthesis by the corpus luteum of the ovary, and then by the placenta. A reduction of these hormone levels, which take a direct part in the flow of basic biochemical and physiological processes in the muscles of the uterus, leads to an increase in the contractile activity of the myometrium, which is shown by the phenomena of placental dysfunction and premature birth.Conclusion. Studying the levels of hormones of the fetoplacental complex in pregnant women at risk will allow predicting the development of premature birth.

Effects of Chaihu Shugan San on Brain Functional Network Connectivity in the Hippocampus of a Perimenopausal Depression Rat Model.

In this study, we used Chaihu Shugan San (CSS), a traditional Chinese herbal formula, as a probe to investigate the involvement of brain functional network connectivity and hippocampus energy metabolism in perimenopausal depression. A network pharmacology approach was performed to discover the underlying mechanisms of CSS in improving perimenopausal depression, which were verified in perimenopausal depression rat models. Network pharmacology analysis indicated that complex mechanisms of energy metabolism, neurotransmitter metabolism, inflammation, and hormone metabolic processes were closely associated with the anti-depressive effects of CSS. Thus, the serum concentrations of estradiol (E2), glutamate (Glu), and 5-hydroxytryptamine (5-HT) were detected by ELISA. The brain functional network connectivity between the hippocampus and adjacent brain regions was evaluated using resting-state functional magnetic resonance imaging (fMRI). A targeted metabolomic analysis of the hippocampal tricarboxylic acid cycle was also performed to measure the changes in hippocampal energy metabolism using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CSS treatment significantly improved the behavioral performance, decreased the serum Glu levels, and increased the serum 5-HT levels of PMS + CUMS rats. The brain functional connectivity between the hippocampus and other brain regions was significantly changed by PMS + CUMS processes but improved by CSS treatment. Moreover, among the metabolites in the hippocampal tricarboxylic acid cycle, the concentrations of citrate and the upregulation of isocitrate and downregulation of guanosine triphosphate(GTP) in PMS + CUMS rats could be significantly improved by CSS treatment. A brain functional network connectivity mechanism may be involved in perimenopausal depression, wherein the hippocampal tricarboxylic acid cycle plays a vital role.

Oestradiol concentrations in trans women with HIV suppressed on unboosted integrase inhibitor regimens versus trans women without HIV taking oral oestradiol: a pilot study.

Feminizing hormone therapy (FHT) is essential to many trans women. Concern about negative drug interactions between FHT and ART can be an ART adherence barrier among trans women with HIV. In this single-centre, parallel group, cross-sectional pilot study, we measured serum oestradiol concentrations in trans women with HIV taking FHT and unboosted integrase strand transfer inhibitor (INSTI)-based ART versus trans women without HIV taking FHT. We included trans women with and without HIV, aged ≥18 years, taking ≥2 mg/day of oral oestradiol for at least 3 months plus an anti-androgen. Trans women with HIV were on suppressive ART ≥3 months. Serum oestradiol concentrations were measured prior to medication dosing and 2, 4, 6 and 8 h post-dose. Median oestradiol concentrations were compared between groups using Wilcoxon rank-sum tests. Participants (n = 8 with HIV, n = 7 without) had a median age of 32 (IQR: 28, 39) years. Among participants, the median oral oestradiol dose was 4 mg (range 2-6 mg). Participants had been taking FHT for a median of 4 years (IQR: 2, 8). Six trans women with HIV were taking bictegravir/emtricitabine/tenofovir alafenamide and two were taking dolutegravir/abacavir/lamivudine. All oestradiol concentrations were not significantly different between groups. Eleven (73%) participants had target oestradiol concentrations in the range 200-735 pmol/L at C4h (75% among women with HIV, 71% among those without HIV). Oestradiol concentrations were not statistically different in trans women with HIV compared with those without HIV, suggesting a low probability of clinically relevant drug-drug interactions between FHT and unboosted INSTI-based ART.

