The objective of this study is to determine whether maintaining a eugonadal state, during severe, sustained energy deficit, attenuates physiological decrements, particularly the loss of lean body mass.

This study will enroll up to 60 physically active men in a 3-phase randomized, placebo-controlled trial. After completing a 14-day (free-living, phase 1), energy-adequate, diet-acclimation phase (protein, 1.6 g∙kg-1∙d-1; fat 30% total energy intake, with remaining energy derived from carbohydrate), participants will be randomized to one of two experimental groups and undergo a 28-day (live-in, phase 2), 55% energy deficit phase: energy deficit alone (DEF) or energy deficit + exogenous testosterone (DEF+TEST). Recovery (free-living, phase 3) will be assessed after completing phase 2 to determine when body mass has been recovered within ± 2.5% of initial body mass (duration will vary, 42-day maximum for phase 3). This study will delineate the contribution of testosterone declines from the physical and mental demands encountered by Warfighters during military training and combat operations on complex markers of physiological and psychological status, addressing a direct, consistently observed, gap in knowledge.

Inclusion Criteria:

• Physically active (at least 2 days per week aerobic and/or resistance exercise)

• Not taking any prescription medications and/or willing to refrain from all medication use prior to and throughout the entire study period, unless provided/approved by the study physician

• Willing to refrain from alcohol, smoking, e-cigarettes, or use of any nicotine product, caffeine, and dietary supplement use throughout the entire study period

  • At the discretion of the study physician, wash-out period for medications, supplements, and over-the-counter medications is ≥ 1 to 4 weeks
  • Wash-out period for caffeine and alcohol is ≥ 7 days

• Willing to live on the Pennington Biomedical Research Center inpatient unit for 28 consecutive days

• Willing to have a urine drug screening

• Meets age-specific U.S. Army body composition standards according to Army Regulation 600-9, which includes estimates of percent body fat based on height, weight, and circumference measures (neck and waist)

• Total testosterone concentration is within the normal physiological range, total testosterone (300-1,000 ng/dL).

Exclusion Criteria:

• Musculoskeletal injuries that compromise exercise capability
• Diagnosed cardiometabolic disorders (i.e., hypertension, hyperlipidemia, kidney disease, diabetes, etc.)
• Allergies or intolerance to foods, vegetarian practices, or history of complications with lidocaine
• Anabolic steroid, human growth hormone, or nutritional testosterone precursor-like supplement use within the past 6 months
• Will not refrain from smoking (any nicotine product), alcohol, caffeine, or any other dietary supplement during the study
• Any use of antibiotics, except topical antibiotics, within 3 months of study participation
• Colonoscopy within 3 months of study participation
• Chronic use of laxatives, stool softeners, antacids, or anti-diarrheal medications (≥ once a week)
• History of gastrointestinal disease (e.g., celiac, irritable bowel syndrome, colitis, Crohn's disease)
• Restrained eater (the Three-Factor Eating Questionnaire) as assessed by the study's psychological and behavioral assessment staff
• Adults unable to consent
• Women
• Prisoners
• Metal implants, claustrophobia, head size incompatible with MRI equipment, etc.
• Sedentary or engages in <2 days of physical activity per week (aerobic and/or resistance training)
• Exceeds age-specific U.S. Army body composition standards according to Army Regulation 600-9
• Previous history of kidney stones unless otherwise approved by the medical investigator
• Systolic blood pressure > 150 or diastolic blood pressure > 95 mmHg
• Previous history of breast or prostate cancer
• Previous history of Chronic Obstructive Pulmonary Disease or Obstructive Sleep Apnea
• Findings of lab results of prostate-specific antigen > 3ng/ml, Hematocrit > 50%, or positive urine drug screening
• Based on the investigative team's clinical judgment, a subject may not be appropriate for participation in the study

Adverse event data was collected from the time of the screening visit until study completion, up to 4 months.