Skip to main content
OpenTrials
Recruiting

NCT Number: NCT07400419

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Muscle Mass and Strength Atrophy Muscular Atrophy Nervous System Diseases Neurologic Manifestations Neuromuscular Manifestations Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Sarcopenia Signs and Symptoms

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Resistance exercise program

Behavioral

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

Behavioral

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

Primary outcomes

  1. 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

  2. Gender congruence

    Time frame: 12 weeks

    Change in gender congruence (utilizing the total scale score from Transgender Congruence Scale) in resistance exercise group

Secondary outcomes

  1. 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

  2. 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

  3. Total fat mass

    Time frame: 12 weeks

    Change in total fat mass (kg) assessed using whole body DEXA in resistance exercise group

  4. Total lean body mass

    Time frame: 12 weeks

    Change in total lean body mass (kg) assessed using whole body DEXA in resistance exercise group

  5. Muscular function

    Time frame: 12 weeks

    Change in muscular function assessed via the 5 X sit to stand test (sec) in resistance exercise group

  6. Hand-grip strength

    Time frame: 12 weeks

    Change in hand-grip strength (kg) assessed using a Lafayette Hand Grip Dynamometer in resistance exercise group

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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. 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

  13. 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

  14. Resting energy expenditure

    Time frame: 12 weeks

    Change in resting energy expenditure (kcal/day) assessed using a metabolic cart in the resistance exercise group

  15. Resting metabolic rate

    Time frame: 12 weeks

    Change in resting metabolic rate (kcal/day) assessed using a metabolic cart in resistance exercise group

  16. Respiratory quotient

    Time frame: 12 weeks

    Change in respiratory quotient (ratio) assessed using a metabolic cart in the resistance exercise group

  17. 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

  18. 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

  19. 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

  20. Between-group change in total fat mass

    Time frame: 12 weeks

    Between-change in total fat mass (kg) assessed using whole body DEXA

  21. 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

  22. 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)

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. Between-group change in respiratory quotient

    Time frame: 12 weeks

    Between-group change in respiratory quotient (ratio) assessed using a metabolic cart

  34. Appearance congruence

    Time frame: 12 weeks

    Change in appearance congruence (utilizing the appearance congruence subscale score from Transgender Congruence Scale) in resistance exercise group

  35. 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

  36. 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)

  37. 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)

Study contacts

Contact information is provided by the study sponsor or research team.

Mabel Toribio, MD

CONTACT

[email protected]

617-724-2826

Sponsors and collaborators

Lead sponsor

Massachusetts General Hospital

Other

Registry information

Acronym: STRENGTH

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Feb 10, 2026
Registry last updated
Jul 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.