Shared genetic influences between eating disorders and gastrointestinal disease in a large, population-based sample of adult women and men.

BACKGROUND: Some preliminary research suggests higher rates of gastrointestinal disease in individuals with eating disorders (EDs). However, research is limited, and it remains unknown what etiologic factors account for observed associations. This was the first study to examine how EDs and dimensional ED symptoms (e.g. body dissatisfaction, binge eating) are phenotypically and etiologically associated with gastrointestinal disease in a large, population-based twin sample. METHODS: Adult female (N = 2980) and male (N = 2903) twins from the Michigan State University Twin Registry reported whether they had a lifetime ED (anorexia nervosa, bulimia nervosa, or binge-eating disorder) and completed a measure of dimensional ED symptoms. We coded the presence/absence of lifetime gastrointestinal disease (e.g. inflammatory bowel disease) based on responses to questions regarding chronic illnesses and medications. We first examined whether twins with gastrointestinal disease had higher rates of EDs and ED symptoms, then used correlated factors twin models to investigate genetic and environmental contributions to the overlap between disorders. RESULTS: Twins with gastrointestinal disease had significantly greater dimensional ED symptoms (ß = 0.21, p < 0.001) and odds of a lifetime ED (OR 2.90, p = 0.001), regardless of sex. Shared genetic factors fully accounted for the overlap between disorders, with no significant sex differences in etiologic associations. CONCLUSIONS: Comorbidity between EDs and gastrointestinal disease may be explained by overlap in genetic influences, potentially including inflammatory genes implicated in both types of disorders. Screening for gastrointestinal disease in people with EDs, and EDs in those with gastrointestinal disease, is warranted.

Estrogen moderation of genetic influences on eating disorder symptoms during gonadarche in girls: Specific effects on binge eating.

The heritability of eating disorder (ED) symptoms increases dramatically across gonadarche in girls. Past studies suggest these developmental differences could be due to pubertal activation of estrogen, but findings have been limited to only one ED symptom (i.e., binge eating). The current study examined whether estrogen contributes to gonadarcheal differences in genetic influences on overall levels of ED symptoms as well as key cognitive symptoms (i.e., weight/shape concerns) that are present across all EDs and are early risk factors for eating pathology. Given that binge eating frequently co-occurs with all of these symptoms, analyses also examined whether estrogen effects exist for overall levels of ED symptoms and body weight/shape concerns after accounting for the known effects of estrogen on genetic risk for binge eating. Participants included 964 female twins (ages 8-16) from the Michigan State University Twin Registry. Overall levels of ED symptoms were assessed with the Minnesota Eating Behavior Survey (MEBS) total score. Weight/shape concerns were assessed with a latent factor modeled using subscales from the MEBS and the Eating Disorder Examination Questionnaire. Estradiol levels were assessed with saliva samples. Twin moderation models were used to examine whether genetic influences on overall levels of ED symptoms and weight/shape concerns differed significantly across estradiol levels. Although initial models suggested modest differences in genetic influences on overall levels of ED symptoms across estradiol levels, these effects were eliminated when binge eating was accounted for in the models. In addition, weight/shape concerns did not show significant moderation of genetic influences by estradiol in models with or without binge eating. Taken together, results are significant in suggesting that individual differences in estradiol levels during gonadarche have a unique and specific impact on genetic risk for binge eating, while other etiologic factors must contribute to increased heritability of cognitive ED symptoms during this key developmental period in girls.

Associations between household income and disordered eating differ across sex and racial identity in a population-based sample of adults.

