Understanding the effects of feminizing hormones on the rectal immune environment in transgender women

Feminizing Hormone Therapy and the Rectal Mucosa Immune Environment in Transgender Women

This study is trying to see how feminizing hormones affect the immune system in the rectal area of transgender women to better understand HIV risk and improve prevention methods.

Quick facts

• Study type: Observational
• Enrollment: 520 (estimated)
• Ages: 18 Years to 59 Years
• Sex: All
• Sponsor: Emory University (Academic / other)
• Locations: 1 site (Atlanta, Georgia)
• Trial ID: NCT04531943 on ClinicalTrials.gov

What this trial studies

This observational study aims to explore the impact of feminizing hormone therapy on the rectal mucosal immune environment in transgender women who have receptive anal intercourse with men. It will recruit approximately 520 participants, dividing them into two cohorts: a cross-sectional study and a longitudinal study, based on specific characteristics. The research focuses on how these hormones may influence HIV transmission risk, with the goal of optimizing current HIV prevention strategies and informing future interventions, including vaccine development.

Who should consider this trial

Good fit: Ideal candidates are transgender women assigned male at birth, aged 18-59, currently using feminizing hormone therapy for at least six months, and HIV negative.

Not a fit: Patients who are not using feminizing hormone therapy or are HIV positive may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved HIV prevention strategies tailored for transgender women.

How similar studies have performed: While studies have explored hormone effects in other contexts, this specific focus on the rectal mucosa in transgender women is relatively novel.

Eligibility criteria

INCLUSION CRITERIA

Cohort 1, TGWSM using feminizing hormone therapy

* Assigned male sex at birth and currently using feminizing hormone therapy
* Aged 18-59 years
* Able to provide informed consent in the official language of the study site's country
* HIV negative
* Taking feminizing hormone therapy for at least the last 6 months with no change in dose for the last 3 months (i.e. no increase or decrease)

  * Feminizing hormone therapy is defined as use of oral, patch, topical, or injection estrogen therapy with or without progesterone therapy in people who were assigned male sex at birth but take feminizing hormones to affirm their current gender identity

    * Approximately half of the cohort to be using estrogen therapy alone and half using estrogen+progesterone
  * Anti-androgen therapy is permissive, but dose must also be stable for the last 3 months at the time of enrollment
* Willing to undergo peripheral blood and rectal biopsy sampling
* Willing to abstain from receptive anal intercourse for 72 hours before and for 1 week after rectal biopsy procedure
* Willing to answer sexual behavior questions

Cohort 1, Cisgender Males

* Assigned male sex at birth, currently identify as male gender (i.e. cisgender), man who has sex with men aged 18-59 years
* Able to provide informed consent in the official language of the study site's country
* HIV negative
* Receptive anal intercourse with a person assigned male sex at birth at least once in lifetime
* No history of taking supplemental steroids including testosterone replacement therapy in the last 12 months
* Willing to undergo peripheral blood and rectal biopsy sampling
* Willing to abstain from receptive anal intercourse for 72 hours before and for 1 week after rectal biopsy procedure.
* Willing to answer sexual behavior questions.

Cohort 2, Longitudinal study with TGWSM planning to initiate feminizing hormone therapy

* Assigned male sex at birth with plans to start feminizing hormone therapy
* Aged 18-59 years
* Able to provide informed consent in the official language of the study site's country
* Naïve to feminizing hormone therapy or no use in the last 6 months, including anti-androgen therapy.
* HIV negative
* Plans to initiate feminizing hormone therapy in next 6 months.

  * Feminizing hormone therapy is defined as use of oral, patch, topical, or injection estrogen therapy with or without progesterone therapy in people who were assigned male sex at birth but take feminizing hormones to affirm their current gender identity.
  * Anti-androgen therapy is permissive, but participants must also be initiating estrogen therapy to be eligible.
* Willing to undergo peripheral blood and rectal biopsy sampling
* Willing to abstain from receptive anal intercourse for 72 hours before and for 1 week after rectal biopsy procedure.
* Willing to answer sexual behavior questions.

EXCLUSION CRITERIA

* History of inflammatory bowel disease or other inflammatory, infiltrative, infectious or vascular condition involving the lower gastrointestinal tract that, in the judgment of the investigators, may be worsened by study procedures or may significantly distort the anatomy of the distal large bowel
* Significant laboratory abnormalities at baseline visit for rectal biopsies, including but not limited to:

  * Hemoglobin (Hgb) ≤ 10 g/dL
  * Partial thromboplastin time (PTT) \> 1.5x upper limit of normal (ULN) or international normalised ratio (INR) \> 1.5x ULN
  * Platelet count \<100,000
* Any known medical condition that, in the judgment of the investigators, increases the risk of local or systemic complications of endoscopic procedures or pelvic examination, including but not limited to:

  * Uncontrolled or severe cardiac arrhythmia
  * Recent major abdominal, cardiothoracic, or neurological surgery in the last 12 months
  * History of uncontrolled bleeding diathesis
  * History of colonic, rectal, or vaginal perforation, fistula, or malignancy
  * History or evidence on clinical examination of ulcerative, suppurative, or proliferative lesions of the anorectal mucosa.
* Use of systemic (oral/IV) antibiotics within the 4 weeks prior to rectal mucosal sampling.

  * Participants may be screened/enrolled who do not meet this criterion, but rectal mucosal sampling will be deferred for at least 4 weeks from last systemic antibiotic use.
* Continued need for, or use during the 14 days prior to enrollment, of the following medications:

  * Aspirin or more than 4 doses of nonsteroidal anti-inflammatory drugs (NSAIDs)
  * Warfarin, heparin (low-molecular weight or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents
  * Any form of rectally administered agent besides products (lubricants or douching) used for sexual intercourse
* Continued need for, or use during the 90 days prior to enrollment, of the following medications:

  * Systemic immunomodulatory agents
  * Supraphysiologic doses of steroids with the exception of short course steroids \<7 days duration at the discretion of the investigator and feminizing hormone therapy as detailed in inclusion criteria
  * Experimental medications, vaccines, or biologicals
* Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements.

Where this trial is running

Atlanta, Georgia

• Hope Clinic — Atlanta, Georgia, United States (Recruiting)

Study contacts

• Principal investigator: Colleen Kelley, MD, MPH — Emory University
• Study coordinator: Colleen Kelley, MD, MPH

Conditions HIV Prevention; Transgender women