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Sustained release microspheres loaded with goserelin are regarded as a promising candidate for treating prostate cancer and other sex hormone diseases. However, their widespread adoption has been hindered by issues such as wide particle size distribution and unstable release characteristics. To address these challenges, we employed a combination of the solid-in-oil-in-water microspheres preparation approach (S/O/W) and innovative premix membrane emulsification technology and deeply investigated the effects of four key parameters on the loaded performance of microspheres and the microscopic mechanisms behind them. With this approach, we successfully produced goserelin-loaded sustained release microspheres of narrow particle size distribution (Span 0.642), remarkable encapsulation efficiency (DL = 4.23 %, EE = 93.98 %), low initial burst release (about 0.50 % within 2 h), and compatibility with small injection needles (23-G, inner diameter 0.33 mm, outer diameter 0.64 mm, maximal force 59 N). In the animal model(administered dose, 2.4 mg·Kg−1), goserelin long-acting sustained release microspheres sustained release for over 32 days, maintaining effective concentrations above 2 ng·mL−1, and effectively reduced serum testosterone concentrations to castration levels (<1.0 ng·mL−1) by day 4, maintaining this inhibition for up to 21 days, exhibiting comparable efficacy to the positive control group. In vivo release kinetics analysis revealed that goserelin-loaded sustained release microspheres exhibited a release pattern dominated by diffusion with corrosion assistance in vivo. In summary, the systematic and comprehensive evaluation of uniform-sized goserelin-loaded sustained release microspheres has highlighted their excellent translational potential, and the study herein may provide new strategies and ideas for the development of microsphere dosage forms. [Display omitted] • Developed uniform-sized goserelin microspheres (GOS-M) with high encapsulation efficiency. • Achieved low initial burst release and sustained release for over 32 days in vivo. • Uniform-sized GOS-M adapted to 23-G needles, ideal for low-pain administration. • Offers New strategies for microsphere release regulation and prescription screening. [ABSTRACT FROM AUTHOR]

The relationship between meningiomas and gonadal steroid hormones has been the subject of debate, and there is limited understanding of the connection between patient, tumor characteristics, and progesterone receptor (PGR) status. This retrospective observational study aims to explore the prognostic correlation between PGR+ and PGR-meningiomas in terms of various clinical, radiological, and surgical predictors. The analysis included 270 patients, divided into 2 groups: group A (PGR-, 194 patients), and group B (PGR+, 76 patients). The analysis showed no significant differences in terms of age, sex, clinical debut, postsurgical complications, total resection, and grading between the 2 groups. However, a significant difference was observed in the mean Karnofsky performance status at all stages of follow-up. Peritumoral edema measured in preoperative magnetic resonance imaging significantly influences the value of Karnofsky performance status in both preoperative (ANOVA, P = 0.05) and postoperative evaluation (postoperative ANOVA, P = 0.014) only in group A. In the multivariate analysis, there are no significant factors related to the clinical, biological, and surgical parameters previously examined for each measurement time (P = 0.826). The study found that PGR + meningioma patients tend to have better postoperative recovery and earlier clinical debut without any association with age prevalence or grading. [ABSTRACT FROM AUTHOR]

Restless legs syndrome (RLS) and periodic leg movements during sleep (PLMS) are prevalent sleep disorders with significant implications for health and well-being. While previous research has highlighted sex-related disparities in RLS and PLMS prevalence, comprehensive understanding of these differences across the lifespan remains limited. This study aims to explore sex differences in RLS and PLMS across diverse age groups, spanning ages 2 to over 80 years, and to investigate the underlying mechanisms influenced by sex hormones. A retrospective analysis was conducted on drug-free patients diagnosed with RLS, including 95 females (age range: 2–83.2 years) and 89 males (age range: 2–79.5 years). Polysomnographic recordings were analyzed to assess leg movement activity, including PLMS index and Periodicity index. A more rapid increase in PLMS index was observed in women starting before age 10, plateauing lower than men until around age 55. An increase in women occurred after 55, lasting over a decade, while in men, PLMS index continued to rise after 75. Conversely, Periodicity index displayed a simpler pattern, increasing progressively from prepuberty to around 35 in males and 45–50 in females. Females maintained a slightly higher Periodicity index than males for over a decade after this age. These findings underscore the complex interplay between sex hormones, age, and sleep disorders, highlighting the need for tailored approaches to diagnosis and management across diverse demographic cohorts. Further research is warranted to elucidate the underlying mechanisms and develop targeted interventions to optimize sleep health outcomes. • PLMS increases with age in both sexes but plateaus earlier in women. • Women over 50 show increased PLMS periodicity, unlike men. • Sex hormones, particularly estrogen, influence sleep motor activity. • Study highlights need for personalized RLS and PLMS management by sex and age. [ABSTRACT FROM AUTHOR]

Composition of the vaginal microbiome in pregnancy is associated with adverse maternal, obstetric, and child health outcomes. Therefore, identifying sources of individual differences in the vaginal microbiome is of considerable clinical and public health interest. The current study tested the hypothesis that vaginal microbiome composition during pregnancy is associated with an individual's experience of affective symptoms and stress exposure. Data were based on a prospective longitudinal study of a medically healthy community sample of 275 mother-infant pairs. Affective symptoms and stress exposure and select measures of associated biomarkers (diurnal salivary cortisol, serum measures of sex hormones) were collected at each trimester; self-report, clinical, and medical records were used to collect detailed data on socio-demographic factors and health behavior, including diet and sleep. Vaginal microbiome samples were collected in the third trimester (34–40 weeks) and characterized by 16S rRNA sequencing. Identified taxa were clustered into three community clusters (CC1–3) based on dissimilarity of vaginal microbiota composition. Results indicate that depressive symptoms during pregnancy were reliably associated with individual taxa and CC3 in the third trimester. Prediction of functional potential from 16S taxonomy revealed a differential abundance of metabolic pathways in CC1–3 and individual taxa, including biosynthetic pathways for serotonin and dopamine. We did not find robust evidence linking symptom- and stress-related biomarkers and CCs. Our results provide further evidence of how prenatal psychological distress during pregnancy alters the maternal-fetal microbiome ecosystem that may be important for understanding maternal and child health outcomes. • Depressive symptoms during pregnancy were reliably associated with the third trimester vaginal microbiome. • Prediction of microbiota functions revealed a differential abundance of biosynthetic pathways for neuroactive metabolites. • Prenatal psychological distress during pregnancy alters the maternal-fetal microbiome ecosystem. [ABSTRACT FROM AUTHOR]

• Sexual and reproductive health (SRH) is an important and emerging area of research in cystic fibrosis (CF). • This report summarizes CF community priorities related to SRH research topics and workshop discussions of an expert panel in this area. • Further research is needed on sex hormones and CF, optimizing SRH care provision, and fertility and assisted reproductive technology. To address sexual and reproductive health (SRH) concerns among people with cystic fibrosis(PwCF), the CF Foundation created the Sexual Health, Reproduction, and Gender Research (SHARING) Working Group. This report summarizes CF community SRH research priorities and workshop discussions/future study planning. Pre-workshop, we distributed a community prioritization survey on CF SRH research/care. During the workshop, we used results and reviewed existing research to establish research priorities and design studies to address identified knowledge gaps. A total of 303 respondents (85 % PwCF, 15 % caregivers) completed the survey. Highly-rated SRH topics were: 1) effects of CF modulator therapy on sex hormones; 2) effects of sex hormones on CF; 3) fertility; 4) pregnancy; and 5) SRH/mental health. Twenty-four workshop participants established the need for further research on sex hormones and CF, optimizing SRH care provision, and fertility/ART. SRH is an important and emerging area in CF and thoughtful consideration of community perspectives can ensure that future research is relevant and responsive. [ABSTRACT FROM AUTHOR]

Sex hormones have biological effects on inflammation, and these might contribute to the sex-specific features of depression. C-reactive protein (CRP) is the most widely used inflammatory biomarker and consistent evidence shows a significant proportion (20–30 %) of patients with major depressive disorder (MDD) have CRP levels above 3 mg/L, a threshold indicating at least low-grade inflammation. Here, we investigate the interplay between sex hormones and CRP in the cross-sectional, observational Biomarkers in Depression Study. We measured serum high-sensitivity (hs-)CRP, in 64 healthy controls and 178 MDD patients, subdivided into those with hs-CRP below 3 mg/L (low-CRP; 53 males, 72 females) and with hs-CRP above 3 mg/L (high-CRP; 19 males, 34 females). We also measured interleukin-6, testosterone, 17-β-estradiol (E2), progesterone, sex-hormone binding globulin (SHBG), follicle-stimulating and luteinising hormones, and calculated testosterone-to-E2 ratio (T/E2), free androgen and estradiol indexes (FAI, FEI), and testosterone secretion index. In males, high-CRP patients had lower testosterone than controls (p = 0.001), and lower testosterone (p = 0.013), T/E2 (p < 0.001), and higher FEI (p = 0.015) than low-CRP patients. In females, high-CRP patients showed lower SHGB levels than controls (p = 0.033) and low-CRP patients (p = 0.034). The differences in testosterone, T/E2 ratio, and FEI levels in males survived the Benjamini-Hochberg FDR correction. In linear regression analyses, testosterone (β = −1.069 p = 0.033) predicted CRP concentrations (R2 = 0.252 p = 0.002) in male patients, and SHBG predicted CRP levels (β = −0.628 p = 0.009, R2 = 0.172 p = 0.003) in female patients. These findings may guide future research investigating interactions between gonadal and immune systems in depression, and the potential of hormonal therapies in MDD with inflammation. • Males with MDD show decreased levels of testosterone and TSI. • Females with MDD and healthy controls have similar sex hormone levels. • Males with MDD with high-CRP have decreased levels of testosterone. • Females with MDD and high-CRP have decreased levels of SHBG. • In MDD, CRP levels are predicted by testosterone in males and by SHBG in females. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects men more than women, with severity increasing post menopause, indicating sex-based disparities in MASLD prevalence and progression. Estrogen protects women from MASLD, while the effects of testosterone vary among men and women. This indicates that different sex-dimorphic mechanisms are involved in sex-hormone signaling. Innate immune cells display significant sexual dimorphism in their response to MASLD, wherein male immune cells evidence a more migratory and proinflammatory phenotype. Sex-specific genetic variants and gut microbiota influence MASLD risk, highlighting the opportunity for developing personalized treatments based on individual genetic or microbiome profiles. Current preclinical MASLD models are male biased, indicating the challenges in translating research findings into clinical therapies for developing gender-specific MASLD treatment. Growing evidence suggests that metabolic dysfunction-associated steatotic liver disease (MASLD) is significantly higher in men versus women. Increased prevalence is observed in postmenopausal women, suggesting that age and sex (hormones) influence MASLD development and progression. Molecular data further reveal that sex regulates the innate immune responses with an essential role in MASLD progression. To date, there has been limited focus on the role of innate immune sexual dimorphism in MASLD, and differences between men and women are not considered in the current drug discovery landscape. In this review, we summarize the sex disparities and innate immune sexual dimorphism in MASLD pathogenesis. We further highlight the importance of harnessing sexual dimorphism in identifying therapeutic targets, developing pharmacological therapies, and designing (pre-) clinical studies for the personalized treatment for MASLD. [ABSTRACT FROM AUTHOR]