BACKGROUND: Most research on socioeconomic status (SES) and eating disorders (EDs) has focused on young White women. Consequently, little is known regarding how SES may relate to EDs/disordered eating in older adults, men, or people with different racial identities. We examined whether associations between SES and EDs/disordered eating differed across age, sex, and racial identity in a large, population-based sample spanning early-to-later adulthood. METHODS: Analyses included 2797 women and 2781 men ages 18-65 (Mage = 37.41, SD = 7.38) from the population-based Michigan State University Twin Registry. We first examined associations between SES and dimensional ED symptoms, binge eating (BE), and self-reported ED diagnoses across age and sex in the full sample. We then examined the impact of racial identity on associations by conducting within- and between-group analyses among Black and White participants. RESULTS: In the full sample, lower SES was associated with significantly greater odds of BE and lifetime EDs in men, but not women, across adulthood. The association between lower SES and greater BE risk was stronger for Black men than for White men, though significant in both groups. Conversely, Black women showed a positive association between SES and dimensional ED symptoms that significantly differed from effects for Black men and White women. CONCLUSIONS: Associations between socioeconomic disadvantage and EDs/disordered eating may be particularly robust for men in adulthood, especially men with a marginalized racial identity. Oppositely, Black women may encounter social pressures and minority stress in higher SES environments that could contribute to somewhat heightened ED risk. PUBLIC SIGNIFICANCE: Little is known regarding how associations between socioeconomic status (SES) and eating disorders (EDs) may differ across age/sex or racial identity. We found lower SES was associated with greater odds of a lifetime ED or binge eating in men only, with a particularly strong association between lower SES and binge eating for Black men. Results highlight the importance of examining how SES-ED associations may differ across other aspects of identity.

The organizational role of ovarian hormones during puberty on risk for binge-like eating in rats.

Puberty is a high-risk period for the development of dysregulated eating, including binge eating. While risk for binge eating in animals and humans increases in both males and females during puberty, the increased prevalence is significantly greater in females. Emerging data suggest that the organizational effects of gonadal hormones may contribute to the female preponderance of binge eating. In this narrative review, we discuss studies conducted in animals that have examined these organizational effects as well as the neural systems that may serve as intermediary mechanisms. Relatively few studies have been conducted, but data thus far suggest that pubertal estrogens may organize risk for binge eating, potentially by altering key circuits in brain reward pathways. These promising results highlight the need for future studies to directly test organizational effects of pubertal hormones using hormone replacement techniques and circuit-level manipulations that can identify pathways contributing to binge eating across development.

Disadvantage and disordered eating in boys: Examining phenotypic and genotype × environment associations across development.

Socioeconomic disadvantage may be a significant risk factor for disordered eating, particularly for individuals with underlying genetic risk. However, little to nothing is known about the impact of disadvantage on disordered eating in boys during the critical developmental risk period. Crucially, risk models developed for girls may not necessarily apply to boys, as boys show different developmental patterns of disordered eating risk (i.e., earlier activation of genetic influences during adrenarche, an early stage of puberty). This is the first study to examine phenotypic and Genotype × Environment (G × E) effects of disadvantage in boys. Analyses examined 3,484 male twins ages 8-17 (Mage = 12.27, SD = 2.96) from the Michigan State University Twin Registry. Disordered eating (e.g., body dissatisfaction, binge eating) was measured using the parent-report Michigan Twins Project Eating Disorder Survey. Neighborhood disadvantage was measured using a census-tract level Area Deprivation Index, and family socioeconomic status was determined from parental income and education. Adrenarche status was determined using multiple indicators, including age and Pubertal Development Scale scores. G × E models suggested that genetic influences on disordered eating were activated earlier for boys experiencing familial or neighborhood disadvantage, with substantial genetic influences in early adrenarche, when genetic influences were low in more advantaged boys. Phenotypically, both neighborhood and familial disadvantage were associated with greater disordered eating for boys in late adrenarche, which could indicate a lasting impact of earlier activation of genetic influences on later risk. Results highlight disadvantage as a novel risk factor for disordered eating in boys, particularly those with genetic vulnerabilities. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A cotwin control study of associations between financial hardship and binge eating phenotypes during COVID-19.

BACKGROUND: COVID-19 was associated with significant financial hardship and increased binge eating (BE). However, it is largely unknown whether financial stressors contributed to BE during the pandemic. We used a longitudinal, cotwin control design that controls for genetic/environmental confounds by comparing twins in the same family to examine whether financial hardship during COVID-19 was associated with BE. METHODS: Female twins (N = 158; Mage  = 22.13) from the Michigan State University Twin Registry rated financial stressors (e.g., inability to afford necessities) daily for 49 consecutive days during COVID-19. We first examined whether financial hardship was associated with BE phenotypes across the full sample. We then examined whether cotwins who differed on financial hardship also differed in BE. RESULTS: Participants who experienced greater mean financial hardship across the study had significantly greater dimensional BE symptoms, and participants who experienced greater financial hardship on a given day reported significantly more emotional eating that day. These results were replicated in cotwin control analyses. Twins who experienced more financial hardship than their cotwin across the study reported greater dimensional BE symptoms than their cotwin, and participants who experienced more financial hardship than their cotwin on a given day reported greater emotional eating that day. Results were identical when restricting analyses to monozygotic twins, suggesting associations were not due to genetic confounds. CONCLUSIONS: Results suggest that BE-related symptoms may be elevated in women who experienced financial hardship during COVID-19 independent of potential genetic/environmental confounds. However, additional research in larger samples is needed. PUBLIC SIGNIFICANCE: Little is known regarding how financial difficulties during the COVID-19 pandemic may have contributed to increased binge eating (BE). We found preliminary evidence that financial hardship during COVID-19 may be associated with greater rates of BE-related symptoms even when comparing twins from the same family. While additional research is needed, results suggest that people who experienced financial hardship during COVID-19 may be at increased risk for BE.

