Protective roles of some natural and synthetic aromatase inhibitors in testicular insufficiency caused by Bisphenol A exposure.

In our study, the protective role of synthetic aromatase inhibitors anastrozole (ANS), letrozole (LTZ) and exemestane (EXM) and natural aromatase inhibitors resveratrol (RSV) and apigenin (APG) against testicular failure caused by exposure to Bisphenol A (BPA) was investigated. The epididymal sperm concentration, sperm motility and sperm morphology were determined. Oxidative stress and inflammatory response parameters were examined and histological examinations were performed in testicular tissues. Our results revealed that BPA exposure decreased serum testosterone and estrogen levels, increased FSH and LH levels (p < 0.05). BPA has been found to increase oxidative stress and inflammatory response and disrupt the histological structure. Also, BPA exposure decreased testicular weight, epididymal sperm concentration and motility, and increased abnormal sperm rate (p < 0.05). These results show that ANS, LTZ and RSV treatments reduce the BPA-induced testicular damage.

The role of gonadal hormones in regulating opioid antinociception.

Opioids are the most prescribed drugs for the alleviation of pain. Both clinical and preclinical studies have reported strong evidence for sex-related divergence regarding opioid analgesia. There is an increasing amount of evidence indicating that gonadal hormones regulate the analgesic efficacy of opioids. This review presents an overview of the importance of gonadal steroids in modulating opioid analgesic responsiveness and focuses on elaborating what is currently known regarding the underlyingmechanism. We sought to identify the link between gonadal hormones and the effect of oipiod antinociception.

Gonadal hormones contribute to the sexual dimorphism of opioid antinociception.Generally, oestradiol is a negative modulator of opioid analgesia via both non-genomic and genomic effects.Testosterone facilitates opioid analgesia mainly through the transcriptional activities of androgen receptors.Under normal physiological conditions, progestin and oestrogen exist in parallel and have a combined effect. However, progestin alone could promote opioid analgesia by increasing the expression of opioid receptors.

Menopause depression: Under recognised and poorly treated.

Menopause is a biological process experienced by all people assigned female at birth. A significant number of women experience mental ill health related to the major brain gonadal hormone shifts that occur in their midlife. There is poor understanding and management of the complex mental ill health issues, with the biological brain hormone changes receiving little formal attention. The current treatment advice is to manage this special type of mental ill health in the same way that all mental ill health is managed. This leads to poor outcomes for women and their families. Many women leave the workforce earlier than expected due to menopause-related depression and anxiety, with subsequent loss of salary and superannuation. Others describe being unable to adequately parent or maintain meaningful relationships - all ending in a poor quality of life. We are a large and diverse group of national and international clinicians, lived experience and social community advocates, all working together to innovate the current approaches available for women with menopausal mental ill health. Above all, true innovation is only possible when the woman with lived experience of menopause is front and centre of this debate.

Gonadal sex and chromosome complement influence the gut microbiome in a mouse model of allergic airway inflammation.

Evidence abounds that gut microbiome components are associated with sex disparities in the immune system. However, it remains unclear whether the observed sex disparity in asthma incidence is associated with sex-dependent differences in immune-modulating gut microbiota, and/or its influence on allergic airway inflammatory processes. Using a mouse model of house dust mite (HDM)-induced allergic inflammation and the four core genotypes (FCGs) model, we have previously reported sex differences in lung inflammatory phenotypes. Here, we investigated associations of gut microbiomes with these phenotypes by challenging FCG mice [mouse with female sex chromosome and male gonad (XXM), mouse with female sex chromosome and female gonad (XXF), mouse with male sex chromosome and male gonad (XYM), and mouse with male sex chromosome and female gonad (XYF); n = 7/group] with HDM (25 µg) or PBS intranasally for 5 wk and collecting fecal samples. We extracted fecal DNA and analyzed the 16S microbiome via Targeted Metagenomic Sequencing. We compared α and ß diversity across genotypes and assessed the Firmicutes/Bacteroidetes (F/B) ratio. When comparing baseline and after exposure for the FCG, we found that the gut F/B ratio was only increased in the XXM genotype. We also found that α diversity was significantly increased in all FCG mice upon HDM challenge, with the highest increase in the XXF, and the lowest in the XXM genotypes. Similarly, ß diversity of the microbial community was also affected by challenge in a gonad- and chromosome-dependent manner. In summary, our results indicated that HDM treatment, gonads, and sex chromosomes significantly influence the gut microbial community composition. We concluded that allergic lung inflammation may be affected by the gut microbiome in a sex-dependent manner involving both hormonal and genetic influences.NEW & NOTEWORTHY Recently, the gut microbiome and its role in chronic respiratory disease have been the subject of extensive research and the establishment of its involvement in immune functions. Using the FCG mouse model, our findings revealed the influence of gonads and sex chromosomes on the microbial community structure before and after exposure to HDM. Our data provide a potential new avenue to better understand mediators of sex disparities associated with allergic airway inflammation.