Subsets of preoperative sex hormones in testicular germ cell cancer: a retrospective multicenter study

Preoperative homeostasis of sex hormones in testicular germ cell tumor (TGCT) patients is scarcely characterized. We aimed to explore regulation of sex hormones and their implications for histopathological parameters and prognosis in TGCT using a data-driven explorative approach. Pre-surgery serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) and prolactin were measured in a retrospective multicenter TGCT cohort (n = 518). Clusters of patients were defined by latent class analysis. Clinical, pathologic and survival parameters were compared between the clusters by statistical hypothesis testing, Random Forest modeling and Peto-Peto test. Cancer tissue expression of sex hormone-related genes was explored in the publicly available TCGA cohort (n = 149). We included 354 patients with pure seminoma and 164 patients with non-seminomatous germ cell tumors (NSGCT), with a median age of 36 years. Three hormonal clusters were defined: ‘neutral’ (n = 228) with normal sex hormone homeostasis, ‘testicle’ (n = 91) with elevated T and E2, low pituitary hormones, and finally ‘pituitary’ subset (n = 103) with increased FSH and LH paralleled by low-to-normal levels of the gonadal hormones. Relapse-free survival in the hormonal subsets was comparable (p = 0.64). Cancer tissue expression of luteinizing hormone- and follicle-stimulating hormone-coding genes was significantly higher in seminomas, while genes of T and E2 biosynthesis enzymes were strongly upregulated in NSGCT. Substantial percentages of TGCT patients are at increased risk of sex hormone dysfunction at primary diagnosis before orchiectomy. TGCT may directly influence systemic hormonal homeostasis by in-situ synthesis of sex hormones.

Resting energy metabolism and sweet taste preference during the menstrual cycle in healthy women.

Differences in blood concentration of sex hormones in the follicular (FP) and luteal (LP) phases may influence energy metabolism in women. We compared fasting energy metabolism and sweet taste preference on a representative day of the FP and LP in twenty healthy women (25·3 (sd 5·1) years, BMI: 22·2 (sd 2·2) kg/m2) with regular self-reported menses and without the use of hormonal contraceptives. From the self-reported duration of the three prior menstrual cycles, the predicted FP and LP visits were scheduled for days 5-12 and 20-25 after menses, respectively. The order of the FP and LP visits was randomly assigned. On each visit, RMR and RQ by indirect calorimetry, sweet taste preference by the Monell two-series forced-choice tracking procedure, serum fibroblast growth factor 21 by a commercial ELISA (FGF21, a liver-derived protein with action in energy balance, fuel oxidation and sugar preference) and dietary food intake by a 24-h dietary recall were determined. Serum progesterone and oestradiol concentrations displayed the expected differences between phases. RMR was lower in the FP v. LP (5042 (sd 460) v. 5197 (sd 490) kJ/d, respectively; P = 0·04; Cohen effect size, d rm = 0·33), while RQ showed borderline significant higher values (0·84 (sd 0·05) v. 0·81 (sd 0·05), respectively; P = 0·07; d rm = 0·62). Also, in the FP v. LP, sweet taste preference was lower (12 (sd 8) v. 16 (sd 9) %; P = 0·04; d rm = 0·47) concomitant with higher serum FGF21 concentration (294 (sd 164) v. 197 (sd 104) pg/ml; P < 0·01; d rm = 0·66). The menstrual cycle is associated with changes in energy expenditure, sweet taste preference and oxidative fuel partitioning.

Interaction of lncRNA Gm2044 and EEF2 promotes estradiol synthesis in ovarian follicular granulosa cells

The functions and molecular mechanisms of long noncoding RNA (lncRNA) in reproduction have been widely studied at present. However, lncRNA regulating hormone synthesis in ovarian follicular granulosa cells has not been sufficiently studied. Our previous research demonstrated that lncRNA Gm2044 could promote estradiol synthesis in follicular granulosa cells. In this study, we identified 21 binding proteins of lncRNA Gm2044 in ovarian follicles using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS). RNA immunoprecipitation (RNA IP) and reverse transcription PCR (RT-PCR) confirmed that lncRNA Gm2044 can interact with eukaryotic translation elongation factor 2 (EEF2) protein. Furthermore, we constructed lncRNA Gm2044 knockout mice using the CRISPR/Cas9 method. Although the follicular development and fertility of female lncRNA Gm2044 knockout mice were not affected, the serum estradiol concentration in female lncRNA Gm2044 knockout mice significantly decreased. Western blotting and ELISA revealed that lncRNA Gm2044 may promote the binding of EEF2 to Nr5a1 mRNA and then enhance the Nr5a1 mRNA translation, and the upregulated NR5A1 protein can strengthen estradiol synthesis. To determine the potential signaling pathway of lncRNA Gm2044 regulating estradiol synthesis, transcriptome sequencing was performed for ovaries of adult lncRNA Gm2044 knockout mice, which identified 565 significant up-regulated genes and 303 significant down-regulated genes, which were then analyzed with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and validated by molecular experiments. Understanding how lncRNA Gm2044/EEF2 protein regulates estradiol synthesis will help treat estrogen-related reproductive diseases.