This study aims to investigate the association between Body Mass Index (BMI) and sex hormone levels utilizing a cross-sectional study design alongside Mendelian randomization (MR) analysis. A cross-sectional study was performed based on National Health and Nutrition Examination Survey (NHANES) 2013–2016. Additionally, a two-sample MR analysis was performed, utilizing Single Nucleotide Polymorphisms (SNPs) associated with BMI identified in a genome-wide association study (GWAS) comprising 339224 individuals. Data on outcomes, including total testosterone (TT, 199569 samples), estradiol (E 2 , 17134 samples), and sex hormone binding globulin (SHBG, 185211 samples), were sourced from the United Kingdom Biobank (UKB). In cross-sectional analysis involving 4092 males, multivariable linear regression demonstrated that each unit increase in BMI was positively correlated with an elevated risk of testosterone deficiency (TD), increased E 2 levels, and a reduced TT, SHBG, free androgen index and TT/E 2. Subsequent quartile division of BMI revealed, through multivariable logistic regression, that higher BMI quartiles were associated with a greater TD risk, elevated E 2 levels, and reduced TT, SHBG, and TT/E 2 levels compared to quartile 1 (P for trend <0.001). In the MR analysis, a causal effect was established, with each unit increase in BMI being associated with decreased TT (β = −0.17; 95 % CI −0.24 to −0.09) and SHBG (β = −0.13; 95 % CI −0.21 to −0.05) levels. Our findings unveil a causal link between BMI and reduced TT and SHBG levels in males. [ABSTRACT FROM AUTHOR]

• Early ovarian cessation even in young women play a role in development of unfavorably altered lipid profile. • Women with newly diagnosed POI exhibited adverse lipid profile along with higher fasting glucose level in contrary to age-matched healthy controls. • Women with non-idiopathic POI present unfavorably altered lipid profile when compared to women with unknown cause of POI. Hypoestrogenism related to the cessation of ovarian function increases the risk of metabolic disorders in postmenopausal women. Women with primary ovarian insufficiency (POI) are exposed to longer period of estrogen deficiency together with a subsequently higher risk of long-term comorbidities. To compare metabolic along with hormonal status among newly diagnosed women with POI with pre- and postmenopausal women. To investigate the impact of POI etiology on both metabolic and hormonal profiles. A case-control study with women assigned to one of the groups: 1) POI (n = 216), 2) age-matched premenopausal (n = 216), 3) postmenopausal (n = 227). Lipid profile, fasting glucose and insulin levels together with insulin resistance were determined among all participants. POI women exhibited increased both total cholesterol (TC, p = 0.04) and low-density lipoprotein cholesterol (LDL-C, p < 0.01) compared to the premenopausal women and higher triglycerides (TG, p < 0.001) than postmenopausal women. POI group showed higher fasting glucose level (p = 0.04) differently to premenopausal women. The idiopathic POI group showed both lower sex hormone binding globulin (p = 0.02) and dehydroepiandrosterone sulfate (p = 0.04) along with reduced TC (p = 0.03) and TG (p = 0.01) together with increased high-density lipoprotein cholesterol (p = 0.04) levels than non-idiopathic POI women. Women with newly diagnosed POI exhibited less favorable lipid profile than pre- or postmenopausal women. The association of negatively changed lipid profile in POI women is mostly mediated by women with unknown cause of premature ovarian cessation. [ABSTRACT FROM AUTHOR]

Females are twice as likely to experience PTSD as compared to males. Although sex differences in prevalence are well-established, little is known about why such sex differences occur. Biological factors that vary with sex, including sex hormone production, may contribute to these differences. Considerable evidence links sex hormones, such as testosterone, to PTSD risk though less is known about the shared genetic underpinnings. The objective of the present study was to test for genetic relationships between testosterone and PTSD. To do so, we used summary statistics from large, publicly available genetic consortia to conduct linkage disequilibrium score regression to estimate the genetic correlations between PTSD and testosterone in males and females, and two-sample, bi-directional Mendelian randomization to examine potential causal relationships of testosterone on PTSD and the reverse. Heritability estimates of testosterone were significantly higher in males (0.17, SE = 0.02) than females (0.11, SE = 0.01; z = 2.46, p = 00.01). The correlation between testosterone and PTSD was negative in males (r g = −0.11, SE = 0.02, p = 6.7 x 10-6), but not significant in females (r g = 0.002, SE = 0.03, p = 0.95). MR analyses found no evidence of a causal effect of testosterone on PTSD or the reverse. Findings are consistent with phenotypic literature suggesting a relationship between testosterone and PTSD that may be sex-specific. This work provides early evidence of a relationship between testosterone and PTSD genotypically and suggests an avenue for future research that will enable a better understanding of disparities in PTSD. [ABSTRACT FROM AUTHOR]

Intracranial dural arteriovenous fistulae (DAVFs) represent a subset of cerebral vascular malformations associated with significant morbidity and mortality. In Japan, DAVF exhibits sex-based differences in anatomical distribution, with female predominance in the cavernous sinus (CS) and male predominance in the transverse sinus (TS). Nevertheless, the pathophysiology of DAVF is not fully understood, and hormonal influences are hypothesized to play a role in its development. This study aimed to investigate changes in the concentrations of sex steroid hormones between intracranial and peripheral sampling sites in patients with CS- and TS-DAVF. We recruited 19 patients with CS-DAVF (n = 12) and TS-DAVF (n = 7) in this study. Blood hormone measurements were obtained from peripheral and jugular bulb samples during endovascular intervention. Hormone concentrations were analyzed using enzyme-linked immunosorbent assay kits, and statistical analyses were performed. Our study revealed a higher prevalence of CS-DAVF in females and TS-DAVF in males, which is consistent with previous studies. Estradiol concentration was significantly lower in the jugular bulb compared with in the periphery in both patients with CS- and TS-DAVF. This decrease in estradiol was observed irrespective of the patient's sex and independent of follicle-stimulating hormone levels. These findings indicate a local decrease in estradiol levels within the intracranial vasculature of patients with DAVF. This suggests a potential multifactorial role of estradiol in the pathomechanism of DAVFs, warranting further investigation to understand its influence on DAVF formation and potential targeted therapies, thereby enhancing patient outcomes. [ABSTRACT FROM AUTHOR]

Maternal immune activation (MIA) during pregnancy is known to increase the risk of development of schizophrenia in the offspring. Sex steroid hormone analogues have been proposed as potential antipsychotic treatments but the mechanisms of action involved remain unclear. Estrogen has been shown to alter N -methyl- d -aspartate (NMDA) receptor binding in the brain. We therefore studied the effect of chronic treatment with 17β-estradiol, its isomer, 17α-estradiol, and the selective estrogen receptor modulator, raloxifene, on MIA-induced psychosis-like behaviour and the effect of the NMDA receptor antagonist, MK-801. Pregnant rats were treated with saline or the viral mimetic, poly(I:C), on gestational day 15. Adult female offspring were tested for changes in baseline prepulse inhibition (PPI) and the effects of acute treatment with MK-801 on PPI and locomotor activity. Poly(I:C) offspring had significantly lower baseline PPI compared to control offspring, and this effect was prevented by 17β-estradiol and raloxifene, but not 17α-estradiol. MK-801 reduced PPI in control offspring but had no effect in poly(I:C) offspring treated with vehicle. Chronic treatment with 17β-estradiol and raloxifene restored the effect of MK-801 on PPI. There were no effects of MIA or estrogenic treatment on MK-801 induced locomotor hyperactivity. These results show that MIA affects baseline PPI as well as NMDA receptor-mediated regulation of PPI in female rats, and strengthen the view that estrogenic treatment may have antipsychotic effects. • Reduced PPI in Maternal Immune Activation (MIA) schizophrenia model in rats. • No NMDA receptor antagonist (MK-801) induced PPI reduction in MIA offspring. • Baseline PPI and MK-801 effects restored by 17β-estradiol and raloxifene. • No effects of MIA or estrogenic treatment on MK-801 locomotor hyperactivity. • Estrogenic treatment may have antipsychotic effects. [ABSTRACT FROM AUTHOR]