Serum gonadal hormones levels and hypogonadism in ART naïve newly diagnosed HIV infected adult males in Mwanza, Tanzania.

BACKGROUND: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is an endemic chronic disease which is characterized with progressive depletion of CD4 T cells and increased susceptibility to opportunistic infections. Previous studies have associated HIV infection with increased hypogonadism. However, the prevalence of hypogonadism remained poorly defined and widely ranging in various studies. This study aims to evaluate the serum gonadal hormonal levels and hypogonadism in antiretroviral therapy (ART) naïve newly diagnosed HIV infected-males in Mwanza, Tanzania. METHODS: This was a comparison study involving 81 ART naïve newly diagnosed HIV-infected adult males as study group and 81 apparently healthy HIV-negative males as comparison group. The participants in the study group and comparison group were matched by body mass index and age. Serum hormones [Total testosterone (TT), follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E) were estimated. Serum testosterone < 300 ng/dl, or testosterone > 300 ng/dl with high LH and FSH (compensatory hypogonadism) were taken as markers of hypogonadism. Data were analyzed using STATA version 15. RESULTS: The median serum testosterone level among ART naïve newly diagnosed HIV-infected adult males was significantly lower as compared to their comparison group (447 [259-534] versus 517 [396-605]; p = 0.0074) and shown to decrease with decreasing CD4 level. The median [IQR] serum FSH level among ART naïve newly diagnosed HIV-infected adult males was significantly higher than among their comparison group (3.8 [2.1-6.5] versus 2.6 [1.8-4.2]; p = 0.0086). The differences in serum LH and Estradiol were not statistically significant. Furthermore, the proportion of hypogonadism was significantly higher among ART naïve newly diagnosed HIV-infected adult males than in their comparison group (37.0% [30/81] versus 14.8% [12/81]; p = 0.0006). Out of these 30, 24 HIV-infected males had secondary hypogonadism, one had primary, and the remaining five had compensatory hypogonadism. CONCLUSION: Serum testosterone was lower and follicle stimulating hormone was higher among ART naïve HIV-infected males as compared to the HIV negative controls. Hypogonadism, mainly secondary, is common endocrine abnormality among ART naïve HIV-infected male patients in this study. HIV is associated with variations in gonadal hormones which may lead to sexual dysfunction in infected individuals.

From pathology to pleasure: Reframing mechanistic studies on same-sex sexual behavior in primates.

Same-sex sexual behaviors (SSB) in primates have historically been studied as sexual perversions, evolutionary paradoxes, and hormone-driven pathologies. Researchers in recent decades have challenged these perspectives, yet some of the original biases still linger. In this paper, we examine how the study of endocrinological mechanisms in SSB has been influenced by the historical framework of pathology. Societal attitudes and cultural conceptions of human sexuality have led researchers to study SSB in primates as the outcome of "abnormal" processes of "feminization" or "masculinization" of sexual behavior. Here, we argue for a renewed attention to other areas of inquiry regarding the relationship between hormones and SSB, such as the role of pleasure. We briefly review how current knowledge on the neuroendocrinology of pleasure in nonhuman primates may relate to the expression of SSB and highlight oxytocin and dopamine as potentially fruitful areas for future research. We argue that future studies on SSB in primates would benefit from 1) acknowledging how the historical study of SSB as a pathology has shaped mechanistic studies and 2) studying SSB with the same holistic approach as is taken with different-sex sexual behavior (DSB).

Sex, hormones and cerebrovascular function: from development to disorder.

