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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how hormone therapy affects insulin sensitivity (how well the body uses sugar) and immune response in transgender individuals. For transwomen, it examines whether estrogen improves insulin sensitivity and boosts the immune system, particularly in older individuals. For transmen, it investigates whether testosterone negatively affects insulin sensitivity. The trial is open to trans individuals on stable hormone therapy (also known as Gender Affirming Hormone Therapy) for six months and healthy volunteers not currently on hormone treatments. Participants should not have diabetes or recent heart issues. As an Early Phase 1 trial, this research aims to understand how hormone therapy works in people, offering participants a chance to contribute to groundbreaking insights.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that gender-affirming hormone therapy (GAHT) is generally safe and well-tolerated when healthcare professionals manage it. For transwomen using estrogen, studies have found this treatment to be safe and effective, though it can affect heart health and blood fat levels. More research is needed to fully understand these changes.

For transmen using testosterone, research indicates that this therapy is also safe and effective. It is a common and standard treatment for those transitioning.

Overall, both estrogen and testosterone therapies have been safely used by many people. They can improve mental well-being and help align physical appearance with gender identity. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Gender Affirming Hormone Therapy because it is specifically tailored for transgender individuals, offering personalized care that aligns with each person's gender identity. Unlike traditional hormone treatments that are often used for other purposes, this therapy focuses on adjusting hormone levels to facilitate gender transition, which can significantly improve the mental health and quality of life for transgender individuals. By understanding the effects of estrogen in male-to-female (MTF) transitions and testosterone in female-to-male (FTM) transitions, researchers hope to optimize treatment protocols, minimizing side effects while maximizing benefits. This trial could pave the way for more informed, compassionate, and effective care for the transgender community.

What evidence suggests that this trial's treatments could be effective for insulin sensitivity and immune response in transgender individuals?

This trial will compare different groups, including transgender individuals undergoing hormone therapy and healthy volunteers. Research has shown that estrogen therapy, which participants in the MTF group of this trial may receive, can boost mental well-being and improve the quality of life for transgender women. It also aids social interactions and reduces anxiety and depression, facilitating changes similar to those during female puberty.

For transgender men, testosterone therapy, which participants in the FTM group of this trial may receive, can enhance mental well-being by aligning their physical appearance with their gender identity. It leads to body changes similar to those seen in men during puberty. While it can affect blood fats, further research is needed to fully understand its impact on health. ^{1 2 3 4 6}

Who Is on the Research Team?

Devjit Tripathy, MD

Principal Investigator

University of Texas Health San Antonio

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. mayoclinic.org mayoclinic.org/tests-procedures/masculinizing-hormone-therapy/about/pac-20385099

Masculinizing hormone therapy Masculinizing hormone therapy is used to make physical changes in the body that are caused by male hormones during puberty.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5182227/

Hormone therapy for transgender patients - PMC Cross-sex hormone therapy has been shown to have positive physical and psychological effects on the transitioning individual and is considered a mainstay ...

3. hopkinsmedicine.org hopkinsmedicine.org/health/treatment-tests-and-therapies/gender-affirming-hormone-therapy-gaht

Gender-Affirming Hormone Therapy (GAHT) Hormone therapy for transgender and gender-fluid people can improve mental well-being and quality of life by more closely aligning someone's outer appearance ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11179057/

Maximizing surgical outcomes with gender affirming ... Gender Affirming Hormone Therapy (GAHT) is an important component of GAS for transgender patients. The significance of this cannot be emphasized ...

5. jacc.org jacc.org/doi/10.1016/j.jacadv.2024.101265

Impact of Gender-Affirming Hormonal Therapy on ... GAHT affects lipid profiles in transgender patients; however, additional studies are needed to determine how these changes impact clinical outcomes.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2214623724000267

Maximizing surgical outcomes with gender affirming ... GAHT has been shown to be safe and effective with concurrent GAS, with higher rates of satisfaction reported among those individuals undergoing GAS with GAHT ...