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Across vertebrate species, gonadal hormones coordinate physiology with behavior to facilitate social interactions essential for reproduction and survival. In adulthood, these hormones activate neural circuits that regulate behaviors presenting differently in females and males, such as parenting and territorial aggression. Yet long before sex-typical behaviors emerge at puberty, transient hormone production during sensitive periods of neurodevelopment establish the circuits upon which adult hormones act. How transitory waves of early-life hormone signaling exert lasting effects on the brain remains a central question. Here we discuss how perinatal estradiol signaling organizes cellular and molecular sex differences in the rodent brain. We review classic anatomic studies revealing sex differences in cell number, volume, and neuronal projections, and consider how single-cell sequencing methods enable distinction between sex-biased cell-type abundance and gene expression. Finally, we highlight the recent discovery of a gene regulatory program activated by estrogen receptor α (ERα) following the perinatal hormone surge. A subset of this program displays sustained sex-biased gene expression and chromatin accessibility throughout the postnatal sensitive period, demonstrating a bona fide epigenetic mechanism. We propose that ERα-expressing neurons throughout the social behavior network use similar gene regulatory programs to coordinate brain sexual differentiation.

We show that hypertension is evident in female 5-HT-deficient TPH2−/− rats when sex hormones are controlled, an effect most evident upon the transition to REM sleep. In addition, our data strongly suggest that increased sympathetic vascular tone contributes to the hypertension present in this 5-HT-deficient model of neurogenic hypertension.

Background: Prior research suggests that women with endometriosis are at greater risk of coronary heart disease. Therefore, our objective was to prospectively investigate the association between laparoscopically confirmed endometriosis and risk of incident stroke during 28 years of follow-up. Methods: Participants in the NHSII cohort study (Nurses’ Health Study II) were followed from 1989 when they were between the ages of 25 to 42 until 2017 for development of incident stroke (ischemic and hemorrhagic). Cox proportional hazard models were used to calculate hazard ratios and 95% CI, with adjustment for potential confounding variables (alcohol intake, body mass index at age 18, current body mass index, age at menarche, menstrual cycle pattern in adolescence, current menstrual cycle pattern, parity, oral contraceptive use history, smoking history, diet quality, physical activity, NSAID use, aspirin use, race/ethnicity, and income). We estimated the proportion of the total association mediated by history of hypertension, hypercholesterolemia, hysterectomy/oophorectomy, and hormone therapy. We also tested for effect modification by age (≥ 50 years), infertility history, body mass index (≥ 25 kg/m 2 ), and menopausal status. Results: We documented 893 incident cases of stroke during 2 770 152 person-years of follow-up. Women with laparoscopically confirmed endometriosis had a 34% greater risk of stroke in multivariable-adjusted models (hazard ratio, 1.34 [95% CI, 1.10–1.62]), compared to those without a history of endometriosis. Of the total association of endometriosis with risk of stroke, the largest proportion was attributed to hysterectomy/oophorectomy (39% mediated [95% CI, 14%–71%]) and hormone therapy (16% mediated [95% CI, 5%–40%]). We observed no differences in the relationship between endometriosis and stroke by age, infertility history, body mass index, or menopausal status. Conclusions: We observed that women with endometriosis were at elevated risk of stroke. Women and their health care providers should be aware of endometriosis history, maximize primary cardiovascular prevention, and discuss signs and symptoms of cardiovascular disease.

Fracture rates have been reported to be higher among older women living with HIV (WLWH) than HIV- women. Hormone therapy with estrogen can reduce vasomotor symptoms (VMS) associated with menopause and prevent fractures. As data are limited on the benefits of hormone therapy use in WLWH, we examined associations of hormone therapy, use and fractures.A prospective study of 1765 (1350 WLWH and 415 HIV-) postmenopausal Women's Interagency HIV Study (WIHS) participants was performed, including self-reported hormone therapy, use and fracture data from 2003 to 2017. Proportional hazard models determined predictors of new fractures at any site or at typical fragility fracture sites (hip, spine, wrist).At the first postmenopausal visit, the median (IQR) age of WLWH was slightly younger than HIV- women [49.8 (46.4-53) vs. 50.7 (47.5-54), P = 0.0002] and a smaller proportion of WLWH reported presence of VMS (17% vs. 26%, P 0.0001). A greater proportion of WLWH than HIV- women reported hormone therapy use (8% vs. 4%, P = 0.007) at the first postmenopausal visit. In multivariate analyses, white race and smoking were significant predictors of incident fracture at any site but hormone therapy ( P = 0.69) and HIV status ( P = 0.53) were not.Our study did not find evidence of benefit or harm with regards to fracture outcomes in postmenopausal WLWH receiving hormone therapy. Further research is needed to determine whether hormone therapy has benefits beyond treatment of VMS, such as prevention of adverse aging-associated outcomes.

Many anticancer therapies (CTx) have cardiotoxic side effects that limit their therapeutic potential and cause long-term cardiovascular complications in cancer survivors. This has given rise to the field of cardio-oncology, which recognizes the need for basic, translational, and clinical research focused on understanding the complex signaling events that drive CTx-induced cardiovascular toxicity. Several CTx agents cause mitochondrial damage in the form of mitochondrial DNA deletions, mutations, and suppression of respiratory function and ATP production. In this review, we provide a brief overview of the cardiovascular complications of clinically used CTx agents and discuss current knowledge of local and systemic secondary signaling events that arise in response to mitochondrial stress/damage. Mitochondrial oxidative stress has long been recognized as a contributor to CTx-induced cardiotoxicity; thus, we focus on emerging roles for mitochondria in epigenetic regulation, innate immunity, and signaling via noncoding RNAs and mitochondrial hormones. Because data exploring mitochondrial secondary signaling in the context of cardio-oncology are limited, we also draw upon clinical and preclinical studies, which have examined these pathways in other relevant pathologies.

Introduction: The Krebs cycle is an important set of reactions that synthesize different molecules and substances that affect various organs. The objective of this paper was to compare the effects of Krebs cycle intermediates on the endocrine system and the immune system. Methods and Materials: The articles used in this paper were obtained from a systematic search of PsycINFO, PubMed, Web of Science, CINAHL, and primary databases. The search terms were “Krebs cycle,” “intermediates,” “endocrine system,” “tricarboxylic acid,” “citric acid cycle,” and “immune system,” and Boolean operators (AND/OR) were used to combine terms. Results: A review of the selected studies showed that Krebs cycle intermediates influence how the endocrine system regulates and controls body processes, including energy uptake. Moreover, these intermediates have both direct and indirect effects on immune function, memory, and activation. Discussion: An understanding of the effects of Krebs cycle intermediates on endocrine and immune processes will provide valuable insights for the development of new therapies. Additionally, this knowledge is a basis for exploring the pathogenesis of the complications related to endocrine system function and for evaluating the immune system response to pathogens. Conclusions: The evidence gathered in this review shows that Krebs cycle intermediates have significant effects on immune and endocrine processes. However, further human and in vivo studies are required to generate additional evidence for the underlying pathways and to identify the potential strategies for targeting these mechanisms to manage specific disorders.

INTRODUCTION: Patients often discuss information obtained from Internet sources during clinic visits, which can be of variable quality and depth. We sought to review and assess information on the Internet regarding common operations within endocrine surgery. METHODS: Using Google’s search engine, the top 100 websites from the search phrase “parathyroid surgery,” and the top 100 websites from the phrase “thyroid surgery” were identified. Each website was evaluated for accessibility, accuracy, and completeness of information about gland hormone function, associated disease processes, and surgery itself. Results were stratified based on the website type, and bivariate analysis was performed to determine accuracy by category. Presence of author credentials, last webpage update, and presence of advertisements were also assessed. Inter-rater reliability was calculated for each variable. RESULTS: For parathyroid surgery, at least two-thirds of all websites included information about surgery, hormone function, and disease processes. For thyroid surgery, 71% of websites included procedure information, but only 52% included information about hormone function and 56% about disease processes. Less than 30% of all websites included advertisements and less than 25% listed author credentials or provided references. Academic or research-affiliated sources were most likely to have zero inaccuracies, but 44% of all websites had at least one potential inaccuracy. Inter-rater reliability achieved at least moderate agreement (>0.41) for 56% of variables. CONCLUSIONS: There is a wide array of information available to patients online, and accuracy varies based on multiple factors including the type of website. Endocrine surgeons and related practitioners must be cognizant of this fact when discussing treatment plans with patients.

