Meal-Related Acyl and Des-Acyl Ghrelin and Other Appetite-Related Hormones in People with Obesity and Binge Eating.

OBJECTIVE: Potential mechanisms of abnormal food intake, such as dysregulation of meal-related appetite hormones, including acyl ghrelin (AG) and des-acyl ghrelin (DAG), were investigated among men and women with obesity, with and without binge eating (BE). METHODS: Participants (n = 42: 19 female, 23 male) were assigned to a liquid meal and water condition in counterbalanced order, and blood samples for measuring hormones were obtained before and after these conditions. RESULTS: Participants with BE had significantly lower fasting and postingestive AG concentrations than participants without BE in both conditions. During the meal condition, postprandial decreases in AG concentrations were significantly smaller for the BE group than for the non-BE group. There were no significant differences in DAG by BE group. Leptin increased significantly less after meals for those with BE compared with those without BE. There were no differences in other hormones by BE group. Fasting and postmeal hunger ratings were significantly higher for those with BE than for those without BE. CONCLUSIONS: In individuals with BE, lower fasting AG may be due to downregulation by habitual overeating, and a smaller postmeal decline in AG may contribute to overeating. Lower postmeal leptin concentrations may also contribute to overeating.

Cognitive remediation therapy plus behavioural weight loss compared to behavioural weight loss alone for obesity: study protocol for a randomised controlled trial.

BACKGROUND: Current research indicates that obese individuals have cognitive deficits in executive function, leading to difficulties with planning, impulse control and decision-making. High levels of inflammation have been proposed to contribute to executive function deficits in individuals with obesity. METHODS/DESIGN: One hundred and seventy-six obese participants will be randomly assigned to one of two groups: (1) behavioural weight loss alone (BWL) group = 8 sessions of individual BWL sessions plus 12 group BWL sessions or (2) Cognitive Remediation Therapy for Obesity (CRT-O) plus BWL group (CRT-O + BWL) = 8 sessions of individual CRT-O plus 12 group BWL sessions. The study is double blind - participants will only be told that two weight-loss treatments are being compared and research assistants conducting outcome assessments will not know participants' group allocation. Blood tests will be conducted to measure inflammatory markers. Measurement points will be at baseline, post treatment and 1-year follow-up. The primary outcomes will be differences between treatment groups in percentage weight loss, executive function, binge eating and an examination of whether changes in executive function predict changes in weight and binge eating. Secondary outcome measures will examine changes on inflammation, quality of life, and grazing behaviour and whether these predict changes in executive function and weight. DISCUSSION: If CRT-O + BWL is more effective in assisting people to lose weight long term than BWL alone it should significantly improve treatment outcomes. This study expands upon our recent trial which showed that CRT-O enhanced executive function and weight loss in obese adults. The current study is strengthened by several factors: it is double-blind, it uses an active control, has a larger sample size, and measures inflammation to examine the mechanisms. TRIAL REGISTRATION: The RCT is registered with the Australian New Zealand Registry of Clinical Trial, trial identifier: ACTRN12616000658415 . Registered on 20 May 2016.

Meal schedule influences food restriction-induced locomotor sensitization to methamphetamine.

RATIONALE: Traditional protocols for inducing sensitization to psychostimulants use an intermittent or "binge"-like drug administration, and binge eating behavior is comorbid with drug abuse in humans. Food restriction increases the reinforcing properties and self-administration of many drugs of abuse. OBJECTIVE: The present study tested the hypotheses that (1) food restriction induces sensitization to the locomotor stimulation observed in response to methamphetamine and (2) a binge-like feeding schedule during food restriction produces increased sensitization compared to equally restricted mice fed in three daily meals. METHODS: Male DBA/2J mice were fed ad libitum or were food restricted to either an 8% or 16% loss of body weight. Additionally, the food-restricted mice were divided into two groups that were fed in either one meal (binge) or three equal-sized meals (meal). After the reduced body weight was stable, mice were tested for locomotor activity following saline and methamphetamine (1 mg/kg) injections. RESULTS: Both 16% body weight loss groups exhibited sensitization to methamphetamine. Opposite to our hypothesis, the 8% meal but not the 8% binge food-restricted group demonstrated locomotor sensitization. Serum corticosterone levels were significantly higher in the meal-fed groups when compared to the binge- and ad libitum-fed groups. CONCLUSIONS: These results support a role for feeding schedule and plasma corticosterone levels in food restriction-induced enhancement of the effects of methamphetamine.

