Actively Recruiting

Phase 4
Age: 18Years - 40Years
All Genders
Healthy Volunteers
ID06455969

Musculoskeletal Resiliency and Adaptation to Sex Steroid Suppression and Replacement During Multi-Stressor Training

Led by Bradley Nindl · Updated on 2025-08-24

120

Participants Needed

1

Research Sites

N/A

Total Duration

On this page

Sponsors

B

Bradley Nindl

Lead Sponsor

U

U.S. Army Medical Research and Development Command

Collaborating Sponsor

AI-Summary

What this Trial Is About

Non-combat-related muscle, tendon, and bone injuries are common among military personnel, especially new recruits, affecting readiness and causing significant medical costs. This research investigates how hormonal changes, specifically sex hormones like testosterone and estrogen, influence muscle, tendon, and bone function as well as physical and psychological performance under stress. The study aims to improve military physical training and reduce injuries by understanding these hormonal effects. Participants will be assigned to different groups including a control group maintaining normal habits and a stress exposure group undergoing a 4-week military-style physical training program. Some men and women in the stress group will receive medications to suppress natural hormone production and then receive hormone replacement or a placebo. Treatments include a GnRH agonist injection and topical testosterone gels or estrogen/progesterone patches, with dosing varying by group and sex. Throughout the approximately 8-week study, participants will undergo measurements such as muscle and tendon imaging, body composition analysis, blood tests for hormone and biochemical markers, and physical and mental performance evaluations. Researchers will monitor changes in these outcomes over time to assess the effects of hormone suppression and replacement on musculoskeletal resilience and adaptation to stress.

CONDITIONS

Brief Title

Adaptions and Resiliency to Multi-Stressor OpeRations

Who Can Participate

Age: 18Years - 40Years
All Genders
Healthy Volunteers

Eligibility Criteria

Eligible

You may qualify if you...

  • Age 18-40 years
  • Body mass index (BMI) between 18 and 30 kg/m2
  • Stable weight within plus or minus 10 pounds in the past 2 months
  • Participate in at least 150 minutes of moderate physical activity per week
  • Currently free from any upper or lower body injury or impairment
  • Able to commit to the full study duration
  • Agree to follow all study requirements
  • Not taking prescription medications or willing to stop prior to and during the study unless approved
  • For men, total testosterone levels within normal range (300-1000 ng/dL)
  • For women, regular menstrual cycles (26-35 days) and no hormonal contraceptive use for past 3 months
Not Eligible

You will not qualify if you...

  • Current smoker
  • Clinical diagnosis of an eating disorder
  • Use of medications that interfere with hormone measurements or study outcomes
  • Oligo/amenorrhea in women
  • Any metabolic or endocrine disease
  • Medical condition preventing exercise
  • Currently pregnant or becomes pregnant during the study
  • History of heart disease or high blood pressure
  • Physician requires medically supervised physical activity only
  • History of drug addiction or regular recreational drug use
  • Current or past mental health treatment
  • Abnormal lab results (e.g., PSA >3 ng/mL)
  • Disorders affecting bone metabolism (e.g., hyperthyroidism, diabetes, renal insufficiency)
  • Use of medications affecting bone metabolism recently
  • History of blood clots or clotting disorders
  • History of stroke or heart attack
  • Low vitamin D levels (below 20 ng/mL)
  • Thyroid dysfunction
  • High serum creatinine levels
  • Personal or first-degree relative history of breast cancer
  • Elevated liver enzymes or bilirubin
  • Recent fracture within 6 months
  • Blood pressure above 160/95
  • Active substance abuse
  • High fasting triglycerides
  • History of hereditary angioedema
  • Chest pain at rest or during activity
  • Musculoskeletal injury causing over a month of inactivity in past 2 years
  • Frequent recreational drug use in past 6 months
  • Vision worse than 20/20
  • Participation in another clinical trial recently
  • Food allergies or special diet needs
  • History of endometriosis or reproductive health issues
  • Undiagnosed abnormal vaginal bleeding
  • Currently breastfeeding or within 2 months after stopping
  • Dietary restrictions or intolerance

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Run-in Period

Duration - Duration as specified by study protocol (not explicitly stated)

Participants undergo an equilibration period after administration of a gonadotropin-releasing hormone agonist to allow steroid hormone concentrations to reduce before starting training and treatment.

1 visit (in-person) for administration and monitoring

Treatment

Duration - 4 weeks

Participants undergo a 4-week multi-stressor physical training program mimicking military training. Male participants in intervention groups receive daily topical testosterone gel after hormone suppression; female participants receive either active or placebo hormone patches following suppression.

Weekly visits for up to 4 weeks

Follow-up

Duration - Up to 8 weeks from baseline

Participants are monitored for changes in biomechanical, body composition, and biochemical measures through study completion, approximately 8 weeks from baseline.

Approximately 2 to 4 visits during follow-up

Trial Site Locations

Total: 1 location

1

Neuromuscular Research Laboratory

Pittsburgh, Pennsylvania, United States, 15203

Actively Recruiting

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Research Team

B

Bradley C Nindl, PhD

K

Kristin J Koltun, PhD

How is the study designed?

Study Type

INTERVENTIONAL

Masking

SINGLE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

BASIC_SCIENCE

Number of Arms

6

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