Bronchopulmonary dysplasia (BPD) is a disease with a significant sexual dimorphism where males have a disadvantage compared with their female counterparts. Although mechanisms behind this sexual dimorphism are poorly understood, sex differences in angiogenesis have been identified as one possible source of the male disadvantage in BPD. Pulmonary angiogenesis was assessed in vitro using a bead sprouting assay with pooled male or female human pulmonary microvascular endothelial cells (HPMECs, 18-19 wk gestation, canalicular stage of human lung development) in standard (sex-hormone containing) and hormone-stripped medium. We identified sex-specific phenotypes in angiogenesis where male HPMECs produce fewer but longer sprouts compared with female HPMECs. The presence of sex hormones from standard culture medium modifies the male HPMEC phenotype with shorter and fewer sprouts but does not influence the female phenotype. Using a conditioned medium model, we further characterized the influence of the sex-specific secretome. Male and female HPMECs secrete factors that increase the maximum length of sprouts in female, but not male HPMECs. The presence of sex hormones abolishes this response. The male HPMEC secretome inhibits angiogenic sprouting in male HPMECs in the absence of sex hormones. Taken together, these results demonstrate that the pulmonary endothelial cell phenotypes are influenced by sex hormones and sex-specific secreted factors in a sex-dependent manner.

Anabolic deficiencies play a pivotal role in left-sided heart failure. Little is known about their impact on idiopathic pulmonary arterial hypertension (iPAH). Therefore, the aim of this study was to assess the impact of multiple hormone-metabolic deficiencies on clinical features and outcomes in idiopathic pulmonary arterial hypertension. We have demonstrated that the assessment of anabolic hormone levels in patients with iPAH allows the identification of a subpopulation with worse exercise capacity, pulmonary hemodynamics, right ventricular size, and function generating the hypothesis about the potential role of hormonal replacement therapy. These data should be confirmed by larger studies.

PURPOSE Metastasis-free survival (MFS), but not event-free survival, is a validated surrogate end point for overall survival (OS) in men treated for localized prostate cancer. It remains unknown if this holds true in biochemically recurrent disease after radical prostatectomy. Leveraging NRG/RTOG 9601, we aimed to determine the performance of intermediate clinical end points (ICEs) as surrogate end points for OS in recurrent prostate cancer. MATERIALS AND METHODS NRG/RTOG 9601 randomly assigned 760 men with recurrence after prostatectomy to salvage radiation therapy with 2 years of placebo versus bicalutamide 150 mg daily. ICEs assessed were biochemical failure (BF) per NRG/RTOG 9601 (prostate-specific antigen nadir + 0.3-0.5 ng/mL or initiation of salvage hormone therapy; [BF1]) and NRG/RTOG 0534 (prostate-specific antigen nadir+2 ng/mL; [BF2]), distant metastasis (DM), and MFS (DM or death). Surrogacy was assessed by the Prentice criteria and a two-stage meta-analytic approach (condition one assessed at the patient level with Kendall's τ and condition two assessed by randomly dividing the entire trial cohort into 10 pseudo trial centers and calculating the average R2 between treatment hazard ratios for ICE and OS). RESULTS BF1, BF2, DM, and MFS satisfied the four Prentice criteria. However, with the two-condition meta-analytic approach, there was strong correlation between MFS and OS (τ = 0.86), moderate correlation between DM and OS (τ = 0.66), and weaker correlation between BF1 (τ = 0.25) or BF2 (τ = 0.40) and OS. Similarly, for condition two, the treatment effect of antiandrogen therapy on MFS and OS were correlated ( R2 = 0.67), but this was not true for BF1 ( R2 = 0.09), BF2 ( R2 = 0.12), or DM ( R2 = 0.18) and OS. CONCLUSION MFS is also a strong surrogate for OS in men receiving salvage radiation therapy for recurrence after prostatectomy. Caution should be used when inferring survival benefit from effects on BF in biochemically recurrent prostate cancer. Lack of comorbidity data did not allow us to assess whether BF in men with no/minimal comorbidity could serve as a surrogate for OS.

Most endocrine disorders are chronic in nature, and thus even a minor effect to increase risk for cardiovascular disease can lead to a significant impact over prolonged duration. Although robust therapies exist for many endocrine disorders (eg suppression of excess hormone amounts, or replacement of hormone deficiencies), the therapies do not perfectly restore normal physiology. Thus, individuals with endocrine disorders are at potential increased cardiovascular disease risk, and maximizing strategies to reduce that risk are needed. This article reviews various endocrine conditions that can impact lipid levels and/or cardiovascular disease risk.

Military operational stress is known to increase adrenal hormones and inflammatory cytokines, while decreasing hormones associated with the anabolic milieu and neuroendocrine system. Less is known about the role of extracellular vesicles (EVs), a form of cell-to-cell communication, in military operational stress and their relationship to circulating hormones. The purpose of this study was to characterize the neuroendocrine, cytokine, and EV response to an intense. 24-h selection course known as the Naval Special Warfare (NSW) Screener and identify associations between EVs and cytokines. Blood samples were collected the morning of and following the NSW Screener in 29 men (18-26 yr). Samples were analyzed for concentrations of cortisol, insulin-like growth factor I (IGF-I), neuropeptide-Y (NPY), brain-derived neurotrophic factor (BDNF), α-klotho, tumor necrosis factor-α (TNFα), and interleukins (IL) -1β, -6, and -10. EVs stained with markers associated with exosomes (CD63), microvesicles (VAMP3), and apoptotic bodies (THSD1) were characterized using imaging flow cytometry and vesicle flow cytometry. The selection event induced significant changes in circulating BDNF (−43.2%), IGF-I (−24.6%), TNFα (+17.7%), and IL-6 (+13.6%) accompanied by increases in intensities of THSD1+ and VAMP3+ EVs (all P < 0.05). Higher concentrations of IL-1β and IL-10 were positively associated with THSD1+ EVs ( P < 0.05). Military operational stress altered the EV profile. Surface markers associated with apoptotic bodies were positively correlated with an inflammatory response. Future studies should consider a multiomics assessment of EV cargo to discern canonical pathways that may be mediated by EVs during military stress.

The objective:to study the structure of gynecological pathology and the hormonal background in women with infertility and various types of thyroid pathology. Materials and methods.The anamnesis of infertile patients was studied. The women, depending on the pathology of the thyroid gland and the method of fertilization were divided into the following groups: the 1st group included 119 women with infertility without thyroid pathology who became pregnant after the use of assisted reproductive technologies (ART); the 2nd group – 47 patients who became pregnant with the help of ART and in whom antibodies to thyroid peroxidase (anti-TPO antibodies) were detected; the 3rd group – 30 women with compensated hypothyroidism, whose pregnancy occurred with ART; the 4th group – 39 women without thyroid pathology and with spontaneous pregnancy; the 5th group – 128 patients with compensated hypothyroidism and spontaneous pregnancy. The concentrations of the following hormones in the blood plasma in the early follicular phase were determined in all the patients: luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, prolactin, testosterone, cortisol, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate. Results.There were no significant differences between the women with infertility and thyroid pathology and the patients with spontaneous pregnancy without thyroid pathology regarding the age of menarche onset, the period of regularity onset of the menstrual cycle after menarche. The most frequent disorder of the menstrual cycle in patients of the 1st (26.9 %), 2nd (25.5 %) and 3rd (26.6 %) groups was dysmenorrhea. Oligomenorrhea was more often detected in women with infertility and thyroid pathology who became pregnant with the help of ART (25.5 % of patients in the 2nd group and 23.3% – in the 3rd group), compared to women with spontaneous pregnancy. The endocrine factor of infertility was most often determined in women with infertility who became pregnant after ART and had thyroid pathology: in the presence of anti-TPO antibodies, this factor was found in 29.8 % of women, hypothyroidism – 23.3 %. External genital endometriosis as a cause of infertility prevailed among patients with infertility without thyroid pathology, who became pregnant after ART (34.4 %), and women with compensated hypothyroidism, whose pregnancy occurred with the help of ART (26.6 %). In patients with infertility and anti-TPO antibodies, who became pregnant after ART, a significant increase of LH concentration was found compared to the patients with spontaneous pregnancy without thyroid diseases. A significant increase of FSH level was also determined in women of the 1st group compared to healthy patients with spontaneous pregnancy. Conclusions.In women with infertility and various types of thyroid pathology the disorders of the ovarian-menstrual cycle such as dysmenorrhea and oligomenorrhea are typical. The main factor of infertility in patients without thyroid diseases is external genital endometriosis, in persons with thyroid pathology – an endocrine factor. In women with infertility and various types of thyroid pathology, a significant increase of luteinizing hormone concentration in the blood plasma in the follicular phase of the menstrual cycle was established.

