Estradiol Concentrations Research Articles

Disentangling the relationships of body mass index and circulating sex hormone concentrations in mammographic density using Mendelian randomization.

Mammographic density phenotypes, adjusted for age and body mass index (BMI), are strong predictors of breast cancer risk. BMI is associated with mammographic density measures, but the role of circulating sex hormone concentrations is less clear. We investigated the relationship between BMI, circulating sex hormone concentrations, and mammographic density phenotypes using Mendelian randomization (MR). We applied two-sample MR approaches to assess the association between genetically predicted circulating concentrations of sex hormones [estradiol, testosterone, sex hormone-binding globulin (SHBG)], BMI, and mammographic density phenotypes (dense and non-dense area). We created instrumental variables from large European ancestry-based genome-wide association studies and applied estimates to mammographic density phenotypes in up to 14,000 women of European ancestry. We performed analyses overall and by menopausal status. Genetically predicted BMI was positively associated with non-dense area (IVW: β = 1.79; 95% CI = 1.58, 2.00; p = 9.57 × 10-63) and inversely associated with dense area (IVW: β = - 0.37; 95% CI = - 0.51,- 0.23; p = 4.7 × 10-7). We observed weak evidence for an association of circulating sex hormone concentrations with mammographic density phenotypes, specifically inverse associations between genetically predicted testosterone concentration and dense area (β = - 0.22; 95% CI = - 0.38, - 0.053; p = 0.009) and between genetically predicted estradiol concentration and non-dense area (β = - 3.32; 95% CI = - 5.83, - 0.82; p = 0.009), although results were not consistent across a range of MR approaches. Our findings support a positive causal association between BMI and mammographic non-dense area and an inverse association between BMI and dense area. Evidence was weaker and inconsistent for a causal effect of circulating sex hormone concentrations on mammographic density phenotypes. Based on our findings, associations between circulating sex hormone concentrations and mammographic density phenotypes are weak at best.

Ovarian function and endocrine phenotypes of lactating dairy cows during the estrous cycle are associated with genomic-enhanced predictions of fertility potential

The objectives of this prospective cohort study were to characterize associations among genomic merit for fertility with ovarian and endocrine function and the estrous behavior of dairy cows during an entire nonhormonally manipulated estrous cycle. Lactating Holstein cows entering their first (n = 82) or second (n = 37) lactation had ear-notch tissue samples collected for genotyping using a commercial genomic test. Based on genomic predicted transmitting ability values for daughter pregnancy rate (gDPR), cows were classified into high (Hi-Fert; gDPR > 0.6, n = 36), medium (Med-Fert; gDPR -1.3 to 0.6, n = 45), and low fertility (Lo-Fert; gDPR < -1.3, n = 38) groups. At 33 to 39 DIM, cohorts of cows were enrolled in the Presynch-Ovsynch protocol for synchronization of ovulation and initiation of a new estrous cycle. Thereafter, the ovarian function and endocrine dynamics were monitored daily until the next ovulation by transrectal ultrasonography and concentrations of progesterone (P4), estradiol, and FSH. Estrous behavior was monitored with an ear-attached automated estrus detection system that recorded physical activity and rumination time. Overall, we observed an association between fertility group and the ovarian and hormonal phenotype of dairy cows during the estrous cycle. Cows in the Hi-Fert group had greater circulating concentrations of P4 than cows in the Lo-Fert group from d 4 to 13 after induction of ovulation and from day -3 to -1 before the onset of luteolysis. The frequency of atypical estrous cycles was 3-fold greater for cows in the Lo-Fert than the Hi-Fert group. We also observed other modest associations between genomic merit for fertility with the follicular dynamics and estrous behavior. We found several associations between milk yield and parity with ovarian, endocrine, and estrous behavior phenotypes as cows with greater milk yield and in the second lactation were more likely to have unfavorable phenotypes. These results demonstrate that differences in reproductive performance between cows of different genomic merit for fertility classified based on gDPR may be partially associated with circulating concentrations of P4, the incidence of atypical phenotypes during the estrous cycles, and, to a lesser extent, the follicular wave dynamics. The observed physiological and endocrine phenotypes might help explain part of the differences in reproductive performance between cows of superior and inferior genomic merit for fertility.

