We report for the first time differences in body composition in males with AN that differ from those reported in females with AN. Boys with AN had lower fat and lean mass than did control subjects, as expected. However, in addition and in contrast with findings in girls with AN, percentage trunk fat was higher than in control subjects, particularly after adjustment for weight and fat mass. This finding is consistent with a sex-specific dichotomy in the association of extreme low body weight with fat distribution and is likely mediated by low concentrations of testosterone.
Few studies have reported differences in body composition between adolescent boys with AN and healthy adolescents. In our study, boys with AN had less fat and lean mass than did control subjects. We reported similar differences between adolescent girls with AN and healthy adolescent girls (4
). However, we observed that lean mass in boys with AN was lower in control subjects than we previously reported in girls with AN (26
) (14% lower in AN boys compared with 5% lower in AN girls compared with control subjects). This may be a consequence of markedly lower testosterone concentrations in pubertal AN boys than in control subjects, testosterone being an important determinant of muscle mass (8
). Many studies in hypogonadal adults have shown an increase in lean mass after testosterone replacement (8
). Consistent with these data, testosterone was an important and independent predictor of regional lean mass in the present study.
Interestingly, regional differences in body composition between boys with AN and control subjects differed greatly from reported differences between girls with AN and healthy girls (4
). For instance, adolescent girls with AN have lower percentage trunk fat than healthy adolescent girls (26
). In contrast, we observed higher weight-adjusted percentage trunk fat and lower percentage extremity fat and percentage extremity lean fat in boys with AN than in control subjects. Similarly, the trunk/extremity fat ratio was higher in boys with AN than in control subjects. To summarize, boys with AN have preferentially lower fat and lean mass in the extremities and higher fat mass in the trunk than do control subjects. In contrast, girls with AN have much lower fat mass in the trunk than in the extremities than do control girls.
Although our study was not designed to determine the cause of this sparing of trunk fat in boys with AN and in healthy adolescent boys, we propose that this is a consequence primarily of low testosterone concentrations, and that the difference from girls with AN reflects differences in effects of sex-specific gonadal steroids on body-composition measures. Hypogonadal men have greater waist-to-hip circumferences and subcutaneous fat than do eugonadal men, and a decrease in these measures occurs after testosterone replacement (8
). Similar effects in hypogonadal AN boys could result in a relative sparing of trunk fat despite the accompanying weight loss. Consistent with this hypothesis, we observed inverse associations of free testosterone with percentage trunk fat and the trunk/extremity fat ratio on regression modeling with bone age (as an index of pubertal maturity), weight, and other hormones known to affect body composition entered into the model. Positive associations of bone age and inverse associations of free testosterone with these measures on regression modeling suggest that older and more mature boys with lower concentrations of testosterone have the highest percentage trunk fat and the greatest relative abdominal adiposity.
Other hormonal aberrations that can cause relative truncal adiposity include GH deficiency and hypercortisolemia. GH decreases fat mass (particularly trunk fat) and increases muscle mass (27
), and conditions of GH deficiency are associated with increased trunk fat (29
). We previously reported associations of IGF-1 with trunk fat in adolescent girls with AN (4
). However, although IGF-1 concentrations were lower in boys with AN than in control subjects, this difference was not statistically significant, and IGF-1 concentrations did not predict body-composition measures in boys with AN. Given that IGF-1 concentrations are markedly lower in girls with AN than in control subjects, associated with a nutritional resistance to GH effects (13
), the relative sparing of IGF-1 concentrations in boys with AN was unexpected, and the reason was unclear. Overall, our data suggest a stronger association of hypogonadism than of the GH-IGF-1 axis with body-composition variables in hypogonadal adolescent males.
Of note, excessive cortisol can cause truncal adiposity and decreased extremity muscle mass (32
), and girls with AN have high cortisol concentrations (33
). Adult women with AN develop increased trunk fat as they recover, and women with the highest cortisol concentrations have the greatest increases in trunk fat with weight recovery (5
). We did not measure cortisol concentrations in our subjects—a study limitation. One can speculate that high cortisol concentrations in boys with AN contributes to both a sparing of trunk fat and a lower extremity lean mass. In fact, we previously reported that girls with AN with the highest cortisol concentrations had the lowest percentage extremity lean mass (26
). Further studies are therefore necessary to determine the effects of cortisol on body composition in AN boys.
Inverse associations of ghrelin with lean mass have been reported in healthy men (15
). In this study, we found no associations of ghrelin with regional body-composition measures after control for bone age, weight, and other hormones. Leptin concentrations were markedly lower in girls with AN than in control subjects (27% of values in control subjects) (16
) and were lower in AN boys in our study (54% of values in control subjects), but not to the extent seen in AN girls. Because leptin is primarily secreted by adipocytes, the fact that leptin concentrations were not as low in AN boys compared with control subjects as reported in AN girls likely reflects the fact that fat mass is not as low in AN boys compared with control subjects as reported in AN girls (26
Study limitations include the fact that we could not obtain a better measure of the duration of a catabolic state in boys with AN than the time since diagnosis. Duration of illness would have been a better measure, however, our subjects and their parents were mostly unsure of the time of onset of this disorder. In addition, although our AN subjects weighed much less than the control subjects, the AN subjects were in active treatment programs, and, in a subset in whom nutritional intake information was available, caloric intake did not differ between AN and control subjects. It is possible that a more profound catabolic state may have resulted in even more profound differences between the groups for both biochemical and body-composition measures. Even though the AN boys weighed much less than the control subjects, our data may reflect a partially recovered state. Therefore, it will be important to follow subjects over time and determine how regional body composition changes with changing weight.
We thus report unique differences in body composition between boys with AN and control subjects, which are predicted by bone age, testosterone, and weight. Low weight in boys with AN is associated with lower weight-adjusted percentage fat and lean mass in the extremities compared with control subjects and a higher percentage trunk fat and trunk/extremity fat ratio. These body-composition differences are related to lower testosterone concentrations in boys with AN than in control boys.