High fetal testosterone and sexually dimorphic cerebral networks in females

Abstract

Active masculinization by fetal testosterone is believed to be a major factor behind sex differentiation of the brain. We tested this hypothesis in a 15O-H2O positron emission tomography study of 11 women with congenital adrenal hyperplasia (CAH), a condition with high fetal testosterone, and 26 controls. Two indices of cerebral dimorphism were measured - functional connectivity and cerebral activation by 2 putative pheromones (androstadienone [AND] and estratetraenol [EST]), previously reported to activate the hypothalamic networks in a sex-differentiated manner. Smelling of unscented air was the baseline condition, also used for measurements of functional connectivity from the amygdala. In CAH women and control women AND activated the anterior hypothalamus, and EST the amygdala, piriform, and anterior insular cortex. The pattern was reciprocal in the male controls. Also the functional connections were similar in CAH women and control women, but different in control men. Women displayed connections with the contralateral amygdala, cingulate, and the hypothalamus, men with the basal ganglia, the insular and the sensorimotor cortex. Furthermore, the connections were in CAH and control women more widespread from the left amygdala, in men from the right amygdala. Thus, we find no evidence for masculinization of the limbic circuits in women with high fetal testosterone.