Background: Klotho is a longevity and neuroprotective hormone encoded by the KLOTHO gene, and heterozygosity for the KL-VS variant confers a protective effect against neurodegenerative disease. Objective: Test whether klotho concentrations in serum or cerebrospinal fluid (CSF) vary as a function of KLOTHO KL-VS genotype, determine whether circulating klotho concentrations from serum and CSF differ from one another, and evaluate whether klotho levels are associated with Alzheimer’s disease risk factors. Methods: Circulating klotho was measured in serum (n = 1,116) and CSF (n = 183) of cognitively intact participants (aged 62.4 ± 6.5 years; 69.5% female). KLOTHO KL-VS zygosity (non-carrier; heterozygote; homozygote) was also determined. Linear regression was used to test whether klotho hormone concentration varied as a function of KL-VS genotype, specimen source, and demographic and clinical characteristics. Results: Serum and CSF klotho were higher in KL-VS carriers than non-carriers. Klotho concentration was higher in CSF than in serum. Females had higher serum and CSF klotho, while younger age was associated with higher klotho in CSF. Conclusion: In a cohort enriched for risk for Alzheimer’s disease, heterozygotic and homozygotic carriers of the KL-VS allele, females, and younger individuals have higher circulating klotho. Fluid source, KL-VS genotype, age, and sex should be considered in analyses of circulating klotho on brain health.

Most studies attempting to address the health care needs of the millions of transgender, nonbinary, and/or gender-diverse (TNG) individuals rely on human subjects, overlooking the benefits of translational research in animal models. Researchers have identified many ways in which gonadal steroid hormones regulate neuronal gene expression, connectivity, activity, and function across the brain to control behavior. However, these discoveries primarily benefit cisgender populations. Research into the effects of exogenous hormones such as estradiol, testosterone, and progesterone has a direct translational benefit for TNG individuals on gender-affirming hormone therapies (GAHTs). Despite this potential, endocrinological health care for TNG individuals remains largely unimproved. Here, we outline important areas of translational research that could address the unique health care needs of TNG individuals on GAHT. We highlight key biomedical questions regarding GAHT that can be investigated using animal models. We discuss how contemporary research fails to address the needs of GAHT users and identify equitable practices for cisgender scientists engaging with this work. We conclude that if necessary and important steps are taken to address these issues, translational research on GAHTs will greatly benefit the health care outcomes of TNG people.

Uterine leiomyosarcoma (ULMS) is an aggressive malignancy for which hysterectomy is often the primary treatment approach. Due to the rarity of these tumors, the role of oophorectomy in the management of ULMS is not clearly established. This study aimed to describe the impact of oophorectomy and estrogen/progesterone (ER/PR) receptor status on clinical outcomes and survival.Women with ULMS treated between 1/2013 and 1/2018 were retrospectively identified. Clinical data was collected; descriptive statistics were performed and predictors of overall survival (OS) and event free survival (EFS) were analyzed using Cox regression and Kaplan-Meier methodology.189 patients were included. Median age was 53 years (20-84 years). The majority of patients had stage IB (58%) and grade 3 (94%) tumors. On pathologic analysis, ER/PR expression was positive in 41% and 33%, respectively. The majority of patients (179, 94.7%) underwent surgery as their primary treatment approach, of which 51 (28.5%) had ovarian conservation. 59.0% were treated with chemotherapy, while 9.9% received radiation therapy. 84.6% of patients experienced a recurrence, but there was no difference in EFS or OS by oophorectomy status, including among those with uterine confined disease. Additionally, ER/PR status was not independently associated with EFS/OS (p = 0.14, p = 0.07) nor did it impact survival among those with ovaries left in situ.Oophorectomy did not influence OS, even though many tumors were hormone receptor positive. ER/PR status was not independently associated with survival, including in the subset of women with uterine confined disease and those who had undergone oophorectomy.

Background: In the Netherlands, treatment with puberty suppression is available to transgender adolescents younger than age 18 years. When gender dysphoria persists testosterone or oestradiol can be added as gender-affirming hormones in young people who go on to transition. We investigated the proportion of people who continued gender-affirming hormone treatment at follow-up after having started puberty suppression and gender-affirming hormone treatment in adolescence. Methods: In this cohort study, we used data from the Amsterdam Cohort of Gender dysphoria (ACOG), which included people who visited the gender identity clinic of the Amsterdam UMC, location Vrije Universiteit Medisch Centrum, Netherlands, for gender dysphoria. People with disorders of sex development were not included in the ACOG. We included people who started medical treatment in adolescence with a gonadotropin-releasing hormone agonist (GnRHa) to suppress puberty before the age of 18 years and used GnRHa for a minimum duration of 3 months before addition of gender-affirming hormones. We linked this data to a nationwide prescription registry supplied by Statistics Netherlands (Centraal Bureau voor de Statistiek) to check for a prescription for gender-affirming hormones at follow-up. The main outcome of this study was a prescription for gender-affirming hormones at the end of data collection (Dec 31, 2018). Data were analysed using Cox regression to identify possible determinants associated with a higher risk of stopping gender-affirming hormone treatment. Findings: 720 people were included, of whom 220 (31%) were assigned male at birth and 500 (69%) were assigned female at birth. At the start of GnRHa treatment, the median age was 14·1 (IQR 13·0–16·3) years for people assigned male at birth and 16·0 (14·1–16·9) years for people assigned female at birth. Median age at end of data collection was 20·2 (17·9–24·8) years for people assigned male at birth and 19·2 (17·8–22·0) years for those assigned female at birth. 704 (98%) people who had started gender-affirming medical treatment in adolescence continued to use gender-affirming hormones at follow-up. Age at first visit, year of first visit, age and puberty stage at start of GnRHa treatment, age at start of gender-affirming hormone treatment, year of start of gender-affirming hormone treatment, and gonadectomy were not associated with discontinuing gender-affirming hormones. Interpretation: Most participants who started gender-affirming hormones in adolescence continued this treatment into adulthood. The continuation of treatment is reassuring considering the worries that people who started treatment in adolescence might discontinue gender-affirming treatment. Funding: None.

In most male mammals, testis undergoes increased proliferation activity and the onset of spermatogenesis during pubertal development. However, their gene expression patterns and roles in sheep remain unclear. Therefore, we used Illumina Hiseq 2000 sequencing to identify differentially expressed genes (DEGs) from 0, 30, 60, 90, 120, 150 and 180 postnatal days and characterize the transcriptional level of sheep testicular development. Among them, the DEGs changed the most in 90-150 stages. a total of 2546 (1454 up and 1092 down) and 6867 (4683 up and 2184 down) DEGs were identified in D120 vs. D90 and D150 vs. D120, respectively. Functional enrichment analysis revealed that in earlier pubertal development, testis showed higher gene expression in organ morphogenesis, vasculogenesis, neurogenesis and hormone secretion, while in later pubertal development, genes with higher expression mainly concentrated in regulating spermatogenesis process. These results indicated that testis development undergoes the transition from organ growth to spermatogenesis and the genes related to hormone secretion were expressed highly earlier than spermatogenesis during pubertal process. In addition, we found several genes such as ZFP36, TNF, HSD3B1, HSD11B2 played key roles in androgen secretion and SPAG family, SYCP family, SPATA family, SPO11, CABYR, TNP1, TNP2 and CFAP43 performed functions during spermatogenesis process. Taken together, multi-genes cooperation prompt testis development in pubertal process. Our transcriptional atlas of sheep testis provides a comprehensive insight about testicular development and pubertal process.

