Recruiting

Resistance Exercise

Sponsor:

Massachusetts General Hospital

Code:

NCT07400419

Conditions

Muscle Mass and Strength

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Resistance Exercise Program

Nutrition and Exercise Counseling

Study Details

Brief summary:

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.

Conditions

Muscle Mass and Strength

Study ID

NCT07400419

Start date

Apr 16, 2026

Status verified date

Jul, 2026

Completion date

Apr 1, 2028

Anticipated

Primary completion date

Apr 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Prevention

Interventions and Outcome Measures

Arms

active comparator: Resistance Exercise Intervention

Participants in this arm will be randomized to a 12-week at-home resistance exercise program.

placebo comparator: No exercise intervention

Participants in this arm will receive educational counseling on nutrition and exercising.

Interventions

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.

Nutrition and Exercise Counseling

Participants will undergo lifestyle counseling related to optimization of their nutrition and exercise regimen.

Primary outcome measure

  • Appendicular lean mass/height^2 [ Time Frame: 12 weeks ]
  • Gender congruence [ Time Frame: 12 weeks ]

Central Contacts and Locations

Central contacts

Mabel Toribio, MD

617-724-2826mptoribio@mgh.harvard.edu

Locations

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Mabel Toribio, MD

617-724-2826mptoribio@mgh.harvard.edu

mptoribio@mgh.harvard.edu

More Information

Sponsor

Massachusetts General Hospital

Last update posted

Jul 13, 2026

Last verified

Jul, 2026

Keywords

  • Transgender women
  • Gender-Diverse
  • Estrogen-dominant gender-affirming hormone therapy
  • Sarcopenia

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Massachusetts General Hospital on 2026-07-13.