Cortisol, dehydroepiandrosterone, and estradiol measured over 24 hours in women with childhood sexual abuse-related posttraumatic stress disorder.

Preclinical studies have shown long-term alterations in several hormonal systems including cortisol, dehydroepiandrosterone (DHEA) and DHEA-Sulfate, and estradiol. The purpose of this study was to assess cortisol, DHEA, and estradiol over a 24-hour period in women with early childhood sexual abuse and posttraumatic stress disorder (PTSD); with early abuse and without PTSD; and women without early abuse or PTSD. Forty-three women with early childhood sexual abuse and PTSD, early abuse without PTSD, and without abuse or PTSD, underwent a comprehensive assessment of hormones in plasma at multiple time points over a 24-hour period. Abused women with PTSD had lower concentrations of cortisol during the afternoon hours (12-8 p.m.) compared with women with abuse without PTSD and women without abuse or PTSD. DHEA-Sulfate was elevated throughout the 24-hour period in PTSD women, although this was of marginal statistical significance. There were no differences between groups in DHEA or estradiol. PTSD women also had increased cortisol pulsatility compared with the other groups. These findings suggest that a resting hypocortisolemia in the afternoon hours with increased cortisol pulsatility is associated with childhood abuse-related PTSD in women.

Plasma ghrelin in anorexia, bulimia, and binge-eating disorder: relations with eating patterns and circulating concentrations of cortisol and thyroid hormones.

The present study was designed to investigate the relations between plasma ghrelin concentrations, eating patterns, and circulating concentrations of cortisol and thyroid hormones in women with anorexia nervosa, bulimia nervosa, and binge-eating disorder. The patterns of disordered eating behavior were assessed using the Eating Attitudes Test (EAT-26) and the Bulimia Test-Revised (BULIT-R). In women with eating disorders, but not in healthy control women, plasma ghrelin concentrations were negatively correlated with body mass index (BMI) and plasma concentrations of thyreotropin (TSH), free T3 and free T4, and positively correlated with plasma concentrations of cortisol. The ghrelin concentrations of women with binge-eating and purging behavior were significantly lower than those of women with anorexia nervosa, restricting type, and there was a negative relation between the frequency and severity of binge-eating and purging behavior, as measured by the BULIT-R total score, and ghrelin concentrations. In a multivariate regression model controlling for the confounding effects of body mass index (BMI) and age, higher ghrelin concentrations were correlated with lower BULIT-R total scores. The results of this study did not confirm the hypothesis advanced in previous studies that ghrelin concentrations are higher in patients with binge-eating/purging forms of eating disorders. Based on these data, we suggest that, in women with eating disorders, ghrelin concentrations best reflect nutritional status rather than specific patterns of disordered eating behavior.

Circulating brain-derived neurotrophic factor is decreased in women with anorexia and bulimia nervosa but not in women with binge-eating disorder: relationships to co-morbid depression, psychopathology and hormonal variables.

BACKGROUND: Several lines of evidence indicate a role of the brain-derived neurotrophic factor (BDNF) in the modulation of eating behaviour. Therefore, alterations in the physiology of this neurotrophin may be involved in the pathogenesis of eating disorders. In the present study, we investigated serum levels of BDNF in patients with anorexia nervosa (AN), bulimia nervosa (BN) and binge-eating disorder (BED). METHOD: Ninety-nine drug-free women (27 with AN, 24 with BN, 24 with BED and 24 healthy controls) underwent both a blood sample collection in the morning and diagnostic and psychopathological assessments by means of structured clinical interviews and ad-hoc rating scales. Serum levels of BDNF, 17 beta-oestradiol, FT3 and FT4 were measured. RESULTS: Compared to healthy controls, serum levels of BDNF were significantly reduced in underweight AN women and in normal weight BN women, but not in overweight BED women. Changes in circulating BDNF levels were not affected by the presence of co-morbid depressive disorders. No significant correlation emerged between neurotrophin concentrations and psychopathological, nutritional, demographic and hormonal variables. CONCLUSIONS: These findings evidentiate alterations in serum BDNF levels in malnourished patients with AN or BN, but not in well-nourished individuals with BED. Since BDNF seems to exert a satiety effect, its reduction may represent an adaptive change to counteract the decreased calorie ingestion of AN and BN individuals.