Effects of Maternal Cigarette Smoking on Trace Element Levels and Steroidogenesis in the Maternal-Placental-Fetal Unit.

This study evaluates the interaction of toxic elements cadmium (Cd) and lead (Pb) due to exposure from cigarette smoking, essential elements, and steroidogenesis in the maternal-placental-fetal unit. In a cohort of 155 healthy, postpartum women with vaginal term deliveries in clinical hospitals in Zagreb, Croatia, samples of maternal blood/serum and urine, placental tissue, and umbilical cord blood/serum were collected at childbirth. The biomarkers determined were concentrations of Cd, Pb, iron (Fe), zinc (Zn), copper (Cu), and selenium (Se), and steroid hormones progesterone and estradiol in maternal and umbilical cord blood and the placenta. Three study groups were designated based on self-reported data on cigarette smoking habits and confirmed by urine cotinine levels: never smokers (n = 71), former smokers (n = 48), and active smokers (n = 36). Metal(loid)s, steroid hormones, urine cotinine, and creatinine levels were analyzed by ICP-MS, ELISA, GC-MS, and spectrophotometry. Cigarette smoking during pregnancy was associated with increased Cd levels in maternal, placental, and fetal compartments, Pb in the placenta, and with decreased Fe in the placenta. In active smokers, decreased progesterone and estradiol concentrations in cord blood serum were found, while sex steroid hormones did not change in either maternal serum or placenta. This study provides further evidence regarding toxic and essential metal(loid) interactions during prenatal life, and new data on sex steroid disruption in cord serum related to cigarette smoking. The results indicate that umbilical cord sex steroid levels may be a putative early marker of developmental origins of the future burden of disease related to harmful prenatal exposure to cigarette smoke.

Use of deslorelin acetate to advance ovulation in goats for timed artificial insemination

The objective of this study was to determine the efficacy of deslorelin in advancing ovulation for timed artificial insemination (AI) protocols in goats. We hypothesized that deslorelin treatment advances the onset of ovulation and improves AI pregnancy rates. Does were synchronized using a 5-day CIDR (controlled internal drug releasing insert) protocol with prostaglandin treatment at CIDR insertion. For Experiment 1, does received 0.2 mg of intramuscular deslorelin (n = 9) or saline (control, n = 10) at CIDR removal. Serial blood collections and transrectal ultrasonography were performed to assess ovarian dynamics and identify ovulation. For Experiment 2, does received 0.2 mg of intramuscular deslorelin (n = 42), 5 ml of PMSG (pregnant mare serum gonadotropin)/hCG (human chorionic gonadotropin) (n = 42), or were left untreated (control, n = 42) at CIDR removal, and were subsequently bred by transcervical AI with fresh semen after 48 to 56 hours. Pregnancy diagnosis was performed at 50 and 90 days after AI. In Experiment 1, compared to control does, deslorelin-treated does had an increased (p &lt; 0.01) number of ovulations and increased (p &lt; 0.01) serum estradiol concentrations from 48 to 72 hours after CIDR removal. Serum progesterone concentrations did not differ between treatments. In Experiment 2, there was a main effect (p = 0.02) of treatment on pregnancy rates, with control does tending (p = 0.06) to have greater pregnancy rates than those treated with deslorelin or PMSG/hCG. Deslorelin treatment also resulted in decreased (p = 0.04) breeding season pregnancy rates and increased (p = 0.05) number of cycles to achieve pregnancy compared to control does. These results demonstrated that deslorelin not only has a super-ovulatory effect but also, at the dose given, can negatively impact does’ subsequent ovarian function and ability to achieve pregnancy.

The effect of calcitriol on the development and implantation capacity of embryos from hyper-stimulated mice.

