Long-term Observational Study to Investigate the Effect of Gender-affirming Hormone Therapy (GAHT) on Heart Function Parameters, Heart, Liver and Pancreatic Fat Content as Well as the Insulin System and the Psychological Impact of GAHT

Background Gender affirming hormone therapy is a treatment used by many transgender individuals aiming for physical transition. During this treatment, the endogenous production of sex hormones is reduced, and they are supplemented by the sex hormones of the gender with which the person identifies. These profound changes in the hormonal profiles of transgender people have been shown to be associated with changes in cardiovascular parameters, the insulin system, body composition, and the psychological state.

In the case of transgender men under GAHT, the treatment seems to be associated with the development of a less favorable, more atherogenic lipid profile, with an increase in triglycerides and low-density lipoprotein (LDL) levels, while also experiencing a decrease in high-density lipoprotein (HDL). On the other hand, transgender women under GAHT seem to develop higher levels of triglycerides, with little to no changes in LDL and HLD levels. Additionally, GAHT seems to have an effect on body composition - in transgender men, GAHT is associated with a decrease in fat mass, on the other hand, in transgender women GAHT is connected to an increase in total body fat. These changes do not seem to be associated with a significant change in the visceral fat mass in either group (Klaver et al., 2022).

Despite the documented effects of GAHT on cardiovascular risk factors, it is still not entirely clear whether these effects are significant enough to cause significant changes in cardiovascular morbidity and mortality. However, the prior findings suggest that transgender women have a higher risk of suffering an ischemic stroke or a myocardial infarction compared to cisgender women, while there is no consistent evidence documenting an increase of cerebrovascular and cardiovascular disease transgender men compared to cisgender men.

The research into changes in glucose homeostasis has not delivered conclusive long-term findings so far. Nevertheless, there is a documented tendency towards a slight worsening of insulin sensitivity in transgender women, while the effects of GAHT on insulin resistance in transgender men are associated with either no change or a small improvement.

Gender affirming hormone treatment also seems to have an impact on the psychological and cognitive state of the patients, for example, it has been brought into connection with an alleviation of depressive symptoms. Furthermore, there are documented morphological and functional changes in the brains of people taking GAHT. These changes might be accompanied by changes in neuropsychological processes, including, for example, emotional regulation. Additionally, there is a lack of data on the possible changes in executive function in transgender people, especially in regard to longitudinal changes under GAHT.