Endocrine care of pediatric and adult patients continues to be plagued by health and health care disparities that are perpetuated by the basic structures of our health systems and research modalities, as well as policies that impact access to care and social determinants of health. This scientific statement expands the Society's 2012 statement by focusing on endocrine disease disparities in the pediatric population and sexual and gender minority populations. These include pediatric and adult lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA) persons. The writing group focused on highly prevalent conditions-growth disorders, puberty, metabolic bone disease, type 1 (T1D) and type 2 (T2D) diabetes mellitus, prediabetes, and obesity. Several important findings emerged. Compared with females and non-White children, non-Hispanic White males are more likely to come to medical attention for short stature. Racially and ethnically diverse populations and males are underrepresented in studies of pubertal development and attainment of peak bone mass, with current norms based on European populations. Like adults, racial and ethnic minority youth suffer a higher burden of disease from obesity, T1D and T2D, and have less access to diabetes treatment technologies and bariatric surgery. LGBTQIA youth and adults also face discrimination and multiple barriers to endocrine care due to pathologizing sexual orientation and gender identity, lack of culturally competent care providers, and policies. Multilevel interventions to address these disparities are required. Inclusion of racial, ethnic, and LGBTQIA populations in longitudinal life course studies is needed to assess growth, puberty, and attainment of peak bone mass. Growth and development charts may need to be adapted to non-European populations. In addition, extension of these studies will be required to understand the clinical and physiologic consequences of interventions to address abnormal development in these populations. Health policies should be recrafted to remove barriers in care for children with obesity and/or diabetes and for LGBTQIA children and adults to facilitate comprehensive access to care, therapeutics, and technological advances. Public health interventions encompassing collection of accurate demographic and social needs data, including the intersection of social determinants of health with health outcomes, and enactment of population health level interventions will be essential tools.

Sex is a significant source of heterogeneity in schizophrenia, with more negative symptoms in males and more affective symptoms and internalizing comorbidity in females. In this narrative review, we argue that there are likely sex differences in the pathophysiological mechanisms of schizophrenia-spectrum disorders (SZ) that originate during puberty and relate to the sex-specific impacts of pubertal maturation on brain development. Pubertal maturation might also trigger underlying (genetic or other) vulnerabilities in at-risk individuals, influencing brain development trajectories that contribute to the emergence of SZ. This review is the first to integrate links between pubertal development and neural development with cognitive neuroscience research in SZ to form and evaluate these hypotheses, with a focus on the frontal-striatal and frontal-limbic networks and their hypothesized contribution to negative and mood symptoms respectively. To test these hypotheses, longitudinal research with human adolescents is needed that examines the role of sex and pubertal development using large cohorts or high risk samples. We provide recommendations for such studies, which will integrate the fields of psychiatry, developmental cognitive neuroscience, and developmental endocrinology towards a more nuanced understanding of the role of pubertal factors in the hypothesized sex-specific pathophysiological mechanisms of schizophrenia.

Background: It has been hypothesized that, whenever estrogen levels decline, psychosis symptoms in women increase. At menopause, this can happen in two main ways: (a) the loss of estrogen (mainly estradiol) can directly affect central neurotransmission, leading to increase in schizophrenia-related symptoms, and (b) the loss of estrogen can decrease the synthesis of enzymes that metabolize antipsychotic drugs, thus weakening their efficacy. Aims and Methods: The aim of this narrative review was to investigate the second possibility by searching PubMed and ClinicalTrials.gov for studies over the last two decades that investigated the metabolism of antipsychotics and their efficacy before and after menopause in women or that studied systemic and local estrogen level effects on the pharmacokinetics and pharmacodynamics of individual antipsychotic drugs. Results: The evidence suggests that symptom level in women with schizophrenia rises after menopause for many reasons beyond hormones but, importantly, there is an estrogen-dependent loss of efficacy related to antipsychotic treatment. Conclusion: Effective clinical intervention is challenging; nevertheless, several promising routes forward are suggested.