The evidence concerning the role of vitamin D (VD) in reproduction is still inconclusive. Calcitriol was given to superovulated female mice at the time of FSH injection (Group A), or at day 0.5 of pregnancy (Group B). The retrieved and cultured embryos were transferred to the uteri of pseudopregnant females. Ten animals from each group conceived naturally, and at day 7.5 of pregnancy, the implantation sites were counted. Serum hormone concentrations were determined by ELISA. The expression of CD70, PD-L1, OX-40L, and PIBF on extracellular vesicles (EVs) was tested by flow cytometry. Calcitriol treatment did not alter serum oestradiol concentrations, while 25(OH) D levels significantly decreased in both treated groups. Progesterone concentrations were significantly higher in group A and lower in group B than in the controls. On EVs produced by group B embryos PIBF, CD70, and OX-40L expression were significantly lower, while that of PD-L1 was significantly higher than that of controls. Calcitriol treatment decreased the fertilization rate in group A, and the blastulation rate of cultured embryos in group B, while the implantation capacity of the embryos was not affected, suggesting that depending on the time of administration, VD has an adverse effect on oocyte maturation and embryo development, but not on the implantation rates.

Effect of hCG administration on ovulation and estrus in Saanen goats subjected to short-term estrus synchronization protocol during the breeding season

This study aimed to compare the effect of hCG administered at 24 or 36 h following a short-term estrus synchronization treatment on the ovulation time and estrus parameters in non-lactating Saanen goats during the breeding season. The estrous cycles of does were synchronized with an intravaginal sponge containing 60 mg of medroxyprogesterone acetate (MAP) for six days, and an injection of 125 µg of d-cloprostenol at the time of sponge insertion in addition to an injection of 300 IU of eCG 24h before sponge removal. After removal of the sponges, does were injected intramuscularly either 1 ml physiological saline (0.9% NaCl) solution after 12 h (Group1/Control; n=10), 100 IU hCG after 24 h (Group2; n=9) or 100 IU hCG after 36 h (Group3; n=9). Estrus behavior after sponge removal was observed twice daily for 84 h using teaser bucks and transrectal ovarian ultrasonography was performed twice a day for seven days to determine small, medium and large follicle numbers, luteal development and the time of ovulation. Blood samples were collected on the same days to determine serum progesterone (P4) and estradiol (E2) concentrations. No significant differences were observed in terms of estrus parameters, ovarian structure and serum P4 and E2 concentrations between the hCG-treated groups and the control group. Average values observed for all groups: estrous response (53.57%), the interval from sponge removal to estrus and ovulation (35.2 h and 67.86 h, respectively), duration of estrus (18.4 h), the interval from estrus onset to ovulation (50.37 h), ovulation rate (96.43%), number of ovulations (1.36), ovulatory follicle diameter (6.86 mm), corpus luteum diameter (8.22 mm), follicle and luteal growth rate (1.17 and 0.68 mm/day, respectively). In conclusion, administration of hCG at 24 or 36 h following a short-term estrous synchronization protocol does not affect ovulation time, estrus parameters, and serum P4 and E2 concentrations in goats during the breeding season.

Contemporary Anti-Retroviral Drugs (ARVDs) Disrupt Follicular Development in Female Wistar Rats.

There are genuine concerns that long-term use of anti-retroviral drugs may be associated with reproductive complications in females. This study aimed to ascertain the effect of highly active anti-retroviral drugs on the ovarian reserve and reproductive potential of female Wistar rats and by extension to HIV-positive human females. A total of 25 female Wistar rats, weighing between 140g and 162g, were randomly allotted into non-intervention and intervention groups, receiving the anti-retroviral drugs, Efavirenz (EFV), Tenofovir Disoproxil Fumarate (TDF), Lamivudine (3TC), and a fixed-dose combination (FDC). The dosage was administered orally at 8 am daily for 4 weeks. Serum concentrations of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinising hormone (LH), and estradiol were measured using standard biochemical techniques (ELISA). Follicular counts were made on fixed ovarian tissue from the sacrificed rats. The mean AMH level for the control group and the EFV, TDF, 3TC, and FDC groups were 11.20, 6.75, 7.30, 8.27, and 6.60 pmol/L, respectively. The EFV and FDC groups had the lowest AMH, compared to the other groups, but there was no statistically significant difference in AMH across the groups. The mean count of antral follicles was significantly lower in the group that received EFV when compared to the other groups. The corpus luteal count was significantly higher in the control group than in the intervention groups. The study demonstrated a disruption in the reproductive hormones of female Wistar rats receiving anti-retroviral regimens containing EFV. Clinical studies are required to determine if these changes are seen in women receiving EFV-based treatment, as this may compromise reproductive function and predispose them to early menopause.

