Cardiometabolic Health in Transgender Males

NCT04977765 | Active Not Recruiting

• 1 other identifier: PRO00040486
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Transgender individuals are those with a gender identity opposite the sex they were assigned at birth. Approximately 1% of the population is transgender, equating to \~60,000 transgender Wisconsinites. A transgender boy or man is someone with a 46,XX karyotype and typical female genitalia but a male gender identity and desire for more male-typical gender expression. Gender-affirming testosterone (hormonal) treatment (GAHT) is the cornerstone of masculinizing therapy for transgender men and boys, resulting in estrogen (E2) suppression and circulating testosterone (T) levels equivalent to cisgender males. Historically, GAHT was initiated after an E2-driven puberty, but the last decade has seen an explosion of referrals for GAHT in transboys, many of whom are exposed to only low E2 levels before puberty is halted with blocker therapy. Knowledge of risks incurred by GAHT rely on low-quality studies, precluding conclusive assessment of GAHT's long-term impact on cardiometabolic outcomes. Data on transboys receiving GAHT before completion of E2-driven puberty are sparser and no studies have addressed mechanisms by which GAHT may affect vascular physiology. The investigators aim to determine the cardiometabolic impact of GAHT in transboys/men and to determine if any differences identified are mechanistically dependent on the timing of GAHT relative to puberty.

Conditions

Transgender; Transgenderism

Outcome Measures

Primary Outcomes (3)

• Change in vascular endothelial function after one year of gender-affirming testosterone therapy as measured by brachial artery ultrasound flow-mediated dilation

  Investigators will examine the effects of gender-affirming testosterone therapy on in vivo endothelial function by brachial artery ultrasound flow-mediated dilation across study visits.

  1 year from baseline study visit

• Change in vascular endothelial function after one year of gender-affirming testosterone therapy as measured by by blood pressure.

  Investigators will examine the effects of gender-affirming testosterone therapy on in vivo endothelial function by blood pressure.

  1 year from baseline study visit

• Change in vascular endothelial function after one year of gender-affirming testosterone therapy as measured by circulating markers of endothelial activation as measured by plasma analysis

  Investigators will examine the effects of gender-affirming testosterone therapy on in vivo endothelial function by circulating markers of endothelial activation as measured by plasma analysis.

  1 year from baseline study visit

Secondary Outcomes (8)

• Change in body composition after one year of gender-affirming testosterone therapy as measured by BMI

  1 year from baseline study visit

• Change in body composition after one year of gender-affirming testosterone therapy as measured by DXA scans.

  1 year from baseline study visit

• Change in body composition after one year of gender-affirming testosterone therapy as measured by the ratio of waist-to-hip circumference.

  1 year from baseline study visit

• Change in lipid profile after one year of gender-affirming testosterone therapy

  1 year from baseline study visit

• Change in systemic inflammation after one year of gender-affirming testosterone therapy

  1 year from baseline study visit

Study Arms (2)

Transgender Males

Individuals assigned female gender at birth but considering gender-affirming testosterone therapy. May self-identify as transgender or nonbinary etc.

Cisgender Controls

Individuals assigned male or female at birth. May identify as cisgender or nonbinary etc. These individuals should not be undergoing or considering any form of hormone therapy.

Eligibility Criteria

• Age: 12 Years - 30 Years
• Gender Eligibility Details: Transgender individuals must have been assigned female at birth but identify as transgender/non-binary and interested in gender-affirming testosterone therapy.
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

EXCLUSION CRITERIA FOR TRANSGENDER AND CISGENDER INDIVIDUALS 1. Any disease affecting glucose, sex steroid, or fat metabolism such as diabetes, polycystic ovary syndrome, or clinical suspicion of insulin resistance) 2. Any medication use that may affect glucose, sex steroid, or fat metabolism such as metformin or glucocorticoids 3. Known cardiovascular disease such as hypertension or atherosclerosis 4. Raynaud's phenomenon or other vascular disease 5. BMI \> 40 kg/m2 for those aged ≥ 18 years or \> 95% percentile for age- and sex-assigned at birth in those aged \< 18 years 6. Pregnancy or lactation 7. Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results.

You may qualify if:

• Sex assigned female at birth and a male gender identity (i.e., transgender male)
• Aged 12-30 years
• Naïve to testosterone or other masculinizing medical therapy
• Cisgender girls/women and transgender boys/men of child-bearing potential (defined as having achieved menarche (first menses), excluding those who have had a hysterectomy or are on GnRH agonist therapy (puberty blockers)) must be willing to use effective birth control (which may include abstinence)) from screening visit until final study visit
• Willing and able to give informed consent or have parent or legal guardian provide informed consent if the subject is \< 18 years of age
• Gender identity concordant with sex assigned at birth (i.e., cisgender)
• Aged 12-30 years
• Not related to a transgender participant enrolled in the study
• Naïve to any sex hormone or pubertal blocker therapy or, specific to cisgender girls/women only, must be ≥ 1 year from use of oral contraceptive or other contraceptive technique (intrauterine device, medroxyprogesterone injections)
• Willing and able to give informed consent or have parent or legal guardian provide informed consent if the subject is \< 18 years of age
• Aged ≥ 18 years
• No history of migraine headaches
• Systolic blood pressure ≥ 110 mm Hg
• No prior past adverse reaction to nitroglycerin
• Has not used a PDE5 inhibitor (i.e., sildenafil, tadalafil, vardenafil) in the past 7 days

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• Advancing a Healthier Wisconsin: collaborator

Study Sites (1)

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Plasma from participants will be stored and analyzed in labs on the Medical College of Wisconsin campus. All samples will be stored and labeled with coded study identification numbers. Only de-identified samples and data will be shared. The use of these samples will be subject to Medical College of Wisconsin IRB policies and procedures. All specimens and records will be held for a minimum of 10 years from the date of the last entry in the record of the last subject enrolled in the study

MeSH Terms

Conditions

Transsexualism

Condition Hierarchy (Ancestors)

Sexuality; Sexual Behavior; Behavior

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: July 27, 2021
• Study Start: September 30, 2021
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: October 3, 2025

Record last verified: 2025-09

Locations

US (1)