Influence of sexual hormones on Chagas disease.

Analyze sex hormone's influence during Chagas´ Disease. Male and female BALB/c mice were divided into six groups, four experimental (sham, orchiectomized, orchiectomized and supplemented with estradiol, orchiectomized supplemented with testosterone, oophorectomized, oophorectomized and supplemented with estradiol, and oophorectomized and supplemented with testosterone), and two control (healthy and intraperitoneally with T. cruzi strain NINOA infected). Clinical data were recorded daily, parasitemia was evaluated using a Neubauer chamber during the infection, and heart histopathological analysis was performed using the paraffin embedding technique. To analyze parasitemia curves and the area under the parametric curves, two-way ANOVA test was performed to correlate groups´ data. P-values <0.05 were considered statistically significant. Higher mortality rates, cardiomegaly, hepatomegaly, ascites, edema, higher parasitemia levels, more amastigote nests, and more severe inflammatory infiltrate were found in higher testosterone concentration mice, whereas in higher estradiol concentration groups, paresia, prostration, edema, and necrosis were found. Our results showed that testosterone increased infection severity, whereas estradiol had the opposite effect. This research improves the understanding of sex hormones´infuence upon this infection to contribute with the handling of Chagas´disease.

Diurnal Fluctuations in Steroid Hormones Tied to Variation in Intrinsic Functional Connectivity in a Densely Sampled Male.

Most of mammalian physiology is under the control of biological rhythms, including the endocrine system with time-varying hormone secretion. Precision neuroimaging studies provide unique insights into how the endocrine system dynamically regulates aspects of the human brain. Recently, we established estrogen's ability to drive widespread patterns of connectivity and enhance the global efficiency of large-scale brain networks in a woman sampled every 24 h across 30 consecutive days, capturing a complete menstrual cycle. Steroid hormone production also follows a pronounced sinusoidal pattern, with a peak in testosterone between 6 and 7 A.M. and nadir between 7 and 8 P.M. To capture the brain's response to diurnal changes in hormone production, we carried out a companion precision imaging study of a healthy adult man who completed MRI and venipuncture every 12-24 h across 30 consecutive days. Results confirmed robust diurnal fluctuations in testosterone, 17β-estradiol-the primary form of estrogen-and cortisol. Standardized regression analyses revealed widespread associations between testosterone, estradiol, and cortisol concentrations and whole-brain patterns of coherence. In particular, functional connectivity in the Dorsal Attention Network was coupled with diurnally fluctuating hormones. Further, comparing dense-sampling datasets between a man and a naturally cycling woman revealed that fluctuations in sex hormones are tied to patterns of whole-brain coherence in both sexes and to a heightened degree in the male. Together, these findings enhance our understanding of steroid hormones as rapid neuromodulators and provide evidence that diurnal changes in steroid hormones are associated with patterns of whole-brain functional connectivity.

Effect of Curcuma longa maceration treatment on ovarian follicular development, serum oestradiol, uterine growth and vascularisation in female albino rats.

Curcuma longa is a well-known medicinal plant with various health benefits. This study was designed to evaluate the administration of Indonesian C. longa maceration for its effect on promoting growth and development of the ovary and uterus before mating in female albino rats. A total of 15 female Sprague Dawley rats in their dioestrous phase were assigned into three different groups: the Control group (mineral water); the Cur-Low group (mineral water with 1% C. longa maceration) and the Cur-High group (mineral water with 5% C. longa maceration). The treatments were given for 20 days. Serum concentrations of follicle-stimulating hormone, oestradiol and progesterone were determined. After the sacrifice of the rats, ovary and uterine relative weight, uterine cornua diameter and length, uterine gland diameter (by histology), the number of primary, secondary, tertiary, and Graafian follicles, the number of corpora lutea and vascular endothelial growth factor (VEGF) expression in the ovary were measured. Uterine vascularisation was also evaluated. Administration of C. longa maceration significantly improved the relative weights of the uterus and ovary; uterine cornua diameter, length and vascularisation; uterine gland diameter; and expression of VEGF in the ovary. It also increased the number of tertiary follicles and corpora lutea, albeit not significantly. Follicle-stimulating hormone serum concentrations were lower in the administered rats. Oestradiol and progesterone levels rose with C. longa maceration treatment. The maceration improved the reproductive organs of unmated rats and had potential to optimise the uterine environment for supporting pregnancy in order to produce high-quality offspring.

