Neuroendocrine abnormalities in anorexia nervosa (AN) include hypercortisolemia, hypogonadism, and hypoleptinemia, and neuroendocrine predictors of menstrual recovery are unclear. Preliminary data suggest that increases in fat mass may better predict menstrual recovery than leptin. High doses of cortisol decrease luteinizing hormone (LH) pulse frequency, and cortisol predicts regional fat distribution. We hypothesized that an increase in fat mass and decrease in cortisol would predict menstrual recovery in adolescents with AN. Thirty-three AN girls 12-18 y old and 33 controls were studied prospectively for 1 y. Body composition [dual energy x-ray absorptiometry (DXA)], leptin, and urinary cortisol (UFC) were measured at 0, 6, and 12 mo. Serum cortisol was measured overnight (every 30 min) in 18 AN subjects and 17 controls. AN subjects had higher UFC/cr x m2 and cortisol area under curve (AUC), and lower leptin levels than controls. Leptin increased significantly with recovery. When menses-recovered AN subjects were compared with AN subjects not recovering menses and controls, menses-recovered AN subjects had higher baseline cortisol levels and greater increases in leptin than controls and greater increases in fat mass than AN subjects not recovering menses and controls (adjusted for multiple comparisons). In a logistic regression model, increasing fat mass, but not leptin, predicted menstrual recovery. Baseline cortisol level strongly predicted increases in the percentage of body fat. We demonstrate that 1) high baseline cortisol level predicts increases in body fat and 2) increases in body fat predict menses recovery in AN.
"Weight rehabilitation is a prerequisite for reestablishing endocrine function [11,18,19]. During weight gain, fat mass increases resulting in the normalization of gonadal hormones and leptin levels. "
[Show abstract][Hide abstract] ABSTRACT: The resumption of menses is an important indicator of recovery in anorexia nervosa (AN). Patients with early-onset AN are at particularly great risk of suffering from the long-term physical and psychological consequences of persistent gonadal dysfunction. However, the clinical variables that predict the recovery of menstrual function during weight gain in AN remain poorly understood. The aim of this study was to investigate the impact of several clinical parameters on the resumption of menses in first-onset adolescent AN in a large, well-characterized, homogenous sample that was followed-up for 12 months.
A total of 172 female adolescent patients with first-onset AN according to DSM-IV criteria were recruited for inclusion in a randomized, multi-center, German clinical trial. Menstrual status and clinical variables (i.e., premorbid body mass index (BMI), age at onset, duration of illness, duration of hospital treatment, achievement of target weight at discharge, and BMI) were assessed at the time of admission to or discharge from hospital treatment and at a 12-month follow-up. Based on German reference data, we calculated the percentage of expected body weight (%EBW), BMI percentile, and BMI standard deviation score (BMI-SDS) for all time points to investigate the relationship between different weight measurements and resumption of menses.
Forty-seven percent of the patients spontaneously began menstruating during the follow-up period.%EBW at the 12-month follow-up was strongly correlated with the resumption of menses. The absence of menarche before admission, a higher premorbid BMI, discharge below target weight, and a longer duration of hospital treatment were the most relevant prognostic factors for continued amenorrhea.
The recovery of menstrual function in adolescent patients with AN should be a major treatment goal to prevent severe long-term physical and psychological sequelae. Patients with premenarchal onset of AN are at particular risk for protracted amenorrhea despite weight rehabilitation. Reaching and maintaining a target weight between the 15th and 20th BMI percentile is favorable for the resumption of menses within 12 months. Whether patients with a higher premorbid BMI may benefit from a higher target weight needs to be investigated in further studies.
"They also reported that baseline ghrelin, peptideYY, and cortisol are the most significant and independent predictors of subsequent changes in lumbar and whole-body bone densities in AN (Misra et al., 2008). However, they did not apply the change in cortisol levels from baseline to the final period as a prognostic predictor , because in their study the change was not significant (Misra et al., 2006b). Our study examined whether such change values of AUC cortisol levels before and after inpatient treatment could be applicable as a prognostic predictor. "
[Show abstract][Hide abstract] ABSTRACT: This study investigated the hypothalamus-pituitary-adrenal (HPA) axis activity in children with anorexia nervosa (AN) before and after inpatient treatment. Salivary cortisol levels were measured to ascertain whether changes in the HPA axis activity following therapeutic intervention could be applicable as a prognostic predictor. This study comprised 21 females with AN and 22 control subjects. Saliva was collected at 2-hour intervals from 9 a.m. to 7 p.m. before and after inpatient treatment. The concentrations for areas under the curve (AUC) were compared with physical parameters, eating attitude score, profile of mood states (POMS), and prognostic factors. Mean salivary cortisol levels at all points and mean AUC cortisol levels in subjects with AN before therapy were significantly higher than those in controls, but returned to control levels after inpatient treatment. Higher AUC cortisol levels were associated with lower standard deviation for weight in AN. A significant positive correlation between the AUC cortisol level and POMS subscale of "Fatigue" was apparent in the control group, but not in the AN group. The increased change values of AUC cortisol level before and after inpatient treatment correlated with increased body weight gain ratio just after treatment, but not with the ratio after one year. The present study indicated that HPA axis activity could reflect severity of illness, but did not show an accurate neuroendocrine response for mood states. Changes in HPA axis activity following treatment could therefore be used to predict prognosis and particularly in the short term.
International journal of psychophysiology: official journal of the International Organization of Psychophysiology 09/2011; 82(2):196-201. DOI:10.1016/j.ijpsycho.2011.08.008 · 2.88 Impact Factor
"Also limiting previous research is the fact that the relationship between physical activity and variables other than weight and BMI is underexplored. Among the various indices of body composition, low percent BF is known to be associated with important health indices such as reduced heart rate, lowered blood pressure, and hematological abnormalities (Lambert et al., 1997; Misra et al., 2006). Thus understanding potential contributors to percent BF in individuals with AN is paramount. "
[Show abstract][Hide abstract] ABSTRACT: The study aimed to compare differences in physical activity, the relationship between physical activity and body composition, and seasonal variation in physical activity in outpatients with anorexia nervosa (AN) and healthy controls. Physical activity (CM-AMT) and time spent in different intensities of 10 female individuals with AN and 15 female controls was assessed across three seasons along with the percentage body fat. The two groups did not differ in their physical activity and both demonstrated seasonal variation. The percentage body fat of individuals with AN, but not that of the controls, was negatively related to CM-AMT and time spent in low-moderate intensity activity (LMI). Seasonal variation in physical activity emerged with increases in engagement in LMI during the summer period for both groups. Possible interpretations of the finding that decreased physical activity was related to a normalization of percentage body fat in the individuals with AN are discussed and implications for treatment are highlighted.
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