TransgenderNCT04977765
Cardiometabolic Health in Transgender Males
An observational study of Transgender and Transgenderism, run by Medical College of Wisconsin at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Transgender, Transgenderism
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2021to 1 Aug 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 30 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
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.
Who may be able to join
- INCLUSION CRITERIA FOR TRANSGENDER BOYS AND TRANSGENDER MEN
- Sex assigned female at birth and a male gender identity (i.e., transgender male)
- Aged 12-30 years
- Have a care provider in the Children's Wisconsin Gender Health Clinic or Froedtert Hospital Inclusion Clinic who has determined the individual meets clinical criteria to start testosterone therapy and plans to initiate this therapy
- 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
Show all 18Show fewer
- 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
- INCLUSION CRITERIA FOR OPTIONAL NITROGLYCERIN ENDOTHELIUM-INDEPENDENT VASCULAR FUNCTION STUDY
- 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
Who cannot join
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: Defining the Cardiometabolic Profile of Transgender Boys and Men on Testosterone Therapy
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.
Read the detailed description
Gender-affirming testosterone (hormonal) treatment (GAHT) is the cornerstone of masculinizing therapy for transgender men, resulting in circulating testosterone (T) levels equivalent to cismen and estrogen (E2) suppression. 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. The vaso-protective benefits of E2 are well-described; higher circulating E2 begins in female puberty, stimulating a long-term increase in the vascular expression of the E2 receptor's alpha isoform (ERα). ERα activation directly stimulates nitric oxide (NO) production from endothelium-derived NO synthase and is critical to maintaining a healthy vascular endothelium. Pre-menopausal women have an increased capacity to produce endothelial NO due to higher E2 levels and vascular ERα expression, resulting in lower cardiovascular disease risk vs age-matched cismen. These data suggest a novel paradigm for the impact of GAHT on vascular health in transmen that differs depending on when GAHT is initiated relative to puberty. The investigators hypothesize that, in transmen who have completed E2-driven puberty, GAHT will induce a regression of vascular endothelial function towards that of cismen by suppressing circulating E2 and ERα expression and that similar regression will not be seen in transboys initiating GAHT prior to pubertal progression. The investigators propose, to our knowledge, a first-of-its-kind longitudinal study of the cardiometabolic impact of 1-year of GAHT in 40 transboys and transmen as compared to cisgender controls with endogenous sex hormones. The impact of GAHT initiation and continuation in transboys/men on in vivo and ex vivo vascular endothelial function, estrogen-stimulated endothelial vasorelaxation, and expression of vascular ERα expression will be determined by measuring changes in conduit vessel endothelium-dependent vasodilation and vascular E2 receptor expression and responsiveness in transboys on puberty blockers and in transmen. The investigators will also determine whether GAHT suppresses the human arteriolar vascular expression of ERα receptors and reduces E2-stimulated endothelial vasorelaxation in transboys/men relative to ciswomen. Secondarily, The investigators will characterize the metabolic, body composition and inflammatory impact of GAHT. This study will provide a novel mechanistic framework for the cardiometabolic impact of GAHT and make available critical information for care providers and patients on how GAHT may affect their cardiovascular risk.
- Conditions
- Transgender, Transgenderism
- Medical subject headings
- Transsexualism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
Investigators will examine the effect of gender-affirming testosterone therapy on body composition as quantified by body mass index (BMI).
Measured: 1 year from baseline study visit
Change in body composition after one year of gender-affirming testosterone therapy as measured by DXA scans.
Investigators will examine the effect of gender-affirming testosterone therapy on body composition as quantified by total body dual-energy X-ray absorptiometry (DXA) scan which provides information about the amount and distribution of fat and muscle in the body.
Measured: 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.
Investigators will examine the effect of gender-affirming testosterone therapy on body composition as quantified by the ratio of waist-to-hip circumference which provides information about the amount and distribution of fat and muscle in the body.
Measured: 1 year from baseline study visit
Change in lipid profile after one year of gender-affirming testosterone therapy
Investigators will measure the effect of gender-affirming testosterone therapy on the various components of a fasting lipid profile (triglyceride level, HDL, LDL, and total cholesterol).
Measured: 1 year from baseline study visit
Change in systemic inflammation after one year of gender-affirming testosterone therapy
Investigators will examine the effect of gender-affirming testosterone therapy on circulating levels of inflammatory cytokines as measured by plasma analysis.
Measured: 1 year from baseline study visit
Change in glucose metabolism after one year of gender-affirming testosterone therapy as measured by fasting insulin level in the blood.
Investigators will examine the effect of gender-affirming testosterone therapy on fasting insulin.
Measured: 1 year from baseline study visit
Change in glucose metabolism after one year of gender-affirming testosterone therapy as measured by fasting blood glucose level.
Investigators will examine the effect of gender-affirming testosterone therapy on fasting glucose.