The prevalence of late-life schizophrenia is increasing with high burden. It is well-documented that schizophrenia affects men and women differently in terms of symptoms. Sex hormones, which play a role in the pathology and symptoms of schizophrenia, are greatly affected by aging. To the best of our knowledge, this is a study to examine the sex differences in psychiatric symptoms and their correlation with sex hormones in participants with late-life schizophrenia. Positive and Negative Syndrome Scale (PANSS) factors were evaluated. Testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and prolactin were measured. Male participants with late-life schizophrenia had more severe negative symptoms than female participants (z = −2.56, P = 0.010), while female participants had more severe anxiety/depression compared to male participants (z = 2.64, P = 0.008). Testosterone levels in male participants were positively associated with negative symptoms (β = 0.23, t = 2.27, P = 0.025), while there was no significant association between sex hormones and symptoms in female participants. In conclusion, higher testosterone levels were associated with more severe negative symptoms in male participants with late-life schizophrenia, suggesting that attention should be paid to the sex differences in late-life schizophrenia in clinical practice. [ABSTRACT FROM AUTHOR]

The underlying etiology of schizophrenia is still not fully understood, and recent studies have pointed to a potential link between hormonal factors and the risk of developing this condition. Sex Hormone-Binding Globulin (SHBG) is a protein that regulates the bioavailability of sex hormones. However, the causal relationship between SHBG levels and schizophrenia remains unclear, this study aimed to investigate the causal relationship based on two-sample Mendelian randomization (MR) analysis. This study was based on the summary data of genome-wide association studies (GWAS) of schizophrenia and SHBG in European populations. Two-sample MR was applied, and genetic factors were used as instrumental variables, and the causal relationship between schizophrenia and SHBG was assessed. We selected 79 single nucleotide polymorphisms with genome-wide significance from the schizophrenia GWAS as instrumental variables. The inverse variance weighting (IVW) method results showed that there is a causal relationship and a positive correlation between schizophrenia and female SHBG, with an odds ratio (OR) of 1.024 (95%CI: 1.007–1.042, P = 0.005), and this result was further confirmed by the Weighted median odds ratio (OR) of 1.032 (95%CI: 1.016–1.048, P = 5.58E-05) and the Weighted mode of 1.035 (95%CI: 1.004–1.067, P = 0.028). Schizophrenia and male SHBG also have a causal relationship and a positive correlation, with an odds ratio (OR) of 1.027 (95%CI: 1.007–1.047, P = 0.008). This study found a positive correlation between schizophrenia and SHBG in both men and women through MR analysis, indicating that the level of SHBG may be elevated in patients with schizophrenia, regardless of gender. [ABSTRACT FROM AUTHOR]

Women show higher prevalence of depression and different symptomatology than men, possibly influenced by sex hormones. Many transgender persons, who face a high risk of depression, use Gender-Affirming Hormone Therapy (GAHT), but the impact of GAHT on depressive symptom profiles is unknown. This study examined depressive symptoms in transgender persons before GAHT and after 3- and 12 months of GAHT. We used the Inventory of Depressive Symptomatology-Self Report to assess depressive symptoms, exploratory factor analysis (EFA) to assess symptom clusters, and linear mixed models to assess changes in symptom clusters. This study included 110 transmasculine (TM) and 89 transfeminine (TF) participants. EFA revealed four symptom clusters: mood, anxiety, lethargy, and somatic symptoms. Changes in total depressive symptoms significantly differed between TM and TF groups. After 3 months of GAHT, TM participants reported improvement in lethargy (−16 %; 95%CI: −29 %; −2 %), and after 12 months TF participants reported worsening in low mood (24 %; 95%CI: 3 %; 51 %), but absolute score changes were modest. Neither group showed changes in anxiety or somatic symptoms. This study had limited sample sizes at 12 months follow-up and did not include relevant biological or psychosocial covariates. Changes in depressive symptoms after GAHT use differ in TM and TF persons: TM persons report slight improvements in lethargy, whereas TF persons report a slight increase in low mood. Starting GAHT represents a significant life event with profound social and physical effects, and further research should assess social and biological effects of GAHT on mood-related symptoms. • Gender-affirming hormone therapy (GAHT) could affect depressive symptoms. • Trans persons show 4 symptom clusters: mood, anxiety, lethargy and somatic symptoms. • After 3 months of masculinizing GAHT, lethargy symptoms temporarily improve. • After 12 months of feminizing GAHT, low mood symptoms worsen. • We find differences between the effects of masculinizing and feminizing GAHT. [ABSTRACT FROM AUTHOR]

• A time-course progression was noted in PFBS innate toxicity. • Hypoxia was more potent than PFBS to disrupt sex endocrine system. • Hypoxia was the major driver of estrogenic activity in coexposure group. • Hypoxia suspended the egg spawn of marine medaka. • PFBS and hypoxia combination skewed the balance of thyroid hormones. Perfluorobutanesulfonate (PFBS) is an emerging pollutant capable of potently disrupting the sex and thyroid endocrine systems of teleosts. However, the hypoxic and temporal variation in PFBS endocrine disrupting toxicity remain largely unknown. In the present study, adult marine medaka were exposed to environmentally realistic concentrations of PFBS (0 and 10 µg/L) under normoxia or hypoxia conditions for 7 days, aiming to explore the interactive behavior between PFBS and hypoxia. In addition, PFBS singular exposure was extended till 21 days under normoxia to elucidate the time-course progression in PFBS toxicity. The results showed that hypoxia inhibited the growth and caused the suspension of egg spawn regardless of PFBS exposure. With regard to the sex endocrine system, 7-day PFBS exposure led to an acute stimulation of transcriptional profiles in females, which, subsequently, recovered after the 21-day exposure. The potency of hypoxia to disturb the sex hormones was much stronger than PFBS. A remarkable increase in estradiol concentration was noted in medaka blood after hypoxia exposure. Changes in sex endocrinology of coexposed fish were largely determined by hypoxia, which drove the formation of an estrogenic environment. PFBS further enhanced the endocrine disrupting effects of hypoxia. However, the hepatic synthesis of vitellogenin and choriogenin, two commonly used sensitive biomarkers of estrogenic activity, failed to initiate in response to the estrogen stimulus. Compared to sex endocrine system, disturbances in thyroidal axis by PFBS or hypoxia were relatively mild. Overall, the present findings will advance our toxicological understanding about PFBS pollutant under the interference of hypoxia. [Display omitted] [ABSTRACT FROM AUTHOR]

The occurrence of benign prostate hyperplasia (BPH) was related to disrupted sex steroid hormones, and metformin (Met) had a clinical response to sex steroid hormone-related gynaecological disease. However, whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear. Here, our clinical study showed that along with prostatic epithelial cell (PEC) proliferation, sex steroid hormones were dysregulated in the serum and prostate of BPH patients. As the major contributor to dysregulated sex steroid hormones, elevated dihydrotestosterone (DHT) had a significant positive relationship with the clinical characteristics of BPH patients. Activation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor (AR)-mediated Yes-associated protein (YAP1)-TEA domain transcription factor (TEAD4) heterodimers. Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells. Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation. Target and molecular mechanism of Met improving sex steroid hormones-induced BPH. Met regained dysregulated sex steroid hormones homeostasis, and inhibited PECs proliferation induced by dysregulated sex steroid hormones in BPH, and the anti-proliferation effects of Met was resulted from the regulation effect of AR-mediated YAP1-TEAD4 complex. [Display omitted] • Sex steroid hormone compositions were dysregulated in the serum and prostate of BPH patients. • Metformin inhibited PEC proliferation of BPH rats and DHT-cultured BPH-1 cells. • Metformin suppressed DHT/AR-induced the formation of YAP1-TEAD4 complex. • YAP1-TEAD4 complex was involved in the anti-proliferative effect of metformin. [ABSTRACT FROM AUTHOR]

While the association of metabolic dysfunction-associated steatotic liver disease (MASLD) with obesity and insulin resistance is widely appreciated, there are a host of complex interactions between the liver and other endocrine axes. While it can be difficult to definitively distinguish direct causal relationships and those attributable to increased adipocyte mass, there is substantial evidence of the direct and indirect effects of endocrine dysregulation on the severity of MASLD, with strong evidence that low levels of growth hormone, sex hormones, and thyroid hormone promote the development and progression of disease. The impact of steroid hormones, e.g. cortisol and dehydroepiandrosterone, and adipokines is much more divergent. Thoughtful assessment, based on individual risk factors and findings, and management of non-insulin endocrine axes is essential in the evaluation and management of MASLD. Multiple therapeutic options have emerged that leverage various endocrine axes to reduce the fibroinflammatory cascade in MASH. [ABSTRACT FROM AUTHOR]

Rheumatic diseases, mainly affecting women, including rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, etc. , are chronic, inflammatory, autoimmune disorders that may involve multiple organs or systems and are closely related to sexual health, which is an important aspect of human physical and mental health. Sjogren's syndrome (SS) is the second most common rheumatic illnesses after rheumatoid arthritis with a female predominance. At present, the research on sexual health of female SS patients is still scarce and difficult to summarize. The objective of our study was to systematically review the literature for the influence of maternal SS on sexual health, such as sexual function, sex hormones, fertility, and pregnancy outcomes. We performed a comprehensive literature search based on PubMed and Web of science databases from inception to 1 November 2022. Outcomes were divided into 4 categories: sex hormones, sexual function, fertility, and pregnancy and offspring outcomes. A total of 756 potentially eligible papers were retrieved. After eliminating duplicate articles and reviewing the titles and abstracts to exclude records, we read the remaining 92 articles in full for further evaluation, and selected 42 studies. Results on sex hormones, sexual function, fertility and pregnancy and offspring outcomes were reported in 13, 12, 3 and 14 SS-related articles, respectively. The levels of some sex hormones in SS patients may have undergone changes. Female patients with SS have a high prevalence of sexual dysfunction compared with controls. Most studies suggested SS had an adverse impact on maternal and fetal outcomes following pregnancy. However, there is insufficient evidence that directly indicating the fertility of SS women is diminished. In summary, certain aspects of sexual health (sexual function, sex hormones and pregnancy outcomes) are impaired in SS women. Screening for sexual health problems in SS female should become an integral part of medical clinical practice. Rheumatologists should be aware of this association and collaborate with gynecologists, obstetricians, psychologists, and other experts on this issue to determine appropriate therapeutic approaches. [ABSTRACT FROM AUTHOR]