The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive treatments, increasing the economic burden of prostate cancer. Here, we aimed to systematically identify and review published economic evaluations (EEs) related to the treatment of mHSPC and assess their quality. A systematic search was performed of the PubMed and Cochrane databases. Three reviewers independently selected EEs by defined inclusion and exclusion criteria. They extracted all data from each EE (general information, study population, data about the EE, interventions and comparators, and outcomes). They also assessed the quality of the selected EEs according to Drummond's checklist. Fourteen EEs published between 2016 and 2021 were eligible for the systematic review. The EEs found ADT + docetaxel to be the most cost-effective of all available treatments as a first-line strategy for mHSPC (abiraterone acetate plus prednisone, enzalutamide, and apalutamide). Five EEs showed that a simple price reduction of abiraterone acetate of 50% to 75% could change the results to render this treatment also cost-effective relative to that with docetaxel. Twelve EEs were of high quality, with a Drummond score ≥ 7. Analysis of the 14 EEs identified by our systematic review, amongst which 78.6% met high quality standards, showed that ADT + docetaxel tends to be the most cost-effective alternative for mHSPC. These results were assessed by sensitivity analysis. The data provided by this systematic review help to provide a better understanding of these treatments and the better use of healthcare resources.

IGF1R plays an important role in regulating cellular metabolism and cell growth, and has been identified as an anti-cancer and diabetes drug target. Although research have been reported many crystal and cryo-EM structures of IGF1R, the mechanism of ligand binding remains controversial, mainly because the structure differences among its cryo-EM, crystal and homologous protein insulin receptor structures. Here, we further determined one new high-resolution symmetric cryo-EM structure of ligand-bound IGF1R and be the first to prove that the receptor could bind to two IGFI molecules by single particle cryo-electron microscopy. And the structure is very different from its homologous protein insulin receptor: the two ligands just exist at the binding site 2 with saturating ligand conditions. Then, our findings resolved the major dispute about the comformational changes of IGF1R, and proposed a new theory how IGF1R binds to its ligands. Meanwhile, these findings imply more attention may be needed to study the relationship between the special conformation and their corresponding physiological functions in future.

Increased utilization of chemotherapy in breast cancer patients has led to improved survival outcomes but it has also resulted in rising incidence of adverse effects. Occurrence of new/unreported side effect poses challenge in front of clinicians. We report the case of a 53-year lady with locally advanced, hormone receptor-positive, and human epidermal growth factor-2 (HER-2) negative right breast carcinoma. She was started on neoadjuvant chemotherapy (NACT) (doxorubicin and cyclophosphamide), to facilitate breast-conserving surgery. She developed an inflammatory reaction involving the affected breast after each of three cycles of NACT (2 cycles of doxorubicin & cyclophosphamide, and 1 cycle of docetaxel). Infectious causes and disease progression were ruled out. She was then prescribed hormone therapy but the disease progressed after three months of therapy and the patient had to be subjected to modified radical mastectomy (MRM). She then received adjuvant radiotherapy and is currently doing well on second-line hormone therapy.

What is the topic of this review? The aim of this systematic review was to evaluate and summarize all published literature examining the impact of various exercise training interventions on endothelial function in postmenopausal women. What advances does it highlight? There was a moderate effect of training on macrovascular and microvascular endothelial function and just under two-thirds of studies demonstrated a significant increase in at least one measure of endothelial function in postmenopausal women. Factors including exercise intensity and duration, vessel type, clinical status, hormone therapy, and menopausal status may influence the effects of training on endothelial function in postmenopausal women.Women experience a rapid decline in endothelial function during menopause. Therefore, it is important to explore interventions, such as exercise training, that may prevent endothelial dysfunction in postmenopausal women. The aim of this systematic review was to evaluate and summarize all published literature examining the impact of various exercise training interventions on endothelial function in postmenopausal women. Three electronic databases (MEDLINE, EMBASE and Web of Science) were used to systematically select studies related to exercise training, endothelial function and postmenopausal women. The major initial and secondary update systematic searches yielded 502 unique articles that were screened for eligibility. Thirty-five studies were included in the systematic review. Two-thirds of all studies demonstrated a group-level increase in at least one measure of endothelial function with training. Most studies investigating biomarkers of endothelial function showed improvement in at least one measured biomarker post-training. There was a moderate effect of training on both macrovascular and microvascular endothelial function in observational and randomized intervention studies. Variability in study designs, training protocols and participant characteristics make it difficult to directly compare studies. Factors including exercise intensity and duration, vessel type, clinical status, hormone therapy, and menopausal status may contribute to the inconsistent effects of training on endothelial function in postmenopausal women. Future research is needed in this population to understand the mechanisms driving inter-study and inter-individual differences in training-induced changes in endothelial function.

Objective: To analyze the perioperative outcomes of neoadjuvant hormone therapy (NHT) before laparoscopic and robot-assisted surgery for localized high-risk prostate cancer in a Chinese cohort. Methods: The clinical data of 385 patients with localized high-risk prostate cancer who underwent radical prostatectomy (RP) in our hospital from January 2019 to June 2021 were analyzed retrospectively, including 168 patients with preoperative NHT and 217 patients with simple surgery. Clinical characteristics were compared in the above two groups, the laparoscopic RP (LRP) cohort (n = 234) and the robot-assisted laparoscopic radical prostatectomy (RALP) cohort (n = 151), respectively. Results: In the overall cohort, compared with the control group, the NHT group had a shorter operative time, less blood loss, a lower positive surgical margin rate, and a higher proportion of Gleason score (GS) downgrading after the operation (p < 0.05). However, there was no significant difference in hospitalization time, biochemical recurrence, urine leakage, urinary continence, or prostate-specific antigen (PSA) progression-free survival (p > 0.05). In the LRP cohort, it was found that the NHT group also had shorter operative time, less blood loss, lower positive surgical margin rate, a higher proportion of GS downgrading after the operation, and faster recovery of urinary control than the control group (p < 0.05). There was no marked difference in hospitalization time, biochemical recurrence, urinary leakage, or PSA progression-free survival. However, in the RALP cohort, the NHT group had a significant difference in the GS downgrading after the operation compared with the control group (p < 0.05). In the overall cohort, multiple analyses showed that initial PSA level, GS at biopsy, clinical T stage, lymph node invasion, use of NHT, and surgical methods were significantly associated with positive surgical margin (p < 0.05) while NHT did not account for biochemical recurrence (p > 0.05). Conclusions: NHT can lower the difficulty of surgery, reduce positive surgical margin rate, and help recovery in short-term urinary control in patients with high-risk prostate cancer after LRP. However, we do not have evidence on the benefit of NHT in high-risk PCa patients treated with RALP. For these patients, surgery can be performed as early as possible.

The World Professional Association for Transgender Health (WPATH) is an international organization that aims to advocate for transgender and gender-diverse (TGD) people by promoting safe and effective ways to access and deliver healthcare to maximize psychological health and well-being. One way this is achieved is through the WPATH's published Standards of Care for the Health of Transsexual, Transgender, and Gender Nonconforming People, a set of guidelines for gender-affirming care that is based on the available science and expert consensus. In anticipation of the release of updated guidelines (Standards of Care Version 8) in 2022 the Radcliffe Institute for Advanced Study at Harvard University hosted an Exploratory Seminar in December 2021 that brought together experts from the United States, Mexico, and the United Kingdom to share knowledge across disciplines in order to propose revisions to the WPATH's updated guidelines. This article shares the workgroup's high-level consensus and recommendations.

