Impact Of Sex Hormones Research Articles

Poster #S90 RELATIONSHIP OF KREMEN1 GENE VARIATION WITH SYMPTOMATOLOGY AND COGNITIVE FUNCTIONING IN SCHIZOPHRENIA

Female patients with schizophrenia tend to have a more benign course and better outcomes than males. One proposed explanation is the differential influence of male and female sex hormones, including estrogen, progesterone, testosterone, and dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). Such benefit may be mediated by their effects on neurotransmitters and neuroprotection. Besides altered estrogen and DHEA/DHEAS levels in female patients, data is equivocal on hormonal differences between patients and controls. However, several reports note a mostly negative correlation between estrogen levels and symptom severity in both genders, and a positive correlation between estrogen levels and neurocognition but mainly in females. Adjunctive estrogen appears to improve symptoms in both genders. Progesterone levels have inconsistent links to symptom severity in both genders, and correlate positively with neurocognition but only in males. Estrogen-progesterone combination shows preliminary benefits as augmentation for both symptoms and neurocognition in females. Testosterone levels correlate inversely with negative symptoms in males and have inconsistent associations with neurocognition in both genders. Testosterone augmentation reduced negative symptoms in male patients in a pilot investigation, but has not been evaluated for neurocognition in either gender. DHEA/DHEAS have mixed results for their association with, and clinical utility for, symptoms and neurocognition in both genders. Overall, data on the impact of sex hormones on clinical course or as treatment for schizophrenia is limited, but estrogen has most evidence for positive influence and clinical benefit. The possibly greater tolerability and broader impact of these hormones versus existing medications support further exploration of their use.

Closer to personalized approach through accepting the gender differences in medicine

Results CLL patients demonstrated significant decrease of T-lymphocytes function. Remarkable increase of serum cortisol level was found in CLL patients, whereas no changes in ACTH concentrations were demonstrated. We can guess the existence of serious dysregulation of the hypothalamic-pituitary-adrenal axis. Values of FSH, LH and E in men with CLL were significantly higher than in healthy persons. No significant differences were demonstrated in the levels of abovementioned hormones in female CLL patients. The dysbalance of sex hormones can influence the immune functions. Negative correlation has been demonstrated between E/T radio and T-lymphocyte function in male CLL patients. We can guess that earlier observed worse survival of male CLL patients compared to females can be connected with the impact of sex hormones dysbalance on immune regulation and through that to overall pathogenesis of disease. Males and females normally have dimorphic immune response. It is reasonable to suggest that in pathologic conditions (for example in CLL) immune regulation is altered in different ways in males and females. Sex hormones dysbalance in CLL can be responsible for that. Further studies are needed to clarify whether CLL male and female patients would need different therapy in connection with diversity of pathogenesis and disease progression. In conclusion, there are some arguments presented that gender-based medicine will become irrelevant if all individual factors can be taken into account. However, large databases reveal that gender remains as an independent risk factor. It is important to consider and find out the impact of gender differences in individualised medicine approach.

Gender differences in paediatric patients of the swiss inflammatory bowel disease cohort study.

PurposeGender differences in paediatric patients with inflammatory bowel disease (IBD) are frequently reported as a secondary outcome and the results are divergent. To assess gender differences by analysing data collected within the Swiss IBD cohort study database since 2008, related to children with IBD, using the Montreal classification for a systematic approach.MethodsData on gender, age, anthropometrics, disease location at diagnosis, disease behaviour, and therapy of 196 patients, 105 with Crohn's disease (CD) and 91 with ulcerative or indeterminate colitis (UC/IC) were retrieved and analysed.ResultsThe crude gender ratio (male : female) of patients with CD diagnosed at <10 years of age was 2.57, the adjusted ratio was 2.42, and in patients with UC/IC it was 0.68 and 0.64 respectively. The non-adjusted gender ratio of patients diagnosed at ≥10 years was 1.58 for CD and 0.88 for UC/IC. Boys with UC/IC diagnosed <10 years of age had a longer diagnostic delay, and in girls diagnosed with UC/IC >10 years a more important use of azathioprine was observed. No other gender difference was found after analysis of age, disease location and behaviour at diagnosis, duration of disease, familial occurrence of IBD, prevalence of extra-intestinal manifestations, complications, and requirement for surgery.ConclusionCD in children <10 years affects predominantly boys with a sex ratio of 2.57; the impact of sex-hormones on the development of CD in pre-pubertal male patients should be investigated.

