Inclusion Criteria:
- Informed consent provided by the participant
- Ages 18-50 years
- English speaking
- GM persons who have been deemed to be an appropriate medical candidate to take gender-affirming hormone therapy for gender incongruence -OR- GM persons who are not taking gender-affirming hormone therapy
Aim 2 (QST and MRI) Additional Inclusion Criteria:
- GM persons who have been deemed to be an appropriate medical candidate to take gender- affirming hormone therapy for gender incongruence
- Stable doses of analgesic medications for at least 30 days prior to screening
- Right handed
- Normal visual acuity or correctable to at least 20/40 for reading instructions in the MRI
- Willingness to refrain from pain medications such as NSAIDs, acetaminophen, and opioid medications for 12 hours prior to neuroimaging and QST
- Willingness to refrain from alcohol and nicotine on day of QST and neuroimaging
- Willingness to refrain from physical activity or exercise that would cause muscle and/or joint soreness for 48 hours prior to testing (routine exercise or activity that does not lead to soreness is acceptable)
- Investigators will attempt to recruit individuals with no chronic daily use of adjunctive pain medications, including tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids as these drugs can influence neuroimaging and QST findings, or have individuals be weaned off of these meds at least two weeks prior to being studied. In previous smaller imaging studies investigators could accomplish this, but this may not be possible in this large of a study. If the study team does need to allow individuals into these cohorts while on such medications because of pragmatic issues, this information will be recorded and patients will be asked to remain on a stable dose for at least two weeks prior to MRI and QST assessments.
- Able to lie still on their back for 1.5 hours for MRI scans
Exclusion Criteria:
- Inability to provide informed consent
- Age less than 18 years or greater than 50 years
- Severe physical impairment (e.g., blindness, deafness, paraplegia)
- Co-morbid medical conditions that may significantly impair physical functional status (e.g., history of non-skin malignancy, or autoimmune disorder)
- Pregnant or nursing
- Liver failure
- Self-reported liver cirrhosis
- Self-reported hepatitis
- Severe Cardiovascular disease (examples: history of myocardial infarction, unstable angina, severe coronary artery disease, congestive heart failure, or severe valvular abnormalities) that are self-reported by patient or by medical record
- Prisoner
- Current litigation for chronic pain
- Current disability proceedings
- Active psychotic or suicidal symptoms
- Current drug or alcohol use disorder
- History of gonadectomy surgery
Aim 2 (QST and MRI) Additional Inclusion Criteria:
- Contraindications to MRI (e.g., metal implants, pacemaker, etc.)
- Severe claustrophobia precluding MRI and evoked pain testing during scanning
- BMI > 40 or unable to lie comfortably in MRI
- Current, recent (within the last 6 months), or habitual use of artificial nails or nail enhancements. (Artificial nails can influence pressure pain sensitivity at the thumbnail)
- Peripheral neuropathy
- Diagnosed epilepsy or seizure history