Metabolic and functional changes in transgender individuals following cross-sex hormone treatment: Design and methods of the GEnder Dysphoria Treatment in Sweden (GETS) study

Background: Although the divergent male and female differentiation depends on key genes, many biological differences seen in men and women are driven by relative differences in estrogen and testosterone levels. Gender dysphoria denotes the distress that gender incongruence with the assigned sex at birth may cause. Gender-affirming treatment includes medical intervention such as inhibition of endogenous sex hormones and subsequent replacement with cross-sex hormones. The aim of this study is to investigate consequences of an altered sex hormone profile on different tissues and metabolic risk factors. By studying subjects undergoing gender-affirming medical intervention with sex hormones, we have the unique opportunity to distinguish between genetic and hormonal effects.

Methods: The study is a single center observational cohort study conducted in Stockholm, Sweden. The subjects are examined at four time points; before initiation of treatment, after endogenous sex hormone inhibition, and three and eleven months following sex hormone treatment. Examinations include blood samples, skeletal muscle-, adipose- and skin tissue biopsies, arteriography, echocardiography, carotid Doppler examination, whole body MRI, CT of muscle and measurements of muscle strength.

Results: The primary outcome measure is transcriptomic and epigenomic changes in skeletal muscle. Secondary outcome measures include transcriptomic and epigenomic changes associated with metabolism in adipose and skin, muscle strength, fat cell size and ability to release fatty acids from adipose tissue, cardiovascular function, and body composition.

Conclusions: This study will provide novel information on the role of sex hormone treatment in skeletal muscle, adipose and skin, and its relation to cardiovascular and metabolic disease.