Many brain diseases, including schizophrenia, affect men and women unequally - either more or less frequently, or at different times in the life cycle, or to varied degrees of severity. With updates from recent findings, this paper reviews the work of my research group over the last 40 years and underscores issues that remain critical to the optimal care of women with schizophrenia, issues that overlap with, but are not identical to, the cares and concerns of men with the same diagnosis. Clinicians need to be alert not only to the overarching needs of diagnostic groups, but also to the often unique needs of women and men.

The aim of this study was to explore the relationship between age at menarche and age at first episode of psychosis, as well as clinical severity and outcome, in a population of women with first-episode psychosis.

Clinical and socio-demographical data, age at menarche and at first-episode psychosis, parental history of psychosis and cannabis-use habits were obtained from 42 subjects with a first episode of psychosis. Positive and Negative Syndrome Scale, Clinical Global Impression, Global Assessment Function, Disability Assessment Schedule, Wechsler Adult Intelligence Scale and Wechsler Intelligence Scale for Children, European Quality of Life, and Lewis and Murray Obstetric Complication Scales were administered. Statistical analysis was performed by means of zero-order correlations and Mann-Whitney U and Kruskal-Wallis tests using SPSS version 17.0.

We found no significant correlation between age at menarche and age at first-episode psychosis, or with the clinical scores performed. We observed that subjects with earlier age at menarche had more parental history of psychosis.

Our negative results do not support the theory of a possible protective role of oestrogen, which seems to be more complex than previously thought. We would suggest that further research is needed to investigate developmental influences of sex steroids on the onset of psychosis and potentially therapeutic benefits based upon oestrogen.

Increasing evidence from clinical practice, as well as from epidemiological and basic research shows that there are gender differences in clinical features of schizophrenia, and this may be related to estrogens. There may be a relationship between earlier puberty and later onset of the disease, because of the protective effects of estrogens in women with schizophrenia. In this study, our aim was to analyze the correlation between age of menarche and age of onset of schizophrenia and to investigate the protective effects of estrogens in schizophrenia.

In this study, we included 289 patients who were diagnosed with schizophrenia. Those with mental deficiency or organic brain disorders were excluded from the study. All subjects were given a socio-demographic form to determine their personal information, age at menarche, age at first odd behavior, age at onset of the disease and first hospitalization. Data on factors which may affect the association between age at onset of schizophrenia and age at menarche such as family history, head or birth trauma etc. were recorded on the information form.

We found out that age at menarche was negatively associated with age at first odd behavior and age at first psychotic symptoms.

Our study verifies the protective effects of estrogens and shows that the earlier puberty may be the cause of later onset of schizophrenia. A gender-sensitive approach in psychiatry improves our understanding of mental illness and our therapeutic strategies.

While birth cohort studies have shown that individuals who develop non-affective psychosis show subtle deviations in cognitive and behavioural developmental trajectories, there is less evidence about deviations in physical growth in these individuals. The purpose of the present study was to examine the association between behaviour and growth and maturation from infancy, through childhood and adolescence to early adulthood and the development of non-affective psychosis in young adults.

Based on a birth cohort of 3801 young adults, weight and length/height were examined at birth and at years 5, 14 and 21, together with pubertal maturation at year 14. Behavioural measures taken at years 5 and 14 were also examined. Screen-positive non-affective psychosis (SP-NAP) was assessed at year 21 using Composite International Diagnostic Interview, or a self-report checklist. The association between the behavioural and growth measures at birth and at years 5, 14 and 21, and SP-NAP at year 21 was examined using logistic regression.

There were 60 subjects in the cohort who were classified as having SP-NAP. In female subjects SP-NAP was significantly associated with being longer with a larger head circumference at birth, and less likely to be associated with being shorter at 21 years, with consistent trend associations for height between. There were no differences for weight. There was no significant association between the variables of interest in male subjects or for the total group. There was also no significant association between pubertal development at age 14 and risk of SP-NAP in either sex.