Proper cerebrovascular development and neurogliovascular unit assembly are essential for brain growth and function throughout life, ensuring the continuous supply of nutrients and oxygen. This involves crucial events during pre- and postnatal stages through key pathways, including vascular endothelial growth factor (VEGF) and Wnt signaling. These pathways are pivotal for brain vascular growth, expansion, and blood-brain barrier (BBB) maturation. Interestingly, during fetal and neonatal life, cerebrovascular formation coincides with the early peak activity of the hypothalamic-pituitary-gonadal axis, supporting the idea of sex hormonal influence on cerebrovascular development and barriergenesis.Sex hormonal dysregulation in early development has been implicated in neurodevelopmental disorders with highly sexually dimorphic features, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Both disorders show higher prevalence in men, with varying symptoms between sexes, with boys exhibiting more externalizing behaviors, such as aggressivity or hyperactivity, and girls displaying higher internalizing behaviors, including anxiety, depression, or attention disorders. Indeed, ASD and ADHD are linked to high prenatal testosterone exposure and reduced aromatase expression, potentially explaining sex differences in prevalence and symptomatology. In line with this, high estrogen levels seem to attenuate ADHD symptoms. At the cerebrovascular level, sex- and region-specific variations of cerebral blood flow perfusion have been reported in both conditions, indicating an impact of gonadal hormones on the brain vascular system, disrupting its ability to respond to neuronal demands.This review aims to provide an overview of the existing knowledge concerning the impact of sex hormones on cerebrovascular formation and maturation, as well as the onset of neurodevelopmental disorders. Here, we explore the concept of gonadal hormone interactions with brain vascular and BBB development to function, with a particular focus on the modulation of VEGF and Wnt signaling. We outline how these pathways may be involved in the underpinnings of ASD and ADHD. Outstanding questions and potential avenues for future research are highlighted, as uncovering sex-specific physiological and pathological aspects of brain vascular development might lead to innovative therapeutic approaches in the context of ASD, ADHD and beyond.

Epigenetic mechanisms underlying sex differences in the brain and behavior.

Sex differences are found across brain regions, behaviors, and brain diseases. Sexual differentiation of the brain is initiated prenatally but it continues throughout life, as a result of the interaction of three major factors: gonadal hormones, sex chromosomes, and the environment. These factors are thought to act, in part, via epigenetic mechanisms which control chromatin and transcriptional states in brain cells. In this review, we discuss evidence that epigenetic mechanisms underlie sex-specific neurobehavioral changes during critical organizational periods, across the estrous cycle, and in response to diverse environments throughout life. We further identify future directions for the field that will provide novel mechanistic insights into brain sex differences, inform brain disease treatments and women's brain health in particular, and apply to people across genders.

Sexual dysfunction and associated factors in Behçet's disease: a case-control study.

Sexual health is an important part of a healthy life. The aim of this study is to define Behçet's sexual dysfunction and the factors affecting it. Sixty-nine patients with Behçet's disease (BD) and 74 healthy controls were included in the study. International Index of Erectile Function (IIEF), the Female Sexual Function Index (FSFI), the Beck Depression Inventory (BDI), and the Short Form Health Survey (SF-36) were filled out by patients and healthy control group (HCG). Follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin and estradiol or testosterone levels according to gender were measured in Behçet's patients. The rate of sexual dysfunction and its relationship with gonadal hormones, Beck depression and SF 36 subgroups were evaluated in Behçet's patients. Sixty-nine patients with BD (mean age 39.55 ± 11.7) and 74 HCG (mean age 36.9 ± 6.84) were included in the study. Sexual dysfunction was observed in 74% (49) of BD and 59.5% (44) of HCG (p = 0.047). Prolactin level is within normal limits in all patients. Although there are abnormal levels of gonadal hormones, no relationship was found with sexual dysfunction. Depression especially is more prevalent compared to the healthy population (p = 0.016). The presence of depression negatively affects sexual life. Depression, SF 36 physical role limitations, energy vitality, vitality and mental health were associated with sexual dysfunction in patients with Behçet's disease. Sexual dysfunction was associated with the presence of depression and SF-36 subscales in Behçet's patients.

Interaction of gonadal hormones, dopaminergic system, and epigenetic regulation in the generation of sex differences in substance use disorders: A systematic review.

