The effects of sex hormone administration on marrow and visceral adiposity

Rationale: Marrow adipose tissue (MAT) is a unique fat depot, different from white and brown fat. The inverse relationship between MAT and bone mass, has led to the paradigm that MAT is a negative regulator of bone mass. MAT increases with ageing and men have more MAT than women below the age of 50 years. After menopause MAT becomes higher in women than in men. Together these data suggest that sex hormones are important regulators of MAT. Another fat depot with a comparable association with sex hormones is visceral adipose tissue (VAT). Men are more susceptible to VAT accumulation than premenopausal women, however VAT also increases in postmenopausal women. Understanding of VAT regulation is important because it is associated with cardiometabolic risks. Finally, epidemiological studies have shown that premenopausal women are relatively protected against cardiovascular disease, whereas after menopause the incidence seems to catch up with that of males. Although much is known about the influence of estradiol on plasmatic coagulation, much less is known about its influence on platelet function, the latter being of far greater importance in arterial CVD.

Objective: To determine the effect of sex hormones on bone marrow fat, visceral fat, and thrombocytes.

Study population: Adults with gender dysphoria, transwomen (before males-to-females) and transmen (before female-to-males), starting gender affirming hormone treatment in the Center of Expertise in the Amsterdam UMC, location VUmc. We will include 24 transmen and 16 transwomen.

We hypothesize that suppression of the gonadal axis will increase bone marrow and visceral fat in biological women and men and subsequent administration of estradiol or testosterone will decrease the amount of bone marrow and visceral fat. We hypothesize that inhibition of conversion of testosterone to estradiol will attenuate the effect of testosterone on marrow and visceral fat.

baseline, week 6, week 8, week 18, week 58

Transwomen will receive a GnRH analogue every 4 weeks from week 0 until week 20 and estradiol from week 6 and cyproterone acetate from week 20 until the end of the study (week 58). Transmen will receive GnRH analogue every 4 weeks from week 0 until week 20, transmen will be randomized to receive either testosterone from week 6 until the end of the study or receive testosterone and an aromatase inhibitor from week 6 until week 18.