Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02518009 |
| Other study ID # |
KI GETS |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 2015 |
| Est. completion date |
May 2022 |
Study information
| Verified date |
June 2022 |
| Source |
Karolinska Institutet |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Gender dysphoria (DSM-5) or transsexualism (ICD10) is a condition in which a person's feeling
of gender identity is not congruent with the physical body. The hormonal treatment includes
inhibition of one's own sex hormone production followed by treatment with testosterone or
estrogen levels that are normal for the opposite sex. Seen as experimental model, this is a
process that provides an opportunity to study the sex hormone dependent influences that
explain differences in morbidity in men and women respectively. The differences that are
especially significant but not well known is 1) metabolic changes in the regulation of
glucose homeostasis and lipid metabolism 2) regulation of vascular function and structural
effects on the heart and arteries 3) regulation of skeletal muscle mass and fat tissue 4)
morphological and functional effects on discrete areas of the brain.
Therefore, the investigators will follow these patients for a year to study how the heart,
blood vessels, brain, and risk factors for cardiovascular disease affected by altered sex
hormone patterns and studying what happens in the muscles and fat in both the short and long
term with respect to particular gene expression and epigenetic changes and link it to
metabolic changes and body composition.
Description:
At the Centre for andrology and sexual medicine at Karolinska University Hospital about 30
genetic males (MtF) and 25 genetic females (FtM) every year start hormone replacement
therapy. This hormonal treatment includes inhibition of one's own sex hormone production
(down regulation of the gonadal axis) followed by treatment with testosterone or estrogen
levels that are normal for the opposite sex. Seen as experimental model, this is a process
that provides an opportunity to study the sex hormone dependent influences that explain
differences in morbidity in men and women respectively. Furthermore, the constitutional
differences distinguish them from those that are dynamically addressable through change in
the hormonal milieu. The differences that are especially significant but not well known is 1)
metabolic changes in the regulation of glucose homeostasis and lipid metabolism 2) regulation
of vascular function and structural effects on the heart and arteries 3) regulation of
skeletal muscle mass and fat tissue 4) morphological and functional effects on discrete areas
of the brain.
It is well known that testosterone has a dose-response effect on body composition in men
while conditions are less well known in women. Thus, it is not known how the adult woman's
body responds to male levels of testosterone, and if the dose response relation is similar or
different than that of men. The clinical impression is that women have less effect of
androgen on muscle mass than men. Furthermore, it is not known whether the qualitative
properties are comparable, i.e. muscle force/unit area. The basic hypothesis is that there
are no constitutional sex differences in androgen response. If there are differences, we are
looking to identify differences in gene expression. Another hypothetical regulatory mechanism
is epigenetic differences which are not dynamically modifiable by androgen exposition.
Difference in cardiovascular morbidity between men and women is well known, but there is
considerable confusion if and how radical changes of sex hormone levels affects the function
of the cardiovascular system both with acute and chronic exposure. Radical change of estrogen
and testosterone levels can also affect the risk for metabolic disorders (lipid, carbohydrate
and protein metabolism) which can cause hazard for both metabolic diseases such as diabetes
and cardiovascular disease in the long term but also be a risk for future muscle weakness and
osteoporosis. Effects on the central nervous system as a result of changes of sex hormone
profile are not well known. However, we have several observations indicating that changes in
sex hormone levels have visual effects (shown by MRI and PET) on distinctive features of the
central nervous system.
Therefore, we will follow these patients for a year to study how the heart, blood vessels,
brain, and risk factors for cardiovascular disease affected by altered sex hormone patterns
and studying what happens in the muscles and fat in both the short and long term with respect
to particular gene expression and epigenetic changes and link it to metabolic changes and
body composition. Forty volunteers with gender dysphoria, 20 MtF and 20 FtM, are studied
before the onset of sex hormone therapy, after a four-week shutdown of endogenous sex
hormones and during one year of sex hormone treatment.