Substance use disorder (SUD) is a chronic condition characterized by pathological drug-taking and seeking behaviors. Remarkably different between males and females, suggesting that drug addiction is a sexually differentiated disorder. The neurobiological bases of sex differences in SUD include sex-specific reward system activation, influenced by interactions between gonadal hormone level changes, dopaminergic reward circuits, and epigenetic modifications of key reward system genes. This systematic review, adhering to PICOS and PRISMA-P 2015 guidelines, highlights the sex-dependent roles of estrogens, progesterone, and testosterone in SUD. In particular, estradiol elevates and progesterone reduces dopaminergic activity in SUD females, whilst testosterone and progesterone augment SUD behavior in males. Finally, SUD is associated with a sex-specific increase in the rate of opioid and monoaminergic gene methylation. The study reveals the need for detailed research on gonadal hormone levels, dopaminergic or reward system activity, and epigenetic landscapes in both sexes for efficient SUD therapy development.

The association between blood heavy metals level and sex hormones among postmenopausal women in the US.

Introduction: Environmental pollutants could be implicated in female endocrine setting Q6 beyond traditional factors. Until now, few study has focused on the association of environmental exposure to heavy metals with sex hormones in postmenopausal women. This study intended to investigate whether serum levels of heavy metals(i.e., Cd, Pb, Hg, Mn, Se) would influence sex hormones in postmenopausal women. Methods and results: A cross-sectional study was performed on 614 nationally representative participants from 2013-2016 National Health and Nutrition Examination Survey (NHANES) in the US. Multivariate linear regression models and restricted cubic spline plots revealed cadmium(Cd) had linear positive association with TT(ß=3.25, 95%CI= 1.12, 5.38), bioavailable TT(ß=1.78, 95%CI=0.36,3.21) and TT/E2(ß=0.76, 95%CI=0.28,1.24), which was more apparent in natural menopausal and obese women. Lead(Pb) had linear positive association with SHBG(ß=12.84, 95%CI= 6.77,18.91), which was apparent in nearly all subgroups except in normal BMI group, and TT/E2 (ß=0.69, 95%CI 0.134,1.25), which was apparent in natural menopausal and normal BMI women. Manganese(Mn) had non-linear association with SHBG, which was more apparent in natural menopausal and obese women, and TT/E2, which was more apparent in natural menopausal and normal BMI women. Selenium(Se) had U shaped non-linear association with TT, which was more apparent in hysterectomy, overweight and obese women, and SHBG, which was apparent in nearly all subgroups except in normal BMI group. Conclusion: In summary, this cross-sectional study indicates a possible role that various degree of environmental exposure to heavy metals plays in the disruption of sex Q5 hormone levels in postmenopausal women. Further experiments are needed to elucidate the underlying mechanisms.

The nano-micellar curcumin improves International Prostate Symptoms Score (IPSS) in patients with benign prostatic hyperplasia: a randomized clinical trial.

PURPOSE: Benign prostatic hyperplasia (BPH) is the main prevalent disorder in men over forty years, usually revealing itself with lower urinary tract symptoms. Despite the existence of different treatments, the incidence of BPH is increasing, so further studies for better management are a necessity. This research was designed to assay the effectiveness of nano-micellar curcumin on biomedical indicators of patients with BPH. METHODS: The present research was a double-blind, randomized, and placebo-controlled trial that enrolled fifty-two patients with BPH between June 2021 and December 2021. Participants were randomized to receive 160 mg/d nano-micellar curcumin (n = 26) or placebo (n = 26) as soft gel during 3 months. Primary end point was changes in International Prostate Symptoms Score (IPSS). Data gathering was occurred using a standard inquiry form and measuring other biomedical parameters based on routine laboratory techniques. To compare the distribution of demographics and covariates, independent t-test and Chi-square were used. RESULTS: Nano-micellar curcumin had significant effect on IPSS (p value: 0.010), low effect on high-sensitive C-reactive protein (hs-CRP) (p value: 0.032), and low to intermediate effect on malondialdehyde (MDA) (p value: 0.014) level as secondary end points after the intervention. The effect of nano-micellar curcumin on other parameters was negligible. CONCLUSION: Overall, this trial indicated 3-month intake of nano-micellar curcumin had considerable effects on IPSS as the most common clinical symptom and also two biomedical parameters including serum hs-CRP and MDA. TRIAL REGISTRATION: http://www.irct.ir : IRCT20170430033730N3.

Menstrual Health Literacy among Adolescents and Young Adults Who Menstruate: Impact of Christian Family Background and United States Region.