Binge Eating Risk During Midlife and the Menopausal Transition: Sensitivity to Ovarian Hormones as Potential Mechanisms of Risk.

PURPOSE OF REVIEW: Recent research suggests that binge eating may be more prevalent among women in midlife than previously believed. The menopausal transition, an important developmental stage during midlife, is characterized by substantial fluctuations and eventual decreases in ovarian hormones that may contribute to increased risk. This narrative review summarizes findings from studies of binge eating during midlife and menopause and discusses the potential role of ovarian hormones in binge eating risk. RECENT FINDINGS: Studies are few in number and findings are mixed, with only some studies showing increased binge eating during midlife and the menopausal transition. Sensitivity to ovarian hormones, potentially through gene x hormone interactions, may influence who experiences increased binge eating risk and could help explain mixed findings in the field. Future studies of hormone sensitivity and gene x hormone interactions are needed to further elucidate midlife and menopausal risk for binge eating in women.

Ovarian Hormones and Binge Eating in Adulthood: Summary of Findings and Implications for Individual Differences in Risk in Women.

Ovarian hormone influences on general food intake have been studied in animals for 60+ years. Yet, extensions of these data to key eating disorder symptoms in humans (e.g., binge eating (BE)) have only recently occurred. In this article, we summarize findings from studies examining the effects of ovarian hormones on BE. Findings suggest ovarian hormones contribute to BE in animals and humans, although studies are few in number, and effects are not present in all women or all animals exposed to high-risk hormonal milieus. Differences in susceptibility may be due to gene x hormone interactions that can explain why some, but not all, women/females develop BE in the presence of risky hormonal environments.

Sociocultural correlates of eating pathology in college women from US and Iran.

Objective: The buffering role of the hijab as a protective factor against eating pathology has been questioned in countries where wearing the hijab is compulsory, such as Iran; and, cross-cultural comparisons of body image in Iranian and Western women are sparse. Consequently, we examined sociocultural correlates of eating pathology in US and Iranian women. Method: College women from the US (n = 709) and Iran (n = 331) completed the Eating Disorder Examination-Questionnaire (EDE-Q) and the Sociocultural Attitude Toward to Appearance Questionnaire-4 (SATAQ-4). Prior to examining main hypotheses, we evaluated whether the scales perform similarly (i.e., establish measurement invariance) by culture. Results: The EDE-Q and SATAQ-4 were not invariant by culture indicating that the scales performed differently across groups, so separate analyses were conducted in each sample. Thin-ideal internalization and pressures for thinness were significant positive predictors of eating pathology in both US and Iranian women. Conclusion: Both pressures for thinness and thin-ideal internalization appear to be relevant to eating pathology in women from both cultures. However, there may be important cross-cultural differences in the interpretation or experience of these constructs. Further understanding of this measurement non-invariance and the ways in which Iranian women may be uniquely impacted by Western values of appearance is a critical next step.

Risk for midlife psychosis in women: critical gaps and opportunities in exploring perimenopause and ovarian hormones as mechanisms of risk.

