Effects of Resistance Exercise Among TGD Individuals Initiating Estrogen-Based Gender-Affirming Hormone Therapy (STRENGTH)

July 9, 2026 updated by: Mabel Toribio, Massachusetts General Hospital
Estrogen-dominant gender-affirming hormone therapy (GAHT) is standard of care for transgender women and gender-diverse individuals and typically consists of estrogen together with anti-androgen/ testosterone therapy. Estrogen and testosterone balance influences fat and muscle mass, muscular strength and the development of sarcopenia. Sarcopenia, a condition characterized by the loss of muscular mass, strength, and function, in turn, is associated with increased mortality and adverse health outcomes. Estrogen-dominant GAHT may have deleterious effects on body composition and muscular performance that place TGD individuals at-risk for sarcopenia. As part of NCT04128488, our investigative team found that appendicular lean mass (ALM)/ height2 decreases after estrogen-based GAHT, thereby portending a higher risk for sarcopenia after GAHT. Early recognition of the changes in body composition and muscular performance leading to sarcopenia are critical, providing potential avenues to intervene and abrogate untoward downstream health effects. A promising intervention is resistance exercise, which has been shown in select populations to improve muscular mass and strength and reduce fat mass, and, thus, mitigate progression to sarcopenia in at-risk populations. For this prospective, pilot clinical trial, investigators will enroll participants who are about to be initiated on estrogen-dominant gender-affirming hormone therapy. Investigators will be randomizing participants 1:1 to either an at-home resistance exercise intervention or no exercise intervention (nutritional and exercise counseling only) for 12 weeks and assess muscle mass, strength, and function both before and after this 12-week period. The exercise intervention group will be provided with the necessary materials to complete the exercise program along with weekly virtual visits with our study team in order to learn their assigned exercises for the week. Further, survey tools will be administered to ascertain whether the resistance exercise intervention may affect gender congruence.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • ≥ 18 years
  • Initiating GAHT with estradiol (oral, sublingual, patch, injection) AND androgen suppression (leuprolide, spironolactone or bicalutamide)
  • Identifies as either a transgender female/woman, gender-diverse, non-binary, gender non-confirming, gender-fluid, and/or gender-queer
  • Assigned male sex at birth

Exclusion Criteria:

  • Current condition(s) which may preclude the ability to participate in a resistance exercise program (including but not limited to conditions which may significantly impair mobility and balance)
  • Current condition(s) where resistance exercise program may be contraindicated (including but not limited to decompensated heart failure, unstable ischemic heart disease, pulmonary hypertension, aortic aneurysm, moderate to severe valvopathies, and/or moderate to severe chronic respiratory insufficiency)
  • Use of testosterone therapy for > 1 month in the last 6 months
  • Use of gender-affirming hormone therapy with androgen/testosterone suppression and/or estradiol therapy within 1 year of enrollment
  • Use of gender-affirming hormone therapy with androgen/testosterone suppression and/or estradiol therapy for > 1 year at any time period prior to enrollment
  • History of an orchiectomy
  • Current resistance exercise (including but not limited to use of resistance bands, suspension equipment, body weight exercise, free weight exercise) of 60 minutes or greater per week
  • Enrollment in another study that the study investigators deem as potentially interfering with study participants or study endpoints

