Research of possible effect of sex steriods to the brain.

Clinical observations demonstrate convincingly that in men and women sex steroids exert effects on the brain.
Studying these sex steroid related functions is important to better understand brain development and potential
benefits of interventions and medication. However, in humans these functions have as yet hardly been studied
under experimental conditions.

Under normal circumstances in the human both in males and in females a combination of androgen and estrogen
exposure is present. This implies that suggested specific effects of male and female sex steroids is not confined
to the female sex hormone estrogen in females and the male sex hormone testosterone in males. With regard
to functioning of the brain, there is evidence that estrogens exert effects in males and that androgens have
effects in females. However, hardly any human studies exist that clearly distinguish estrogen only and androgen
only effects on brain function either in the male or the female.

This confusion is because in males a substantial quantity of androgens are converted into estrogens by the
enzyme aromatase and in females the ovaries but also the adrenals produce androgens.

With our research paradigms we can contribute to this field of sexsteroid dependant brain function in a unique
way.



Objective of the study:

The overall aim of the present work is to evaluate the individual role of androgens and estrogens on brain
function in the human with a focus on cognition. Both clinical models give us the opportunity to evaluate
cognitive functions and brain activity in unique conditions. By testing cognitive functions and brain activity on
different time points with different sex steroid levels, we hope to understand more about the effects of sex
steroids on cognitive functioning. Furthermore, we want to study several aspects of brain function when a clear
imbalance between these hormones in particular in women is present due to overexposure to androgens.



Study design:

Model 1: Transsexuals:

After diagnosis, the first phase of sex reassignment is a hormonal therapy to suppress endogenous secondary
sex characteristics and to stimulate upcoming of secondary characteristics of the desired other sex. During
suppression and after admiration of cross-sex steroids the subjects will be evaluated with a neuropsychological
assessment and functional MRI (fMRI).

Model 2: Women with PCOS:

Also the women with PCOS will be examined twice. Before and after three months of anti androgen treatment
the subjects will be evaluated with a neuropsychological assessment and an fMRI. The healthy control group will
be examined twice without any intervention.

The general objectives of this study is to test whether estrogens and androgens in both males and females affect cognitive functions and brain activity.

N/A

Model 1: Transsexuals:

After diagnosis, the first phase of sex reassignment is a hormonal therapy to suppress endogenous secondary
sex characteristics and to stimulate upcoming of secondary characteristics of the desired other sex. During
suppression and after admiration of cross-sex steroids the subjects will be evaluated with a neuropsychological
assessment and functional MRI (fMRI).



Model 2: Women with PCOS:

Also the women with PCOS will be examined twice. Before and after three months of anti androgen treatment
the subjects will be evaluated with a neuropsychological assessment and an fMRI. The healthy control group will
be examined twice without any intervention.