In this study of underweight amenorrheic women with AN, normal-weight women with HA, OB women, and normal-weight healthy women, overnight serum Cortisol and fasting PYY levels were associated with disordered eating psychopathology, independent of BMI.
Levels of hormones involved in appetite and feeding behavior, including Cortisol, PYY, leptin, and ghrelin, differ based on body weight and fat (1
), and abnormal levels of these hormones have been reported in women with AN (7
) and in functional HA (17
), a disorder commonly associated with subclinical disordered eating (18
). It is unknown whether appetite-regulating hormone abnormalities contribute to disordered eating symptomatology. We hypothesized that these hormones would be associated with severity of disordered eating attitudes and behaviors regardless of body weight.
Cortisol, a key component of the hypothalamic-pituitary-adrenal axis, is released in response to psychological or physical ‘stress’ and may stimulate appetite (3
). AN and HA are both associated with elevated levels of endogenous Cortisol, which is presumably stress related (9
). An alternative possibility is that hypercortisolemia is an adaptive response to increase and mobilize energy stores in the face of decreased weight or body fat and/or increased demand. Exposure to high levels of Cortisol, for example, in Cushing’s syndrome or exogenous corticosteroid administration, stimulates appetite and weight gain with central fat accumulation when there is sufficient substrate. For example, when patients with AN gain weight, preferential truncal fat gain is seen (35
). In contrast, characteristic symptoms of adrenal insufficiency are anorexia and weight loss. Other studies have reported an association between measures of Cortisol and dietary restraint in pre- and post-menopausal women (36
). We have shown that in comparison to healthy controls, average overnight Cortisol levels were higher in women with HA and AN (24
). In this study, across groups of women of differing weights, pooled overnight serum Cortisol levels were positively associated with disordered eating attitudes and behaviors as assessed by the EDE-Q and EDI-2, independent of BMI. Furthermore, the relationships between overnight Cortisol levels and dietary restraint and eating concern measures of EDE-Q core disordered eating psychophathology were independent of depressive symptoms. Therefore, hypercortisolemia may be an adaptive mechanism to starvation, which further exacerbates an underlying pattern of disordered eating.
PYY is an anorexigenic polypeptide hormone secreted by the intestine in response to food intake (39
). In the hypothalamus, PYY modulates appetite by binding to Y2 receptors in the arcuate nucleus, promoting anorexigenic in favor of orexigenic pathways (40
). PYY levels are elevated in AN (7
) and HA (31
), and low in obesity (1
), and are inversely associated with BMI (1
). In a 2003 study of 12 obese and 12 lean subjects, Batterham et al
) reported that infusion of PYY resulted in a similar reduction of appetite and caloric intake in each group. A study of exercising women with HA and exercising and sedentary healthy controls found that PYY levels were associated with drive for thinness as assessed by the EDI-2 (31
). We demonstrated that PYY levels are correlated with characteristics of disordered eating as well as associated features, and that some of these relationships, including core disordered eating psychopathology measures of EDE-Q eating concern and EDI-2 drive for thinness, remained significant after controlling for BMI. Although abnormal PYY levels may be secondary to disordered eating thinking and behavior, low levels of PYY in obesity and high levels in AN despite PYY’s function in signaling satiety argue for a possible etiologic role.
There is some evidence suggesting that PYY may be involved in hypothalamic–pituitary–adrenal axis signaling. Administration of i.v. PYY to dogs stimulates secretion of ACTH and Cortisol (42
). Consistent with these data, we found a strong positive correlation between morning fasting PYY levels and mean overnight Cortisol levels. PYY and Cortisol were independently associated with different features of disordered eating as measured by the EDE-Q and EDI-2, suggesting specific effects of these hormones on disordered eating pathology.
Leptin, an anorexigenic hormone secreted by adipocytes, correlates with BMI and fat mass (5
). Levels are low in AN (8
) and HA (19
), and high in obesity (10
). After long-term recovery from AN, leptin levels normalize (46
). A recent study demonstrated an inverse association between leptin levels and drive for thinness on the EDI-2 in women with AN, but not in healthy controls (47
). Monteleone et al
) found no relationship between leptin levels and EDI scores in 21 women with AN, 32 with bulimia nervosa, 14 with binge eating disorder, and 25 controls. In contrast, Ehrlich et al
) showed a negative correlation between leptin and drive for thinness on the EDI-2 when controlling for BMI in 57 women with AN, but not in controls. In our study, leptin was inversely associated with scores on the eating concern subscale of the EDE-Q and with several associated psychological features measured by the EDI-2 in the entire sample. However, these relationships were no longer significant after controlling for BMI. This may reflect leptin’s role as a marker for fat, where women with the lowest body fat (AN) have increased eating disorder pathology, rather than as a mediator of disordered eating thought and behavior.
Ghrelin, an orexigenic hormone secreted by the stomach, is elevated in AN (7
) and HA (20
), low in obesity (2
), and inversely related to BMI (2
). Schneider et al
) reported an association between ghrelin levels and elevated scores on the Eating Attitude Test, a measure of abnormal eating thinking and behavior, in normal-weight women with HA. A correlation between ghrelin and drive for thinness subscale of the EDI-2 has been reported in a study of exercising women with HA and controls (31
). Consistent with a previous report (46
), we found that ghrelin was associated only with the maturity fears subscale of the EDI-2; however, this relationship was no longer significant after controlling for BMI.
This study has several limitations. First, sample sizes across groups were small, which may have limited power to detect differences. Owing to the cross-sectional study design, causality cannot be determined. In addition, we measured total but not acylated ghrelin levels. Acylated ghrelin is considered the most active form of ghrelin, but due to rapid degradation requires special collection techniques with a preservative for accurate assessment (49
). It is possible that had we measured the active form of ghrelin, we would have identified associations with disordered eating psychopathology. Furthermore, the EDE-Q and EDI-2 are excellent measures of disordered eating psychopathology in AN. Additional instruments may have been useful to tap into subclinical disordered eating psychopathology in HA and OB. For example, nuanced measures that more carefully assess the nature of exercise (e.g. motivation, compulsivity, and intensity) may be useful in HA, or those that assess the psychopathology of binge eating disorder (e.g. measures of emotional eating) may be useful for individuals with overweight and obesity.
In summary, we found a strong association between overnight Cortisol and fasting morning PYY levels and disordered eating attitudes and behaviors, independent of BMI. These findings suggest that these appetite-regulating hormones may be factors in disordered eating symptomatology. Further research on the role of appetite-regulating hormones in the development of disordered eating will be important.