Adipose tissue microvascular blood flow (MBF) is stimulated postprandially to augment delivery of nutrients and hormones to adipocytes. Adipose tissue MBF is impaired in type 2 diabetes (T2D). Whether healthy individuals at-risk of T2D show similar impairments is unknown. We aimed to determine whether adipose tissue MBF is impaired in apparently healthy individuals with a family history of T2D. Overnight-fasted individuals with no family history of T2D for two generations (FH

In the context of climate change, the magnitude and frequency of temperature extremes (low and high temperatures) are increasing worldwide. Changes to the lower extremes of temperature, known as cold stress (CS), are one of the recurrent stressors in many parts of the world, severely limiting agricultural production. A series of plant reactions to CS could be generalized into morphological, physiological, and biochemical responses based on commonalities among crop plants. However, the differing originality of crops revealed varying degrees of sensitivity to cold and, therefore, exhibited large differences in these responses among the crops. This review discusses the vegetative and reproductive growth effects of CS and highlights the species-specific aspect of each growth stage whereby the reproductive growth CS appears more detrimental in rice and wheat, with marginal yield losses. To mitigate CS negative effects, crop plants have evolved cold-acclimation mechanisms (with differing capability), characterized by specific protein accumulation, membrane modification, regulation of signaling pathways, osmotic regulation, and induction of endogenous hormones. In addition, we reviewed a comprehensive account of management strategies for regulating tolerance mechanisms of crop plants under CS.

Hormone-dependent gynaecological disorders, such as polycystic ovary syndrome (PCOS) or endometriosis, have been recently discussed as potential risk factors for venous thromboembolism (VTE). Combined hormonal contraceptive (CHC) therapy, which is a well-known risk factor for VTE, is usually used to alleviate symptoms related to these gynaecological disorders. Nevertheless, prevalence of hormone-dependent gynaecological disorders at the time of VTE event and the management of hormonal contraceptives are not well known.To assess retrospectively the prevalence of hormone-dependent gynaecological disorders in patients with VTE event and the hormonal therapy at the time of VTE event and at the time of inclusion in the present study.Women aged between 18 to 50-year-old who were hospitalized at Saint-Joseph Hospital (Paris) for a VTE event from January 1st, 2016 to December 31st, 2020 were included in this retrospective observational study.In total, 125 women were included. At the time of VTE event, mean age was 39-years-old (±8) and mean body mass index (BMI) 26kg/mThe present study, including 125 young women with a mean age of 39 years, allowed a description of gynecological pathologies and history of contraceptive use potentially involved in VTE events.

Selenophosphate synthetases use selenium and ATP to synthesize selenophosphate. This is required for biological utilization of selenium, most notably for the synthesis of the non-canonical amino acid selenocysteine (Sec). Therefore, selenophosphate synthetases underlie all functions of selenoproteins, which include redox homeostasis, protein quality control, hormone regulation, metabolism, and many others. This protein family comprises two groups, SelD/SPS2 and SPS1. The SelD/SPS2 group represent true selenophosphate synthetases, enzymes central to selenium metabolism which are present in all Sec-utilizing organisms across the tree of life. Notably, many SelD/SPS2 proteins contain Sec as catalytic residue in their N-terminal flexible selenium-binding loop, while others replace it with cysteine (Cys). The SPS1 group comprises proteins originated through gene duplications of SelD/SPS2 in metazoa in which the Sec/Cys-dependent catalysis was disrupted. SPS1 proteins do not synthesize selenophosphate and are not required for Sec synthesis. They have essential regulatory functions related to redox homeostasis and pyridoxal phosphate, which affect signaling pathways for growth and differentiation. In this review, we summarize the knowledge about the selenophosphate synthetase family acquired through decades of research, encompassing their structure, mechanism, function, and evolution.

Objective To verify the association between vocal perception and Common Mental Disorders (CMD) suspicion in trans women. Methods Cross-sectional observational study including 24 adult trans women with a minimum time of presentation as a woman of six months. The sampling of the subjects was supported by the “Snowball" technique. Three questionnaires were applied for data collection: sociodemographic and health data, Self-Reporting Questionnaire (SRQ-20) and Trans Woman Voice Questionnaire (TWVQ). The sociodemographic and health data collected were: age, marital status, education, smoking habits, speech therapy, use of hormones, and whether they had undergone Sex Reassignment Surgery (SRG). SRQ-20 was used for suspicion of CMD evaluation, such as depressive and anxiety symptoms. TWVQ is a vocal self-report questionnaire for trans women living the full-time gender role in which they self-identify. TWVQ has a minimum score of 30 points and a maximum of 120 points. Higher scores are associated with perceptions of a higher frequency of voice-related difficulties and psychosocial impacts. For statistical analysis, data were analyzed descriptively and statistically using Fisher's and Mann-Whitney's exact tests, both with a significance level of 5%. Results The average participants’ age in this study was 28.2 years old (SD = 6.5 / minimum = 21 and maximum = 48); 83.3% were single; most (41.7%) were high school graduates; and most (95.83%) had not undergone Sex Reassignment Surgery. All subjects reported using hormones; 37.5% were smokers; 4.2% had undergone speech therapy; and the average number of years of experience in the female role was 8.8 years (SD = 7.2). The average TWVQ score was 55.4 points (SD = 4.3). Through SRQ-20, it was verified the prevalence of suspected CMD in 58.3% of the participants. The study results indicated that communicative dissatisfaction in trans women due to inconsistent voice with the recognized gender is associated with probable CMD such as depression and anxiety (P= 0.001). Conclusion Trans women who reported greater difficulties and voice-related effects in their lives had more symptoms of anxiety and depression. Although more research is needed, results indicate the need for inter-professional preventive and therapeutic actions directed towards assisting trans women. This fact encourages reflection on the care of this population and the role of health professionals, enhancing scientific production, clinical practice and the inclusion of the “transsexuality” theme in Speech Language and Hearing Sciences.

The rhizosphere is the region around the plant roots where maximum microbial activities occur. In the rhizosphere, microorganisms' beneficial and harmful activities affect plant growth and development. The mutualistic rhizospheric bacteria which improve plant growth and health are known as plant growth-promoting rhizobacteria (PGPR). They are very important due to their ability to help the plant in diverse ways. PGPR such as Pseudomonas, Bacillus, Azospirillum, Azotobacter, Arthrobacter, Achromobacter, Micrococcus, Enterobacter, Rhizobium, Agrobacterium, Pantoea and Serratia are now very well known. Rhizomicrobiome plays critical roles in nutrient acquisition and assimilation, improved soil texture, secreting and modulating extracellular molecules such as hormones, secondary metabolites, antibiotics and various signal compounds, all leading to the enhancement of plant growth and development. The microbes and compounds they secrete constitute valuable biostimulants and play pivotal roles in modulating plant stress responses. In this review, we highlight the rhizobacteria diversity and cutting-edge findings focusing on the role of a PGPR in plant growth and development. We also discussed the role of PGPR in resisting the adverse effects arising from various abiotic (drought, salinity, heat, heavy metals) stresses.

The transgender community has expressed concerns regarding drug-drug interactions between HIV-pre-exposure prophylaxis (PrEP) and gender-affirming hormones. In this study, we evaluated emtricitabine (F, FTC)/tenofovir (TFV) disoporoxil fumarate (TDF) pharmacokinetics (PK) among adolescent and young adult transgender persons receiving gender-affirming hormone therapy (GAHT). This was a prospective, observational study among transgender women (TW) and men (TM) without HIV, 15-24 years of age, receiving GAHT (estradiol with/without spironolactone, or testosterone). Participants received 1 month of directly observed daily F/TDF. Weekly convenience blood samples were collected for plasma TFV and FTC, and intracellular TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP) in peripheral blood mononuclear cells (PBMC) and dried blood spots (DBS). After 2-3 weeks of F/TDF dosing, intensive PK sampling was conducted. PK parameters were estimated using noncompartmental methods. Data were log-transformed and compared between TM and TW, and to historical data among cisgender adults. Plasma TFV exposures were similar between TM and TW [geometric mean ratio (GMR); confidence interval (95% CI): 1.06 (0.89-1.28)], whereas FTC plasma exposures were 21% higher in TM versus TW (95% CI: 1.07-1.38). TFV-DP in PBMC and DBS and FTC-TP in DBS did not differ between TM versus TW after controlling for creatinine clearance (CrCl), but FTC-TP in PBMC remained 46% (95% CI: 1.15-1.86) higher in TM versus TW. All PK exposures were within expected ranges based on historical studies. TM had higher FTC exposures compared with TW, but overall plasma and intracellular exposures for both drugs were within the range of historical studies, suggesting high PrEP efficacy will be retained in adolescent and young adult transgender persons. Registered at ClinicalTrials.gov (NCT03652623).