Women show a heightened risk for psychosis in midlife that is not observed in men. The menopausal transition (i.e. perimenopause) and accompanying changes in ovarian hormones are theorized to account for this midlife increase in risk. This narrative review aims to empirically examine these theories by reviewing studies of midlife and perimenopausal psychosis risk in women and potential ovarian hormone mechanisms of effects. Clinical and pre-clinical studies examining the effects of midlife age, menopausal stage, and ovarian hormones across adulthood on psychosis risk were identified. Synthesis of this body of work revealed that the peak ages of midlife psychosis risk in women overlap with the age range of key menopausal stages (especially the perimenopausal transition), although studies directly assessing menopausal stage are lacking. Studies examining ovarian hormone effects have almost exclusively focused on earlier developmental stages and events (e.g. pregnancy, the menstrual cycle) and show increases in psychotic symptoms in women and female rats during periods of lower estradiol levels. Estrogen treatment also tends to enhance the effects of neuroleptics in females across species at various reproductive phases. Initial data are promising in suggesting a role for menopausal stage and ovarian hormones in psychosis risk. However, critical gaps in our knowledge base remain, as there is a tendency to rely on indirect and proxy measures of menopausal status and hormones. Opportunities for future research are discussed with the goal of increasing research in this critical area of women's health.

Elucidating early pubertal timing effects on disordered eating symptoms in young adult women.

INTRODUCTION: Early pubertal timing increases risk for disordered eating (DE) in females, but the extent to which associations persist after puberty and are relevant to all types of DE symptoms is unclear. Factors that link pubertal timing and DE also remain unknown, although leading theories posit that adiposity and body-focused psychosocial factors play a key role. Thus, this study examined pubertal timing effects on several types of DE symptoms in young adult women and evaluated whether body mass index (BMI), pressures for thinness, thin-ideal internalization, and/or history of weight-based teasing account for such associations. METHODS: This study included a racially and ethnically diverse sample of 342 female college students (Mage = 20.44, SD = 3.46). Women retrospectively reported their age at onset of menses, which served as the pubertal timing indicator, and completed self-report questionnaires on DE symptoms, perceived pressures for thinness, thin-ideal internalization, and history of weight-based teasing. BMI was calculated from height/weight measurements. RESULTS: Earlier pubertal timing was associated with body dissatisfaction and binge eating, but not other DE symptoms (dieting, excessive exercise, muscle building) in young adult women. BMI accounted for pubertal timing effects on body dissatisfaction, whereas none of the examined factors explained pubertal timing effects on binge eating. CONCLUSIONS: Earlier pubertal timing may exert long-term effects on only some DE symptoms in women, and the etiologic factors underlying pubertal timing effects on DE outcomes may differ across symptom types.

Pubertal Emergence of Testosterone Effects on Depressive Symptoms in Boys.

Background: Puberty-driven increases in the secretion of testosterone may be a biological factor that protects males against the development of depression. Although all males produce testosterone, there are substantial between-person differences that could contribute to differential vulnerability to depression among pre-adolescent and adolescent boys, particularly after pubertal onset. Indeed, experimental animal and human data have shown that low testosterone increases risk for depressive-like symptoms in males, whereas higher levels of testosterone may be protective; however, prior studies have primarily investigated these effects in adulthood. This study investigated whether lower circulating levels of testosterone predict depressive symptoms in pre-adolescent and adolescent boys, and in particular, whether the testosterone-depression association becomes prominent with advancing pubertal maturation. Methods: Male twins (N = 213; ages 10-15 years) from the Michigan State University Twin Registry self-reported their depressive symptoms and pubertal status using the Children's Depression Inventory and the Pubertal Development Scale, respectively. Salivary testosterone was assayed using high-sensitivity enzyme immunoassays. Mixed Linear Models (MLMs), which could account for the non-independence of twin data, were used for analyses. Results: As expected, lower testosterone concentrations were associated with higher depressive symptoms, and the magnitude of this effect increased with advancing pubertal status. In contrast, boys with higher levels of testosterone showed low levels of depressive symptomatology at all stages of pubertal maturation. Conclusions: Overall, these findings enhance understanding of within-sex variability in risk for depression in boys - average-to-high testosterone levels may underlie the general male resilience to depression after pubertal onset, whereas lower levels may increase vulnerability during/after puberty.

Gonadal Hormone Influences on Sex Differences in Binge Eating Across Development.

