Inclusion Criteria:

* age 18-40yrs
* BMI 18.5-38 kg/m2
* Fasting glucose \< 100 mg/dL
* No gender affirming gonadal surgery

We seek to enroll 6 patients in each group who have been on GAHT for more than 10 months with minimal interruptions in treatment.

Exclusion Criteria:

* Pregnancy
* Use of hormonal forms of birth control within the previous 3 months
* Use of glucocorticoids, estradiol, testosterone, progestin, antiandrogens, or antiestrogens besides those received as part of a supervised hormone therapy.
* Gender-affirming gonadal surgery
* Prior use of gonadotropin releasing hormone (GnRH) analogues during puberty
* Coronary artery disease or heart failure.
* A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples:

* Inpatient psychiatric treatment in the past 6 months
* Presence of a known adrenal disorder
* Abnormal liver function test results (Transaminase \>2 times the upper limit of normal); testing required for subjects taking medications known to affect liver function or with diseases known to affect liver function
* Abnormal renal function test results (calculated GFR \<45 mL/min/1.73m2); testing required for subjects with diabetes duration of greater than 5 years post onset of puberty
* Active gastroparesis
* If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, lack of stability on the medication for the past 2 months prior to enrollment in the study
* Uncontrolled thyroid disease (TSH undetectable or \>10 mlU/L); testing required within three months prior to admission for subjects with a goiter, positive antibodies, or who are on thyroid hormone replacement, and within one year otherwise
* Abuse of alcohol or recreational drugs
* Infectious process not anticipated to resolve prior to study procedures (e.g. meningitis, pneumonia, osteomyelitis).
* Uncontrolled arterial hypertension (Resting diastolic blood pressure \>90 mmHg and/or systolic blood pressure \>160 mmHg) at the time of screening.
* A recent injury to body or limb, muscular disorder, use of any medication, any carcinogenic disease, or other significant medical disorder if that injury, medication, or disease in the judgment of the investigator will affect the completion of the protocol (exercise testing or muscle biopsy).
* Medications that may impact study end points such as mitochondrial biology e.g. beta blockers
* Anti-hyperglycemic drugs including metformin
* Any other medication that the investigator believes is a contraindication to the subject's participation.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 06/12/2024. Questions regarding updates should be directed to the study team contact.