Effect of Transgender Therapy on Muscle, Fat and Tissue Receptors

Effect of Transgender Therapy on Hormone Receptors, Adipogenesis, Myogenesis and Inflammation

The purpose of this research is to find out if hormone therapy in transgender subjects' changes hormone receptors in blood, muscle and fat; fat production; muscle production; and inflammation processes.

Study Overview

• Status: Terminated
• Conditions: Transgenderism; Gender Incongruence
• Intervention / Treatment: Drug: testosterone cypionate; Drug: Estradiol Valerate

Detailed Description

Throughout recorded history, some men and women have experienced emotional distress at being physically "trapped" in wrong gender. Gender incongruence refers to the state where one's internal sense of gender differs from the gender assigned at birth. Advances in psychology and in our understanding of human sexuality have permitted the recognition of gender incongruence (also called transgender) as a biological phenomenon. The acceptance by the society has led to an expansion of health care services available to these individuals for supportive treatment. Gender affirming hormone therapy, usually provided by endocrinologists, is pivotal for the transition of these individuals into their desired gender. This therapy typically consists of testosterone or estrogen (male and female sex hormones) to transition into transmen or transwomen, respectively. The hormone treatment results in a "second puberty", wherein biological men receiving estrogen gain fat around hips and thighs, lose muscle and develop breasts. Biological women receiving testosterone lose fat, gain muscle, stop having menses and develop a deeper voice. However, our knowledge of the mechanisms of these hormones at the tissue level in transgender population is lacking. In this study, we plan to evaluate

1. hormone receptors that carry out the action of sex hormones in fat tissue and mononuclear cells (a type of immune cell in blood) following gender affirming therapy.
2. the mechanism that lead to growth or suppression of fat mass or lean mass
3. effect on inflammation (a cardiovascular risk marker) The hormone treatment of gender incongruence is a relatively untested therapy. The treatment is based on extrapolations and assumptions from hormone treatment in hypogonadal (hormone deficient) in cis-gender (same gender, no incongruence) individuals. We expect that our mechanistic studies will initiate an understanding into the actions of transgender therapy at the cellular level.

• Study Type: Observational
• Enrollment (Actual): 4

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis Univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

We plan to conduct a prospective, open label study in individuals initiating gender affirming therapy for gender incongruence. We will recruit 20 transmen and 20 transwomen in this study.

Description

Inclusion Criteria:

• Diagnosed with gender incongruence by a mental health professional and willing to start gender affirming therapy

Exclusion Criteria:

• Used hormone therapy in last 6 months,
• Pregnancy,
• Planning to have biological children in the next one year,
• HIV Additional exclusion criteria for transmen: 1) hematocrit >50% for transmen, 2) transmen with allergy to cottonseed oil (component of intramuscular testosterone injection), 3) uncompensated heart failure, 4) renal failure Additional exclusion criteria for transwomen: 1) allergy to castor oil (component of intramuscular estradiol injection), 2) Known or suspected estrogen-dependent neoplasia, 3) Active deep vein thrombosis, pulmonary embolism or a history of these conditions, 4) Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction), 5) Liver enzymes (AST or ALT) >3 times the upper limit of normal, 6) Known or suspected pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Transmen; Subjects starting testosterone therapy as part of standard of care for gender incongruence	Drug: testosterone cypionate; intramuscular injection every 2 weeks. Dose will be titrated based on blood levels
transwomen; Subjects starting estradiol therapy as part of standard of care for gender incongruence	Drug: Estradiol Valerate; intramuscular injection every week. Dose will be titrated based on blood levels

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Androgen receptor	change in Androgen receptor expression in subcutaneous adipose tissue in transmen	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estrogen receptor and aromatase	Expression and protein content of estrogen receptor alpha and aromatase in muscle and fat of transmen and transwomen	6 months
inflammation	expression of inflammatory mediators in fat tissue and circulating levels in serum	6 months
autophagy	Assessment of autophagic flux in fat and muscle biopsies	6 months

Collaborators and Investigators

• Sponsor: St. Louis University
• Investigators: Principal Investigator: Sandeep Dhindsa, MD, St. Louis University

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2020
• Primary Completion (Actual): January 18, 2023
• Study Completion (Actual): January 18, 2023

Study Registration Dates

• First Submitted: September 9, 2020
• First Submitted That Met QC Criteria: September 9, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Sexual Dysfunctions, Psychological; Gender Dysphoria; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Androgens; Anabolic Agents; Estradiol; Testosterone; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: 31184

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No