STUDY OBJECTIVE: To compare menstrual health literacy among adolescents and young adults on the basis of family religious background and United States region METHODS: We conducted a cross-sectional online survey of post-menarcheal US adolescents and young adults aged 14-24 years who identified their family religious background, including Christian or non-religious, with recruitment via the social media platform TikTok. We asked participants several questions to assess their health literacy regarding common myths about the use of gonadal steroid hormones for menstrual suppression. RESULTS: From 3250 online survey respondents, 2997 met the criteria for analysis, with 1989 identifying their family as Christian (66.4%) and 1008 identifying their family as non-religious (33.6%), with equal representation by US region. Health literacy was lower among those with a Christian family background, with concerns that menstrual suppression is unhealthy (16.4% vs 10.5% with non-religious background, P < .01), is unsafe (31.4% vs 24.2%, P < .01), and could lead to infertility (32.6% vs 20.0%, P < .01). Similarly, adolescents and young adults from the US South were worried that menstrual suppression is unhealthy (31.5%; P < .01) and would lead to infertility (33.8%; P < .01). CONCLUSION: Health literacy is lower among adolescents and young adults with a Christian family background and those who live in the South. These results demonstrate a need for an evidence-based national curriculum that addresses the safe and effective use of hormonal medications for menstrual suppression.

Connecting dots in disorders of gut-brain interaction: the interplay of stress and sex hormones in shaping visceral pain.

Visceral pain and stress are tightly intertwined bodily and emotional phenomena, which enable a flexible adaptation to environmental challenges by activating a response repertoire to restore homeostasis along the gut-brain axis. However, visceral pain and stress can persist widely independent of the initial cause, acquiring independent disease values and posing major health burdens as predominant features in disorders of gut-brain interaction (DGBI). Epidemiological data consistently documents an increased prevalence for women to suffer from chronic visceral pain, possibly shaped by sex hormones and modulated by stress and its biological and psychosocial correlates. Yet, mechanisms underlying the complex interactions between altered visceroception, stress and sex remain widely elusive, especially in clinical populations with DGBI. We herein selectively review mechanisms of interactions between stress and sex in the complex pathophysiology of DGBI. A particular emphasis is laid on visceral pain, in which stress constitutes a major risk factor as well as mediator, and sex-related differences are particularly pronounced. Building on the neurobiology of stress and mechanisms of gut-brain interactions, we highlight putative target mechanisms via which visceral pain and stress may converge with sex effects into a triad. Accommodating a global demographic shift, we propose a lifespan perspective in future research, which may enable a more fine-tuned evaluation of this complex interplay exerting distinct challenges during vulnerable developmental phases. This viewpoint may advance our understanding of pathophysiological processes and can ultimately inspire novel tailored prevention strategies and therapeutic approaches in the treatment of chronic visceral pain and DGBI across the lifespan.

Neurodevelopmental Model Explaining Associations between Sex Hormones, Personality, and Eating Pathology.

Clinical scientists have been investigating the relationships between sex hormones, personality, and eating disorders for decades. However, there is a lack of direct research that addresses whether personality mediates or moderates the relationships between sex hormones and eating pathology. Moreover, the neural mechanisms that underlie the interactive associations between these variables remain unclear. This review aims to summarize the associations between these constructs, describe a neural mechanism mediating these relationships, and offer clinical strategies for the early identification and intervention of eating disorders. The gathered evidence shows that aggressiveness, impulsivity, and obsessive-compulsiveness may mediate or moderate the relationships between sex hormones and eating pathology, but only among females. Furthermore, sex hormone receptor density in the mesocorticolimbic dopamine pathway may explain the neural mechanism of these associations. Future research should use more comprehensive personality measurements and assess the mediation and moderation effects of temperament while taking the hormone levels of women across menstrual cycles into account. Additionally, electroencephalography and functional magnetic resonance imaging should be implemented to directly assess brain activity and corroborate these findings.