Unlike developmental behavioural problems, which showed continuity from childhood through adolescence, SP-NAP was not associated with marked deviations in growth trajectory for male subjects, but the present data suggests that female subjects with SP-NAP had an altered skeletal growth trajectory.

Changes in puberty timing have implications for the treatment of individual children, for the risk of later adult disease, and for chemical testing and risk assessment for the population. Children with early puberty are at a risk for accelerated skeletal maturation and short adult height, early sexual debut, potential sexual abuse, and psychosocial difficulties. Altered puberty timing is also of concern for the development of reproductive tract cancers later in life. For example, an early age of menarche is a risk factor for breast cancer. A low age at male puberty is associated with an increased risk for testicular cancer according to several, but not all, epidemiologic studies. Girls and, possibly, boys who exhibit premature adrenarche are at a higher risk for developing features of metabolic syndrome, including obesity, type 2 diabetes, and cardiovascular disease later in adulthood. Altered timing of puberty also has implications for behavioral disorders. For example, an early maturation is associated with a greater incidence of conduct and behavior disorders during adolescence. Finally, altered puberty timing is considered an adverse effect in reproductive toxicity risk assessment for chemicals. Recent US legislation has mandated improved chemical testing approaches for protecting children's health and screening for endocrine-disrupting agents, which has led to changes in the US Environmental Protection Agency's risk assessment and toxicity testing guidelines to include puberty-related assessments and to the validation of pubertal male and female rat assays for endocrine screening.

Variation in the age at onset of a multifactorial disease often reflects variation in cause. Here we show a linear latitudinal gradient in the mean age at onset of schizophrenia in 13 northern hemisphere cities, ranging from 25 years old in Cali, Columbia (at 4 degrees north) to 35 years old in Moscow, Russia (at 56 degrees north). To our knowledge, this striking association has not been previously reported. We consider several explanations, including the effects of pathogen stress, natural selection, sexual selection, migration, life-history profiles, or some combination of these factors, and we propose a test of competing causal hypotheses.

Males and females of many species differ with regard to neurodevelopment, ongoing brain function and behavior. For many years, it was assumed that these differences primarily arose due to hormonal masculinization of the male brain (and to a lesser extent hormonal feminization of the female brain). Recent elegant experiments in model systems have revealed that, while gonadal hormones undoubtedly play an important role in sexual differentiation of the brain, they are not the only possible mechanism for this phenomenon. In the present review, we discuss the concept that genes residing upon the sex chromosomes (which are asymmetrically inherited between males and females) may influence sexually dimorphic neurobiology directly, and suggest possible mechanisms. Future work will be directed towards understanding the extent and specificity with which sex-linked genes and hormones define brain structure and function, and towards elucidating potential interactions between the two mechanisms. Ultimately, it is hoped that such studies will provide insights into why men and women are differentially vulnerable to certain mental disorders, and will enable the development of effective sex-tailored therapeutics.

Women are relatively protected against schizophrenia. The illness has a similar rate in women and men, but it starts later in women and is less severe. It is tempting to attribute this to the neuroprotective effect of estrogen, but the story is not straightforward and contains many unknowns. Women begin their schizophrenia trajectory later in development compared with men and this probably accounts for their relatively superior prognosis. Estrogen agonists are potential therapeutic agents but need to be proven safe, and the timing of administration may be crucial. This article examines what is known about estrogen and the development of schizophrenia.