Estrogens and androgens are sex steroid hormones that are critical for animal development and homeostasis. Microbes within the gut can produce, degrade, and modify sex steroids (both estrogens and androgens) in quantities that are biologically significant and affect host physiology. Microbe-induced changes to active systemic hormone levels are significant enough to provoke or ameliorate disease. The ability to manipulate the systemic sex steroids through the gut microbiota is a concrete therapeutic possibility that needs to be studied further. Recent progress in microbial endocrinology has propelled this field from initially providing correlational links to defining the mechanisms by which microbes influence systemic sex hormones. Importantly, the interaction between the gut-resident bacteria and host-secreted hormones has been shown to be critical for host development as well as hormone-mediated disease progression. This review investigates how microbes affect active sex hormone levels, with a focus on gut-associated bacteria hormonal modifications and the resulting host physiological status. Specifically, we focus on the ability of the microbiota to reactivate estrogens and deactivate androgens and thereby influence systemic levels of host hormones in a clinically significant manner. [ABSTRACT FROM AUTHOR]

Puberty may be impaired in children with sickle cell anemia (SCA). Therefore, we aimed to explore the clinical and hormonal features of puberty in Cameroonian children. In a case–control study, we included 64 children aged 8–18 years with SCA matched to healthy controls. We assessed height, weight, body mass index, body composition, and Tanner stages. Hormonal measurements included anti-mullerian hormone, follicle-stimulating hormone, luteinizing hormone, and sex hormones (estrogens/testosterone). We used the Mann–Whitney Wilcoxon test to compare the median values between cases and controls. We looked for associations between the severity criteria of SCA and delayed puberty through multivariate analysis. Delayed puberty was reported in 27.3% of girls and 10% of boys with SCA. The median age of menarche was delayed by 2 years compared to controls. SCA patients had a low lean body mass compared to controls (p = 0.03). Anti-mullerian hormone levels were significantly higher in boys with SCA than those of controls (45.9 ng/mL vs. 17.65 ng/mL; p = 0.018). A history of severe infection, acute chest syndrome, and low hemoglobin level was associated with delayed sexual maturation in children with SCA. Our study revealed delayed puberty in children with SCA. Moreover, puberty is affected by the severity of the disease. This highlights the importance of regular monitoring of puberty during the follow-up of these children. [ABSTRACT FROM AUTHOR]

Females have historically been disregarded in memory research, including the thousands of studies examining roles for the hippocampus, medial prefrontal cortex, and amygdala in learning and memory. Even when included, females are often judged based on male-centric behavioral and neurobiological standards, generating and perpetuating scientific stereotypes that females exhibit worse memories compared with males in domains such as spatial navigation and fear. Recent research challenges these dogmas by identifying sex-specific strategies in common memory tasks. Here, we discuss rodent data illustrating sex differences in spatial and fear memory, as well as the neural mechanisms underlying memory formation. The influence of sex steroid hormones in both sexes is discussed, as is the importance to basic and translational neuroscience of studying sex differences. Although male rodents are thought to exhibit better spatial and fear memories compared with females, the sexes often respond differently to learning stimuli, resulting in mischaracterization of female memory abilities. Responses to learning stimuli are influenced by sex steroid hormones and sex. High hormone levels are associated with place strategies in spatial tasks. In fear tasks, males use passive strategies, whereas females use passive and active strategies. The sexes differ in neural mechanisms underlying memory formation, as indicated by basal, learning-induced, and hormone-driven brain region- and cell type-specific sex differences in cellular activity and morphology. Better understanding of how sex differences in neural function contribute to sex differences in memory is vital and will lead to next-generation therapies for memory disorders in both sexes. [ABSTRACT FROM AUTHOR]

17β-Trenbolone (17-TB) is well documented as an environmental endocrine disruptor in aquatic biological studies, but its effects on mammals remain poorly understood. Furthermore, 17-TB acts as a hormone with properties similar to testosterone, and the consequences of juvenile exposure on adult social behavior remain uncertain. Bisphenol A (BPA) acts as an estrogen-like hormone, compared to 17-TB. Three-week-old male Balb/c mice were exposed orally to 17-TB (100 µg/(kg·day)) and BPA (4 mg/(kg·day)) for 28 days. Assessments of social interactions and a three-chamber test showed that 17-TB increased virility in male mice, intensified both male and female sexual behavior, and attracted and accepted female mice. It also increased social dominance through tube tests in male mice and markedly activated the c-Fos+ immune response in the medial prefrontal cortex (mPFC) and basal amygdala (BLA). ELISA data showed that 17-TB and BPA exposure significantly affected serum gonadotropin-releasing hormone (GnRH), growth hormone (GH), estradiol (E2), and luteinizing hormone (LH) levels, as well as testicular lesions and androgen receptor (ARβ) and estrogen receptor (ERα) synthesis. Testicular transcriptomic analysis further confirmed that could disrupt steroid synthesis and linoleic acid-related biometabolic processes. These findings suggest the influence of 17-TB and BPA exposure on sexual behavior and fertility in male mice, possibly through modulation of the hypothalamic-pituitary-gonadal axis. This study provides insights relevant to human reproductive health and neuro-social behavioral research, and the potential risk of environmental disturbances should not be overlooked. [Display omitted] [ABSTRACT FROM AUTHOR]

Physiological mechanisms of seasonal changes in testicular function in birds are not fully elucidated. The balance between androgens and estrogens and testis sensitivity for gonadotropin and gonadal steroids are still unclear. The aim of the study was to examine: (1) the changes in circulating and intra-testicular steroid hormone levels and their relationship; (2) the mRNA expression of testicular gonadotropin, prolactin (PRL), progesterone (P4), androgen, and estrogen receptors, and (3) key steroidogenesis processes-related genes with immunofluorescent localization of aromatase in gander testes during the annual period. Testes from ganders (n = 25) in the first reproduction season were obtained at five breeding stages, i.e., prebreeding (PrB), peak of reproduction (PR), postbreeding (PoB), nonbreeding (NB), and onset of reproduction (OR). Males were kept under breeding conditions. It was found that plasma P4 levels decreased at the PoB and NB stages, whereas intra-testicular P4 was the highest in the NB stage. Intra-testicular estradiol (E2) levels were higher at the PoB and NB stages than the other stages, whereas testosterone (T) levels showed a nearly opposite pattern. The plasma estradiol – to – testosterone ratios were higher at the PrB, PoB and NB stages compared to other stages. The transcript abundances for luteinizing hormone receptor (LHR) , PRL receptor (PRLR) , estrogen receptor alpha (ERα), and estrogen receptor beta (ERβ) also change in testicular tissue during the annual period. Moreover, StAR mRNA expression was upregulated at the PoB and NB stages, and CYP11A1 transcript level was the highest at the PoB stage. Stage-dependent changes in the CYP19A1 mRNA and aromatase protein levels with higher abundances of transcript at PoB and NB stages and protein at the NB stage were observed. Localization and immunofluorescent signal intensity for aromatase also differed in relation to the examined stages. It may be suggested that differential E2 levels, as well as aromatase expression and localization across annual stages are responsible for the seasonal activation/inactivation stages of testis spermatogenesis in domestic ganders. These data strongly suggest a role of aromatase in the control of gander steroidogenesis as changes in this enzyme level are associated with alternation in gonadal steroid hormones. In addition, joint action with others hormones, like PRL and LH, seems to be important in the final effect of seasonal reproduction potential. • Physiological basis of annual testicular function changes in ganders were studied. • Testicular stages were associated with a shift in gonadal steroid biosynthesis. • Testicular stage-related transcript abundances for LHR, PRLR, and ERs were shown. • Upregulation of ERs and CYP19A1 transcripts in non-reproduction stages was found. • Testicular stage-related changes in intensity of aromatase immunoreactivity were noted. [ABSTRACT FROM AUTHOR]

Sex differences in the prevalence, symptomatology, severity, and other aspects of various neuropsychiatric diseases have been consistently reported. Stress and fear-related psychopathologies, such as anxiety disorders, depression, and post-traumatic stress disorder, are more prevalent in women. Investigations of the mechanisms underlying this sex disparity have described the influence of gonadal hormones in both humans and animal models. However, gut microbial communities are also likely to play a role, as these communities differ between the sexes, are involved in a bidirectional cycling of sex hormones and their metabolites, and are associated with changes in fear-related psychopathologies when gut microbiota are altered or removed. Here, we focus our review on: (1) the role of gut microbiota-brain connections in stress- and fear-based psychiatric disorders, (2) gut microbiota interactions with sex hormones with a particular focus on estrogen, and (3) investigations of these estrogen-gut microbiome interactions in fear extinction, a laboratory model of exposure therapy, to elucidate potential targets for psychiatric treatment. Finally, we call for more mechanistic research using female rodent models and humans. • The gut microbiome influences fear extinction with implications for mental health. • There are bidirectional effects of ovarian hormones on the gut microbiome. • Microbiota interactions with estradiol may strengthen extinction processes. • Sex hormone-gut microbiome interactions may uniquely impact women's health. [ABSTRACT FROM AUTHOR]

