Effects of DHEA and Exercise on Bone Marrow Fat in Postmenopausal Women

Prior treatment

• does not meet Centers for Disease Control and Prevention (CDC) recommendations for home isolation because has had a positive severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) test less than 10 days before study entry; or has had fever within the past 3 days and respiratory symptoms have not improved; or symptoms first appeared less than 10 days before study entry.
• pulmonary disease requiring use of oral steroids within the previous 6 months or the use of supplemental oxygen ≥ 4 liters with physical exertion
• hip fracture, hip or knee replacement, or spinal surgery in the past 6 months
• undergoing physical therapy involving the lower extremities
• use in the past 6 months of any medications known to alter bone metabolism (e.g., oral glucocorticoids, bone anti- resorptive agents)
• No metal implants (detailed above) if participating in the optional MRI study

Other illness

• history of hospitalization for Corona Virus Disease 2019 (COVID-19)
• not willing to provide evidence of completed COVID-19 vaccination.
• uncontrolled hypertension defined as resting systolic BP \>150 mmHg or diastolic BP \>90 mmHg; participants who do not meet these criteria at first screening will be re-evaluated, including follow-up evaluation by their primary care provider (PCP) with initiation or adjustment of anti-hypertensive medications.
• diagnosed ischemic heart disease or indicators of unstable ischemic heart disease (e.g., angina) or arrhythmias at rest or during the graded exercise test (GXT) without negative follow-up evaluation will be cause for exclusion; follow-up evaluation must include diagnostic testing (e.g., thallium stress test) with interpretation by a cardiologist
• diagnosis of heart failure, clinically significant aortic stenosis, uncontrolled angina, or uncontrolled arrhythmia.
• confirmed history of osteoporotic fracture
• documented history of cognitive impairment or dementia or Mini-Cog \< 4.
• personal history of breast, ovarian, metastatic endometrial, or cervical cancer
• any cancer requiring treatment in the past 3 years except non-melanoma skin cancers
• undiagnosed vaginal bleeding
• women who, in the judgment of the study physician, appear incapable of safely participating in the exercise (e.g., neuromuscular/musculoskeletal impairment).

Lab values

• acute liver disease indicated by liver function tests (ALT, aspartate aminotransferase, alkaline phosphatase) ≥ 1.5 times the upper limits of normal
• estimated glomerular filtration rate (eGFR) \< 45, using Modification of Diet in Renal Disease Study (MDRD) equation
• poorly controlled diabetes mellitus based on HbA1c \> 8.5% or use of insulin.
• fasted serum triglycerides \> 400 mg/dL
• serum 25-hydroxy vitamin D \< 20 ng/mL; volunteers will be re-considered for participation in the study after initiation or adjustment of vitamin D supplementation, per the study's vitamin D repletion protocol.

Other

• orthopedic problems (e.g., severe osteoarthritis, rheumatoid arthritis) that greatly limit the ability to perform moderate to high intensity resistance exercise (e.g., unable to be properly positioned in exercise equipment or to have severely restricted range of motion even after modifications have been made)
• hematocrit \> 54%
• thyroid dysfunction, defined as an ultrasensitive thyroid stimulating hormone (TSH) \< 0.4 or \> 10 micro units/mL, without signs or symptoms of clinical hypo- or hyperthyroidism.volunteers with abnormal TSH values will be re-considered for participation in the study after follow-up evaluation by their PCP with initiation or adjustment of thyroid hormone replacement
• use of DHEA supplementation or sex hormones in the past 6 months. Use of prescription low dose vaginal estrogen creams (Premarin or Estrace) 3 days per week or less will not be exclusionary.
• lumbar spine, total hip, or femoral neck aBMD t-scores \< -3.0.
• secondary osteoporosis
• current smoker
• Known claustrophobia if participating in the optional MRI study

• women aged 55 to 85 years
• non-frail, as determined by Short Physical Performance Battery score \> 9 (0-12 scale)
• 5 years or longer since menopause (defined as last menstrual period)
• willing to participate in a 36-week exercise program that will start at a moderate intensity and gradually progress to a higher intensity
• willing to take DHEA (50mg/d) or a placebo pill daily and remain blinded for up to 36 weeks
• not performing resistance exercise training or high impact weight-bearing exercise (e.g., jogging) ≥ 2 days per week in the past 6 months
• ambulatory without assistive devices
• serum DHEAS \< 140 μg/dL (3.8 μmol/L)
• low bone mass or moderate osteoporosis indicated by lumbar spine, total hip, or femoral neck aBMD t-scores \< -1.0 and ≥ -3.0
• refusal of standard osteoporosis treatment in women with moderate osteoporosis (BMD ≥-3.0 and ≤ -2.5)
• evidence of a negative (no findings suspicious for breast cancer) mammogram within the past 12 months
• planning to reside in the Denver area for the duration of the study
• willing to provide evidence of completed COVID-19 vaccination
• no implanted metal or electronic devices
• no metallic foreign body in the eye
• no "triggerfish" contact lenses
• no gastric reflux device
• no insulin pumps
• no temporary transvenous pacing leads
• no aneurysm clips
• no cardiac pacemakers
• no implanted cardioverter defibrillator
• no magnetically-activated implant or device
• no neurostimulation system
• no spinal cord stimulator
• no cochlear implant
• no bone growth/bone fusion stimulator
• no known claustrophobia