Prenatal and postnatal exposure to polychlorinated biphenyls alter follicle numbers, gene expression, and a proliferation marker in the rat ovary

Polychlorinated biphenyls (PCBs) were used in industrial applications until they were banned in the 1970s, but they still persist in the environment. Little is known about the long-term effects of exposure to PCB mixtures on the rat ovary during critical developmental periods. Thus, this study tested whether prenatal and postnatal exposures to PCBs affect follicle numbers and gene expression in the ovaries of F1 offspring. Sprague-Dawley rats were treated with vehicle or Aroclor 1221 (A1221) at 1 mg/kg/day during embryonic days 8–18 and/or postnatal days (PND) 1–21. Ovaries from F1 rats were collected for assessment of follicle numbers and differential expression of estrogen receptor 1 (Esr1), estrogen receptor 2 (Esr2), androgen receptor (Ar), progesterone receptor (Pgr), and Ki-67 (Ki67) at PNDs 8, 32, and 60. Sera were collected for measurement of estradiol concentrations. Prenatal exposure to A1221 significantly decreased the number of primordial follicles and the total number of follicles at PND 32 compared to control. Postnatal PCB exposure borderline increased Ki67 gene expression and significantly increased Ki67 protein levels (PND 60) compared to control. Combined prenatal and postnatal PCB exposure borderline decreased Ar expression (PND 8) compared to control. However, PCB exposure did not significantly affect the expression of Pgr, Esr1, and Esr2 or serum estradiol concentrations compared to control at any time point. In conclusion, these data suggest that PCB exposure affects follicle numbers and levels of the proliferation marker Ki67, but it does not affect expression of some sex steroid hormone receptors in the rat ovary.

Correlates of serum estradiol concentration among postmenopausal women in Ilorin, North-Central Nigeria.

There are limited data on the associated factors of circulating endogenous estradiol among Nigerian postmenopausal women. The main objective of this study is to assess the relationship between serum estradiol levels and some menstrual, clinical, and sociodemographic factors in postmenopausal women attending a family medicine clinic in Nigeria. This was a hospital-based cross-sectional study involving 372 postmenopausal women. Sociodemographic, menstrual, and clinical data of the participants were collected, and their serum estradiol concentrations were assayed. The collected data were analyzed using IBM SPSS version 21 statistical software. A χ2 test of association and logistic regression analysis were done to identify significant correlates of serum estradiol concentration among the participants. The mean ages at menarche and menopause among the participants were 15.6 and 48.1 years respectively. Approximately half of them (51.1%) were receiving chronic medical care for systemic hypertension and/or diabetes. The mean estradiol concentration of the participants in the study was 20.69 pg/mL. The participants' marital status and clinical presentation pattern (chronic vs others) were found to have statistically significant associations with their serum estradiol concentration; P = 0.048 and P = 0.001, respectively. Logistic regression analysis revealed that only the clinical presentation pattern had a significant relationship with serum estradiol concentration among the participants ( P = 0.002). Of all the studied factors, the only significant correlate of low serum estradiol concentration found in this study was chronic medical care presentation for hypertension and/or diabetes.

Age But Not Menopausal Status Is Linked to Lower Resting Energy Expenditure.