Transgender persons can use gender-affirming hormone therapy (GAHT) to align their physical appearance with their identified gender. Many transgender persons report poor sleep, but the effects of GAHT on sleep are unknown. This study examined the effects of a 12 months of GAHT use on self-reported sleep quality and insomnia severity. A sample of 262 transgender men (assigned female at birth, started masculinizing hormone use) and 183 transgender women (assigned male at birth, started feminizing hormone use), completed self-report questionnaires on insomnia (range 0–28), sleep quality (range 0–21) and sleep onset latency, total sleep time and sleep efficiency before start of GAHT and after 3, 6, 9, and 12 months of GAHT. Reported sleep quality showed no clinically significant changes after GAHT. Insomnia showed significant but small decreases after 3 and 9 months of GAHT in trans men (−1.11; 95%CI: -1.82; −0.40 and −0.97; 95%CI: -1.81; −0.13, respectively) but no changes in trans women. In trans men, reported sleep efficiency decreased by 2.8% (95%CI: -5.5%; −0.2%) after 12 months of GAHT. In trans women, reported sleep onset latency decreased by 9 min (95%CI: -15; −3) after 12 months of GAHT. These findings show that 12 months of GAHT use did not result in clinically significant changes in insomnia or sleep quality. Reported sleep onset latency and reported sleep efficiency showed small to modest changes after 12 months of GAHT. Further studies should focus on underlying mechanisms by which GAHT could affect sleep quality. • Sex hormones can affect insomnia and sleep quality. • Effects of gender-affirming hormone therapy (GAHT) on sleep are unknown. • Reported insomnia and sleep quality were assessed during 12 months of GAHT. • Insomnia symptoms marginally decreased after 3 and 9 months in trans men. • Participants reported slight changes in sleep onset latency and sleep efficiency. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aim to evaluate whether treatment with metformin would reduce Anti-Müllerian Hormone levels in patients with polycystic ovary syndrome. A search was performed in Medline, Embase, Web of Science, and Cochrane Library databases and grey literature (Google Scholar). The following keywords were used in the search strategy: "Polycystic Ovary Syndrome", "Anti-Mullerian Hormone", "Metformin". The search was limited to human studies, with no language restriction. 328 studies were found, 45 studies were selected for full-text reading and 16 of those studies, six randomized controlled trial and 10 non-randomized studies were included. The synthesis of randomized controlled trials, metformin showed a reduction in serum levels of Anti-Müllerian Hormone compared to control groups (SMD – 0.53, 95 %CI − 0.84 to − 0.22, p < 0.001, I2 = 0 %, four studies, 171 participants, high quality of evidence). Six non-randomized studies evaluated data before and after the metformin intervention. The synthesis showed that using metformin reduced serum Anti-Müllerian Hormone values (SMD – 0.79, 95 %CI − 1.03 to − 0.56, p < 0.001, I2 = 0 %, six studies, 299 participants, low quality of evidence). Metformin administration in women with polycystic ovary syndrome is associated significantly with reduced Anti-Müllerian Hormone serum levels. • This study assesses whether treatment with metformin reduces AMH in PCOS women. • Metformin in women with PCOS reduce Anti-Müllerian Hormone serum levels. • Anti-Müllerian Hormone could be used to evaluate the treatment with insulin. [ABSTRACT FROM AUTHOR]

Background: Over a quarter of organ transplant recipients have low immunoglobulin levels in their early posttransplant course, which is associated with increased risk of infection and mortality. Although immunoglobulin level varies by sex among healthy individuals, it is unknown how such differences are affected by transplantrelated immunosuppression. This study compared post-liver transplant immunoglobulin G (IgG) between sexes at varying ages. Methods: Serum specimens from a prospective cohort of 130 liver transplant recipients were analyzed. IgG was measured at time of transplant and from one-month post-transplant samples. Post-transplant IgG was compared between sexes using multivariable linear regression. Four age and sex categories were created (women<50, women>50, men<50, men>50) and the model repeated with this as the explanatory variable. The relationship between sex hormone concentrations and post-transplant IgG was also explored. Infection type and incidence were examined within groups. Results: The cohort included 99 men, 31 women (mean age 53). In adjusted linear regression, post-transplant IgG was not significantly different by sex (p = 0.92). However, when broken into four categories by age and sex, the contrast in IgG levels between younger versus older patients was strikingly greater among women than among men. An interaction term including age and sex was statistically significant (p = 0.03). The combined age-sex categorical variable was also significantly associated with post-transplant IgG (p = 0.01). Finally, an association was identified between baseline estradiol level and post-transplant change in IgG (p = 0.04). Conclusions: Sex and age have an important relationship with post-transplant IgG with older women demonstrating lowest concentrations. Immunoglobulin levels have previously demonstrated association with posttransplant outcomes. [ABSTRACT FROM AUTHOR]

Sex differences exist in the prevalence of major depressive disorder (MDD). Comparing with males, females are at a higher risk of depression, especially in some reproductive statuses with significant changes in sex hormones. Based on the positive effect on menopausal symptoms in human and on depression-like behaviors in animals, exogenous estrogen was considered as a potential therapeutic approach to the treatment of female depression, however, with inconsistent conclusions in previous studies. In the present systematic review and meta-analysis, 14 eligible randomized controlled trials (RCTs) were included to investigate the effect of exogenous estrogen on depressive mood in women. The results indicated that exogenous estrogens were superior to the control group either alone or in combination with progesterone or antidepressants. Female individuals in perimenopause are more sensitive to estrogen than those in other reproductive statuses, which might be the reason that depressive mood during this stage is more associated with estrogen fluctuations, and exogenous estrogen supplementation can moderate these drastic changes. The finding of meta-regressions that the effect of exogenous estrogen was associated with age in perimenopause and post-menopause rather than the dose or administration of exogenous estrogen, showed again that a stable level of estrogen is more beneficial than a high serum level. This study provides strong evidence of the important role of estrogen fluctuations but not estrogen levels in female depression. • Both exogenous estrogens alone and in combination with progesterone or antidepressants are superior to the control group. • During peri- and post-menopause, there is a negative association between age and the therapeutic effect of exogenous estrogen. • Transdermal patch is slightly more effective than the oral preparation. • This study provides strong evidence that exogenous estrogen exerts its antidepressant effect by stabilizing estrogen levels. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer, with good prognosis, but the rate of lymph node metastasis (LNM) is high, and the difference between men and women is significant. Therefore, the related risk factors for LNM of PTC based on gender were examined in this study in order to draw attention to gender factor in PTC. We retrospectively analyzed the clinicopathological data of 2103 patients with surgically confirmed PTC at the Fourth affiliated Hospital of Hebei Medical University West Side between January 2016 and December 2019. LNM was detected in 1124 of the 2103 cases of PTC. Logistic regression analysis showed that LNM was associated with age (p < 0.001, OR:0.547), gender (p < 0.001, OR:2.609), tumor diameter (p < 0.001, OR:2.995), bilaterality (p =0.003, OR:1.683), and extrathyroid extension (p < 0.001, OR:1.657). After propensity score matching, female gender (p < 0.001, OR: 0.393) remained an independent factor of LNM in patients with PTC. LNM in men was only associated with diameter (p < 0.001, OR: 3.246). LNM in woman was associated with menopausal history (p = 0.012, OR=0.684), reproductive history (p < 0.001, OR=0.360), abortion history (p = 0.011, OR=0.725), tumor diameter >1 cm (p < 0.001, OR=2.807), bilaterality (p =0.006, OR:1.728), and extrathyroid extension (p < 0.001, OR=1.879). Although the invasion is high in female patients, the rate of LNM is significantly reduced due to the influence of sex hormones and reproductive factors. For female patients of childbearing age who were not pregnant and did not have children, it is suggested to take a positive attitude towards their lymph nodes. [ABSTRACT FROM AUTHOR]

Biological sex contributes to phenotypic sex effects through genetic (sex chromosomal) and hormonal (gonadal) mechanisms. There are profound sex differences in the prevalence and progression of age-related brain diseases, including neurodegenerative diseases. Inflammation of neural tissue is one of the most consistent age-related phenotypes seen with healthy aging and disease. The pro-inflammatory environment of the aging brain has primarily been attributed to microglial reactivity and adoption of heterogeneous reactive states dependent upon intrinsic (i.e., sex) and extrinsic (i.e., age, disease state) factors. Here, we review sex effects in microglia across the lifespan, explore potential genetic and hormonal molecular mechanisms of microglial sex effects, and discuss currently available models and methods to study sex effects in the aging brain. Despite recent attention to this area, significant further research is needed to mechanistically understand the regulation of microglial sex effects across the lifespan, which may open new avenues for sex informed prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Prostatic hyperplasia (PH) is an androgen-dependent condition associated with increased prostatic size that is common in intact dogs, and similar to the condition in men. In dogs, the increase in prostatic size is most prominent the first years, and after approximately four years (in beagles), a plateau is reached, and further growth is slower. Why the prostate continues to grow more in some individuals is not clear. Most testosterone in the circulation is bound to albumin or sex hormone binding globulin (SHBG) and only a minor part is unbound and biologically active. The binding to SHBG has higher affinity than that to albumin. In addition, SHBG has own biological functions, modifying testosterone action. The aim of the present study was to investigate if there is an association between relative prostatic size and the variables total testosterone concentration, SHBG concentration, an estimation of bioavailable testosterone: the ratio between testosterone and SHBG (free androgen index, FAI), estradiol concentration, the estradiol/testosterone ratio, dog age and dog weight. Hormone concentrations were measured in serum from 79 intact male dogs aged ≥ four years, weighing ≥ five kg. The size of the prostate was estimated using ultrasonography, and relative prostate size, S rel , was calculated as the estimated size related to the normal size for a 4-year-old dog of the same weight. There as a negative correlation between testosterone concentration and age (ρ = −0.27, P = 0.018) and a positive correlation between age and S rel (ρ = 0.27, P = 0.016) and between SHBG and weight (ρ = 0.38, P = 0.001). The FAI was negatively correlated with dog weight (ρ = −0.32, P = 0.004). There were no significant correlations between S rel and SHBG or FAI or between estradiol or estradiol/testosterone and S rel , age or weight. A multiple regression analysis showed significant associations between log S rel and log testosterone concentration, log age and log weight of the dog, with an adjusted R2 of 9.5%. Although the variables total testosterone concentration, age and weight of the dog were all significantly associated with S rel , the coefficient of determination was low, indicating that they only explained a minor part of the prostatic size. The results support the analysis of total testosterone in studies of prostatic growth in the dog. • Large dogs have relatively larger prostates - relative size increases with weight. • The prostatic size is positively associated with testosterone concentrations. • Factors other than age, weight and testosterone are important for prostatic size. • Analysis of total testosterone gives useful information. [ABSTRACT FROM AUTHOR]