Psycho-medical care of transsexuals in Spain in the era of depathologization of transsexualism as a mental disorder. An overall review

Abstract Objective To identify the strengths and weaknesses of Spanish healthcare protocols for transsexual persons and to compare them to current international protocols. To review the current status as regards transsexuality etiology and prevalence. To suggest measures to optimize care to achieve a significant improvement, including options for saving financial resources. Methods A comparison of the contents of texts related to transsexualism in the ICD-10, DSM- IV , and guidelines of the Spanish gender units with international standards of care for transgender persons and the last draft version of the DSM-5. Systematic revision of the literature related to the etiology and prevalence of transsexualism. Results Significant discrepancies have been found as regards the minimum time period for diagnosis, access to hormone replacement therapy and to genital surgery, and the requirement of the so-called real-life experience. Impact of sex hormones on the etiology of transsexualism and underestimation of its prevalence was confirmed. Conclusions The access to hormonal and surgical treatment requires a profound review, and decentralization of transsexual care is recommended, because all university hospitals have psychiatrists, clinical psychologists, and endocrinologists available. Although gender reassignment surgery also requires plastic surgery specialists, plastic surgeons currently receive training in this field.

Microbiome, sex hormones, and immune responses in the reproductive tract: Challenges for vaccine development against sexually transmitted infections

The female and male reproductive tracts are complex eco-systems where immune cells, hormones, and microorganisms interact. The characteristics of the reproductive tract mucosa are distinct from other mucosal sites. Reproductive tract mucosal immune responses are compartmentalized, unique, and affected by resident bacterial communities and sex hormones. The female and male genital microbiomes are complex environments that fluctuate in response to external and host-associated stimuli. The female vaginal microbiota play an important role in preventing colonization by pathogenic organisms. Sex hormones and their duration of exposure affect the composition and stability of the microbiome as well as systemic and mucosal immune responses. In addition to the characteristics of the pathogen they are targeting, successful vaccines against sexually transmitted pathogens must take into account the differences between the systemic and mucosal immune responses, the compartmentalization of the mucosal immune responses, the unique characteristics of the reproductive tract mucosa, the role of the mucosal bacterial communities, the impact of sex hormones, and the interactions among all of these factors.

Atención psicomédica a personas transexuales en España en la era de la despatologización de la transexualidad como trastorno mental. Una revisión global

ObjectiveTo identify the strengths and weaknesses of Spanish healthcare protocols for transsexual persons and to compare them to current international protocols. To review the current status as regards transsexuality etiology and prevalence. To suggest measures to optimize care to achieve a significant improvement, including options for saving financial resources. MethodsA comparison of the contents of texts related to transsexualism in the ICD-10, DSM-IV, and guidelines of the Spanish gender units with international standards of care for transgender persons and the last draft version of the DSM-5. Systematic revision of the literature related to the etiology and prevalence of transsexualism. ResultsSignificant discrepancies have been found as regards the minimum time period for diagnosis, access to hormone replacement therapy and to genital surgery, and the requirement of the so-called real-life experience. Impact of sex hormones on the etiology of transsexualism and underestimation of its prevalence was confirmed. ConclusionsThe access to hormonal and surgical treatment requires a profound review, and decentralization of transsexual care is recommended, because all university hospitals haves psychiatrists, clinical psychologists, and endocrinologists available. Although gender reassignment surgery also requires plastic surgery specialists, plastic surgeons currently receive training in this field.

Distinct Th17 inductions contribute to the gender bias in CVB3-induced myocarditis

Viral myocarditis is often caused by coxsackievirus B3 (CVB3) infection and occurs more frequently in males. So far, the mechanisms for this sex difference are not fully elucidated. As a new proinflammatory T cell population, Th17 cells are required for the development of CVB3-induced myocarditis, but their impact on the gender bias in viral myocarditis is still unknown. Male and female mice were intraperitoneally infected with CVB3; 7 days later, the frequency of splenic Th17 cells and the expression of associated cytokines and transcriptional factors were compared. Meanwhile, the impact of sex hormones on Th17 cell differentiation post CVB3 infection was also evaluated. In infected male mice, Th17 cell frequency was remarkably increased and significantly higher than that in female mice. Accordingly, the expression of associated cytokines and transcriptional factors was also obviously augmented in males. When neutralizing interleukin-17 by monoclonal antibody, the male prevalence of myocarditis was obviously abolished, further confirming the effect of Th17 cells on gender bias in viral myocarditis. It was also found that estradiol significantly inhibited the Th17 differentiation post CVB3 infection both in vitro and in vivo. However, testosterone showed no such effects. Th17 cells were predominantly induced in CVB3-infected males than females as the inhibitory effect of estrogen on Th17 differentiation and played an important role in the sex differences in the sensitivity to CVB3-induced myocarditis. This study may help us understand the role of Th17 cells in viral myocarditis and facilitate the development of corresponding therapeutic strategies.