PURPOSE OF REVIEW: Binge eating is a transdiagnostic symptom that disproportionately affects females. Sexually dimorphic gonadal hormones (e.g., estradiol, testosterone) substantially impact eating behavior and may contribute to sex differences in binge eating. We examine recent evidence for the role of gonadal hormones in binge eating risk across development. RECENT FINDINGS: Both organizational (long-lasting impact on the central nervous system (CNS)) and activational (transient influences on the CNS) hormone effects may contribute to sex differences in binge eating. Gonadal hormones also impact within-sex variability in binge eating, with higher estradiol levels in females and higher testosterone levels in males protective across development. Emerging evidence suggests that the impact of gonadal hormones may be greatest for people with other risk factors, including genetic, temperamental (e.g., high negative affect), and psychosocial (e.g., exposure to weight-based teasing) risk. Gonadal hormones contribute to sex differences and within-sex variability in binge eating across development.

The effects of puberty on associations between mood/personality factors and disordered eating symptoms in girls.

OBJECTIVE: Negative and positive urgency, anxiety, and depressive symptoms are significant factors of disordered eating (DE) symptoms in early adolescence through young adulthood. However, it is unclear how puberty-a critical developmental milestone that is associated with increased risk for DE symptoms-affects the relationship between these factors and DE symptoms, given that the role of pubertal status has rarely been considered in relation to these associations. Thus, the present study examined whether puberty moderates associations between mood/personality factors and DE in pre-adolescent and adolescent girls. METHOD: Participants included 981 girls (aged 8-16 years) from the Michigan State University Twin Registry. Mood/personality factors, pubertal status, and DE were assessed with self-report questionnaires. RESULTS: Puberty significantly moderated associations between several factors (negative urgency, positive urgency, trait anxiety, depressive symptoms) and the cognitive symptoms of DE (e.g., shape/weight concerns, body dissatisfaction). Associations between mood/personality factors and cognitive DE were stronger in girls with more advanced pubertal status. By contrast, no significant moderation effects were detected for mood/personality-dysregulated eating (e.g., binge eating, emotional eating) associations. DISCUSSION: Findings identify pubertal development as an important moderator of mood/personality-DE symptom associations, especially for cognitive DE symptoms that are known to predict the later onset of clinical pathology.

The effects of puberty and ovarian hormone removal on developmental trajectories of palatable food and chow intake in female rats.

OBJECTIVE: Palatable food (PF) intake is significantly greater in females than males and increases during adolescence. Previous data suggest that puberty and ovarian hormones may contribute to these sex and developmental differences, but few studies have examined this possibility. The aim of the current study was to address these gaps by examining trajectories of PF and chow intake during pre-puberty, puberty, and adulthood in intact female rats (Study 1) as well as in those receiving pre-pubertal ovariectomies (P-OVX) (Study 2). METHOD: We examined our study aims using archival data from 66 intact Sprague-Dawley female rats (Study 1) and 77 P-OVX and 79 intact Sprague-Dawley female rats (Study 2). PF and chow intake were measured using a free-choice, intermittent exposure paradigm in which rats were exposed to both food types starting in pre-puberty and continuing into adulthood. RESULTS: Mixed linear models revealed a specific effect of puberty on PF intake in both studies. PF intake increased substantially during puberty in all rats, but increases were particularly pronounced in P-OVX rats in Study 2. By contrast, chow intake increased significantly during pre-puberty (rather than puberty) in both studies, and these increases were relatively unaffected by P-OVX. DISCUSSION: Findings confirm a specific effect of puberty and ovarian hormone removal on PF intake in female rats. Differential trajectories of PF versus chow intake highlight potential reward-based processes in pubertal and ovarian hormone effects on PF intake in females.

A Narrative Review of Sex Differences in Eating Disorders: Is There a Biological Basis?

PURPOSE: Eating disorders and their core symptoms (eg, binge eating, body weight/shape concerns) disproportionately affect females, and these sex-differentiated effects become prominent during and after puberty. Although psychosocial influences such as heightened sociocultural pressures for thinness in girls and women contribute to this sex imbalance, biological factors could also play an important role. METHODS: This narrative review summarizes evidence of biological factors underlying the sex-differentiated prevalence of eating pathology as well as within-sex variability in risk. FINDINGS: There are sex differences in the pubertal emergence of genetic effects on eating pathology (adrenarche in males; gonadarche in females), and at least some genetic contributions to eating pathology seem to vary between the sexes. Furthermore, sex steroid hormones (eg, testosterone, estradiol, progesterone) are leading contributors to differential risk for eating pathology in males and females across the life span. Emerging data suggest that between-sex and within-sex variability in risk might occur via hormone-driven modulation (activation/deactivation) of genetic influences and neural responsiveness to food-related cues. IMPLICATIONS: There is a biological basis to heightened risk for eating pathology in females, relative to males, as well as unique biological influences within each sex. Findings from this review highlight the importance of studying both sexes and considering sex-specific biological mechanisms that may underlie differential risk for eating pathology.

