GEnder Dysphoria Treatment in Sweden
Condition: Transsexualism
Study type: Observational

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.
    

Detailed 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.
    

Intervention name(s): Genetic men treated with estrogen; Genetic women treated with androgen
Intervention type(s): Other; Other
Intervention description(s): Observational during estrogen treatment; Observational during androgen treatment
Intervention MeSH terms: Estrogens; Androgens
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Subjects that are under investigation for gender dysphoria that have been accepted but not
        yet started their treatment with contrary sex hormones are asked if they want to
        participate.
      
Biospecimen description: 
      Tissue samples from blood, skin, muscle and fat