Enhanced serum cholesterol and triglyceride levels in bulimia nervosa: relationships to psychiatric comorbidity, psychopathology and hormonal variables.

Increased levels of cholesterol have been reported in patients with bulimia nervosa (BN), but all but one of the published studies were performed on non-fasting subjects, which limits the interpretation of this finding. Moreover, the relationships between serum lipids and comorbid psychiatric disorders or bulimic psychopathology have scarcely been investigated. We measured serum levels of total cholesterol, triglycerides, glucose, 17beta-estradiol and thyroid hormones in 75 bulimic women and 64 age-matched healthy females after an overnight fast. Compared with healthy women, bulimic patients exhibited significantly enhanced serum levels of cholesterol and triglycerides, but similar values of glucose, 17beta-estradiol, FT3 and FT4. No significant differences emerged in these variables between patients with or without comorbid depression, borderline personality disorder or lifetime anorexia nervosa. Circulating cholesterol was positively correlated to the patients' drive for thinness, ineffectiveness, enteroceptive awareness and impulse regulation sub-item scores of the Eating Disorder Inventory-2. These findings confirm that BN is associated with increased levels of serum lipids. This alteration may be involved in the pathophysiology of certain psychopathological characteristics of BN and cannot be explained by the co-occurrence of other psychiatric disorders.

Plasma ghrelin concentrations are lower in binge-eating disorder.

Binge-eating disorder (BED), characterized by binge meals without purging afterward, is found in about 30% of obese individuals seeking treatment. The study objective was to ascertain abnormalities in hormones influencing appetite in BED, especially ghrelin, an appetite-stimulating peptide, which was expected to be elevated. Measurements were made of plasma insulin, leptin, glucagon, cholecystokinin, and ghrelin, as well as glucose following an overnight 12-h fast, prior to and after ingestion (from 0 to 5 min) of a nutritionally complete liquid meal (1254 kJ) at 0830 h, at -15, 0, 5, 15, 30, 60, 90, and 120 min. Appetite ratings including hunger and fullness were also obtained. An acetaminophen tracer was used to assess gastric emptying rate. Three groups of comparably obese women (BMI = 35.9 +/- 5.5; % body fat = 44.9 +/- 4.7) participated: 12 nonbinge eating normals (NB), 14 subthreshold BED, and 11 BED. The BED subjects, compared to NB subjects, had lower baseline ghrelin concentrations prior to the meal, a lower area under the curve (AUC), with lower levels at 5, 15, 30, 90, and 120 min, and a smaller decline in ghrelin postmeal (all P < 0.03). The other blood values did not differ among groups, and neither did gastric emptying rate nor ratings of fullness. The BED subjects were then randomly assigned to treatment with cognitive-behavior therapy and diet (n = 5) or to a wait-list control (n = 4). Baseline ghrelin (P = 0.01) and AUC increased (P = 0.02), across both conditions, in which most subjects (7 of 9) stopped binge eating. The lower fasting and postmeal plasma ghrelin levels in BED are consistent with lower ghrelin levels in obese compared to lean individuals and suggests downregulation by binge eating.

New contributions to the prevalence of eating disorders in Spanish adolescents: detection of false negatives.

BACKGROUND: Although the epidemiology of Eating Disorders (ED) has been highly developed in Spain, further research considering false negatives and also the prevalence of these disorders in males are needed. They were the aims of the present study. METHODS: One thousand and seventy six adolescents (500 males and 576 females) participated in a two-stage survey. At the age of 13, apart from exploring numerous clinical and psychosocial variables, they were assessed by means of self-administered screening instruments, the eating attitude test (EAT), bulimic investigatory test Edinburgh (BITE), and body shape questionnaire (BSQ). The subjects were interviewed again 2 years later. Afterwards, 159 probable cases and 150 controls were interviewed by means of the structured interview SCAN. RESULTS: Prevalence of ED in adolescents was 3.71% (95% CI 2.58-4.83; 6.4% of females, 0.6% of males): anorexia nervosa 0.1%, bulimia nervosa 0.75%, eating disorder not otherwise specified (EDNOS) = 2.88%. The rate of false negative was 2.6% of the control group and most of them were EDNOS. CONCLUSIONS: The prevalence of ED obtained in our study, higher than others found in previous Spanish research, and a relatively high percentage of false negatives both indicate that up to now the prevalence of ED in Spanish adolescents could be underestimated.

