Hormone Therapy for Transgender Individuals

Overseen By Emina Case

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: The University of Texas Health Science Center at San Antonio

Must be taking: Estrogen, Testosterone

Disqualifiers: Diabetes, Cardiovascular event, Anemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The study will test: 1. whether estrogen treatment in transwomen is associated with improved insulin sensitivity and beta cell function 2. whether testosterone treatment in transmen is associated with worsening insulin sensitivity and beta cell function 3. whether estrogen therapy leads to enhanced immune response in older transwormen

Will I have to stop taking my current medications?

The trial requires that participants have been on stable hormone treatment (estrogen or testosterone) for at least 6 months, so you will not need to stop taking these medications if you meet this criterion.

What data supports the effectiveness of the treatment Gender Affirming Hormone Therapy (GAHT) for transgender individuals?

Research shows that GAHT significantly improves mental health outcomes for transgender individuals, including reducing depression, anxiety, and gender dysphoria (distress due to a mismatch between gender identity and sex assigned at birth). Both feminizing and masculinizing hormone regimens are considered safe when following established protocols. ^{1 2 3 4 5}

Is hormone therapy for transgender individuals generally safe?

Gender affirming hormone therapy (GAHT) is generally safe when used within established protocols and can improve mental health outcomes. However, there are some health risks associated with it, such as cardiovascular disease and bone health issues, so it's important to follow guidelines and monitor health regularly. ^{1 2 3 6 7}

How is Gender Affirming Hormone Therapy (GAHT) unique compared to other treatments for transgender individuals?

Gender Affirming Hormone Therapy (GAHT) is unique because it specifically involves the use of hormones like estrogen and testosterone-lowering medications to align an individual's physical characteristics with their gender identity, which significantly improves mental health outcomes such as reducing depression and anxiety. Unlike other treatments, GAHT is tailored to either feminize or masculinize the body, depending on the individual's needs, and is considered a medically necessary step in gender transition. ^{1 2 3 8 9}

Research Team

Devjit Tripathy, MD

Principal Investigator

University of Texas Health San Antonio

Eligibility Criteria

This trial is for transgender individuals who have been on stable hormone therapy (estrogen or testosterone) for at least 6 months and do not have diabetes. Healthy male and female volunteers can also participate, provided they are not currently treated with hormones.

Inclusion Criteria

I have been on a stable hormone treatment for at least 6 months.

I am a healthy individual.

I am a transgender woman.

Exclusion Criteria

I am not currently taking estrogen or testosterone.

I am a transgender person with less than 6 months on stable hormone therapy.

I have anemia with low hemoglobin and kidney function.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Gender Affirming Hormone Therapy (GAHT) and undergo various tests including OGTT and DXA scan

6 months

Multiple visits for OGTT and DXA scan

Follow-up

Participants are monitored for changes in insulin sensitivity and beta cell function after treatment

4 weeks

Treatment Details

Interventions

• Gender Affirming Hormone Therapy

Trial Overview The study examines the effects of estrogen in transwomen on insulin sensitivity and immune response, as well as the impact of testosterone in transmen on glucose metabolism. It involves a Botnia Clamp procedure and temporary withdrawal from Gender Affirming Hormone Therapy.

Participant Groups

Group I: Healthy Volunteer Male Active Control 1 Intervention

Healthy male currently on no testosterone treatment

Group II: Healthy Volunteer Female Active Control 1 Intervention

Healthy female currently on no estrogen treatment

Group III: MTF group Active Control 2 Interventions

MTF transgender currently on estrogen treatment

Group IV: FTM group Active Control 2 Interventions

FTM transgender group currently on testosterone treatment

Gender Affirming Hormone Therapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Gender Affirming Hormone Therapy for:

• Gender Dysphoria
• Transgender Health Care

Approved in United States as Gender Affirming Hormone Therapy for:

• Gender Dysphoria
• Transgender Health Care

Approved in Canada as Gender Affirming Hormone Therapy for:

• Gender Dysphoria
• Transgender Health Care

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

Foundation for advancing Veterans Health Research (FAVHR)

Collaborator

Trials

1

Recruited

60+

Foundation for Advancing Veterans' Health Research

Collaborator

Trials

3

Recruited

330+

Foundation for advancing Veterans Health Research (FAVHR)

Collaborator

Trials

1

Recruited

60+

Findings from Research

From 2000 to 2018, the use of gender affirming hormonal treatment (GAHT) among transgender individuals in Denmark significantly increased, with rates for transgender women rising from 4.0 to 20.6 events per 100 person-years and for transgender men from 4.2 to 18.8 events per 100 person-years.

The study found a low discontinuation rate of GAHT at 0.06 per person-year, indicating high adherence to treatment among transgender individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gender affirming hormonal treatment in Danish transgender persons: A nationwide register-based study. Glintborg, D., Rubin, KH., Kristensen, SB., et al.[2022]

Gender-affirming hormone therapy (GAHT) is crucial for improving the quality of life for gender-incongruent individuals, highlighting its importance in their medical management.