Higher number of steps is related to lower endogenous progesterone but not estradiol levels in women.

Sex steroid hormones are important not only for reproduction but also for many aspects of women's health, including the risk of breast cancer. Physical activity has been shown to influence sex hormone levels in women. This study aimed to investigate a relationship between the average daily number of steps and the sex hormone (estradiol and progesterone) levels in premenopausal women. Data were collected from 85 healthy, urban women of reproductive age who performed at least 180 minutes/week of moderate physical activity for two complete menstrual cycles. Physical activity was measured using wrist bands. Estradiol and progesterone concentrations were measured in daily-collected saliva samples in the second menstrual cycle. There was a significant negative association between the average number of steps taken daily and salivary progesterone levels after adjusting for potential confounding factors (age, BMI). Women who took more than 10,000 steps a day had significantly lower progesterone levels compared to women who took less than 10,000 steps. The association between physical activity and estradiol levels was statistically insignificant. Our results indicate that taking at least 10,000 steps a day reduces progesterone levels, but this intensity of physical activity may not be high enough to affect estradiol levels. Daily step tracking is a valuable element of health promotion, but currently recommended levels of physical activity may not be high enough for healthy premenopausal women to significantly reduce both sex hormone levels and thus their risk of postmenopausal breast cancer.

Effect of High Energy Diet Supplementation during Periparturient Period on Ovarian Steroids and Reproductive Performance in Vrindavani Cows

The objective of the study was to assess the effect of high energy diet supplementation during periparturient period on ovarian steroids and reproductive performance in vrindavani cows. Postpartum vrindavani cows (n= 20) of second to fourth parity with lactation yield of &gt; 10 L/day were divided in to two groups (n=10 cow/group). Group I (CON) cows were fed with basal diet to serve as control. Group II (TRT) cows were provided with 20% extra concentrates in the form of energy. 20% additional concentrate diet was supplemented from second week to eight week after calving. Blood samples were collected at weekly interval from 4 week before calving to8weeks after calving. Blood samples were collected to determine estradiol (E2) and progesterone (P4) in the serum using RIA. Postpartum reproductive performance was assessed in terms occurrence of first postpartum estrus, calving to conception interval, conception rate and number of service per conception. Serum estradiol and progesterone concentration increased significantly(P&lt;0.05) from 2 to 8 week postpartum in Group II as compared to Group I. Marked significant(P&lt;0.05)improvement in the postpartum reproductive performance in terms of early occurrence of first postpartum estrus(67.0Vs 53.0), reduced calving to conception interval(85.87 Vs74.4), service per conception (1.62 Vs 1.2), days from calving to first AI(88.5 Vs 65.73), higher first AI conception rate(40 Vs 80%) and cumulative conception rate(88.52 Vs 65.73%) in group II as compared to group I. In conclusion, additional high energy diet supplemented group showed significant increased ovarian steroid hormonal concentrations and marked improvement in the reproductive performance in Vrindavani cows.

Endocrine-disrupting chemical concentrations in follicular fluid and follicular reproductive hormone levels

PurposeTo determine correlations between chemicals in follicular fluid (FF) and follicular reproductive hormone levels.MethodsThe analysis was part of a larger cohort study to determine associations between exposure to EDCs and in vitro fertilization (IVF) outcomes. FF was aspirated from a single leading follicle per participant. Demographics and data on exposure to EDCs were self-reported by the participants using a questionnaire. The concentrations of estradiol (E2), progesterone (PG), anti-Mullerian hormone (AMH), and inhibin B, as well as that of 12 phthalate metabolites and 12 phenolic chemicals were measured in each FF sample. Multivariate linear regression model was used to identify the drivers of hormone levels based on participant’s age, BMI, smoking status, and chemical exposure for the monitored chemicals detected in more than 50% of the samples. Benjamini–Hochberg false discovery rate (FDR) correction was applied on the resulting p values (q value).ResultsFF samples were obtained from 72 women (mean age 30.9 years). Most of the phthalates and phenolic substances monitored (21/24, 88%) were identified in FF. Ten compounds (7 phthalate metabolites, 3 phenols) were found in more than 50% of samples. In addition, there were positive associations between E2 levels and mono-n-butyl phthalate (MnBP) (beta = 0.01) and mono-isobutyl phthalate (MiBP) (beta = 0.03) levels (q value < 0.05).ConclusionHigher concentrations of several phthalate metabolites, present among others in personal care products, were associated with increased E2 levels in FF. The results emphasize the need to further investigate the mechanisms of action of such EDCs on hormonal cyclicity and fertility in women.