The female-to-male (FtM) sex transition requires lifelong supplementation with male sex hormones, resulting in high prevalence of weight gain, fat redistribution and other metabolic changes. Although sleep-disordered breathing (SDB) data for this group of patients are very limited, increased prevalence is expected. We report a mini-series of six case reports of FtM transsexuals treated in our centre. All reported cases are consecutive patients referred to a department of respiratory diseases and tuberculosis of a university hospital from 2017 to 2022. The standard pulmonary examination was performed, followed by limited polysomnography. In all FtM subjects, SDB was present and continuous positive airway pressure (CPAP) therapy was indicated. The sex transition process was completed in three individuals while the other three only took testosterone supplementation at the assessment time. The subjects' age ranged from 21 to 38 years, the apnoea-hypopnea index ranged from 17.3 to 104.1, and the BMI was 33.48–43.41. The CPAP therapy was effective in five patients, with one requiring bi-level positive airway pressure therapy. One subject committed suicide before the first check-up, four patients had a good level of compliance at one-year follow-up, and one had insufficient CPAP adherence. SDB decreases the quality of life and life expectancy of FtM individuals. Their prognosis is undoubtedly better with effective treatment. Hence, obese FtM subjects should be considered at risk and screened for SDB. • The female-to-male sex change requires the life-long supplementation of male sex hormones, resulting in prevalent numbers in weight gain, fat redistribution and other metabolic changes. • Sex transition from female to male is as a risk factor for sleep disordered breathing. • The clinically significant SDB decreases the life quality and worsens the prognosis of subjects with sex transition from female to male (FtM). [ABSTRACT FROM AUTHOR]

Gender differences in the functionality of the immune system have been attributed, in part, to direct and indirect effects of sex steroids, especially estrogens, on immune cell repertoire and activity. Notable are studies that have defined roles for estrogens in the regulation of the biology of dendritic cells (DCs), macrophages, T cells and natural killer (NK) cells. Although estrogens can modulate eosinophil function, the mechanisms by which this occurs and how it contributes to the pathobiology of different diseases remains underexplored. Furthermore, although the importance of eosinophils in infection is well established, it remains unclear as to how these innate immune cells, which are present in different tumors, impact the biology of cancer cells and/or response to therapeutics. The observation that eosinophilia influences the efficacy of immune checkpoint blockers (ICBs) is significant considering the role of estrogens as regulators of eosinophil function and recent studies suggesting that response to ICBs is impacted by gender. Thus, in this review, we consider what is known about the roles of estrogen(s) in regulating tissue eosinophilia/eosinophil function and how this influences the pathobiology of breast cancer (in particular). This information provides the context for a discussion of how estrogens/the estrogen receptor (ER) signaling axis can be targeted in eosinophils and how this would be expected to influence the activity of standard-of-care interventions and contemporary immunotherapy regimens in cancer(s). Tissue eosinophilia has an important role in the pathobiology of inflammatory diseases, such as infections, asthma, and cancer. Estrogen signaling modulates immune cell function(s), which, in turn, regulates the function of eosinophils and tissue eosinophilia. Tumor-associated tissue eosinophilia (TATE) can have either positive or negative effects on tumor biology, the degree of which is influenced by tumor type. A positive role for TATE in breast cancer has been established and it is likely that manipulation of eosinophil function by appropriate use of estrogen receptor modulators will increase the efficacy of contemporary immunotherapeutics in this disease. [ABSTRACT FROM AUTHOR]

• AMH and E2 changes relate differently to lipid/lipoprotein profile in midlife women. • Lower midlife E2 may be related to atherogenic lipid/lipoprotein profile in women. • Lower midlife AMH may be related to HDL dysfunctionality in women. The menopause transition (MT) is linked to adverse changes in lipids/lipoproteins. However, the related contributions of anti-Müllerian hormone (AMH) and estradiol (E2) are not clear. To evaluate the independent associations of premenopausal AMH and E2 levels and their changes with lipids/lipoproteins levels [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1)] over the MT. SWAN participants who transitioned to menopause without exogenous hormone use, hysterectomy, or bilateral oophorectomy with data available on both exposure and outcomes when they were premenopausal until the 1st visit postmenopausal were studied. The study included 1,440 women (baseline-age:mean ± SD=47.4 ± 2.6) with data available from up to 9 visits (1997-2013). Lower premenopausal levels and greater declines in AMH were independently associated with greater TC and HDL-C, whereas lower premenopausal levels and greater declines in E2 were independently associated with greater TG and apo B and lower HDL-C. Greater declines in AMH were independently associated with greater apoA-1, and greater declines in E2 were independently associated with greater TC and LDL-C. AMH and E2 and their changes over the MT relate differently to lipids/lipoproteins profile in women during midlife. Lower premenopausal and/or greater declines in E2 over the MT were associated with an atherogenic lipid/lipoprotein profile. On the other hand, lower premenopausal AMH and/or greater declines in AMH over the MT were linked to higher apo A-1 and HDL-C; the later found previously to be related to a greater atherosclerotic risk after menopause. [ABSTRACT FROM AUTHOR]

To evaluate changes in body composition and strength after menstrual cycle-based or traditional undulating resistance training (RT) programs in women. Ten resistance-trained and eumenorrheic women (26.6 ± 3.0 years; 164.7 ± 6.5 cm; 62.3 ± 6.8 kg) were randomly assigned to a menstrual cycle-based periodized upper/lower training (n = 5, MC) or an undulating training group (n = 5, UT) for 8 weeks. The number of repetitions and load were adjusted to each phase of the menstrual cycle. Fat free mass (FFM) and fat mass (FM) were evaluated by dual x-ray absorptiometry (DXA); maximal strength was assessed by the 1 repetition maximum (1-RM) test in the back squat (SQ) and bench press (BP); and muscle power was assessed by the countermovement jump (CMJ) test using a jump contact mat. A significant increase in FFM was observed for UT (1.4 ± 0.9 kg, P = 0.043, ES = 0.58) with no difference in MC (1.7 ± 1.8 kg, P = 0.080, ES = 0.25). No changes in FM were observed for either condition (MC: 0.9 ± 1.2 kg, p = 0.225, ES = 0.21 and UT: 0.5 ± 1.0 kg, P = 0.345, ES = 0.13). Strength increases were observed for both MC an UT in the BP (8.9 ± 3.4 kg, p = 0.042, ES = 0.87 and 5.0 ± 1.8 kg, p = 0.039, ES = 0.67, respectively) and SQ (15.3 ± 9.2 kg, P = 0.043, ES = 0.93 and 16.4 ± 7.6 kg, P = 0.042, ES = 1.38, respectively). CMJ showed differences in MC (4.0 ± 2.5 cm, P = 0.043, ES = 1.12). We observed a between-group difference in BP (P = 0.041) favoring MC; no other interactions were found. Eight weeks of a menstrual cycle-based periodized training combined with a hyperenergetic diet versus a non-matched undulating RT program have a differential impact on body composition and muscular adaptations in trained women. [ABSTRACT FROM AUTHOR]

It has been demonstrated that benzophenone-3 is one of the endocrine-disrupting compounds which are considered as potential risk factors of adverse health effects. However, whether benzophenone-3 exposure can influence the sex steroid hormones levels remains unknown. We used data from the National Health and Nutrition Examination Survey, which is a cross-sectional dataset, from 2013 to 2016. A total of 1690 male US participants aged 18 or above were included. Urinary benzophenone-3, serum total testosterone, serum estradiol, serum sex hormone-binding globulin were measured. Confounders including age, body mass index, race, education level, urinary creatinine, ratio of family income to poverty, alcohol use, time of venipuncture, cardiac arterial diabetic score, energy intake, bisphenol A, triclosan and total parabens were controlled. After full adjustment (Model III), the upper benzophenone-3 quintiles had odds ratios (95 % confidence intervals) of testosterone deficiency of 1.75 (1.03, 2.99), 2.47 (1.53, 3.98), 2.08 (1.13, 3.84) and 1.74 (0.94, 3.23) compared with quintile 1. Compared with quintile 1, percent changes (95 % confidence intervals) in testosterone were − 12 % (−19 %, −5 %) and − 9 % (−17 %, −1 %) for quintile 3 and quintile 5 in Model III. Estradiol and sex hormone-binding globulin were generally similar to total testosterone in the associations with benzophenone-3. In conclusion, our results demonstrated that adult men in the US with higher urinary benzophenone-3 had a higher risk of testosterone deficiency and had inverse associations with total testosterone, estradiol and sex hormone-binding globulin. To confirm the causal links between benzophenone-3 and sex steroid hormones, prospective studies are needed. • The inverse associations between benzophenone-3 and sex steroid hormones among the US male adults is proposed. • Benzophenone-3 exposure was a risk factor for testosterone deficiency. • Subgroup analyses were designed to explore the stratified relationships between benzophenone-3 and risk factors. [ABSTRACT FROM AUTHOR]

