Pubertal Blockade and Hormone Therapy in Transgender Youth

There will be a total of 6 study visits: baseline A, baseline B, 1 month after starting
testosterone (visit A and B) and 12 months after starting testosterone (visit A and B). No
medications will be administered as a part of this study.

Visit A procedures: Physical Examination, Laboratory, and Oral Glucose Tolerance Test (OGTT)
visit.

This will be conducted at Childrens Hospital Colorado (CHCO) Clinical & Translational
Research Centers (CTRC) facilities. Physical examination will include vital signs,
anthropometric measurements, and breast/pubic hair staging as applicable (some subjects may
have already undergone mastectomy/chest masculinizing surgery) by the PI. Subjects will fast
for 8 hours prior to blood draw. Fasting blood work will be obtained, followed by an oral
glucose load (75g glucola). Blood glucose and insulin concentrations will be drawn at
baseline and 30, 60, 90 and 120 minutes after glucola administration. Serum will be obtained
at baseline and 2 hours post-OGTT and used for bile acid and lipid metabolomic profile. The
following questionnaires will be administered: REDCap Health Questionnaire, PedsQLTM 4.0
generic core questionnaire, PROMIS Pediatric Anxiety Short Form, PROMIS Pediatric Depressive
Symptoms Short Form, Insomnia Severity Index, Morningness and Eveningness Scale. Participants
will be mailed or emailed the 3-day dietary log prior to the visit and return it at this
visit. They will be given a stool microbiome collection kit and urine collection kit to
return at visit B. The medical chart will be reviewed for relevant health information and
medications.

Part B: Vascular Imaging, MR-based imaging and spectroscopy, Exercise Capacity and
Dual-energy X-ray (DXA) visit.

This will be conducted at the University of Colorado Denver Energy Balance Core and UCD Brain
Imaging Center. The participant will be fasting for a minimum of 4 hours prior to the
beginning of the study visit. The investigators will perform the tests in the following
order:

1. Participants will return stool microbiome and urine collection kit.

2. Vascular imaging: carotid artery stiffness and intimal medial thickness and brachial
artery flow-mediated dilation

3. Magnetic Resonance (MR) based imaging and spectroscopy

4. Oxygen consumption (VO2) peak exercise test on a stationary bicycle.

5. Total body dual energy x-ray absorptiometry (DXA)

6. Participants will be provided with an accelerometer and actigraphy watch to wear for a
period of 7 days to measure level of habitual physical activity and sleep, respectively.
They will also be provided a handout with instructions and a sleep and activity diary to
be filled out each day during the 7 days of wear.

Inclusion Criteria:

- Identify as female-to-male

- Age 13-16 years at the time of enrollment

- If on a gonadotropin-releasing hormone analogue, > 6 months exposure

- Plan to start testosterone clinically in < 6 months.

Exclusion Criteria:

- Cognitive, psychiatric, or physical impairment resulting in inability to tolerate the
study procedures

- Diabetes

- Antipsychotic medication

- Hypertension (resting BP ≥ 140/90 mm/Hg)

- Weight > 400 lbs (DXA and MRI limit)

- On estrogen and/or progesterone medications