Understanding the Gender Disparity in Bladder Cancer Risk: The Impact of Sex Hormones and Liver on Bladder Susceptibility to Carcinogens

It has long been known that bladder cancer (BC) incidence is approximately four-fold higher in men than in women in the United States, and a similar disparity also exists in other countries. The reason for this phenomenon is not known, which impedes progress in BC prevention. However, BC incidence is also significantly higher in male animals than in their female counterparts after treatment with aromatic amines, which are principal human bladder carcinogens. These animal studies and related studies in the context of available human data provide significant insight into what may drive the excessive BC risk in men, which is the focus of this article. The carcinogenicity and biotransformation of bladder carcinogens as well as the impact of sex hormones on these processes are discussed, highlighting the novel concept that the gender disparity in BC risk may result primarily from the interplay of androgen, estrogen, and liver, with the liver functioning via its metabolic enzymes as the main decider of bladder exposure to carcinogens in the urine and the male and female hormones exerting opposing effects on carcinogenesis in the bladder and likely also on liver enzymes handling bladder carcinogens. The findings may facilitate further investigation into the mechanism of gender disparity in BC risk and may also have important implications for BC prevention.

Foreword

Viral myocarditis is often caused by coxsackievirus B3 (CVB3) infection and occurs more frequently in males. So far, the mechanisms for this sex difference are not fully elucidated. As a new proinflammatory T cell population, Th17 cells are required for the development of CVB3-induced myocarditis, but their impact on the gender bias in viral myocarditis is still unknown.Male and female mice were intraperitoneally infected with CVB3; 7 days later, the frequency of splenic Th17 cells and the expression of associated cytokines and transcriptional factors were compared. Meanwhile, the impact of sex hormones on Th17 cell differentiation post CVB3 infection was also evaluated.In infected male mice, Th17 cell frequency was remarkably increased and significantly higher than that in female mice. Accordingly, the expression of associated cytokines and transcriptional factors was also obviously augmented in males. When neutralizing interleukin-17 by monoclonal antibody, the male prevalence of myocarditis was obviously abolished, further confirming the effect of Th17 cells on gender bias in viral myocarditis. It was also found that estradiol significantly inhibited the Th17 differentiation post CVB3 infection both in vitro and in vivo. However, testosterone showed no such effects.Th17 cells were predominantly induced in CVB3-infected males than females as the inhibitory effect of estrogen on Th17 differentiation and played an important role in the sex differences in the sensitivity to CVB3-induced myocarditis. This study may help us understand the role of Th17 cells in viral myocarditis and facilitate the development of corresponding therapeutic strategies.

Abstract 464: Progesterone Signaling in Endothelial Cells Results in Increased Vascular Permeability and Platelet Adhesion

Epidemiological studies have indicated the rather significant, yet unclear, impact of sex hormones on cardiovascular physiology and disease. Both observational studies and clinical trials have produced conflicting evidence as to the benefits of female sex hormones, particularly with regards to progesterone. Prolonged exposure to progesterone leads to break-through bleeding, vessel fragility and venous thromboembolisms. Currently, little is known on the molecular and cellular effects of progesterone on the cardiovascular system, or its cell specific functions. In fact, the vascular effects attributed to progesterone have been viewed, for the most part, as secondary consequences of its multiple systemic activities. Using a PRLacZ reporter mouse we have determined that progesterone receptor (PR) expression in the vasculature is restricted to endothelial cells of veins and lymphatics of the reproductive tract. Conditional deletion of PR from endothelial cells using VE-cadherin Cre leads to decreased vascular permeability in the uterus and ovary following treatment with progesterone. Transgenic misexpression of PR in the lung results in pathological vascular leakage and intravascular platelet adhesion in response to progesterone. Additionally, activation of PR within endothelial cells leads to the development of stress fibers, formation of inter-cellular gaps, increased permeability and changes in expression of cell-cell junctional proteins. These results reveal a previously unknown and direct role for PR on endothelial cell function with consequences for physiological permeability, blood vessel integrity and homeostasis.

