The effects of sex hormone administration on marrow and visceral adiposity

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 the regulation of VAT is
important since it is associated with cardiometabolic risks.

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

Secondary Objective(s):
* To determine the effect of sex hormones on visceral and liver fat.
* To test whether DXA can be used to calculate the amount of visceral fat in
transgender patients and if so, what algorithm to use.
* To assess the influence of sex steroids on blood platelets, as measured by
different methods;
* To assess the influence of high dose sex steroids on the general
cardiovascular laboratory risk assessment;

This study is a partly randomized open-label intervention study.

MtFs who participate in the SHAMVA and TRANS study will receive a GnRH analogue
every 4 weeks from week -6 until week 12 (last injection at week 8) and
cyproterone acetate from week 12 until the end of the study (week 52) and
estradiol from week 0 until the end of the study (week 52).

MtFs who participate in the TRANS study will receive a GnRH analogue every 4
weeks from week 0 untill week 12 (last injection at week 8) and cyproterone
acetate from week 12 untill the end of the study (week 52) and estradiol from
week 0 until the end of the study (week 52).

FtMs will receive GnRH analogue every 4 weeks from week 0 until week 12, FtMs
will be randomized to receive either testosterone from week 0 until week 52 or
receive testosterone and an aromatase inhibitor from week 0 until week 12.

MtF subjects who participate in the SHAMVA and TRANS study need to visit the
AMC and/or VUmc five times for MRI QCSI in 58 weeks. MtF subjects who
participate in the TRANS study need to visit the VUmc three times in 52 weeks.
The FtMs not receiving an aromatase inhibitor will need to visit the AMC and/or
VUmc four times in 52 weeks, FtMs receiving an aromatase inhibitor will have
three visits in 12 weeks. The appointment at baseline, 12 and 52 weeks can be
made on the same day as the regular appointments at the VUmc. Venous blood
sampling will be performed at all visits and the total amount of blood will not
exceed 300ml. Finally, two whole-body and lateral DXA-scans will be performed,
one at baseline and one at 52 weeks. The visits will take approximately one
hour each visit.

The MRI QCSI procedure is a non-invasive, non-ionizing imaging technique
without contrast administration. The radiation dose of a DXA-scan is
negligible. MtF subjects and half of the FtM subjects receive standard
cross-sex hormone treatment, and are therefore not exposed to additional risks.
FtM subjects who will receive additional anastrozole are exposed to additional
risks. The most common side effects include hot flushes, headache, mood swings,
nausea, rash, joint pain, asthenia and osteoporosis. In a 12 week period,
anastrozole will not lead to osteoporosis.