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Resistance Exercise Intervention
Participants in this arm will be randomized to a 12-week at-home resistance exercise program.
Behavioral: Resistance Exercise Program
Participants will initiate this program at the time that they start their gender-affirming hormone therapy and will be instructed to complete resistance exercises for three 60-minute sessions per week for 12 weeks. Participants will have a weekly video call to demonstrate the exercises for that week, have a supervised training session to ensure exercises are performed safely and as instructed, monitor their continued participation in the exercise intervention, and answer any questions or issues that arise as part of the program. Further, participants will be provided with resistance bands, a TRX suspension trainer, and dumbbell weights in order to complete the resistance exercises for the program. Examples of how each exercise can be modified depending on a participant's limitations will also be provided as needed. The study team will ascertain whether they can progress to the next week's exercises depending on their ability to achieve the number of repetition's of the prior week.
Behavioral: Nutrition and Exercise Counseling
Participants will undergo lifestyle counseling related to optimization of their nutrition and exercise regimen.
Placebo Comparator: No exercise intervention
Participants in this arm will receive educational counseling on nutrition and exercising.
Behavioral: Nutrition and Exercise Counseling
Participants will undergo lifestyle counseling related to optimization of their nutrition and exercise regimen.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Appendicular lean mass/height^2
Time Frame: 12 weeks
Change in appendicular lean mass/height^2 (kg/m^2) assessed via whole body DEXA in resistance exercise group
12 weeks
Gender congruence
Time Frame: 12 weeks
Change in gender congruence (utilizing the total scale score from Transgender Congruence Scale) in resistance exercise group
12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Visceral adipose tissue mass
Time Frame: 12 weeks
Change in total visceral adipose tissue mass (g) assessed using whole body DEXA in resistance exercise group
12 weeks
Visceral adipose tissue volume
Time Frame: 12 weeks
Change it total visceral adipose tissue volume (cm3) assessed using whole body DEXA in resistance exercise group
12 weeks
Total fat mass
Time Frame: 12 weeks
Change in total fat mass (kg) assessed using whole body DEXA in resistance exercise group
12 weeks
Total lean body mass
Time Frame: 12 weeks
Change in total lean body mass (kg) assessed using whole body DEXA in resistance exercise group
12 weeks
Muscular function
Time Frame: 12 weeks
Change in muscular function assessed via the 5 X sit to stand test (sec) in resistance exercise group
12 weeks
Hand-grip strength
Time Frame: 12 weeks
Change in hand-grip strength (kg) assessed using a Lafayette Hand Grip Dynamometer in resistance exercise group
12 weeks
Horizontal shoulder adduction strength
Time Frame: 12 weeks
Change in horizontal shoulder adduction strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer in resistance exercise group
12 weeks
Shoulder extension strength
Time Frame: 12 weeks
Change in shoulder extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer in resistance exercise group
12 weeks
Elbow flexion strength
Time Frame: 12 weeks
Change in elbow flexion strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer in resistance exercise group
12 weeks
Elbow extension strength
Time Frame: 12 weeks
Change in elbow extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer in resistance exercise group
12 weeks
Knee extension strength
Time Frame: 12 weeks
Change in knee extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer in resistance exercise group
12 weeks
Knee flexion strength
Time Frame: 12 weeks
Change in knee flexion strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer in resistance exercise group
12 weeks
Hip extension strength
Time Frame: 12 weeks
Change in hip extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer in resistance exercise group
12 weeks
Resting energy expenditure
Time Frame: 12 weeks
Change in resting energy expenditure (kcal/day) assessed using a metabolic cart in the resistance exercise group
12 weeks
Resting metabolic rate
Time Frame: 12 weeks
Change in resting metabolic rate (kcal/day) assessed using a metabolic cart in resistance exercise group
12 weeks
Respiratory quotient
Time Frame: 12 weeks
Change in respiratory quotient (ratio) assessed using a metabolic cart in the resistance exercise group
12 weeks
Between-group change in appendicular lean body mass/ height^2
Time Frame: 12 weeks
Between-group change in appendicular lean body mass/ height^2 (kg/m^2) assessed via whole body DEXA
12 weeks
Between-group change in total visceral adipose tissue mass
Time Frame: 12 weeks
Between-group change in total visceral adipose tissue mass (g) assessed using whole body DEXA
12 weeks
Between-group change in visceral adipose tissue volume
Time Frame: 12 weeks
Between-change in total visceral adipose tissue volume (cm3) assessed using whole body DEXA
12 weeks
Between-group change in total fat mass
Time Frame: 12 weeks
Between-change in total fat mass (kg) assessed using whole body DEXA
12 weeks
Between-group change in total lean body mass
Time Frame: 12 weeks
Between-group change in total lean body mass (kg) assessed using whole body DEXA
12 weeks
Between-group change in muscular function via the 5x sit to stand test
Time Frame: 12 weeks
Between-group change in muscular function assessed via the 5 X sit to stand test (sec)
12 weeks
Between-group change in hand-grip strength
Time Frame: 12 weeks
Between-group change in hand-grip strength (kg) assessed using a Lafayette Hand Grip Dynamometer
12 weeks
Between-group change in horizontal shoulder adduction strength
Time Frame: 12 weeks
Between-group change in horizontal shoulder adduction strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer
12 weeks
Bwtween-group change in shoulder extension strength
Time Frame: 12 weeks
Between-group change in shoulder extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer
12 weeks
Between-group change in elbow flexion strength
Time Frame: 12 weeks
Between-group change in elbow flexion strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer
12 weeks
Between-group change in elbow extension strength
Time Frame: 12 weeks
Between-group change in elbow extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer
12 weeks
Between-group change in knee extension strength
Time Frame: 12 weeks
Between-group change in knee extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer
12 weeks
Between-group change in knee flexion strength
Time Frame: 12 weeks
Between-group change in knee flexion strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer
12 weeks
Between-group change in hip extension strength
Time Frame: 12 weeks
Between-group change in hip extension strength (kgf) assessed using a Hogan Scientific MicroFET2 Handheld dynamometer
12 weeks
Between-group change in resting energy expenditure
Time Frame: 12 weeks
Between-group change in resting energy expenditure (kcal/day) assessed using a metabolic cart
12 weeks
Between-group change in resting metabolic rate
Time Frame: 12 weeks
Between-group change in resting metabolic rate (kcal/day) assessed using a metabolic cart
12 weeks
Between-group change in respiratory quotient
Time Frame: 12 weeks
Between-group change in respiratory quotient (ratio) assessed using a metabolic cart
12 weeks
Appearance congruence
Time Frame: 12 weeks
Change in appearance congruence (utilizing the appearance congruence subscale score from Transgender Congruence Scale) in resistance exercise group
12 weeks
Gender identity acceptance
Time Frame: 12 weeks
Change in gender identity acceptance (utilizing the gender identity acceptance subscale score from Transgender Congruence Scale) in resistance exercise group
12 weeks
Between-group change in appearance congruence
Time Frame: 12 weeks
Between-group change in appearance congruence (utilizing the appearance congruence subscale score from Transgender Congruence Scale)
12 weeks
Between-group change in gender identity acceptance
Time Frame: 12 weeks
Between-group change in gender identity acceptance (utilizing the gender identity acceptance subscale score from Transgender Congruence Scale)
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 16, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 28, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 6, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 10, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 9, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2025P003023

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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