Measured: 1 year from baseline study visit
Change in glucose metabolism after one year of gender-affirming testosterone therapy as measured by HbA1c
Investigators will examine the effect of gender-affirming testosterone therapy on HbA1c levels.
Measured: 1 year from baseline study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2021
- Study start30 Sep 2021
- Primary completion31 Mar 2027 (estimated)
- Study completion1 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TransgenderStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Collaborators
- Advancing a Healthier Wisconsin Endowment
- Responsible party
- Principal investigator, Susanne Cabrera, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04977765
- Sponsor's protocol ID
- PRO00040486
- Status last verified
- Sep 2025
- First submitted
- 25 May 2021
- Last updated
- 3 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defining the Cardiometabolic Profile of Transgender Boys and Men on Testosterone Therapy
- ClinicalTrials.gov ID
- NCT04977765
- Acronym / sponsor ID
- PRO00040486
- Conditions
- Transgender, Transgenderism
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Collaborators
- Advancing a Healthier Wisconsin Endowment
- Study start
- 30 Sep 2021 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 1 Aug 2027 (estimated)
- First posted
- 27 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Gender-affirming testosterone (hormonal) treatment (GAHT) is the cornerstone of masculinizing therapy for transgender men, resulting in circulating testosterone (T) levels equivalent to cismen and estrogen (E2) suppression. 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. The vaso-protective benefits of E2 are well-described; higher circulating E2 begins in female puberty, stimulating a long-term increase in the vascular expression of the E2 receptor's alpha isoform (ERα). ERα activation directly stimulates nitric oxide (NO) production from endothelium-derived NO synthase and is critical to maintaining a healthy vascular endothelium. Pre-menopausal women have an increased capacity to produce endothelial NO due to higher E2 levels and vascular ERα expression, resulting in lower cardiovascular disease risk vs age-matched cismen. These data suggest a novel paradigm for the impact of GAHT on vascular health in transmen that differs depending on when GAHT is initiated relative to puberty. The investigators hypothesize that, in transmen who have completed E2-driven puberty, GAHT will induce a regression of vascular endothelial function towards that of cismen by suppressing circulating E2 and ERα expression and that similar regression will not be seen in transboys initiating GAHT prior to pubertal progression. The investigators propose, to our knowledge, a first-of-its-kind longitudinal study of the cardiometabolic impact of 1-year of GAHT in 40 transboys and transmen as compared to cisgender controls with endogenous sex hormones. The impact of GAHT initiation and continuation in transboys/men on in vivo and ex vivo vascular endothelial function, estrogen-stimulated endothelial vasorelaxation, and expression of vascular ERα expression will be determined by measuring changes in conduit vessel endothelium-dependent vasodilation and vascular E2 receptor expression and responsiveness in transboys on puberty blockers and in transmen. The investigators will also determine whether GAHT suppresses the human arteriolar vascular expression of ERα receptors and reduces E2-stimulated endothelial vasorelaxation in transboys/men relative to ciswomen. Secondarily, The investigators will characterize the metabolic, body composition and inflammatory impact of GAHT. This study will provide a novel mechanistic framework for the cardiometabolic impact of GAHT and make available critical information for care providers and patients on how GAHT may affect their cardiovascular risk.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 12 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (18 listed)
- INCLUSION CRITERIA FOR TRANSGENDER BOYS AND TRANSGENDER MEN
- 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)
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in vascular endothelial function after one year of gender-affirming testosterone therapy as measured by brachial artery ultrasound flow-mediated dilation
Time frame: 1 year from baseline study visit
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.
Change in vascular endothelial function after one year of gender-affirming testosterone therapy as measured by by blood pressure.
Time frame: 1 year from baseline study visit
Investigators will examine the effects of gender-affirming testosterone therapy on in vivo endothelial function by blood pressure.
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
Time frame: 1 year from baseline study visit
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.
8 secondary outcomes
Change in body composition after one year of gender-affirming testosterone therapy as measured by BMI
Time frame: 1 year from baseline study visit
Change in body composition after one year of gender-affirming testosterone therapy as measured by DXA scans.
Time frame: 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.
Time frame: 1 year from baseline study visit
Change in lipid profile after one year of gender-affirming testosterone therapy
Time frame: 1 year from baseline study visit
Change in systemic inflammation after one year of gender-affirming testosterone therapy
Time frame: 1 year from baseline study visit
Change in glucose metabolism after one year of gender-affirming testosterone therapy as measured by fasting insulin level in the blood.
Time frame: 1 year from baseline study visit
Change in glucose metabolism after one year of gender-affirming testosterone therapy as measured by fasting blood glucose level.
Time frame: 1 year from baseline study visit
Change in glucose metabolism after one year of gender-affirming testosterone therapy as measured by HbA1c
Time frame: 1 year from baseline study visit
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Transgender and Transgenderism, run by Medical College of Wisconsin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in vascular endothelial function after one year of gender-affirming testosterone therapy as measured by brachial artery ultrasound flow-mediated dilation (time frame: 1 year from baseline study visit). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2025.