Time-varying associations of gestational and childhood triclosan with pubertal and adrenarchal outcomes in early adolescence.

Triclosan is an endocrine-disrupting chemical, but associations with pubertal outcomes remain unclear. We examined associations of gestational and childhood triclosan with adolescent hormone concentrations and pubertal stage. We quantified urinary triclosan concentrations twice during pregnancy and seven times between birth and 12 years in participants recruited from Cincinnati, OH (2003-2006). We averaged concentrations across pregnancy and childhood and separately considered individual exposure periods in multiple informant models. At 12 years, we measured serum hormone concentrations (males [n = 72] and females [n = 84]-dehydroepiandrosterone-sulfate, luteinizing hormone, follicle-stimulating hormone; males-testosterone; females-estradiol). Also at age 12 years, participants self-reported physical development and menarchal timing. We estimated associations (95% confidence interval) of triclosan with hormone concentrations, more advanced physical development, and age at menarche. For females, each doubling of childhood triclosan was associated with 16% lower estradiol concentrations (-29%, 0%), with stronger associations for measures closer to adolescence. We found suggestive evidence that higher triclosan at any age was associated with ~10% (for gestational triclosan: -18%, -2%) lower follicle-stimulating hormone concentrations among males and early postnatal (1-3 years) triclosan was associated with 63% (5%, 96%) lower odds of advanced pubic hair development in females. In multiple informant models, each doubling of gestational triclosan concentrations was associated with 5% (0%, 9%) earlier age at menarche, equivalent to 5.5 months. Gestational and childhood triclosan concentrations were related to some pubertal outcomes including hormone concentrations and age at menarche. Our findings highlight the relevance of elucidating potential sex-specific and time-dependent actions of triclosan.

Visuospatial Function in Women with Premenstrual Dysphoric Disorder.

Background/Objectives: Premenstrual dysphoric disorder (PMDD) is an understudied psychiatric condition affecting reproductive-age women who experience negative mood in the luteal phase of the menstrual cycle. Cognitive functions in PMDD are not well understood as patients have been tested in the luteal phase. This may confound study results due to noted emotional interferences, as well as the potential opposing effects of the sex hormones estradiol and progesterone. In the present study, we evaluated visuospatial function in the follicular phase in women with PMDD and healthy controls, and further examined the effect of estradiol as research into the hormonal mediation of visuospatial function in reproductive-age women has produced mixed results. Methods: To this end, we analyzed estradiol concentrations using the gold standard mass spectrometry. Serum samples were collected in the early follicular and mid/late follicular subphases when estradiol is low and high, respectively, while progesterone is low and steady. We assessed visuospatial function using the classic mental rotation task. Results: Women with PMDD had a higher mental rotation total score (t = 2.17; p < 0.05). The addition of six demographic, biological, and anthropomorphic variables in a hierarchical fashion accounted for 45.3% of the total variance in the final model with diagnosis remaining statistically significant (t = 4.36; p < 0.001). Estradiol did not mediate the group difference and was not significantly associated with visuospatial function. Conclusions: The present results provide support for new research directions into the potential biological mechanisms that underlie the pathophysiology of PMDD, represented as enhanced visuospatial ability in women with PMDD in the follicular phase. We review the theory that PMDD is a disorder of the enhanced excitation-to-inhibition ratio, with a focus on findings to date from brain imaging research.

