Abnormal sex hormone exposure of the brain; possible neuroendocrine implications for cognition in adult transsexuals and women with polycystic ovarian syndrome as clinical models

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.

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.

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 subjects will not be exposed by other risks then the regular health care.
Their treating physician will start the hormonal treatment needed. This project
will add two time points to evaluate brain functions and activity with a
neuropsychological assessment and an MRI. Magnetic resonance has no known risks
so far.