Altered ghrelin and peptide YY responses to meals in bulimia nervosa.

OBJECTIVE: In recent years great advances have been made in our understanding of the peripheral signals produced within the gastrointestinal tract that regulate appetite, such as ghrelin and peptide YY (PYY). While ghrelin elicites hunger signals, PYY elicites satiety. Therefore, alterations in hormone physiology may play a role in the pathogenesis of bulimia nervosa (BN). In this study, we investigated the postprandial profile of ghrelin and PYY levels in patients with BN. DESIGN AND PATIENTS: Postprandial plasma ghrelin and PYY levels and insulin and glucose responses were measured in 10 patients with BN and 12 control patients in response to a standard 400 kcal meal. RESULTS: Basal ghrelin levels present in BN subjects (265.0 +/- 25.5 pmol/l) were significantly higher than those in healthy controls (199.3 +/- 18.4 pmol/l, P < 0.05), while basal PYY levels were equivalent in BN (14.6 +/- 1.3 pmol/l) and control (12.8 +/- 1.1 pmol/l, P = 0.30) subjects. Postprandial ghrelin suppression (decremental ghrelin area under the curve) was significantly attenuated in BN patients, compared to controls (-96.3 +/- 26.8 pmol/l x 3 h vs. -178.2 +/- 25.7 pmol/l x 3 h, P < 0.05). After a meal, the incremental PYY area under the curve in BN patients was significantly blunted from that observed in controls (9.2 +/- 2.6 pmol/l x 3 h vs. 26.8 +/- 3.2 pmol/l x 3 h, P < 0.01). Glucose and insulin responses to meals were similar between the two groups. CONCLUSIONS: BN patients exhibit elevated ghrelin levels before meals with reduced ghrelin suppression after eating. In bulimia nervosa subjects, the rise in PYY levels after meals is also blunted. A gut-hypothalamic pathway involving peripheral signals, such as ghrelin and PYY, may be involved in the pathophysiology of BN.

Circulating ghrelin is decreased in non-obese and obese women with binge eating disorder as well as in obese non-binge eating women, but not in patients with bulimia nervosa.

Ghrelin is a peripheral gastric peptide involved in the regulation of eating behavior and energy homeostasis. While changes in ghrelin plasma levels have been found in anorexia nervosa, bulimia nervosa (BN) and obesity, no study has assessed circulating ghrelin in binge eating disorder (BED). Therefore, we measured plasma levels of this peptide in women with BED as compared to women with BN, obesity and healthy controls. One hundred and eighty-two drug-free women (56 bulimics, 13 non-obese and 34 obese BED subjects, 28 obese non-binge eating women and 51 non-obese healthy women) underwent psychopathological and nutritional assessments and blood sample collection for glucose and ghrelin assays in the morning. As compared to non-obese healthy women, both non-obese and obese BED women as well as obese non-binge eating women had significantly increased values of body weight, body mass index and body fat mass. Moreover, plasma ghrelin concentrations were significantly decreased in both non-obese (P<0.01) and obese (P<0.0001) BED women as well as in obese non-binge eating women (P<0.001) but not in women with BN. No significant correlations emerged between plasma ghrelin values and the frequency of binge/vomiting in BN subjects or the frequency of bingeing in BED individuals. The reduction of plasma ghrelin in non-obese and obese binge eaters as well as in obese non-binge eaters may represent a secondary change aiming to counteract their positive energy imbalance.

No changes in serum ghrelin levels in female patients with bulimia nervosa.

It has been reported that fasting plasma ghrelin levels may play a role in the pathophysiology of eating disorders. In this study, the authors examined whether serum levels of ghrelin were altered in the patients with bulimia nervosa (BN). We enrolled 18 female patients with BN, and 21 age-matched female controls for this study. Eating-related psychopathology, depressive symptoms were evaluated by using the Bulimic Investigatory Test, Edinburgh (BITE) and the 17-item Hamilton Depression Rating Scale (HDRS). Serum levels of ghrelin were measured by Ghrelin enzyme immunoassay kit. There were no significant differences in serum ghrelin levels between the patients with BN and normal controls. Furthermore, the authors did not found correlation between serum ghrelin levels and clinical parameters in the patients with BN. Our study suggests that serum ghrelin levels in the patients with BN were indistinguishable from normal controls. Therefore, it is unlikely that ghrelin plays a role in the pathophysiology of BN.