Experimental pain thresholds and psychosocial features across menstrual cycle in myofascial orofacial pain compared to healthy individuals: cross-sectional study / Limiares de dor experimental e características psicossociais ao longo do ciclo menstrual na dor miofascial orofacial em comparação com indivíduos saudáveis: estudo transversal

ABSTRACT BACKGROUND AND OBJECTIVES: The hormonal impact on pain perception during the menstrual cycle is a major focus of study, and further elucidation in temporomandibular disorders (TMD) field is necessary. Thus, this cross-sectional study evaluated experimental pain thresholds, psychosocial features, and clinical pain report on TMD women across menstrual cycle versus healthy controls. METHODS: A total of 220 women's clinical files were screened, with 80 selected and divided into control group (healthy individuals, n=40) and TMD group (myofascial pain, n=40). Regarding the menstrual cycle phases, the files were divided into Pre-Luteal and Luteal. The Perceived Stress Scale (PSS), Pain Catastrophizing Scale (PCS), Mechanical Pain Threshold (MPT), Wind-up (WUR), Pressure Pain Threshold (PPT), Conditioned Pain Modulation (CPM) and Visual Analogue Scale (VAS) were analyzed at a 5% significance level, by Two-Way ANOVA test and post hoc Tukey test. RESULTS: PSS and PCS were significantly different between TMD and control group (p<0.001), regardless of menstrual cycle. Healthy individuals in the Luteal phase presented higher MPT values compared to the other phases (p<0.001). PPT showed significant difference across menstrual phases (p=0.022), but no differences in multiple comparisons. VAS values showed no difference between menstrual cycle phases (p=0.376). CONCLUSION: Finally, healthy individuals in the Luteal phase have higher MPT and PPT values on the orofacial region. Pain report in patients with TMD showed no difference throughout the menstrual cycle, showing that small alterations on experimental pain thresholds may not be clinically relevant. The presence of chronic pain seems to be more related to psychosocial features than hormonal fluctuations.

RESUMO JUSTIFICATIVA E OBJETIVOS: O impacto do ciclo menstrual na percepção da dor é um foco importante de estudo, sendo necessária uma maior elucidação na disfunção temporomandibular (DTM). Assim, este estudo transversal avaliou limiares de dor experimental, características psicossociais e relatos de dor em mulheres com DTM ao longo do ciclo menstrual, comparadas com controles saudáveis. MÉTODOS: 220 prontuários de mulheres foram analisados, sendo 80 selecionados para os grupos de controle (saudáveis, n=40) e DTM (dor miofascial, n=40). Nas fases do ciclo menstrual, as pacientes foram divididas nas categorias Pré-Luteal e Luteal. Os instrumentos Escala de Estresse Percebido (PSS), Escala de Pensamentos Catastróficos (PCS), Limiar de Dor Mecânica (MPT), Wind-up Ratio (WUR), Limiar de Dor à Pressão (PPT), Modulação Condicionada da Dor (CPM) e Escala analógica visual (EAV) foram analisados com nível de significância de 5%, pelos testes ANOVA de dois fatores e Tukey post hoc. RESULTADOS: As escalas PSS e PCS foram significativamente diferentes entre os grupos DTM e controle (p<0,001), independentemente do ciclo menstrual. Indivíduos saudáveis na fase luteal apresentaram MPT maior em comparação com outras fases (p,0,001). O PPT mostrou diferença significativa entre as fases menstruais (p=0,022), sem diferença nas comparações múltiplas. Os valores da EAV não apresentaram diferença entre as fases menstruais (p=376). CONCLUSÃO: Indivíduos saudáveis na fase luteal têm MPT e PPTl maior na região orofacial. Os relatos de dor em pacientes com DTM não mostraram diferença ao longo do ciclo menstrual, indicando que pequenas alterações nos limiares experimentais podem ser clinicamente relevantes. A presença de dor crônica parece estar mais relacionada com características psicossociais do que com flutuações hormonais.

Estrogen modulation of cortical spreading depression.

BACKGROUND AND AIMS: Cortical spreading depression (CSD), a transient neuronal and glial depolarization that propagates slowly across the cerebral cortex, is the putative electrophysiological event underlying migraine aura and a headache trigger. Migraine is three times more prevalent in women than men, linked to circulating female hormones. High estrogen levels or estrogen withdrawal may be a migraine trigger for many women. We, therefore, aimed to examine whether sex, gonadectomy, and female hormone supplementation and withdrawal affect the susceptibility to CSD. METHODS: To determine CSD susceptibility, we recorded the frequency of CSDs triggered during 2-h topical KCl application in intact or gonadectomized female and male rats, without or with estradiol or progesterone supplementation via daily intraperitoneal injections. Estrogen or progesterone treatment followed by withdrawal was studied in a separate cohort. To take the first step towards identifying potential mechanisms, we studied glutamate and GABAA receptor binding using autoradiography. RESULTS: The CSD frequency in intact female rats was higher than intact male and ovariectomized rats. We did not detect a change in CSD frequency during different stages of the estrous cycle in intact females. Daily estrogen injections for three weeks did not change CSD frequency. However, one-week estrogen withdrawal after two weeks of treatment significantly increased CSD frequency compared with the vehicle group in gonadectomized females. The same protocol of estrogen treatment and withdrawal was ineffective in gonadectomized males. In contrast to estrogen, daily progesterone injections for three weeks elevated CSD susceptibility, and one-week withdrawal after two weeks of treatment partially normalized this effect. Autoradiography did not reveal significant changes in glutamate or GABAA receptor binding density after estrogen treatment and withdrawal. CONCLUSIONS: These data suggest that females are more susceptible to CSD, and sexual dimorphism is abrogated by gonadectomy. Moreover, estrogen withdrawal after prolonged daily treatment enhances CSD susceptibility. These findings may have implications for estrogen-withdrawal migraine, although the latter tends to be without aura.

