Effect of Transgender Therapy on Muscle, Fat and Tissue Receptors

• ClinicalTrials.gov Identifier: NCT04551144
• Recruitment Status: Active, not recruiting
• First Posted: September 16, 2020
• Last Update Posted: December 3, 2021
• Sponsor: St. Louis University
• Information provided by (Responsible Party): Sandeep Singh Dhindsa, M.D., F.A.C.E, St. Louis University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Gender Incongruence; Transgenderism	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 Design

• Study Type: Observational
• Actual Enrollment: 4 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Effect of Transgender Therapy on Hormone Receptors, Adipogenesis, Myogenesis and Inflammation
• Actual Study Start Date: October 6, 2020
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: December 31, 2023

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. Androgen receptor [ Time Frame: 6 months ]
   change in Androgen receptor expression in subcutaneous adipose tissue in transmen

Secondary Outcome Measures :

1. Estrogen receptor and aromatase [ Time Frame: 6 months ]
   Expression and protein content of estrogen receptor alpha and aromatase in muscle and fat of transmen and transwomen
2. inflammation [ Time Frame: 6 months ]
   expression of inflammatory mediators in fat tissue and circulating levels in serum
3. autophagy [ Time Frame: 6 months ]
   Assessment of autophagic flux in fat and muscle biopsies

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: 2 groups based on gender identity: transowmen and transmen
• 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.

Criteria

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

Contacts and Locations

Locations

United States, Missouri

Saint Louis Univeristy

Saint Louis, Missouri, United States, 63104

Sponsors and Collaborators

St. Louis University

Investigators

• Principal Investigator: Sandeep Singh Dhindsa F.A.C.E, MD; St. Louis University

More Information

• Responsible Party: Sandeep Singh Dhindsa, M.D., F.A.C.E, Professor of Medicine, St. Louis University
• ClinicalTrials.gov Identifier: NCT04551144
• Other Study ID Numbers: 31184
• First Posted: September 16, 2020
• Last Update Posted: December 3, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Gender Dysphoria; Sexual Dysfunctions, Psychological; Mental Disorders; Methyltestosterone; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol; Polyestradiol phosphate; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Androgens; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Anabolic Agents