Ghrelin and leptin responses to food ingestion in bulimia nervosa: implications for binge-eating and compensatory behaviours.

BACKGROUND: Ghrelin and leptin are endogenous peripheral proteins involved in the regulation of eating behaviour. In particular, ghrelin stimulates hunger and promotes food ingestion, whereas leptin increases satiety and reduces food consumption. Therefore, alterations in the physiology of these peptides may play a role in the pathogenesis of eating disorders such as bulimia nervosa. In the present study, we investigated ghrelin and leptin responses to food ingestion in patients with bulimia nervosa. METHOD: Nine symptomatic drug-free bulimic women and 12 age-matched healthy women ingested a meal of 1207 kcal (60% carbohydrates, 23% fat and 17% proteins) at 12.00 a.m. and underwent blood sample collection before and 45, 60, 90, 120 and 180 min after the meal. Plasma levels of ghrelin, leptin, insulin and glucose were measured. RESULTS: In healthy women, circulating ghrelin exhibited a drastic decrease after the food intake whereas, in bulimic patients, this response was significantly blunted. No difference between the two subjects groups was observed in post-prandial profiles of plasma leptin, insulin and glucose. CONCLUSIONS: The lack of a leptin response to food ingestion, in both bulimic and healthy women, is compatible with the role of this peptide as long-term rather than short-term modulator of eating behaviour. The blunted ghrelin response to food ingestion may support the occurrence in bulimic subjects of an impaired suppression of the drive to eat following a meal. This may have implications for binge-eating.

Serum electrolytes in bulimic patients with parotid swellings.

OBJECTIVE: The purpose of this study was to determine whether electrolyte levels can be used to diagnose bulimia nervosa (BN). STUDY DESIGN: Four patients with bilateral parotid swellings and BN or suspected BN were examined. Their serum electrolyte levels were retrospectively reviewed. RESULTS: In this limited study, hypochloremia, hypokalemia, and metabolic alkalosis were present in 1 patient. One patient showed both hypochloremia and hypokalemia, whereas a third patient had only hypochloremia and a low normal serum potassium. The fourth patient demonstrated suspiciously low serum levels of Cl(-) and K(+). CONCLUSION: Because BN patients tend to be secretive regarding their disorder, serum electrolyte levels may serve as useful tools in diagnosing parotid swellings initiated by bulimia.

Fasting plasma ghrelin levels in subtypes of anorexia nervosa.

Ghrelin has a role in regulating eating behavior and energy metabolism in the central nervous system, and has been reported to play an important role in the pathophysiology of anorexia nervosa (AN). The aim of the present study was to compare fasting plasma ghrelin levels in different subtypes of untreated AN patients. The subjects included 39 female AN patients and 11 female controls. The patients were then divided into two subtypes as follows: 19 AN patients with restricting (AN-R) and 20 AN patients with binge-eating/purging (AN-BP) form of the illness. Blood samples from subjects after an overnight fast were used to analyze plasma ghrelin concentrations. Plasma ghrelin concentrations in both AN-R and AN-BP were negatively correlated with body mass index (BMI). The mean plasma ghrelin levels in both AN-R and AN-BP were significantly higher than that in controls. The mean ghrelin level in AN-BP was significantly higher than that in AN-R. However, mean BMI and serum potassium in both groups were not significantly different. These results suggest that both BMI and the presence of binge-eating/purging may have some influence on fasting plasma ghrelin levels in patients with AN.

Habitual binge/purge behavior influences circulating ghrelin levels in eating disorders.