Polymorphic variation in the androgen receptor gene: Association with risk of testicular germ cell cancer and metastatic disease

Increasing incidence of testicular germ cell cancer (TGCC) is most probably related to environment and lifestyle. However, an underlying genetic predisposition may play a role and since sex steroids are assumed to be important for the rise and progression of TGCC, a study of androgen receptor (AR) gene polymorphisms in relation to the risk, histological type and progression of TGCC was undertaken.In 367 TGCC cases and 214 controls, AR CAG and GGN repeat lengths were determined and 11 haplotype-tagging single nucleotide polymorphisms (SNPs) were genotyped. By binary logistic regression, odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the risk of TGCC, non-seminoma versus seminoma and metastatic versus localised (stage I) disease.For the non-coding SNP, rs12014709, the minor genotype (G) was found in 10% of the cases and in 5.1% of the controls, conferring an OR of 2.07 (95% CI: 1.03–4.15) for having TGCC. Furthermore, short GGN (<23) was associated with an increased risk of metastatic disease (OR: 2.15; 95% CI: 1.04–4.45).The AR polymorphisms found by us might be involved in gene–environment interaction by increasing the susceptibility to the effect of endocrine disruptors. From a biological point of view, our findings strengthen the hypothesis of the importance of androgen action in the aetiology and pathogenesis of testicular malignancy. Future studies should focus on the impact of sex hormones on foetal germ cell development and the interaction between environmental factors and androgen receptor variants in relation to the risk of testicular malignancy.

Impact of sex hormones on cutaneous neurovascular responses in humans

PurposeWe examined the impact of estradiol (E2) and progesterone (P4) on skin local heating (LH) to 42°C and reactive hyperemia (RH) responses in 23 healthy young women.MethodsSubjects were studied for 3 trials over 10–12 days. Endogenous sex hormones were suppressed with a gonadotropin‐releasing hormone antagonist (GnRHa). Subjects were studied on day 4 (trial 1) of GnRHa only. Subjects were studied 3–4 days later (trial 2) following treatment with either 0.1mg/day E2 by transdermal patch or 200mg/day P4 orally. Subjects were studied again 3–4 days later (trial 3), following treatment with both E2 and P4. Subjects underwent identical LH and RH protocols on all study days.ResultsAll blood flow values are given as percent of maximum cutaneous vascular conductance (%CVCmax). E2 alone increased initial peak CVC from 71 ± 2 to 79 ± 2% (p=0.01). P4 alone increased initial peak CVC from 73 ± 2 to 78 ± 2% (p=0.01). E2 alone increased nadir CVC from 56 ± 3 to 65 ± 2% (p=0.02). P4 increased nadir CVC from 62 ± 2 to 66 ± 3% (p=0.07). Neither E2 nor P4 increased plateau CVC, although a small statistically significant increase was seen between suppression and P4 alone (p=0.04). No significant changes were seen between trials 2 and 3 for either group. No differences were observed for the RH response.ConclusionsBoth E2 and P4 increase initial peak and nadir CVC when added back following GnRH suppression.Supported by NIH Grant HL081671

Influence of Sex Hormones and Phytoestrogens on Heart Disease in Men and Women

Cardiovascular disease (CVD) is the number one cause of morbidity and mortality in men and women worldwide. According to the WHO, by 2015, almost 20 million people will die from CVD each year. It is well established that men and women differ not only in baseline cardiac parameters, but also in the clinical presentation, diagnosis and treatment outcomes of CVD. Women tend to develop heart disease later in life than men. This difference has been attributed to the loss of estrogen during the menopausal transition; however, the biological explanations for the sexual dimorphism in CVD are more complex and seem unlikely to be due to estrogen alone. The current controversy that has arisen regarding the effects of HRT on CVD in women is a case in point. In this review, the sex-based differences in cardiac (patho-) physiology are discussed with emphasis on the impact of sex hormones, hormone receptors and diet on heart disease.

1328: The Impact of Sex-Hormones on Erectile Dysfunction. Results from the Massachusetts Male Aging Study (MMAS)

1328: The Impact of Sex-Hormones on Erectile Dysfunction. Results from the Massachusetts Male Aging Study (MMAS)

