It is not clear whether the differences associated with the additional X chromosome are due to hypogonadism or more direct dosage effects of genes on the X chromosome. Of the two studies which were able to compare subjects based on whether they had received testosterone supplementation, one suggested that gray matter was less diminished in the group that had additional testosterone, whereas the other found no difference. Another means of investigating this is to look at the impact of an additional X chromosome in 47,XXX females, who typically have normal pubertal development and fertility.
