Topical Estrogen for Transgender Men Undergoing Hysterectomy

Overseen By Beth Cronin, MD

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Women and Infants Hospital of Rhode Island

Must be taking: Testosterone

Disqualifiers: Under 18, Estrogen allergy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 43

Duration: Immediate (single application)

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if applying topical estrogen cream (a hormone treatment) to the surgical area at the end of a hysterectomy (removal of the uterus and cervix) can reduce bleeding and discomfort for transgender men after surgery. The goal is to assess whether this cream should become a standard part of post-surgical care. The trial includes two groups: one will receive the estrogen cream, and the other will receive a placebo (a treatment without active medicine). Transgender men who have been on testosterone for at least six months and are planning a hysterectomy may be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking care improvements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since participants must have been on testosterone for at least 6 months, it seems you can continue taking testosterone.

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

Research has shown that applying estrogen cream on the skin is generally safe. Studies have found that this form of estrogen does not seem to increase the risk of blood clots, a serious side effect of hormone treatments.

Specifically, research on transdermal estrogen suggests it poses a lower risk of blood clots in veins, making it a suitable option for those needing hormone treatment while avoiding certain risks.

Currently, there is no strong evidence of serious side effects from using estrogen cream after surgery, like the one under study. However, it is important to monitor for any unusual reactions and discuss them with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for transgender men undergoing hysterectomy, which typically involves hormone treatment through injections or patches, the use of topical estradiol offers a unique delivery method. Researchers are excited about this approach because it allows for the direct application of estrogen to the surgical site, potentially enhancing healing and reducing surgical recovery time. This topical method could provide more localized effects with potentially fewer systemic side effects compared to traditional hormone therapies.

What evidence suggests that topical estrogen might be an effective treatment for improving postoperative experience in transgender men undergoing hysterectomy?

Research has shown that applying estrogen cream on the skin might reduce bleeding and discomfort after surgery for transgender men who have undergone a hysterectomy. In this trial, some participants will receive topical estradiol, which studies suggest could lower the risk of bleeding. Although limited information exists about using estrogen after surgery in gender-diverse groups, it appears promising for alleviating discomfort related to gender identity. Additionally, hormone treatments that include estrogen have proven safe and effective when combined with surgery, leading to greater satisfaction. These findings suggest that estrogen cream might be beneficial after surgery for transgender men. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for transgender men who are undergoing a hysterectomy and may be concerned about postoperative bleeding or experiencing gender dysphoria. Participants should not have used any hormonal treatments recently.

Inclusion Criteria

I have been on testosterone for 6+ months and am planning a gender-affirming hysterectomy with potential post-surgery estrogen use.

Must agree to allow their medical data to be used for research purposes

Must have access to a device to receive text messages for study follow up

Exclusion Criteria

Known allergy to topical estrogen

I am under 18 years old.

I haven't taken testosterone for 6 months before my planned hysterectomy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Application of topical estradiol at the conclusion of surgery to improve postoperative experience

Immediate (single application)

Postoperative Monitoring

Participants are monitored for postoperative bleeding and dysphoria symptoms

2 weeks

Postoperative days: 1, 3, 7, 14

Follow-up

Participants are monitored for safety and effectiveness after treatment, including quality of life measures

6 weeks

Final postoperative visit at ~42 days

What Are the Treatments Tested in This Trial?

Interventions

• Topical Estrogen

Trial Overview The study is testing if applying topical estrogen cream right after a hysterectomy can reduce bleeding and discomfort related to gender dysphoria. It's comparing patients who get the cream with those who don't, to see if it should be standard care.

How Is the Trial Designed?

Group I: Estradiol Experimental Treatment 1 Intervention

Application of topical estradiol at conclusion of surgery

Group II: Placebo Placebo Group 1 Intervention

Standard surgical treatment will be provided

Who Is Running the Clinical Trial?

Women and Infants Hospital of Rhode Island

Lead Sponsor

Trials

119

Recruited

59,200+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06969326

Topical Estrogen: Brief Intervention to Improve ... Postoperative estrogen has limited data in gender diverse populations but presents as promising measure for decreasing postoperative dysphoria among transgender ...

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

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 ...

3. withpower.com withpower.com/trial/phase-3-postoperative-hemorrhage-4-2025-d4f29

Topical Estrogen for Transgender Men Undergoing ... Trial Overview The study is testing if applying topical estrogen cream right after a hysterectomy can reduce bleeding and discomfort related to gender dysphoria ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1530891X2035607X

Estrogen Levels Do Not Rise With Testosterone Treatment ... Estradiol levels remain within the normal range in medically treated transgender men and do not rise. Thus, there is no evidence for elevated estradiol levels.

5. transcare.ucsf.edu transcare.ucsf.edu/guidelines/feminizing-hormone-therapy

Overview of feminizing hormone therapy Sexual and gonadal effects include reduction in erectile function, changes in libido, reduced or absent sperm count and ejaculatory fluid, and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10072899/

Cardiovascular Risk in Transgender People With Gender- ... Collectively, the available data indicate that estrogen therapy does not appear to have adverse effects on blood lipids and lipoproteins in ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0015028221005811

The uterus in transgender men In practice, the data suggest that very few transgender men carry a pregnancy and/or use their oocytes after gender-reaffirming treatment. Clinicians should ...

8. lgbtqiahealtheducation.org lgbtqiahealtheducation.org/wp-content/uploads/COM-2245-The-Medical-Care-of-Transgender-Persons-v31816.pdf

The Medical Care of Transgender Persons Transdermal estradiol has been demonstrated to be much safer in regard to the risk of venous thromboembolism. Oral or sublingual estradiol also appears to be ...