It remains uncertain whether aging before late adulthood and menopause are associated with fat-free mass and fat mass-adjusted resting energy expenditure (REEadj). We investigated whether REEadj differs between middle-aged and younger women and between middle-aged women with different menopausal statuses. We repeated the age group comparison between middle-aged mothers and their daughters to partially control for genotype. We also explored whether serum estradiol and FSH concentrations explain REEadj in midlife. We divided 120 women, including 16 mother-daughter pairs, into age groups; group I (n = 26) consisted of participants aged 17 to 21, group II (n = 35) of those aged 22 to 38, and group III (n = 59) of those aged 41 to 58 years. The women in group III were further categorized as pre- or perimenopausal (n = 19), postmenopausal (n = 30), or postmenopausal hormone therapy users (n = 10). REE was assessed using indirect calorimetry, body composition using dual-energy X-ray absorptiometry, and hormones using immunoassays. The REEadj of group I was 126 kcal/day [95% confidence interval (CI): 93-160] higher than that of group III, and the REEadj of group II was 88 kcal/day (95% CI: 49-127) higher. Furthermore, daughters had a 100 kcal/day (95% CI: 63-138 kcal/day) higher REEadj than their middle-aged mothers (all P < .001). In group III, REEadj was not lower in postmenopausal women and did not vary by sex hormone concentrations. We demonstrated that REEadj declines with age in women before late adulthood, also when controlling partially for genetic background, and that menopause may not contribute to this decline.

Seasonal variation of serum and intrafollicular concentrations of melatonin and estradiol in relation to follicular development

The main objective of this study was to compare the effect of season on serum and intrafollicular concentrations of melatonin (MT). The relationship between follicular size, MT and estradiol (E2) concentrations was also explored. Twelve mares were used. Aspiration of fluid from all follicles larger than 5 mm was carried out in each mare during the breeding season and during the anovulatory season. All aspirations were carried out between 7AM and 8AM, and a serum sample was obtained at the same time. Follicles were classified into small (≤ 15 mm); medium (16-30 mm); and large (> 30 mm). MT and E2 concentrations were measured by enzymatic immunoassay (Melatonin ELISA Mybiosource, MBS1603596; Estradiol ELISA DRG, EIA-2693). Analysis of Variance was used to evaluate the effects of season, fluid type (follicular vs serum) and follicle size. Intrafollicular concentrations of MT were higher than serum concentrations both in the reproductive season (127±1.41 vs 69.59±1.73 ng/L) and in the anovulatory season (118.5±2.93vs 115.45±3.06 ng/L). MT concentrations in serum were higher during the anovulatory season than during the reproductive season (p<0.05), but the opposite was the case for intrafollicular MT. During the ovulatory season MT was higher (p<0.05) in large follicles (141.39±2.13ng/L) than in medium (130.25±2.55 ng/L) and small follicles (109.36±2.57 ng/L). The difference between medium and small follicles was also significant(p<0.05). In contrast during the anovulatory season MT concentration was not different between small and medium follicles (123.43±3.79 vs 109.92±5.55 ng/mL). Intrafollicular levels of E2 were higher during the ovulatory season than during the anovulatory season in medium (211.89±20.4 vs 126.18±0.07) and small follicles (67.42±2.4 vs 14.78±1.06 ng/mL). E2 concentrations in large follicles during the ovulatory season was 4,312.83±65.8 ng/mL. The results of this study indicate that while serum MT concentrations were different between seasons due to the known negative correlation between pineal MT secretion and day length, this seasonal effect was not found in the case of intrafollicular MT concentrations. Also, in this study there was no correlation between serum and intrafollicular MT concentrations. Together, these findings suggest photoperiod-independent intrinsic follicular MT synthesis. E2 concentrations were correlated with follicle size in both ovulatory and anovulatory seasons but were always higher during the ovulatory season for a given size. During this season there was a positive correlation between intrafollicular MT and estradiol concentrations, thus suggesting that intrafollicular estradiol may stimulate intrafollicular melatonin synthesis. It is concluded that intrafollicular MT concentrations in the mare are at least in part of intrinsic origin and may be stimulated by estradiol.

Effects of chronic exposure to cold stress on ovarian functions in prepubertal rats.

Ovarian functions are modulated by the hypothalamus-pituitary-ovary axis and neural signals. Stress modifies the activity of the sympathetic nervous system. In adult female rats, cold stress results in higher noradrenergic and steroidogenic activity of the ovary, anovulation and the presence of ovarian cysts; however, it is unknown whether this response occurs in prepubertal rats. The purpose of this study was to analyse the effects of cold stress initiated in the prepubertal stage of female rats on ovarian function. Female rats 24 days old were exposed to three, five or eight weeks of cold stress. Autopsies were performed at the end of each stress period. The parameters analysed were the number of ova shed by ovulating animals; the number of ovulating animals; the serum concentrations of progesterone, testosterone, and oestradiol; and the ovarian concentrations of norepinephrine and 3-methoxy-4-hydroxyphenyl-glycol. Our results show that chronic cold stress applied to prepubertal rats did not modify the number of ovulating animals, the total number of ova shed, or progesterone and testosterone concentrations in any of the periods analysed. Oestradiol concentration was lower in the animals exposed to five or eight weeks of stress. The ovarian norepinephrine concentration was higher in the animals exposed to three weeks of stress and was lower at eight weeks of stress. No changes in ovarian morphology were observed. Our data suggest that the changes in noradrenergic activity resulting from chronic cold stress experienced in the prepubertal stage do not modify ovarian architecture or affect the ovulatory response in adulthood.