This document provides essential protocols for clinicians in India regarding GAHT, including counseling, baseline evaluations, therapy choices, and monitoring, addressing the lack of large cohort studies on GAHT outcomes and adverse events in the region.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine Therapy of Adult Gender-Incongruent Individuals Seeking Gender Reaffirmation. Majumder, A.[2022]

Gender affirming hormone therapy (GAHT) is a crucial and medically necessary treatment for many transgender individuals, leading to significant improvements in mental health outcomes such as reduced depression, anxiety, and gender dysphoria.

Both feminizing and masculinizing hormone regimens are considered safe when following established protocols, highlighting the importance of clinicians being knowledgeable about best practice guidelines for GAHT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormone Therapy for Transgender Adults. Radix, A.[2019]

In a study of 755 transgender individuals (302 AFAB and 453 AMAB) over a period from 2005 to 2022, transgender AFAB individuals reached their hormone therapy goals more quickly and with fewer adjustments compared to AMAB individuals.

Both groups showed no significant increase in cardiovascular events, indicating that gender-affirming hormone treatment is safe for long-term use, but AMAB individuals may need more frequent check-ups to improve adherence to their treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gender-affirming hormone treatment: friend or foe? Long-term follow-up of 755 transgender people. Santi, D., Spaggiari, G., Marinelli, L., et al.[2023]

In a survey of 696 transgender adults from the STRONG cohort, 80% reported being satisfied or very satisfied with their current gender-affirming hormone therapy, although transfeminine participants and older respondents reported lower satisfaction levels.

Transfeminine individuals expressed goals for additional hormone therapy focused on physical changes like breast growth and body fat distribution, while transmasculine individuals aimed for muscle mass increase and reduced dysphoria, highlighting the need for comprehensive care beyond hormone therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Satisfaction with current hormone therapy and goals of additional gender-affirming care in transgender adults. Siira, M., Getahun, D., Silverberg, MJ., et al.[2023]

Gender-affirming hormonal therapy (GAHT) can interact with certain antiretrovirals (ARVs) and hepatitis C direct acting antivirals (DAAs), potentially affecting the effectiveness and safety of the treatments, particularly with non-nucleoside reverse transcriptase inhibitors and protease inhibitors.

Clinicians need to carefully assess drug-drug interactions and overlapping side effects when prescribing GAHT alongside ARVs or DAAs to ensure safe and effective care for transgender patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Interactions with Gender-Affirming Hormone Therapy: Focus on Antiretrovirals and Direct Acting Antivirals. Cirrincione, LR., Senneker, T., Scarsi, K., et al.[2022]

Feminizing gender-affirming hormone therapy (GAHT) is effective for transfeminine transgender and gender diverse individuals, helping them achieve desired physical changes and improving their psychological and social well-being.

While feminizing GAHT generally has a low risk profile, it is important to understand potential health risks such as cardiovascular issues and cancer, especially as more research is needed to address these concerns in aging TGD populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feminizing gender-affirming hormone therapy for the transgender and gender diverse population: An overview of treatment modality, monitoring, and risks. Sudhakar, D., Huang, Z., Zietkowski, M., et al.[2023]

Transgender women using progestogens as part of their gender-affirming hormone therapy showed a significant decrease in high-density lipoprotein (HDL) levels and an increased risk of thromboembolism, indicating potential cardiovascular risks.

There was no conclusive evidence that progestogens improved breast development or quality of life in transgender women, highlighting the need for further research on their effects in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progestogen Use in Gender-Affirming Hormone Therapy: A Systematic Review. Patel, KT., Adeel, S., Rodrigues Miragaya, J., et al.[2022]

A study of 527 transgender women in Thailand revealed that self-prescribed gender-affirming hormone therapy (GAHT) regimens, particularly the commonly used combined oral contraceptive pill, were largely ineffective in achieving the target female range testosterone concentrations, with only 25.2% of participants reaching levels below 50 ng/dL.

The findings suggest that self-prescription of GAHT may not provide adequate hormonal control, highlighting the importance of involving healthcare providers for effective monitoring and prescription of hormone therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormone Concentrations in Transgender Women Who Self-Prescribe Gender Affirming Hormone Therapy: A Retrospective Study. Salakphet, T., Mattawanon, N., Manojai, N., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Gender affirming hormonal treatment in Danish transgender persons: A nationwide register-based study. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Endocrine Therapy of Adult Gender-Incongruent Individuals Seeking Gender Reaffirmation. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Hormone Therapy for Transgender Adults. [2019]

4. Italy pubmed.ncbi.nlm.nih.gov

Gender-affirming hormone treatment: friend or foe? Long-term follow-up of 755 transgender people. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Satisfaction with current hormone therapy and goals of additional gender-affirming care in transgender adults. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Drug Interactions with Gender-Affirming Hormone Therapy: Focus on Antiretrovirals and Direct Acting Antivirals. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Feminizing gender-affirming hormone therapy for the transgender and gender diverse population: An overview of treatment modality, monitoring, and risks. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Progestogen Use in Gender-Affirming Hormone Therapy: A Systematic Review. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Hormone Concentrations in Transgender Women Who Self-Prescribe Gender Affirming Hormone Therapy: A Retrospective Study. [2023]