The gay frog has taken on a surprisingly prominent role in contemporary environmental culture. Primarily associated with American shock jock Alex Jones and the so-called alt-right, fears of frogs being turned gay by hormones in water have nevertheless entered the mainstream, while gay frog memes are shared online by users from across the political spectrum. This article offers a genealogy of the gay frog, situating this recent moment in the longer history of “sex panics” over gay animals described by queer ecologists, and in the context of an ongoing backlash against feminism and trans liberation. It argues that the potency of the gay frog as alt-right symbol derives from the capacity of the frog to instantiate racialized and sexualized anxieties about border crossings. By examining the role of humor in gay frog clips and memes, this article shows how liberal mockery of Jones has inadvertently mainstreamed far-right beliefs and served to consolidate alt-right notions of victimhood. In spite of this, it argues that the comic potential of the gay frog holds promise for queer ecologists seeking to think differently about sex and nature.

Although there are current studies on breast cancer brain metastasis, population-level analysis is still lacking. As treatment for metastatic breast cancer has improved, an updated population-level analysis is necessary. Our aim was to use the SEER database to characterize the incidence and survival of patients with brain metastases at the initial diagnosis of breast cancer.Patients with breast cancer from 2010 to 2018 were identified using the SEER database. The stratified incidence and median survival of patients with BM at diagnosis were described. Multivariate logistic and Cox regression were performed to determine the covariates associated with brain metastasis and survival outcomes, respectively. Multiple comparisons based on Cox proportional hazards model were performed for the analysis of interactive effects on overall survival.A total of 2,248 patients with brain metastases at the initial diagnosis of breast cancer were identified, accounting for 0.40% of all patients with breast cancer, and 7.26% of patients with metastatic disease. Incidence proportions were highest, and survival outcomes were worst among patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive and triple-negative subtypes. For patients with brain metastases, the prognostic differences among different molecular subtypes have been gradually narrowing, and the survival benefits from various treatment methods have been all increased over time.Our study provides an updated population-level estimate of the incidence and survival for patients with brain metastases at the diagnosis of breast cancer, thus may help early identification, prognostic stratification and treatment planning for such patients.

The effect of systemic hormone therapy (HT) on dementia risk is unclear. Our aim was to investigate the association between HT and dementia.This register-based study consists of a nested case-control study and a co-twin control design, which controls for familial confounding, including shared genetics.Through Danish national registries from 1995 to 2011, we identified: a) 2700 female singletons with incident dementia and 13,492 matched controls; b) 288 female twins with incident dementia and co-twins without dementia. Data on HT and education were retrieved, and analyses were performed using conditional logistic regression and McNemar's χThe odds ratio (OR) for the association between systemic HT and dementia was 1.05, 95% CI = [0.93-1.19] in singletons and 2.10, 95% CI = [0.99-4.46] in twins. A statistically significant association was found for systemic HT before 2003 in both populations, with an OR of 1.14, 95% CI = [1.01-1.28] in singletons and an OR of 2.20, 95% CI = [1.04-4.65] in twins.Using Danish nationwide registries and controlling for education and for familial factors in a subsample, systemic HT was found to be associated with increased dementia risk if used before 2003, when HT was more commonly prescribed.

Alzheimer's disease (AD) is a central nervous system disease that can lead to cognitive impairment and progressive memory loss. An increasing number of studies have shown that intestinal flora play a crucial role in regulating the brain-gut axis. Short-chain fatty acids are metabolites of intestinal flora that regulate hormone synthesis and play an essential role in microbial-intestinal-brain communication. An imbalance of intestinal flora can promote microglia to secrete proinflammatory factors, cause nerve inflammation, and then affect cognitive and learning ability. However, the mechanism is not clear. From this, we infer that endogenous hormones may be the medium for intestinal flora to affect the process of AD. This review of the relationships among AD, endogenous hormones, and intestinal flora expounds on the critical role of various hormones in the brain-gut axis. It discusses intervention measures aimed at intestinal flora to prevent or delay AD occurrence. Finally, the potential development prospects of fecal microbiota transplantation in treating AD are put forward, which provide potential ideas for future AD research.

To date, an identification protocol for endocrine disruptors that bind to the thyroid hormone receptor (TR) has not been established. A method for screening and identifying TR-binding substances is highly required due to the existence of unknown TR-binding substances from the environment. Here, we conceived a chromatographic method using a molecularly imprinted polymer (MIP) to create a novel screening protocol for the endocrine disruptors. A receptor-imitating MIP was prepared using

OBJECTIVE: To extend knowledge about the long-term use of hormones in hormone therapy or oral contraception as prognostic factors in breast cancer. METHODS: The MCC-Spain project is a cohort of 1,685 women with incident breast cancer recruited in Spain. Recruitment was carried out between 2007 and 2010, and the follow-up finished in December 2017. The impact of hormone therapy or oral contraception on breast cancer prognosis was analyzed considering year of birth and menopausal status (1,095 women [65%] were postmenopausal). Hazard ratios (HRs) were estimated using Cox regression models. Death by any cause was considered as the event, and hormone therapy or oral contraception were analyzed as regressors. RESULTS: Oral contraception use for less than 5 years shows an HR of 1.10 (95% CI, 0.75 to 1.62), whereas use for 5 or more years shows an HR of 1.46 (95% CI, 0.95 to 2.25), with a P trend of 0.01, showing a dose-dependent response. Regarding hormone therapy and restricting the analysis to postmenopausal women born between1940 and 1959, where most hormone therapy (consumption) is concentrated, the results did not show any trend. CONCLUSION: Concerning oral contraception use, our results demonstrate that their use is related to poor prognosis in breast cancer. However, research in this field is limited and controversial, indicating the need for more research in this area. Regarding hormone therapy consumption, our results indicate no association with better prognosis, which contradicts what has previously been published.

Diabetic nephropathy (DN) is one microvascular complication of diabetes. About 30% of diabetic patients can develop DN, which is closely related to the high incidence and mortality of heart diseases, and then develop end-stage renal diseases. Therefore, early detection and screening of high-risk patients with DN is important. Herein, we explored the differences of serum transcriptomics between DN and non-DN in type II diabetes mellitus (T2DM) patients. We obtained 110 target genes using weighted correlation network analysis. Gene Ontology enrichment analysis indicates these target genes are mainly related to membrane adhesion, alpha-amino acid biosynthesis, metabolism, and binding, terminus, inhibitory synapse, clathrinid-sculpted vesicle, kinase activity, hormone binding, receptor activity, and transporter activity. Kyoto Encyclopedia of Genes and Genomes analysis indicates the process of DN in diabetic patients can involve synaptic vesicle cycle, cysteine and methionine metabolism, N-Glycan biosynthesis, osteoclast differentiation, and cAMP signaling pathway. Next, we detected the expression levels of hub genes in a retrospective cohort. Then, we developed a risk score tool included in the prediction model for early DN in T2DM patients. The prediction model was well applied into clinical practice, as confirmed by internal validation and several other methods. A novel DN risk model with relatively high prediction accuracy was established based on clinical characteristics and hub genes of serum detection. The estimated risk score can help clinicians develop individualized intervention programs for DN in T2DM. External validation data are required before individualized intervention measures.