Low responsiveness of peripheral lymphocytes in extraparenchymal neurocysticercosis

The morbidity and mortality of extraparenchymal neurocysticercosis (EP-NC) remain high and effectiveness of current medical treatment is suboptimal. Various factors have been implicated in the severity of EP-NC and in the poor response to treatment, but the possible role of host immune and endocrine systems has not yet been examined thoroughly. 42 participants with EP-NC before receiving standard treatment and 25 healthy controls were included in the study. Treatment response was assessed by comparing pre/post treatment parasite volumes from 3D MRI. Prior to treatment among participants with EP-NC, specific stimulation induced an increased specific proliferative response accompanied by a significant increase in IL-4, NK, NKT, Bregs and Tregs cells, whereas in healthy controls, specific stimulation induced a significant increase in IL-1β, IL-5, CCL5, IL-6, TNF-α, NK and Bregs cells. Significant differences between participants with EP-NC and healthy controls in the specific inflammatory response were observed. Participants with EP-NC prior to treatment had significantly weaker responses of proinflammatory cytokines (IL-6, TNF-α) and NK cells, and stronger IL-4 response. Anthelmintic treatment did not promote significant peripheral immunological changes at any time, although inflammation was sustained in the cerebrospinal fluid. Serum estradiol concentration significantly decreased after anthelmintic treatment among males, and cortisol correlated negatively with IL-6 and positively with IFN-γ levels. No pre-treatment immunologic or endocrinologic parameters were significantly associated with response to treatment. Prior to anthelmintic treatment, EP-NC was characterized by low lymphocyte reactivity accompanied by a regulatory response, which may be involved in the lack of peripheral immunological changes during and after treatment, although a central inflammatory response was present. This weak specific peripheral response could favor the chronicity of the infection and the poor response to treatment. Our findings highlight the need for new anti-inflammatory treatment focused on the central nervous system with less systemic immunosuppressive effects.

Safety and serum estradiol levels in hormonal treatments for vulvovaginal atrophy in breast cancer survivors: A systematic review and meta-analysis.

e24049 Background: Vulvo-Vaginal Atrophy (VVA) or Genitourinary Syndrome of Menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing antiestrogen therapy. Despite being an option in refractory cases, the safety of hormonal treatment remains uncertain in this population. The aim of this study was to review the safety and serum estrogen levels of hormonal therapy in patients with BC history presenting with VVA symptoms. Methods: Pubmed, Embase, and Cochrane were searched for studies comparing different hormonal treatment options for VVA in breast cancer survivors. Statistical analysis was performed using a random effects model and heterogeneity using Cochran's Q-statistic and the I2 index. Results: We included 17 studies, of which 5 were randomized controlled trials (RCTs). Treatment modalities included in this study were topical vaginal estradiol and estriol preparations, vaginally applied testosterone, DHEA, and ospemifene. We found that, among patients treated with the estriol and estradiol preparations, there was an average increase of 7.67pg/ml (SMD 7.67 pg/mL; 95% CI -1.00, 16.35; p &lt; 0.001). Analysis of the testosterone group found temporary peaks of serum estradiol levels, but one study showed persistent elevation above normal postmenopausal levels. One study with prasterone revealed no elevation of serum estradiol concentration. One study with ospemifene demonstrated no increase in the risk of BC recurrence. Conclusions: In conclusion, among treatments available for BC survivors, low-dose vaginal estrogen showed the smallest changes in serum estradiol levels and had the most evidence, but safety remains unclear, especially for patients on aromatase inhibitors. Alternative treatments such as ospemifene need more data supporting safety and efficacy. These results suggest that concerns related to cancer recurrence should keep aiming for the lowest possible concentration.