Changes in the mechanical properties of the thigh and lower leg muscle-tendon units during the early follicular and early luteal phases.

This study aimed to determine changes in the muscle and tendon stiffness of the thigh and lower leg muscle-tendon units during the early follicular and early luteal phases, and check for possible relations between muscle and tendon stiffness in each phase. The sample consisted of 15 female university students with regular menstrual cycles. The basal body temperature method, ovulation kit, and salivary estradiol concentration measurement were used to estimate the early follicular and early luteal phases. A portable digital palpation device measured muscle-tendon stiffness in the early follicular and early luteal phases. The measurement sites were the rectus femoris (RF), vastus medialis (VM), patellar tendon (PT), medial head of gastrocnemius muscle, soleus muscle, and Achilles tendon. No statistically significant differences in the thigh and lower leg muscle-tendon unit stiffness were seen between the early follicular and early luteal phases. Significant positive correlations were found between the stiffness of the RF and PT (r = 0.608, p = 0.016) and between the VM and PT (r = 0.737, p = 0.002) during the early luteal phase. The present results suggest that the stiffness of leg muscle-tendon units of the anterior thigh and posterior lower leg do not change between the early follicular and early luteal phases and that tendons may be stiffer in those women who have stiffer anterior thigh muscles during the early luteal phase.

Effects of high-calorie diet-induced visceral obesity on reproductive hormones and muscle tissues in male and female Wistar rats

Overweight and obesity are associated with alterations in the reproductive system, which affect the anabolic supply to peripheral muscle tissues. The study aimed to investigate the effects of a high-calorie diet (HCD) on the development of obesity, reproductive hormone levels, and morphofunctional characteristics of muscle tissues in Wistar rats (i.e., 54 sexually mature male and female Wistar rats) for 16 weeks. Male rats fed with an HCD displayed (i) visceral obesity and hypogonadism, (ii) a decrease in the mass of the musculus triceps surae, (iii) increased levels of total protein, cholesterol, glucose, lactate, lactate dehydrogenase, and malonic dialdehyde (MDA) and superoxide dismutase (SOD) activities, and (iv) stable concentrations of estradiol and testosterone in the muscle tissues. In contrast, female rats fed with HCD displayed (i) visceral obesity, (ii) alterations in reproductive hormones toward hyperandrogenism, (iii) decreased metabolism in the muscle tissues, and (iv) increased levels of estradiol and MDA (without SOD activation). The cross-sectional area of the muscle fiber was significantly reduced by 20% in male and 44% in female rats on HCD. In addition, the total muscle edema was reportedly increased by twofold in both male and female rats. In summation, obese male and female rats developed an imbalance of reproductive hormones and alterations in muscle tissue metabolism.

Influence of sex hormones on the aggressive behavior during peck order establishment and stabilization in meat and egg type chickens

In the poultry industry, broiler and layer strains are genetically selected for different purposes (e.g., high meat-yield and high egg-production). Genetic selection for productivity can have unintended consequences on the behavioral repertoire of the birds, including aggression. Alongside the increasing societal concern regarding the welfare of animal in agriculture, the number of countries that are advocating the prohibition of using battery cages for laying hens has resulted in the transition and adoption of cage-free or free-range systems. Thus, both broiler and layer chickens are housed in large flocks rather than housed individually in cages. Housing birds in groups increases the opportunity for birds to engage in social behaviors, including aggression, that are used to establish social status. Aggressive interactions are associated with the risk of injury and the potential for a subordinate animal to have unmet needs (e.g., access to feed). The aim of this study was to characterize the relationships among aggressive behavior, neurobiology, and hormones during peck order establishment and social hierarchy stabilization of 2 divergently selected strains (meat- and egg-type chicken). Meat-type strains performed more male on male (P < 0.001), male on female (P < 0.0001), and female on female (P < 0.0001) non-reciprocal aggression behavior (NRA) than egg-type strains. Greater serum testosterone and estradiol concentrations in the weeks after the peck order establishment were observed in meat-type birds compared those in egg-type birds for both males and females (all P < 0.05). Greater (P < 0.05) cellular densities of androgen receptors, but not estrogen receptors, were observed in the hypothalamus of meat-type birds compared to egg-type birds. These findings suggest that greater sex hormone concentrations in the meat-type birds may be a consequence of genetic selection for rapid growth resulting in more sex hormones-induced aggressive behavior.

