Testosterone administration attenuates regional brain hypometabolism in women with anorexia nervosa

Abstract

Abnormalities in brain metabolism have not been consistently well localized in anorexia nervosa (AN), and effects of specific therapies on these functional abnormalities have not been studied. Androgen replacement therapy improves mood, well-being and cognitive function in men with androgen deficiency. We therefore hypothesized that women with AN and relative androgen deficiency would exhibit regional brain hypometabolism compared with healthy controls, and that low-dose physiologic androgen replacement would attenuate the hypometabolism in some of these brain loci. We used FDG PET and statistical parametric mapping methods to investigate regional brain glucose metabolism in (1) 14 women with AN and 20 healthy control subjects of similar mean age and (2) women with AN after randomization to low-dose replacement testosterone therapy or placebo. Cerebral metabolism was decreased in the posterior cingulate, pregenual anterior cingulate, left middle temporal, right superior temporal, and left dorsolateral prefrontal cortex in the AN group compared with controls. In AN patients receiving testosterone, cerebral metabolism increased in the posterior cingulate, subgenual anterior cingulate, premotor cortex, right caudate and right parietal lobes. In conclusion, our data demonstrate distinct loci of regional brain hypometabolism in women with AN compared with controls. Moreover, abnormalities in one of these regions—the posterior cingulate cortex—were attenuated towards normal with low-dose testosterone replacement therapy. Further study is warranted to replicate these findings, as well as to determine their physiological and clinical significance.