This study examined the efficiency of pumpkin seed oil (PSO) to rescue the colchicine (CHC)-induced adverse impacts on sperm characteristics, male sex hormones, testicular architecture, oxidative status, DNA content, collagen deposition, and immune expression of desmin and PCNA. Male Sprague Dawley rats were divided into four experimental groups (n = 10 each): control (distilled water), CHC (0.6 mg/kg b.wt), PSO (4 mL/kg b.wt), and CHC + PSO. After 60 days of dosing, CHC significantly reduced sperm motility (19%), sperm concentration (38%), estradiol (52%), testosterone (37%), luteinizing hormone (54%), and follicle-stimulating hormone (29%) compared to the control. Yet, the testicular tissues of CHC-administered rats exhibited elevated abnormal sperms (156%), malondialdehyde (354%), lactate dehydrogenase (73%), Caspase-3 (66%), and 8-hydroxyguanosine (65%) but lower reduced glutathione (74%), catalase (73%), and superoxide dismutase (78%) compared to the control group. Moreover, CHC induced testicular degeneration, distorted seminiferous tubules, apoptotic cells, exfoliated spermatogenic cells, reduced DNA content, decreased PCNA and desmin immune-expression, and increased collagen deposition. PSO effectively reversed the CHC-induced alterations in sperm quality and testicular function and architecture, likely through its antioxidant, antifibrotic, anti-apoptotic, and DNA-protective properties. These results suggest that PSO may be a beneficial intervention for long-term CHC users and may protect against CHC-induced male reproductive toxicity. [ABSTRACT FROM AUTHOR]

• Lifetime exposure to TCEP impaired testicular development and spermatogenesis of zebrafish. • Long-term exposure to TCEP disturbed the balance of sex hormones. • Lifetime exposure to TCEP interfered with biosynthesis of steroid hormones through multiple pathways. • Paternal exposure to TCEP reduced the fertilization success and survival of the offspring. Tris (2-chloroethyl) phosphate (TCEP), a commonly used organophosphate flame retardant, has garnered considerable concern owing to its pervasive presence in the environment and its toxic effects on living organisms. The perpetuation of populations and species hinges on successful reproduction, yet research into the mechanisms underlying reproductive toxicity remains scant, particularly in aquatic species. In this work, zebrafish embryos were exposed to TCEP (0, 0.8, 4, 20, and 100 µg/L) for 120 days until sexual maturation, and multiple reproductive endpoints were investigated in male zebrafish. Our results showed that the body weight, body length, and gonadal-somatic index (GSI) were remarkably decreased in all TCEP treatment groups (except GSI in the 0.8 µg/L TCEP-treated group). Long-term exposure to TCEP led to reduced reproductive capacity of male zebrafish, as evidenced by decreased fertilization. Histological observation gave an indication of delayed testicular development and inhibited spermatogenesis under TCEP stress. The content of testosterone (T) was significantly elevated in all TCEP treatment group, whereas 17 β-estradiol (E2) levels remained stable. Transcriptome analysis revealed a lot of downregulated genes involved in steroid hormone biosynthesis, energy metabolism, and sperm motility, which might account for the imbalance of steroid hormone levels, retarded spermatogenesis and declined fertilization success. Overall, these findings offered a thorough understanding of the mechanisms underlying the male reproductive toxicity caused by TCEP, highlight the risk of TCEP on reproductive health of fish. [ABSTRACT FROM AUTHOR]

Globally, hormone-responsive cancers afflict millions of people contributing to cancer-related morbidity and mortality. While hormone-responsive cancers overburden patients, their close families, and even health budgets at the local levels, knowledge of these cancers particularly their biology and possible avenues for therapy remains poorly exploited. Herewith, this review highlights the role of sex hormones (estrogens and androgens) in the pathophysiology of hormone-responsive cancers and the exploration of therapeutic targets. Major scientific databases including but not limited to Scopus, PubMed, Science Direct, Web of Science core collections, and Google Scholar were perused using a string of search terms: Hormone-responsive cancers, androgens and cancers, estrogens and cancer, androgen receptor signalling, estrogen receptor signalling, etc. [Display omitted] • Sex hormone receptor signaling is implicated in hormone-responsive cancers. • Andro-estrogen receptor signaling influence complexities of hormone-responsive cancers. • Upstream and downstream targets of andro-estrogen receptor signaling provide a repertoire of avenues for therapeutic strategies against hormone-responsive cancers. [ABSTRACT FROM AUTHOR]

Since steroids are crucial for diagnosing endocrine disorders, the lack of research on factors that affect hormone levels makes interpreting the results difficult. Our study aims to assess the stability of the pre-analytical procedure and the impact of hormonal physiological fluctuations using real-world data. The datasets were created using 12,418 records from individuals whose steroid hormone measurements were taken in our laboratory between September 2019 and March 2024. 22 steroid hormones in plasma by a well-validated liquid chromatography tandem mass spectrometry method were measured. After normalization transformation, outlier removal, and z-score normalization, generalized additive models were constructed to evaluate preanalytic stability and age, sex, and sample time-dependent hormonal fluctuations. Most hormones exhibit significant variability with age, particularly steroid hormone precursors, sex hormones, and certain corticosteroids such as aldosterone. 18-hydroxycortisol, 18-oxocortisol. Sex hormones varied between males and females. Levels of certain hormones, including cortisol, cortisone, 11-deoxycortisol, 18-hydroxycortisol, 18-oxocortisol, corticosterone, aldosterone, estrone, testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, 11-ketotestosterone, and 11-hydroxytestosterone, fluctuated with sampling time. Moreover, levels of pregnenolone and progesterone decreased within 1 hour of sampling, with pregnenolone becoming unstable with storage time at 4 degrees after centrifugation, while other hormone levels remained relatively stable for a short period of time without or after centrifugation of the sample. This is the first instance real-world data has been used to assess the pre-analytic stability of plasma hormones and to evaluate the impact of physiological factors on steroid hormones. • Pre-analytical stability of 22 plasma steroid hormones were evaluated. • Plasma steroids were stable whether centrifuged or not, except pregnenolone. • Levels of steroid hormones varied with age and sex. • Daytime rhythm of cortical hormones were observed using real world data. [ABSTRACT FROM AUTHOR]

Difficulties in fear regulation can sometimes result in maladaptive fear responses. To better understand how to improve fear regulation, it is important to determine how known factors, such as sex hormone status and stress, might interact to influence fear memory. Research has shown that women with high estradiol levels (mid-cycle) and men exhibit better extinction retention compared to women with low estradiol levels (women in the early follicular cycle or using oral contraceptives). Stress has also been demonstrated to affect both the learning and retention of extinction. Despite documented interactions between stress and sex hormones, their combined effects have not been thoroughly studied. This study aims to examine the impact of stress as a function of sex hormone status on extinction learning and retention. A total of 168 non-clinical participants were studied, including men (n = 46), women using oral contraceptives (n = 38), women in the early follicular phase (n = 40), and women in mid-cycle (n = 44). On Day 1, fear acquisition training was performed. On day 2, prior to extinction training, half of the participants were exposed to a psychosocial stressor, while the other half performed a non-stressful control task. On day 3, extinction retention was tested. Fear was quantified using skin conductance responses, while stress hormones were quantified through saliva samples. Exposure to stress prior to extinction training did not affect extinction learning, regardless of sex hormone status. In contrast, pre-extinction stress exposure had different effects on extinction retention depending on hormone status. Stressed men showed impairment in extinction retention compared to controls, while the experimental condition had no effect on naturally cycling women. Regardless of stress exposure, early follicular women exhibited a deficit in fear regulation, while mid-cycle women showed effective fear regulation. Among women using oral contraceptives, the stress group demonstrated better extinction retention compared to the control group. These results demonstrate the importance of considering sex hormone status and stress exposure during extinction learning, as both components may modulate extinction retention. These results could help identifying hormonal conditions that may enhance the effectiveness of extinction-based psychological therapies used in the treatment of fear-related disorders. • Sex hormone status modulates the effect of stress on fear regulation. • In men, stress exposure before extinction learning impaired extinction retention. • In women using oral contraceptives, stress improved extinction retention. • Naturally cycling women were not affected by the experimental conditions. • Considering both stress exposure and sex hormone status is important. [ABSTRACT FROM AUTHOR]

Empathic pain refers to an individual's perception, judgment, and emotional response to others' pain. This complex social cognitive ability is crucial for healthy interactions in human society. In recent years, with the development of multidisciplinary research in neuroscience, psychology and sociology, empathic pain has become a focal point of widespread attention in these fields. However, the neural mechanism underlying empathic pain remain a controversial and unresolved area. This review aims to comprehensively summarize the history, influencing factors, neural mechanisms and pharmacological interventions of empathic pain. We hope to provide a comprehensive scientific perspective on how humans perceive and respond to others' pain experiences and to provide guidance for future research directions and clinical applications. This article is part of the Special Issue on "Empathic Pain". • Empathetic pain is influenced by a wide range of complicated factors, including gender, age, cognition, social connections, and medication history. • According to the mainstream perspective, ACC-NAc projection, VTA-NAc projection, and IC-BLA projection are involved in the induction of empathetic pain. • Misuse of analgesics, sex hormones, glucocorticoids and antidepressants may affect empathic pain. [ABSTRACT FROM AUTHOR]

