Transsexuals experience themselves as being of the opposite sex, despite ha
ving the biological characteristics of one sex. A crucial question resultin
g from a previous brain study in male-to-female transsexuals was whether th
e reported difference according to gender identity in the central part of t
he bed nucleus of the stria terminalis (BSTc) was based on a neuronal diffe
rence in the BSTc itself or just a reflection of a difference in vasoactive
intestinal polypeptide innervation from the amygdala, which was used as a
marker. Therefore, we determined in 42 subjects the number of somatostatin-
expressing neurons in the BSTc in relation to sex, sexual orientation, gend
er identity, and past or present hormonal status. Regardless of sexual orie
ntation, men had almost twice as many somatostatin neurons as women (P < 0.
006). The number of neurons in the BSTc of male-to-female transsexuals was
similar to that of the females (P = 0.83). In contrast, the neuron number o
f a female-to-male transsexual was found to be in the male range. Hormone t
reatment or sex hormone level variations in adulthood did not seem to have
influenced BSTc neuron numbers. The present findings of somatostatin neuron
al sex differences in the BSTc and its sex reversal in the transsexual brai
n clearly support; the paradigm that in transsexuals sexual differentiation
of the brain and genitals may go into opposite directions and point to a n
eurobiological basis of gender identity disorder.