The landscape of metastatic hormone sensitive prostate cancer (mHSPC) has evolved rapidly in recent years with new data from landmark trials supporting upfront treatment intensification. The developments come not only on the fronts of systemic agents but also in area of therapy to primary tumour and metastases.More recently, the ARASENS and PEACE trials have taken the concept of treatment intensification further by demonstrating survival benefit from combination of chemotherapy (docetaxel) and androgen receptor pathway inhibitors (abiraterone and darolutamide) in addition to backbone therapy of androgen deprivation therapy (ADT). Intensification of treatment has also seen evidence supporting local therapy to the primary tumour with overall survival and biochemical recurrence-free survival although only evident in low volume synchronous metastases. There is emerging evidence for metastases-directed therapy as well with pooled data suggesting improved biochemical-free and ADT-free survival.Robust clinical data has demonstrated survival benefits with treatment intensification and this should be the new standard of care. Subgroup analysis has highlighted the importance of tailoring mHSPC treatment for patients with high- and low-volume metastatic disease. However, defining the volume of disease is becoming increasingly controversial due to heterogeneity of trial patient populations and next generation molecular imaging.

Official public health pronouncements about sun exposure and vitamin D can be summarized as follows: First, there is no such thing as a safe tan. Therefore, avoid exposing the skin to sunshine. Second, in the absence of sunshine, a daily intake of 800 IU/day (20 mcg/d) vitamin D or less is sufficient for the health needs of almost all members of the population. However, exposure of the skin to sunlight induces multiple mechanisms that lower blood pressure, while also initiating production of vitamin D, which is needed to produce a hormone that regulates multiple systems including the cellular biology that affects cancer mortality. Disease-prevention relationships point to a beneficial threshold for serum 25-hydroxyvitamin D [25(OH)D; the index of vitamin D nutrition] that is at least 75 nmol/l (30 ng/ml). To ensure the threshold for all adults, an average per-day minimum total input of vitamin D3 from sunshine/UVB exposure, and/or from food (natural food like fish or fortified food like milk), and/or vitamin supplementation of at least 4,000 IU/d (100 mcg/d) is required. Strong, although not Level-1, evidence indicates that the maintenance of that threshold will lower mortality overall, lower mortality from cancer, and lower the risk of certain other diseases such as respiratory infection and COVID-19.

Acrylamide is classified as a probable human carcinogen by the International Agency for Research on Cancer but epidemiologic evidence on the carcinogenicity of acrylamide from dietary sources is limited.This study aimed to investigate the associations between dietary acrylamide and breast cancer risk in the NutriNet-Santé cohort, accounting for menopausal and hormone receptor status.This prospective cohort study included 80,597 French females (mean ± SD age at baseline: 40.8 ± 14 y) during a mean ± SD follow-up of 8.8 ± 2.3 y. Acrylamide intake was evaluated using repeated 24-h dietary records (n ± SD = 5.5 ± 3.0), linked to a comprehensive food composition database. Associations between acrylamide intake and breast cancer risk (overall, premenopausal, and postmenopausal) were assessed by Cox hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors).The mean ± SD dietary acrylamide intake was 30.1 ± 21.9 µg/d (main contributors: coffee, potato fries and chips, pastries, cakes, bread). During follow-up, 1016 first incident breast cancer cases were diagnosed (431 premenopausal, 585 postmenopausal). A borderline significant positive association was observed between dietary acrylamide exposure and breast cancer risk overall (HR for quartile 4 compared with 1: 1.21; 95% CI: 1.00, 1.47) and a positive association was observed with premenopausal cancer (HRQ4vs.Q1: 1.40; 95% CI: 1.04, 1.88). Restricted cubic spline analyses suggested evidence for nonlinearity of these associations, with higher HRs for intermediate (quartile 2) and high (quartile 4) exposures. Receptor-specific analyses revealed positive associations with estrogen receptor-positive breast cancer (total and premenopausal). Acrylamide intake was not associated with postmenopausal breast cancer.Results from this large prospective cohort study suggest a positive association between dietary acrylamide and breast cancer risk, especially in premenopausal females, and provide new insights that support continued mitigation strategies to reduce the content of acrylamide in food.This trial was registered at clinicaltrials.gov as NCT03335644.

Short-term starvation and severe food deprivation (FD) reduce dietary iron absorption and restricts iron to tissues, thereby limiting the amount of iron available for erythropoiesis. These effects may be mediated by increases in the iron regulatory hormone hepcidin; however, whether mild to moderate FD has similar effects on hepcidin and iron homeostasis is not known.To determine the effects of varying magnitudes and durations of FD on hepcidin and indicators of iron status in male and female mice.Male and female C57BL/6J mice (14 wk old; n = 170) were randomly assigned to consume AIN-93M diets ad libitum (AL) or varying magnitudes of FD (10%, 20%, 40%, 60%, 80%, or 100%). FD was based on the average amount of food consumed by the AL males or females, and food was split into morning and evening meals. Mice were euthanized at 48 h and 1, 2, and 3 wk, and hepcidin and indicators of iron status were measured. Data were analyzed by Pearson correlation and one-way ANOVA.Liver hepcidin mRNA was positively correlated with the magnitude of FD at all time points (P 0.05). At 3 wk, liver hepcidin mRNA increased 3-fold with 10% and 20% FD compared with AL and was positively associated with serum hepcidin (R = 0.627, P 0.0001). Serum iron was reduced by ∼65% (P ≤ 0.01), and liver nonheme iron concentrations were ∼75% greater (P ≤ 0.01) with 10% and 20% FD for 3 wk compared with AL. Liver hepcidin mRNA at 3 wk was positively correlated with liver Bmp6 (R = 0.765, P 0.0001) and liver gluconeogenic enzymes (R =0.667, P 0.05) but not markers of inflammation (P 0.05).FD increases hepcidin in male and female mice and results in hypoferremia and tissue iron sequestration. These findings suggest that increased hepcidin with FD may contribute to the disturbances in iron homeostasis with undernutrition.

Background: The substantial female hormone fluctuations associated with pregnancy and postpartum have been linked to a greater risk of developing depressive symptoms, particularly in high-risk women (HRW), i.e. those with histories of mood sensitivity to female hormone fluctuations. We have shown that glutamate (Glu) levels in the medial prefrontal cortex (MPFC) decrease during perimenopause, a period of increased risk of developing a major depressive episode. Our team has also demonstrated that percentage gray matter (%GM), another neural correlate of maternal brain health, decreases in the MPFC during pregnancy. Objective: To investigate MPFC Glu levels and %GM from late pregnancy up to 7 weeks postpartum in HRW and healthy pregnant women (HPW). Methods: Single-voxel spectra were acquired from the MPFC of 41 HPW and 22 HRW using 3- Tesla in vivo proton magnetic resonance spectroscopy at five different time points. Results: We observed a statistically significant interaction between time and group for the metabolite Glu, with Glu levels being lower for HRW during pregnancy and early postpartum (p Conclusion: This investigation suggests that the vulnerability towards PPD is associated with unique fluctuations of MPFC Glu levels during pregnancy and early postpartum period. Our results also suggest that the decline in MPFC %GM associated with pregnancy seems to progressively recover over time. Further investigations are needed to determine the specific role that female hormones play on the physiological changes in %GM during pregnancy and postpartum.

To explore the mechanism of intracavitary physiotherapy combined with acupuncture to improve the receptivity of thin endometrium.From October 2020 to April 2021, 40 patients diagnosed with thin endometrium and preparing for hormone replacement cycle freeze-thaw embryo transfer in our centre for Reproduction were included, 40 patients were randomized to treatment group and control group. 20 patients with normal endometrium during the same period were selected as the normal group.All patients underwent freeze-thaw embryo transfer using hormone replacement cycles.The treatment group added endovascular physiotherapy combined with acupuncture.The endometrial receptivity of the patients with thin endometrium was significantly lower than that of the normal group(P 0.01). Endovascular therapy combined with acupuncture can significantly increase endometrial thickness in patients with thin endometrium and the proportion of patients with type A endometrium, reduce bilateral Uterine arterial pulsatilityindex (PI), Uterine arterial resistance index (RI), and peaksystolicvelocity/diastolicvelocity (S/D), upregulate the expression of HOXA10 protein and mRNA in endometrium tissue, and improve the rate of embryo implantation and clinical pregnancy(P 0.01).there was no significant difference between the treatment group and the normal group (P 0.05). This may be related to the regulation of the AMPK/mTOR signalling pathway by intracavitary physiotherapy combined with acupuncture, downregulation of the expression of the AMPK gene and protein and upregulation of the expression of the mTOR gene and protein.1. Abnormal energy metabolism is present in the endometrium of patients with thin endometrium, which affects the autophagy process and leads to a decrease in the receptivity of thin endometrium. 2. Intracavitary physiotherapy combined with acupuncture mediated the AMPK/mTOR pathway to improve energy metabolism, promote the autophagy process, improve endometrial morphology and ultrasonic indicators of patients, upregulate the expression of endometrial receptivity-related HOXA10 genes and proteins, and improve the embryo implantation rate and clinical pregnancy rate.