Puberty is a time of significant change in preparation for adulthood. Here, we examined how stressful experience affects cognitive and related hormonal responses in male and female rats prior to, during and after puberty. Groups were exposed to an acute stressor of brief periodic tailshocks and tested 24 h later in an associative memory task of trace eyeblink conditioning. Exposure to the stressor did not alter conditioning in males or females prior to puberty but enhanced conditioning in both males and females during puberty. The enhancement occurred in pubescent females irrespective of the estrous cycle. In adulthood, sex differences in trace conditioning and the response to stress emerged: females outperformed males under unstressed conditions, but after stressor exposure, trace conditioning in females was impaired whereas that in males was enhanced. These differences were not related to changes in gross motor activity or other nonspecific measures of performance. The effects of acute stress on corticosterone, estradiol, progesterone, and testosterone were also measured. Stressor exposure increased the concentration of corticosterone in all age groups, although sex differences were only evident in adults. All reproductive hormones except estradiol increased with age in a predictable and sex dependent fashion and none were affected by stressor exposure. Estradiol decreased in male rats across age, and remained stable for female rats. Together, these data indicate that males and female respond similarly to learning opportunities and stressful experience before and during puberty; it is in adulthood that sex differences and the opposite responses to stress arise.

The "estrogen hypothesis" posits that this hormone serves as a protective factor in the development of schizophrenia. If true, then it is expected that the earlier the age of menarche, the later the onset of schizophrenia (as has been reported by some investigators). This study attempts to replicate this relationship in a sample of women with schizophrenia and schizoaffective disorder.

Self-report menarche age, clinical status, and onset of disorder were collected in a sample of 68 women (55 diagnosed with schizophrenia and 13 with schizoaffective disorder).

Menarche age and schizophrenia onset were not negatively correlated as would be predicted by the estrogen hypothesis. Two clinical measures, however, did correlate with age of menarche as predicted. Higher negative symptom scores (total SANS) and greater functional impairment (lower GAF) were reported in subjects who reported a later age at menarche.

This study suggests that an earlier age at menarche might predict improved clinical outcome after schizophrenia onset (in support of the estrogen hypothesis). Our data, however, do not support Cohen et al.'s findings regarding the relationship between age at menarche, and the timing of the onset of the disorder. Further investigations regarding the relationship between estrogen and schizophrenia development in women are needed. It is suggested that other developmental factors, both biological and psychosocial, might play a crucial role in both the age at onset and the outcome of the disorder in women.

The term 'schizophrenia' refers to a group of disorders that have been described in every human culture. Two apparently well established findings have corroborated the need for an evolutionary explanation of these disorders: (1) cross-culturally stable incidence rates and (2) decreased fecundity of the affected individuals. The rationale behind this relates to the evolutionary paradox that susceptibility genes for schizophrenia are obviously preserved in the human genepool, despite fundamental reproductive disadvantages associated with the disorders. Some researchers have therefore proposed that a compensatory advantage must exist in people who are carriers of these genes or in their first-degree relatives. Such advantages were hypothesised to be outside the brain (e.g. greater resistance against toxins or infectious diseases), or within the social domain (e.g. schizotypal shamans, creativity). More specifically, T.J. Crow has suggested an evolutionary theory of schizophrenia that relates the disorders to an extreme of variation of hemispheric specialisation and the evolution of language due to a single gene mutation located on homologous regions of the sex chromosomes. None of the evolutionary scenarios does, however, fully account for the diversity of the symptomatology, nor does any one hypothesis acknowledge the objection that the mere prevalence of a disorder must not be confused with adaptation. In the present article, I therefore discuss the evolutionary hypotheses of schizophrenia, arguing that a symptom-based approach to psychotic disorders in evolutionary perspective may improve upon the existing models of schizophrenia.

During the past decade, possible advancement in timing of puberty has been reported in the United States. In addition, early pubertal development and an increased incidence of sexual precocity have been noticed in children, primarily girls, migrating for foreign adoption in several Western European countries. These observations are raising the issues of current differences and secular trends in timing of puberty in relation to ethnic, geographical, and socioeconomic background. None of these factors provide an unequivocal explanation for the earlier onset of puberty seen in the United States. In the formerly deprived migrating children, refeeding and catch-up growth may prime maturation. However, precocious puberty is seen also in some nondeprived migrating children. Attention has been paid to the changing milieu after migration, and recently, the possible role of endocrine- disrupting chemicals from the environment has been considered. These observations urge further study of the onset of puberty as a possible sensitive and early marker of the interactions between environmental conditions and genetic susceptibility that can influence physiological and pathological processes.