Identification of psychometric and biological markers to assess androgen and serotonergic sensitivity in relation to sexual functioning in women.

Several studies have demonstrated that for women suffering from HSDD whose low
initial sensitivity to sexual cues was boosted by sublingual testosterone, the
combination of testosterone and a PDE-5 inhibitor induced higher levels of
vaginal blood flow when exposed to sexual stimuli, coupled with subjective
reports of more intense genital sensations and sexual lust . It was also shown
that neither testosterone nor a PDE-5 inhibitor produced these effects in women
with HSDD when administered separately . In these same studies, subjects who
did show an increased pre-attentional bias for sexual stimuli before
testosterone administration, showed a decrease in pre-attentional bias after
testosterone administration. Since these women showed no increase in vaginal
blood flow or subjective reports of genital sensations in any of the drug
conditions, and because most of them had a history of negative sexual
experiences, it was hypothesized that this group suffered from maladaptive
activity of sexual inhibitory systems. To further investigate this last group
the genotype of the serotonin transporter and 5HT1A receptor is measured. We
hypthesize that women with one variant of the SERT/5HT1a genotype are at
greater risk to develop sexual dysfunction.

Various testosterone concentrations within the normal range more or less
saturate androgen receptors. Thus, it can be argued that within the range of
normal hypothalamic-pituitary-gonadal (HPG) -axis function and eugonadal plasma
testosterone concentration, genetically determined functional difference in
androgen receptor activity in target tissues can be observed and will be of
clinical significance.
The influence of testosterone on sensitivity of the brain might be mediated by
different possibly interrelated variables. A first possible intervening
variable is associated with the androgen receptor. Variations in CAG repeat
length polymorphism ([CAG]n)of the androgen receptor gene causes variation in
the influence of testosteron on androgen sensitivity. We assume that women
with a relative long [CAG]n and low serum free testosterone might have a
relative less functioning androgen system, and consequently a relative
insensitive system for sex. A second possible intervening variable is related
to the differentiation between organizational and activational effects of
testosterone on the brain. 2D:4D digit ratio is suggested to be a retrospective
marker of prenatal testosterone exposure. We assume that women with a relative
long [CAG]n have higher 2D:4D ratios than women with a relative short [CAG]n.

Primary objective:
To evaluate variations of androgenicity and androgen (re) activity in
(apparently) eugonadal females by using CAG repeat length polymorphism ([CAG]n)
of the androgen receptor, free testosterone levels, 2D:4D ratio and attention
for erotic stimuli (Stroop task).

Secondary objectives:
- To validate questionnaires involving subjective rating of sexual satisfaction
and sexual functioning.
- To investigate a possible biological basis for maladaptive sexual inhibitory
systems by genotyping the polymorphisms in the Serotonin Transporter (SERT) and
5HT1a receptor.
- To explore possible correlations between blood serum levels ADT-G, 3α-diol-G,
DHEA and DHEA(s) and [CAG]n/2D:4D ratio.

This is a cross-sectional study with a total of two hundred subjects visiting
the study site once. During this visit subjects perform a Stroop task and fill
out questionnaires partly based on a retrospective sexual event. A hand scan
will be made and at the end of the visit a blood sample will be drawn.

There are no risks associated with participation in this study.