The Association Between Sex and Mortality Among Burn Patients as Modified by Age

Although an increased risk of death among female patients suffering thermal injury has been noted, the differential influence of age has received little attention. Because experimental evidence suggests that sex hormones influence the immune response to thermal injury, an age-related sex influence on patient mortality is biologically plausible as the hormone milieu changes with the onset of menopause. The goal of this study was to estimate the association between sex and mortality after thermal injury in a large, population-based sample. The National Trauma Data Bank yielded data for more than 6200 burn patients 20 years of age or older. Logistic regression was used to calculate mortality odds ratios (OR) with 95% confidence intervals (CIs) for men relative to women, both overall and by age. Adjustments for age, race, burn etiology, percent body surface area burned, comorbid conditions, and inhalation injury were performed. For the overall study population, the adjusted risk of death was approximately 30% lower for males (OR 0.67, 95% CI 0.52-0.87). Within age strata, the adjusted association was statistically significant only in those aged 20 to 34 years (OR 0.45; 95% CI 0.24-0.87); 35 to 49 years (OR 0.71; 95% CI 0.39-1.30); 50 to 64 years (OR 0.55; 95% CI 0.31-1.00); and 65 years or older (OR 0.85; 95% CI 0.57-1.27). The results of the present study not only indicate that women have an increased odds of mortality after thermal injury but also demonstrate a differential effect of age on the association between sex and mortality. On the basis of the findings of the present study as well as the results of experimental studies, further clinical research is needed to investigate the impact of sex hormones on mortality among burn patients.

A conversation with Fernando Nottebohm, PhD. Interviewed by Michael Eisenstein.

During the last 30 years, a number of revolutionary discoveries in the field of neuroscience have come from what was, at first, an unexpected direction: songbird research. Investigations into seasonal and sex-specific differences in birdsong development have led to important revelations about the impact of sex hormones on brain development and the hormonally controlled plasticity of brain structure, as well as the particularly surprising discovery that neurogenesis continues to occur in the adult brain (see Harding, p. 28). The work of Fernando Nottebohm is widely recognized as having played a key role in bringing these findings to light and thus forcing a general re-examination of established principles of neuroscience. Fernando Nottebohm is Dorothea L. Leonhardt Distinguished Professor at The Rockefeller University, and Director of The Rockefeller Field Research Center for Ethology and Ecology, a 1,200-acre facility located in Millbrook, NY, that provides researchers the opportunity to study behavior and brain function under natural conditions. Nottebohm's pioneering work on the neural control of birdsong has led to major discoveries with large impacts in the fields of animal behavior and neuroscience, and has made him one of the founders of neuroethology, the study of how the nervous system controls animal behavior. Nottebohm is a Member of the National Academy of Sciences, USA, and a Fellow of the American Association for the Advancement of Science and of the American Academy of Arts and Sciences. We had a chance to sit down with him to discuss his distinguished career working with laboratory birds.

Gender Issues in the Use of Virtual Environments

Gender differences in cognitive and behavioral performance have been reported throughout the psychological literature. Consequently, gender differences should be considered and controlled for when cognitive research is conducted in virtual environments (VEs). These variables may include gender-related differences in cognitive performance, susceptibility for cybersickness, and the impact of sex hormones on cognition. Such issues are addressed in the context of a recent VE study of the visuospatial ability referred to as mental rotation. The Mental Rotation Test (MRT), a paper and pencil measure, has been shown to produce one of the largest gender differences in the cognitive literature. The outcomes of the MRT are in favor of males. However, results reported from a Virtual Reality Spatial Rotation (VRSR) test demonstrate no gender differences when subjects were able to manually manipulate the stimuli in a VE. Further analysis uncovers gender differences in the patterns of associations between verbal and spatial tasks and performance on VRSR. Results are discussed in terms of dimensionality factors and hemispheric lateralization.

Preliminary findings in search of a genetic linkage of schizophrenia to a locus on chromosome 5

Female patients with schizophrenia tend to have a more benign course and better outcomes than males. One proposed explanation is the differential influence of male and female sex hormones, including estrogen, progesterone, testosterone, and dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). Such benefit may be mediated by their effects on neurotransmitters and neuroprotection. Besides altered estrogen and DHEA/DHEAS levels in female patients, data is equivocal on hormonal differences between patients and controls. However, several reports note a mostly negative correlation between estrogen levels and symptom severity in both genders, and a positive correlation between estrogen levels and neurocognition but mainly in females. Adjunctive estrogen appears to improve symptoms in both genders. Progesterone levels have inconsistent links to symptom severity in both genders, and correlate positively with neurocognition but only in males. Estrogen-progesterone combination shows preliminary benefits as augmentation for both symptoms and neurocognition in females. Testosterone levels correlate inversely with negative symptoms in males and have inconsistent associations with neurocognition in both genders. Testosterone augmentation reduced negative symptoms in male patients in a pilot investigation, but has not been evaluated for neurocognition in either gender. DHEA/DHEAS have mixed results for their association with, and clinical utility for, symptoms and neurocognition in both genders. Overall, data on the impact of sex hormones on clinical course or as treatment for schizophrenia is limited, but estrogen has most evidence for positive influence and clinical benefit. The possibly greater tolerability and broader impact of these hormones versus existing medications support further exploration of their use.