It is thought that both individuals are affected psychologically and sexually in couples experiencing abortion. In addition to the stress caused by infertility, sexual life may also be negatively affected in couples who experience psychogenic wear, such as abortion and curettage. The aim of this study is to evaluate male sexual functions in infertile couples with a history of abortion and male infertility component.Five hundred forty-seven male patients' data were evaluated retrospectively. Group 1 was the included the males of the couples without abortion history and the rest with abortion history was group 2. In addition to demographic data, abortion history, libido level, presence of morning erection and intercourse frequency were evaluated. Hormone levels of all patients were evaluated. After that we created sub-group 1 and sub-group 2 from these groups, respectively, due to whether the patients fulfilled the international index of erectile function (IIEF), Beck anxiety inventory (BAI) and Beck depression inventory (BDI).There were not any significant differences between the groups regarding psychiatric scale scores, hormone levels, libido, intercourse frequency and IIEF scores. Only orgasmic dysfunction was significant in the males of the couples with abortion history.Man is not affected from abortion process in which woman get involved. Men only have orgasmic dysfunction when there is one or more abortion history in couples.

Understanding how symptoms cluster after premenopausal risk-reducing salpingo-oophorectomy (RRSO) can inform patient expectations but information is lacking. We aimed to identify symptom profiles after RRSO, changes over time, and the effect of hormone therapy (HT).Participants were premenopausal women from a longitudinal controlled study (What Happens After Menopause? (WHAM)). Menopausal symptoms were prospectively measured in three groups: pre-menopausal comparisons who retained their ovaries (n = 99), RRSO HT users (n = 57) and RRSO non-HT users (n = 38). Symptoms (hot flashes, night sweats, low desire, vaginal dryness, poor sleep, anxiety/depression) were measured at baseline (pre-surgery) and at 3, 6 and 12 months using standardised questionnaires. Latent transition analysis was used to identify symptom profiles post-RRSO, and the probability of changing profiles over time.Three symptom profiles were identified: Most Symptoms (81-87% non-HT; 36-41% HT; 7-9% comparisons), Few Symptoms (7-13% non-HT; 36-42% HT; 77-80% comparisons), and Sexual Symptoms (0-10% non-HT; 17-27% HT; 14-15% comparisons). Most of the non-HT group reported Most Symptoms at 3 months with only a 2% chance of improvement by 12 months. The HT group were split between profiles at 3 months with a 5-13% chance of improvement by 6 months (14% chance of worsening), and a 12-32% chance of improvement by 12 months (4-25% chance of worsening).Symptoms cluster into distinct profiles after premenopausal RRSO. Most non-HT users are highly symptomatic with little chance of improvement by 12 months. In contrast, two-thirds of HT users have fewer symptoms and a much higher chance of improvement. These findings can inform patient decision-making and expectations.

The participation of females in sports has increased significantly since the passage of Title IX. Sports participation may place young athletes at risk for knee injuries, including patellofemoral pain syndrome (PFPS), osteochondritis dissecans (OCD), and anterior cruciate ligament (ACL) rupture. Differences in anatomy, hormone production, and neuromuscular patterns between female and male athletes can contribute to disparities in knee injury rates with female athletes more vulnerable to PFPS and ACL injury. Biological differences between sexes alone cannot fully explain worldwide differences in musculoskeletal health outcomes. Social, cultural and societal attitudes toward gender and the participation of girls and women in sports may result in a lack of accessible training for both injury prevention and performance optimization; one must recognize the effects of gender disparities on injury risk. More nuanced approaches to assess the complex interplay among biological, physiologic, and social influences are needed to inform best practices for intervention and sports injury prevention.

Organic chromium is of great interest and has become an important chromium supplement resource in recent years because of its low toxicity and easy absorption. In our previous study, we synthesized a novel organic chromium [GLP-Cr] through the chelation of Ganoderma lucidum polysaccharide and chromium (III). The purpose of this study was to investigate the beneficial effects of GLP-Cr on the improvement of metabolic syndromes (MetS) in mice fed with a high-fat and high-fructose diet (HFHFD) and its mechanism of action. The results indicated that oral administration of GLP-Cr inhibited the excessive exaltation of body weight, glucose tolerance, fasting blood glucose and lipid levels, hepatic total cholesterol (TC), triglyceride (TG) levels caused by HFHFD. Besides, 16S rRNA amplicon sequencing showed that GLP-Cr intervention evidently ameliorated intestinal microbiota dysbiosis by changing the proportions of some intestinal microbial phylotypes. In addition, correlation network-based analysis indicated that the key intestinal microbial phylotypes were closely related to biochemical parameters associated with MetS under GLP-Cr intervention. Liver metabolomics analysis suggested that GLP-Cr intervention significantly regulated the levels of some biomarkers involved in alpha-linolenic acid metabolism, fatty acid biosynthesis, steroid hormone biosynthesis, glycerophospholipid metabolism, glycerolipid metabolism, steroid hormone biosynthesis, primary bile acid biosynthesis, and so on. Moreover, GLP-Cr intervention regulated liver mRNA levels of key genes associated with glucose and lipid metabolism. The mRNA level of glucose transporter type 4 (Glut4) was markedly increased by GLP-Cr intervention, and the mRNA levels of phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6Pase) in the liver were significantly decreased. Meanwhile, GLP-Cr intervention significantly decreased hepatic mRNA levels of cluster of differentiation 36 (Cd36), acetyl-CoA carboxylase 1 (Acc1) and sterol regulatory element binding protein-1c (Srebp-1c), indicating that GLP-Cr intervention inhibited the excessive accumulation of free fatty acids in the liver. These findings suggest that the prevention of hyperglycemia and dyslipidemia by GLP-Cr may be closely related to the regulation of gut microbial composition and hepatic metabolic pathways, thus GLP-Cr can be serving as a functional component in the prevention of MetS.

Malaria varies in severity, with complications ranging from uncomplicated to severe malaria. Severe malaria could be attributed to peripheral hyperparasitemia or cerebral malaria. The metabolic interactions between the host andiPlasmodium/ispecies are yet to be understood during these infections of varied pathology and severity. An untargeted metabolomics approach utilizing the liquid chromatography-mass spectrometry platform has been used to identify the affected host metabolic pathways and associated metabolites in the serum of murine malaria models with uncomplicated malaria, hyperparasitemia, and experimental cerebral malaria. We report that mice with malaria share similar metabolic attributes like higher levels of bile acids, bile pigments, and steroid hormones that have been reported for human malaria infections. Moreover, in severe malaria, upregulated levels of metabolites like phenylalanine, histidine, valine, pipecolate, ornithine, and pantothenate, with decreased levels of arginine and hippurate, were observed. Metabolites of sphingolipid metabolism were upregulated in experimental cerebral malaria. Higher levels of 20-hydroxy-leukotriene Bsub4/suband epoxyoctadecamonoenoic acids were found in uncomplicated malaria, with lower levels observed for experimental cerebral malaria. Our study provides insights into host biology during different pathological stages of malaria disease and would be useful for the selection of animal models for evaluating diagnostic and therapeutic interventions against malaria. The raw data files are available via MetaboLights with the identifier MTBLS4387.