Previous studies have reported that fasting plasma ghrelin concentrations play an important role in the pathophysiology of eating disorders. The purpose of this study was to examine the relationship between plasma ghrelin levels and frequency of abnormal eating behaviors, nutritional parameters in eating disorders. Fasting blood samples were obtained in 40 female anorexia nervosa (AN) patients, 21 restricting type (AN-R) and 19 binge-eating/purging type (AN-BP), in 31 bulimia nervosa (BN) patients, 18 purging type (BN-P) and 13 non-purging type (BN-NP), in 15 female healthy volunteers (control) before the initiation of active treatment. The fasting plasma ghrelin concentrations in all subjects were negatively correlated with nutritional parameters such as body mass index, percent body fat and serum cholinesterase concentration. The mean plasma ghrelin level in BN-P was higher than that in both BN-NP and controls despite similar nutritional parameters. The plasma ghrelin levels in both AN-R and AN-BP did not differ from BN-P despite difference of nutritional parameters. For both AN-BP and BN-P patients with habitual binge/purge behavior, there were significant correlations among plasma ghrelin values, frequencies of binge/purge cycles and serum amylase values. In BN-NP, there were no significant correlations among plasma ghrelin values, frequencies of binge-eating episodes and serum amylase values. These results suggest that habitual binge/purge behavior may have some influence on circulating plasma ghrelin levels in both BN-P and AN-BP. Habitual binge/purge cycles with vomiting as opposed to binge-eating episodes without vomiting may have a greater influence on fasting plasma ghrelin concentration in eating disorders.

Leptin secretion is related to chronicity and severity of the illness in bulimia nervosa.

OBJECTIVE: A reduction in circulating leptin has been reported in some patients with BN, but not in others. The reasons for such diversity have not been explained. Therefore, we measured plasma levels of leptin and other hormones in a large sample of patients with eating disorders and in healthy controls and explored differences between bulimics with low plasma leptin levels and those with normal concentrations of the hormone. METHOD: One hundred and twenty-seven women participated in the study. They were 33 patients with AN, 56 women with BN, and 38 healthy volunteers. All were drug free for at least 6 weeks. Blood samples were collected in the morning for determination of hormone levels. Eating-related psychopathology and depressive symptoms were rated by using specific psychopathological scales. RESULTS: As compared with healthy women, both underweight AN and normal-weight BN patients exhibited decreased plasma levels of leptin, prolactin, and 17beta-estradiol. Plasma levels of cortisol were increased in AN but not in BN women. In bulimics, circulating leptin was inversely correlated with the duration of the illness and the frequency of bingeing/vomiting. Moreover, 29 bulimics had anorexic-like plasma leptin concentrations; the remaining 27 had circulating leptin similar to normal controls. The former had a significantly longer duration of the illness and a higher frequency of bingeing/vomiting compared with the latter. Moreover, a higher number of patients with concomitant borderline personality disorder were found in bulimics with low leptin concentrations. No significant differences between the two groups emerged in BW, BMI, mean plasma levels of cortisol, PRL, 17beta-estradiol and other clinical parameters. CONCLUSIONS: Present data show that leptin production is decreased in the subgroup of bulimic patients with a more chronic disease and with a greater severity of the bingeing/vomiting behavior. These findings support the idea that factors other than body weight changes (especially chronic malnutrition and bingeing behavior) may impair profoundly and persistently leptin secretion in patients with BN.

[Gynecologic and endocrinologic sequelae of bulimia--hormonal changes]. / A bulimia nógyógyászati és endokrinológiai következményei--hormonális eltérések.

INTRODUCTION: Gynecological problems are one of the most frequent somatic complications of eating disorders. AIMS: The purpose of the present study was to assess the role of improper eating habits causing menstrual disturbances, anovulation and related hormonal changes. Latent bulimia nervosa is in the focus of attention since amenorrhea is considered as a diagnostic criterion of anorexia nervosa. METHOD: Subjects of the BITE (Bulimia Investigation Test, Edinburgh) test were infertile patients (n = 34) of the gynecological outpatient departments after medical examination, blood-test (LH, FSH, androstenedione, DHEAS, progesterone, testosterone, SHBG, prolactin) and ultrasonic examination (uterus and ovaries). RESULTS: Symptoms and severity subscales of the BITE test and body mass index (BMI) were close correlation (p = 0.003, p = 0.033). In comparison with previous results, EDNOS (Eating Disorders Not Otherwise Specified) prevalence was 48%. Of hormonal changes, low LH and FSH levels (6/6) and hyperandrogenism (5/6) were significant in patients with subclinical eating disorders (n = 6) by infertile women as compared with the "normal" infertile group (n = 18; 7/18, 8/18). CONCLUSION: The recent results suggests that unsatisfactory nutrition (bulimic binges, "crash diet") is as relevant in hormonal dysfunction, menstrual disturbances and infertility as pathologically low weight in anorexia nervosa. Excessive application of contraceptives in therapy has to be taken into consideration.