Changes in Visual Long-Term Potentiation Show Preserved Cyclicity in Human Females Taking Combined Oral Contraceptives.

INTRODUCTION: The combined oral contraceptive (COC) pill is often employed to address physical and neurological symptoms in menstrual cycle-related disorders by suppressing shifts in endogenous gonadal hormone fluctuations. Symptom persistence, especially in the lead up to the hormone-free interval (HFI), suggests an underlying neurobiological mechanism of preserved cycling. Our study utilised a non-invasive method of visually inducing long-term potentiation (LTP) to index changes in neural plasticity in the absence of hormonal fluctuations. METHODS: Visually induced LTP was recorded using electroencephalography in 24 healthy female COC users across three sessions: days 3 and 21 during active hormone pills, and day 24 during the HFI. The Daily Record of the Severity of Problems (DRSP) questionnaire tracked premenstrual symptoms. Dynamic causal modelling (DCM) was used to elucidate the neural connectivity and receptor activity changes associated with LTP across different days of COC. RESULTS: Visually induced LTP was greater on day 21 than day 3 (p = 0.011) and was localised to the P2 visually evoked potential. There was no effect of the HFI (day 24) on LTP. DCM of differences between days 3 and 21 showed changes to inhibitory interneuronal gating of LTP in cortical layer VI. The DRSP only showed a significant increase in symptoms in the HFI, meaning the LTP result appeared more sensitive to cyclicity. CONCLUSIONS: This study provides objective evidence of preserved cyclicity in COC users through enhanced LTP on day 21 compared to day 3 of a 28-day COC regimen, indicating that relatively higher excitation in the brain despite peripheral gonadal suppression may underlie and exacerbate menstrual cycle-related disorders.

Sex differences in neuroimmunoendocrine communication. Involvement on longevity.

Endocrine, nervous, and immune systems work coordinately to maintain the global homeostasis of the organism. They show sex differences in their functions that, in turn, contribute to sex differences beyond reproductive function. Females display a better control of the energetic metabolism and improved neuroprotection and have more antioxidant defenses and a better inflammatory status than males, which is associated with a more robust immune response than that of males. These differences are present from the early stages of life, being more relevant in adulthood and influencing the aging trajectory in each sex and may contribute to the different life lifespan between sexes.

Sex and timing of gonadectomy relative to puberty interact to influence weight, body composition, and feeding behaviors in mice.

Gonadal sex steroids are important regulators of energy balance in adult rodents, and gonadectomy (GDX) has opposing effects on weight gain in sexually mature males and females. Puberty is associated with the emergence of sex differences in weight, body composition, and feeding behaviors, yet the role of gonadal hormones at puberty remains unclear. To address this, we performed GDX or sham surgery in male and female C57Bl/6 mice at postnatal day (P)25 (prepubertal) or P60 (postpubertal) timepoints and measured weight and body composition for 35 days, after which ad libitum and operant food intake was measured using Feeding Experimentation Device 3 (FED3s) in the home cage. Consistent with previous studies, postpubertal GDX caused weight gain in females and weight loss in males and increased adiposity in both sexes. However, prepubertal GDX decreased weight gain and altered body composition across the adolescent transition (P25 to P60) in males but had no effect in females. Despite the varied effects on weight, GDX decreased food intake and motivation for food as assessed in operant tasks regardless of sex or timing of surgery relative to puberty. Our findings indicate that GDX interacts with both sex and age at surgery to influence weight, body composition, and feeding behavior.