Low testosterone is associated with dysregulated eating symptoms in young adult men.

OBJECTIVE: Extant animal and human data indicate that natural variation in circulating levels of testosterone may contribute to differential risk for dysregulated eating among males. Indeed, testosterone ablation in postpubertal male rodents results in stimulatory effects on sweet-taste preferences, and lower levels of circulating testosterone in adolescent boys have been found to predict dysregulated eating symptoms during mid-to-late puberty. Nonetheless, no prior study has examined whether lower testosterone is associated with dysregulated eating in adulthood. The current study examined this possibility. METHOD: Participants were 154 young adult men (ages = 18-33) from a large Southwestern University. The Eating Disorder Examination Questionnaire, Eating Pathology Symptoms Inventory, and Loss of Control Over Eating Scale were used to assess three types of dysregulated eating symptoms: eating concerns, binge eating, and loss-of-control eating. Afternoon saliva samples were assayed for testosterone using high-sensitive enzyme immunoassays. RESULTS: Consistent with animal data and prior research in adolescent boys, men with lower testosterone reported significantly higher levels of dysregulated eating symptoms even after controlling for depressive symptoms, body mass index, and age. DISCUSSION: Lower testosterone concentrations might serve as a sex-specific biological factor that contributes to dysregulated eating among men.

Examining associations between emotion-based rash action and dysregulated eating symptoms in men and women.

Negative urgency (NU: tendency to act rashly when distressed) is the facet of impulsive personality that has been most predictive of binge eating, but less is known about the relative role of positive urgency (PU: tendency to act rashly in response to positive emotions). In addition, most studies have exclusively focused on women and the examination of pathological eating outcomes, using a dimensional symptom approach, has been somewhat limited. This study aimed to replicate and extend upon prior work. We examined the extent to which NU and/or PU are uniquely associated with dysregulated eating, using a latent factor comprised of dimensional symptoms, and directly tested whether effects differ by sex. Two independent cross-sectional samples of women and men were used (Sample 1: Midwestern university, 437 females, 348 males; Sample 2: Southwestern university, 301 females, 236 males). NU and PU were assessed with the UPPS-P Impulsive Behavior Scale, and dysregulated eating symptoms (i.e., binge eating, loss of control eating, eating concerns) were assessed with well-validated self-report questionnaires. Although both NU and PU showed significant positive associations with dysregulated eating, NU showed the strongest unique relationship with dysregulated eating in both samples. The relative role of PU was weakened in Sample 1 and completely attenuated in Sample 2 once its shared variance with NU was accounted for. All results were similar in men and women. Overall, findings continue to suggest that NU is the form of impulsivity that is most relevant to dysregulated eating in both men and women.

Ovarian Hormones and Reward Processes in Palatable Food Intake and Binge Eating.

Ovarian hormones are associated with risk for binge eating in women. Recent animal and human studies suggest that food-related reward processing may be one set of neurobiological factors that contribute to these relationships, but additional studies are needed to confirm and extend findings.

The Disruptive Effects of Estrogen Removal before Puberty on Risk for Binge Eating in Female Rats.

Recent research suggests that estrogen is protective against binge eating in adult females, and that pubertal estrogen may be critical for these effects. Nonetheless, to date, no study has examined the role of pubertal estrogen in adult binge eating phenotypes in females, potentially due to difficulties experimentally manipulating estrogen in humans to examine causal effects. We used a novel animal model to examine whether estrogen removal prior to puberty (via pre-pubertal ovariectomy (P-OVX)) increases rates of binge eating prone (BEP) phenotypes in adulthood in females. A total of 77 P-OVX and 79 intact rats were followed from pre-puberty into adulthood and phenotyped for BEP status in adulthood. Results showed significantly increased rates (~2-8x higher) of adult BEP phenotypes in P-OVX as compared to intact rats. Findings confirm that estrogen removal substantially increases later risk for binge eating in females, potentially by disrupting typical adolescent brain development.