Chemical characterization, safety profile and antileiomyoma effects of Tetrapleura tetraptera Taubert (Fabaceae) fruit ethanol extract in Sprague Dawley rats

BackgroundTetrapleura tetraptera Taubert (Fabaceae) fruits are employed by herbal practitioners in the management of uterine leiomyoma, but its usage in this regard and level of safety in chronic administration has not been sufficiently established. This study evaluated the toxicity effects of T. tetraptera ethanol fruit extract and explored its antileiomyoma effect in female Sprague Dawley (SD) rats.MethodsSub-chronic toxicity test of the extract was done, with biochemical and hematological changes as well as histopathology of organs assessed. Leiomyoma formation was induced in SD rats with monosodium glutamate (MSG) and the extract given at 100, 200 and 400 mg/kg doses, following both the preventive and curative methods. Total serum cholesterol, protein and estradiol were determined, as well as histopathology assessment of the uterus. Phytochemical profiling of the extract was evaluated by analytical high-performance liquid chromatography (HPLC).ResultsNo significant alterations were seen in the biochemical and hematological indices in the toxicity test. The vital organs showed no changes at 200 mg/kg, but at 800 mg/kg it appeared to induce multiplication of glandular epithelium and stromal fibrosis in the uterus, and induced perivascular inflammation around the vessels of the heart. Total serum cholesterol and estradiol were significantly elevated (P ≤ 0.05) on treating normal female rats with 800 mg/kg MSG. Preventive and curative treatment of MSG-treated animals with the extract significantly decreased the elevated serum cholesterol (P ≤ 0.01) and estradiol (P ≤ 0.05). Histological studies of the uterus showed an amelioration of the proliferating fibroid cells with administration of the extract, which was more evident in the curative treatment. Result of HPLC analysis of the extract revealed rich composition in bioactive compounds such as umbelliferone, ferulic acid, aridanin, echinocystic acid, naringenin and hentriacontane.ConclusionThe ethanol fruit extract of T. tetraptera is relatively safe in Sprague Dawley rats in low doses and has antifibroid potential as seen in its significant reduction in the elevated total cholesterol and estradiol content as well as its ability to decrease uterine leiomyoma proliferation, which may be due to its array of phytochemical constituents.

Biochemical profiling of the follicular environment to predict oocyte competence in cattle.

To identify markers of oocyte competence, we compared the biochemical characteristics of fluid and cells from follicles containing oocytes with different capacities to form an embryo. Follicles (5-6 mm) were dissected, and follicular fluid (FF), granulosa cells (GC), cumulus cells (CC) from immature and mature cumulus-oocyte-complexes (COC) were individually collected. The oocytes were matured, fertilized, and cultured individually until day 8 (D8) of development. On D8, the samples were grouped according to embryo production into those that gave rise to blastocysts (EMB) and those that did not reach the blastocyst stage (NEMB). In CCs from immature and mature COCs and GCs, expression of CASP3, SERPINE2, VCAN, LUM, FSHR, EGFR, PGR, and GHR genes was quantified. Cell-free DNA (cfDNA), progesterone, and estradiol concentrations in the FF were determined. Data were analyzed by Mann-Whitney U test (GraphPad Prism 9). GHR was highly expressed in immature CCs from the EMB group, whereas CASP3 was highly expressed in mature CCs from the NEMB group (P<0.05). During maturation, the expression of CASP3 and GHR genes increased only in the NEMB group. ART2 cfDNA was highly detected in FF of the NEMB compared to the EMB group. Progesterone concentration was similar between the groups, whereas estradiol concentration was higher (P<0.05) in the EMB than in the NEMB group. It was concluded that a higher level of GHR transcripts in immature CCs, lower CASP3 expression in CCs from matured COCs, lower levels of ART2, and higher estradiol concentrations in FF may indicate oocytes with greater potential for development.

Clinically Relevant Laboratory Monitoring of Gender-Affirming Hormone Therapy in Transgender People-Experiences from a Teaching Hospital in the Netherlands.

