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Jiska S Peper, Rachel M Brouwer, G Caroline M van Baal, Hugo G Schnack, Marieke van Leeuwen, Dorret I Boomsma, René S Kahn, and Hilleke E Hulshoff Pol


Brain volume of boys is larger than that of girls by ∼10%. Prenatal exposure to testosterone has been suggested in the masculinization of the brain. For example, in litter-bearing mammals intrauterine position increases prenatal testosterone exposure through adjacent male fetuses, resulting in masculinization of brain morphology.


The influence of intrauterine presence of a male co-twin on masculinization of human brain volume was studied in 9-year old twins.


Magnetic resonance imaging brain scans, current testosterone, and estradiol levels were acquired from four groups of dizygotic (DZ) twins: boys from same-sex twin-pairs (SSM), boys from opposite-sex twin-pairs (OSM), girls from opposite-sex twin-pairs (OSF), and girls from same-sex twin-pairs (SSF; n=119 individuals). Data on total brain, cerebellum, gray and white matter volumes were examined.


Irrespective of their own sex, children with a male co-twin as compared to children with a female co-twin had larger total brain (+2.5%) and cerebellum (+5.5%) volumes. SSM, purportedly exposed to the highest prenatal testosterone levels, were found to have the largest volumes, followed by OSM, OSF and SSF children. Birth weight partly explained the effect on brain volumes. Current testosterone and estradiol levels did not account for the volumetric brain differences. However, the effects observed in children did not replicate in adult twins.


Our study indicates that sharing the uterus with a DZ twin brother increases total brain volume in 9-year olds. The effect may be transient and limited to a critical period in childhood.

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Hilleke E Hulshoff Pol, Peggy T Cohen-Kettenis, Neeltje E M Van Haren, Jiska S Peper, Rachel G H Brans, Wiepke Cahn, Hugo G Schnack, Louis J G Gooren, and René S Kahn

Objective: Sex hormones are not only involved in the formation of reproductive organs, but also induce sexually-dimorphic brain development and organization. Cross-sex hormone administration to transsexuals provides a unique possibility to study the effects of sex steroids on brain morphology in young adulthood.

Methods: Magnetic resonance brain images were made prior to, and during, cross-sex hormone treatment to study the influence of anti-androgen + estrogen treatment on brain morphology in eight young adult male-to-female transsexual human subjects and of androgen treatment in six female-to-male transsexuals.

Results: Compared with controls, anti-androgen + estrogen treatment decreased brain volumes of male-to-female subjects towards female proportions, while androgen treatment in female-to-male subjects increased total brain and hypothalamus volumes towards male proportions.

Conclusions: The findings suggest that, throughout life, gonadal hormones remain essential for maintaining aspects of sex-specific differences in the human brain.