The effect of sex steroids on body fat distribution in transgender persons
Authors:   , Tebbens Marieke 
Published: January 2023

Main findings
In chapter 2 we showed that estrone concentrations are not associated with
change in body fat or breast development or in trans women receiving either
oral or transdermal estradiol. Moreover, no difference in clinical outcomes was
observed between oral and transdermal administration of estradiol, despite the
fact that oral estradiol was clearly associated with much higher estrone levels
compared with transdermal estradiol. This suggests that only estradiol and not
estrone exerts effect on body fat distribution. In chapter 3 we demonstrated that
in trans women, suppressing testosterone and increasing estradiol results in an
increase in subcutaneous fat and a decrease in VAT/SAT ratio and liver fat. In trans
men, we showed that the increase in testosterone concentrations in combination
with lower estradiol concentrations results in an increase in visceral fat, VAT/
SAT ratio and liver fat. In chapter 4 we demonstrated that DXA is a valid method
to estimate visceral fat in trans women and trans men at baseline and after 12
months of hormone treatment. However, the change in visceral fat after 12 months
of hormone treatment is underestimated by DXA, compared to MRI. In chapter 5,
we demonstrated a rapid increase in bone marrow fat fraction after testosterone
and estradiol suppression in trans women, followed by a rapid decrease after
start of estradiol treatment. In trans men, on the other hand, we observed a rapid
increase in bone marrow fat fraction after testosterone treatment and suppression
of estradiol by triptorelin and anastrozole. In trans men without anastrozole, the
bone marrow fat fraction increased only after 12 weeks and decreased to baseline
after 52 weeks. Together these results suggest that estradiol and not testosterone
is the major sex steroid regulating the bone marrow fat fraction in both women
and men. In chapter 6 we demonstrated that this effect of estradiol on bone
marrow fat is not caused by a change in number of adipocytes, lipid droplet area
or adipokine expression. The effect of estradiol on bone marrow fat might be
exerted earlier in the differentiation of adipocytes or via other cell types. Finally,
in chapter 7 we observed that gender affirming hormone treatment induces an
increase in cheek tissue in trans women and a decrease in cheek tissue in trans
men. The cheeks consist mostly of subcutaneous adipose tissue and therefore
we can conclude that sex steroids exert the same effect on subcutaneous tissue
in the abdomen and the face.

Conclusions
In conclusion, this thesis has shown that in trans women, suppressing testosterone
and increasing estradiol results in an increase in subcutaneous fat, both abdominal
and facial; and a decrease in VAT/SAT ratio, liver fat and bone marrow fat. In trans
men, an increase in testosterone concentrations in combination with a decrease
in estradiol concentrations results in an increase in visceral fat, VAT/SAT ratio,
liver fat and bone marrow fat, and no significant changes in subcutaneous fat.
These results suggest that estradiol is the major sex steroid regulating body fat
distribution in women and men. However, estradiol does not seem to directly
affect mature adipocytes with respect to adipocyte number, lipid droplet area
or adipokine expression. The effect of testosterone on body fat distribution acts
mainly through the aromatization of testosterone into estradiol.