Transgender care is shifting from academic to nonacademic settings leading to use of common (immunoassay) compared to sophisticated (mass spectrometry) methods to monitor estradiol and testosterone during gender-affirming hormone therapy (GAHT). The type of assay can influence results and have significant implications for clinical decision making. An evidence gap is present in recommendations regarding the assay needed to monitor GAHT. The present study aimed to summarize current evidence and evaluate immunoassay estradiol and testosterone concentrations in transgender people visiting a nonacademic hospital for GAHT. Clinical practice guidelines on GAHT and scientific literature on assay methodologies were screened and summarized. Laboratory and medical data from 252 patients who visited the transgender outpatient clinic of the Maasstad Hospital for GAHT between 2020 and 2022 were retrospectively analyzed. Our research showed that the most used clinical practice guidelines for GAHT provide hormonal target values without recommending a preferred method. A comprehensive literature search on agreement between immunoassay and mass spectrometry showed substantial heterogeneity in results. Retrospective analysis of our immunoassay measured data in transgender people showed hormonal changes during GAHT that are to be expected from the medication used. We demonstrate that laboratory monitoring of GAHT in a nonacademic hospital can be done safely by immunoassay in most cases. Only in cases where clinical observation is discordant with the hormonal results do more sophisticated methods need to be deployed. A best practice model was proposed for transgender care in nonacademic hospitals.

Estradiol mediates greater germinal center responses to influenza vaccination in female than male mice.

Adult females of reproductive age develop greater antibody responses to inactivated influenza vaccines (IIV) than males. How sex, age, and sex steroid concentrations impact B cells and durability of IIV-induced immunity and protection over 4 months post-vaccination (mpv) was analyzed. Vaccinated adult females had greater germinal center B cell and plasmablast frequencies in lymphoid tissues, higher neutralizing antibody responses 1-4 mpv, and better protection against live H1N1 challenge than adult males. Aged mice, regardless of sex, had reduced B cell frequencies, less durable antibody responses, and inferior protection after challenge than adult mice, which correlated with diminished estradiol among aged females. To confirm that greater IIV-induced immunity was caused by sex hormones, four core genotype (FCG) mice were used, in which the testes-determining gene, Sry, was deleted from chromosome Y (ChrY) and transferred to Chr3 to separate gonadal sex (i.e., ovaries or testes) from sex chromosome complement (i.e., XX or XY complement). Vaccinated, gonadal female FCG mice (XXF and XYF) had greater numbers of B cells, higher antiviral antibody titers, and reduced pulmonary virus titers following live H1N1 challenge than gonadal FCG males (XYM and XXM). To establish that lower estradiol concentrations cause diminished immunity, adult and aged females received either a placebo or estradiol replacement therapy prior to IIV. Estradiol replacement significantly increased IIV-induced antibody responses and reduced morbidity after the H1N1 challenge among aged females. These data highlight that estradiol is a targetable mechanism mediating greater humoral immunity following vaccination among adult females.IMPORTANCEFemales of reproductive ages develop greater antibody responses to influenza vaccines than males. We hypothesized that female-biased immunity and protection against influenza were mediated by estradiol signaling in B cells. Using diverse mouse models ranging from advanced-age mice to transgenic mice that separate sex steroids from sex chromosome complement, those mice with greater concentrations of estradiol consistently had greater numbers of antibody-producing B cells in lymphoid tissue, higher antiviral antibody titers, and greater protection against live influenza virus challenge. Treatment of aged female mice with estradiol enhanced vaccine-induced immunity and protection against disease, suggesting that estradiol signaling in B cells is critical for improved vaccine outcomes in females.