Key stakeholders in aquaculture play a crucial role in shaping public awareness, policymaking, and decision-making. Therefore, the adoption of certain negative perceptions by this group can pose a challenge to the sustainable management of aquaculture. This study analyzed stakeholder perceptions towards the aquaculture sector, assessing their alignment with scientific evidence through an online survey (n = 400). The results revealed that many stakeholders have negative perceptions towards aquaculture. The location, occupation, and income significantly influenced key stakeholders' perceptions about the quality of farmed fish. These categories claim that farmed fish, especially tilapia, the major farmed species, are of poor quality because of the use of steroid hormones in tilapia sex reversal, which poses potential health risks to consumers. There is also a common belief among key stakeholders that farmed fish are raised in poor-quality water and may feed on animal waste. Additionally, they believe that capture fisheries can meet Egypt's fish demand, thereby rendering aquaculture unnecessary. Also, fish marketers and traders foster negative perceptions of the quality of farmed fish. Given the potential threat of these perceptions to the future of the sector, appropriate preventive interventions are needed. These interventions include providing evidence-based and transparent information about aquaculture practices and product quality, ensuring effective communication among key stakeholders, adopting a regulatory approach that promotes key stakeholder engagement, supporting collaborative alliances, and establishing clear certification systems, standards, and regulations to ensure compliance measurement. These measures will help address the negative perceptions and ensure the sustainability of the aquaculture sector. • We studied the perception of key stakeholders towards aquaculture in Egypt. • Location, occupation, and income influence perceptions of farmed fish quality. • Fish traders have the highest influence on negative perceptions. • Negative perceptions relate to aquaculture's significance, feed, water, and hormones. • Several actions were suggested to change these negative perceptions. [ABSTRACT FROM AUTHOR]

Zuogui Pill (ZGP) is a traditional herbal formula of Chinese Medicine with a long history of use in alleviating ovarian aging. To examine the impact of ZGP on oxidative stress and the stemness of oogonial stem cells (OSCs) in cyclophosphamide (CTX)-induced ovarian aging, as well as its molecular mechanisms involving the nuclear factor erythroid 2-related factor 2 (Nrf2, NFE2L2)/heme oxygenase-1 (HO-1, Hmox1) pathway. Female Sprague-Dawley (SD) rats were randomly divided into seven groups: control, model (CTX), estradiol valerate (EV, 0.103 mg/kg), ZGP-L (low dose Zuogui Pill, 1.851 g/kg), ZGP-H (high dose Zuogui Pill, 3.702 g/kg), ML385 (30 mg/kg), and ML385+ZGP-L. After CTX modeling, the EV, ZGP-L, ZGP-H, and ML385+ZGP-L groups were treated by gavage for 8 weeks, while the ML385 and ML385+ZGP-L groups were administered the Nrf2 antagonist ML385 twice a week. OSCs were isolated after modeling and then treated with drug serum containing 10% ZGP or 10 μM ML385. The general conditions of the rats, including body weight, ovarian weight/body weight ratio, and estrous cycle, were observed. Ovarian ultrastructure, follicle and corpus luteum counts were assessed via hematoxylin and eosin (H&E) staining. Serum hormone levels were measured using enzyme-linked immunosorbent assay (ELISA). Nrf2/HO-1 pathway, stem cell, germ cell, and cell cycle biomarkers were analyzed by qPCR and Western blot. Cell viability was assessed by cell counting kit-8 (CCK-8) assay. Oxidative stress biomarkers were evaluated using flow cytometry and assay kits. Immunofluorescence was employed to detect and locate OSCs in the ovary, quantify the average fluorescence intensity, and identify OSCs. After ZGP treatment, rats with CTX-induced ovarian aging exhibited improved general condition, increased body weight, higher total ovarian weight to body weight ratio, and a restoration of the estrous cycle similar to the control group. Serum levels of estradiol (E 2) and follicle stimulating hormone (FSH), two sex hormones, were also improved. Ovarian ultrastructure and follicle count at all stages showed improvement. Moreover, the viability and proliferation capacity of OSCs were enhanced following ZGP intervention. The Nrf2/HO-1 pathway was found to be down-regulated in CTX-induced aging ovarian OSCs. However, ZGP reversed this effect by activating the expression of Nrf2, HO-1, and NAD(P)H oxidoreductase 1 (NQO1), increasing the activity of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and reducing the accumulation of malonaldehyde (MDA) and reactive oxygen species (ROS), thus restoring resistance to oxidative stress. Additionally, ZGP improved the cell cycle of OSCs, up-regulated the expression of Cyclin D1 and Cyclin E1, restored cell stemness, promoted proliferation, enhanced the expression of cell stemness markers octamer-binding transcription factor 4 (Oct4) and mouse VASA homolog (MVH), and down-regulated the expression of P21, thereby inhibiting apoptosis. The therapeutic effects of ZGP against oxidative stress and restoration of cell stemness were attenuated following inhibition of the Nrf2 signaling pathway using ML385. ZGP protected against CTX-induced ovarian aging by restoring normal ovarian function, alleviating oxidative stress in aging OSCs, promoting OSCs proliferation, and restoring their stemness in rats, possibly through regulating the Nrf2/HO-1 pathway. [Display omitted] • ZGP restores ovarian function impaired by cyclophosphamide-induced ovarian aging. • ZGP mitigates oxidative stress in aging ovaries via Nrf2/HO-1. • ZGP reduces oxidative stress and restores stemness in aging OSCs via Nrf2/HO-1. [ABSTRACT FROM AUTHOR]

Microglial cells are integral to the pathogenesis of Alzheimer's disease (AD). The observed sex disparity in AD prevalence, with a notable predominance in women, implies a potential influence of sex hormones, such as androgens, on disease mechanisms. Despite this, the specific effects of androgens on microglia remain unclear. This study is designed to delineate the interplay between androgens and the survival and inflammatory profile of microglial cells, as well as to explore their contribution to the progression of AD. To create a chronic androgen deficiency model, 3-month-old wild-type (WT) mice and APP/PS1 mice underwent bilateral orchiectomy (ORX), with age-matched sham-operated controls. Cognitive and memory were evaluated at 5 and 12 months, paralleled by assessments of amyloid-beta (Aβ) and microglial morphology in hippocampal and cortical areas. The ORX treatment in mice resulted in diminished microglial populations and morphological alterations, alongside an increase in Aβ plaques and a concomitant decline in cognitive performance that exacerbated over time. In vitro, dihydrotestosterone (DHT) was found to stimulate microglial proliferation and ameliorate Aβ 1 – 42 -induced apoptosis. These findings suggested that androgens may exert a protective role, maintaining the normal proliferation and functionality of microglial cells. This preservation could potentially slow the progression of AD. As a result, our study provided a conceptual framework for the development of novel therapeutic strategies for AD. [Display omitted] • Bilateral orchiectomy in mice leads to a significant decrease in the number of microglial cells in the brain. • Bilateral orchiectomy in mice exhibit an increase in amyloid-beta deposition. • The cognitive abilities of mice subjected to bilateral orchiectomy are markedly diminished. [ABSTRACT FROM AUTHOR]

Outcomes and susceptibility to out-of-hospital cardiac arrest (OHCA) are known to differ by sex, yet little is known about changes in sex hormones after OHCA. We sought to determine the trajectory of sex hormones after OHCA and their association to survival and neurological outcome. Plasma samples were collected from those that survived to hospital admission at four time points (1, 6, 24, and 48 h) and estrone, estradiol, progesterone, and testosterone concentrations were quantified via liquid chromatography-mass spectrometry. Trends in hormones were plotted over time by sex and outcomes. The association between sex, hormone levels with survival and neurological outcome (cerebral performance category 1–2 indicating good outcome and 3–5 for poor outcome) were determined using generalized estimating equation models. Of the 94 OHCA patients, 50 were males and 44 females, with a mean age of 61.3 (+15.7) years. Despite older age and lower BCPR in females compared to males, females had higher proportion of good neurological outcome compared to males. Over the 48 h, estrone increased, testosterone decreased, and estradiol and progesterone remained flat. Survivors had lower levels of estrone at all time points but only at early time points for estradiol, progesterone and testosterone. Lower estrone level predicted survival at discharge, even after adjusting for time, sex, age, and hormones independently (β = −3.38, 95% CI = −5.71, −0.85). Females had better neurological scores compared to males after adjusting for estrone (β = 1.27, 95% CI = 0.01, 2.53) and estradiol (β = 2.92, 95% CI = 1.13, 4.70). Survivors and those with favorable neurological outcome had lower trend in estrone. The sex hormone estrone, present in both males and females, may be a predictor of survival. When adjusted for estrogens, female sex had better neurological recovery compared to males. The difference in neurological outcome by sex is not explained by estrogens. However, these finding open the door for exploration of other sex-specific pathways in resuscitation after OHCA. [ABSTRACT FROM AUTHOR]

• Adult zebrafish are more sensitive to F-53B than embryos, with a lower 96 h LC50. • F-53B exposure impairs the gill structure of zebrafish. • F-53B exposure leads to an increase in erythrocyte numbers in zebrafish. • F-53B decreases egg production and increases the GSI in zebrafish. • F-53B disrupts steroidogenic gene expression and sex hormone production in zebrafish. 6:2 Chlorinated polyfluorinated ether sulfonate, commonly known as F-53B, is widely used as a mist suppressant in various industries and is frequently detected in the environment. Despite its prevalent presence, the adverse effects of F-53B are not well understood and require future investigation. This study utilized zebrafish embryos and adults to examine the toxic effects of F-53B. Our findings revealed that F-53B impaired gill structure and increased erythrocyte numbers in adult zebrafish. Notably, F-53B demonstrated a higher sensitivity for inducing mortality (LC 50 at 96 h) in adult zebrafish compared to embryos. Additionally, F-53B disrupted the expression of critical steroidogenic genes and hindered sex hormone production, which negatively affecting egg production. In conclusion, this study underscores the detrimental impact of F-53B on gill structure and reproductive toxicity in zebrafish, providing valuable insights into its overall toxicity. [ABSTRACT FROM AUTHOR]