102 Estradiol and follicular growth are associated with estrous behavior monitored by an accelerometer in grazing beef cows

Abstract In beef cattle, 40% of cows that display estrus do not remain pregnant after embryo transfer (ET). Estrus is a physiological behavior influenced by the concentration of sex-steroids. The use of accelerometer devices for estrus detection is a common practice in dairy operations. It remains unclear if this same artificial intelligence software can accurately measure reproductive behavior in beef females. We hypothesized that estrous variables detected by an accelerometer are associated with ovarian, hormonal, pregnancy outcome, and fertility-related variables measured in the cow. Fifty Bos indicus-influenced, cyclic, primiparous cows were fitted with an accelerometer collar (SCR Engineers, Israel) and a breeding indicator (Estrotectâ) to detect estrus after a synchronization protocol in five subsequent experimental replicates (n = 50*5 = 250). Only cows that showed estrus (d 0) remained in the study. The following variables were used from the accelerometer software: Activity Peak, Rumination Nadir, Estrus Duration, and Heat Index, calculated by proprietary algorithms. Dominant follicle (DF) diameter and plasma concentration of estradiol were measured on d -2 (day of progesterone device removal) and on d 0. On d -1 and d 4, endometrial thickness and luminal fluid accumulation were measured by ultrasonography. On d 7, two embryos were transferred/cow. Pregnancies were diagnosed on d 45 and terminated. After 30 d, a new replicate started. Cows included in at least two replicates that remained pregnant 100%, 99-50%, or less than 50% were classified as fertile, sub fertile, and infertile, respectively. Estrus display was recorded for 166 cows (66%). Estrus detection by accelerometer and Estrotect had excellent agreement rate (kappa coefficient 0.76). Cows detected in estrus only by Estrotect had 66% less pregnancy/ET than cows in estrus by both (9/21 vs. 97/145; P = 0.01). The DF diameter on d 0 was not associated with accelerometer variables. Cows with greater and moderate Activity Peak had a greater growth rate of the DF from d -2 to d 0 than lower Activity Peak cows (interaction day*Activity Peak; P = 0.06). Estradiol on d -1 was positively associated with the Activity Peak (P &amp;lt; 0.0001). Cows with lower Activity Peak had a thicker endometrium on both d -1 and d 4 (P=0.02), and greater uterine luminal fluid score on d -1 (P=0.03). Fertility status was not associated with any accelerometer variables. In conclusion, the Activity Peak is associated positively with estradiol concentration and DF growth, however no association was found with pregnancy outcome and fertility. Therefore, the main advantage of accelerometers in beef ranches is the ability to detect estrus at a similar accuracy as breeding indicators, using less labor. Future enhancements in hardware and software to allow prediction of pregnancy outcomes are expected to increase reproductive efficiency in cow-calf operations.

Mechanisms of adverse mammary effect induced by olanzapine and therapeutic interventions in rat model.

BackgroundOlanzapine antagonizes dopamine receptors and is prescribed to treat multiple psychiatric conditions. The main side effect of concern for olanzapine is weight gain and metabolic syndrome. Olanzapine induces hyperprolactinemia, however its effect on the mammary gland is poorly documented. MethodsRats received olanzapine by gavage or in drinking water at 1, 3, and 6 mg/kg/day for 5–40 days or 100 days, with and without coadministration of bromocriptine or aripiprazole and using once daily or continuous administration strategies. Histomorphology of the mammary gland, concentrations of prolactin, estradiol, progesterone, and olanzapine in serum, mammary gland and adipose tissue, and mRNA and protein expressions of prolactin receptors were analyzed. ResultsIn adult and prepubescent female rats and male rats, olanzapine induced significant development of mammary glands in dose- and time-dependent manners, with histopathological hyperplasia of mammary ducts and alveoli with lumen dilation and secretion, marked increase of mammary prolactin receptor expression, a marker of breast tissue, and with mild increase of circulating prolactin. This side effect can be reversed after medication withdrawal, but long-term olanzapine treatment for 100 days implicated tumorigenic potentials indicated by usual ductal epithelial hyperplasia. Olanzapine induced mammary development was prevented with the coaddition of the dopamine agonist bromocriptine or partial agonist aripiprazole, or by continuous administration of medication instead of a once daily regimen. ConclusionsThese results shed light on the previously overlooked effect of olanzapine on mammary development and present experimental evidence to support current clinical management strategies of antipsychotic induced side effects in the breast.

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

AbstractObjectiveTo 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.MethodsWithin 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.ResultsOverall, 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).ConclusionsEstradiol and progesterone levels in the second trimester vary between pregnant women with a live and demised foetus.