Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effects of Testosterone Replacement on Atherosclerosis Progression in Older Men With Low Testosterone Levels
Brief Summary: As men grow older, their testosterone levels decrease with age. One-third of men, 70 years of age or older, have low testosterone levels. It is known that short-term testosterone replacement is safe, and can increase muscle strength and physical function, but the risks of long-term testosterone replacement in older men with low testosterone levels are incompletely understood.

Atherosclerosis is characterized by thickening of the artery walls, and the narrowing of the blood vessels as cholesterol is deposited in the lining of the arteries. It is the major cause of cardiovascular disease including ischemic heart disease (heart attacks) and stroke. Although, historically, there has been a widespread perception that higher levels of testosterone might increase the risk of atherosclerosis, the evidence from research does not support this. In observational studies, higher testosterone levels have been correlated with more favorable cardiovascular risk factors, and supplementation with testosterone to bring older men into the normal range for healthy younger men appears to improve several cardiovascular risk factors, and may slow the progression of atherosclerosis.

The primary purpose of this study is to look at the effects of testosterone replacement on the progression of atherosclerosis in older men. This study is also being done to find out whether replacement with testosterone in older men with low testosterone levels improves their health-related quality of life.


Options:
A: Inclusion Criteria:

* A signed informed consent to participate in the study
* Men aged 35 to 70 with testosterone levels below 12 nmol/L or free testosterone below 225 pmol/L
* Presence of the metabolic syndrome according to the IDF definition

Exclusion Criteria:

* Patients under 35 or above 70 years.
* Participation in any clinical study within 30 days before the first injection of the drug
* Simultaneous participation in another clinical study
* Incapable subjects as well as prisoners
* Suspicion of a serious organic or mental disease according to medical history and/or clinical examination
* Prostate cancer, breast cancer or suspicion thereof
* Presence or history of hepatic tumors
* Acute or chronic hepatic disease
* Presence of renal diseases with renal failure
* Changes in biochemical or hematological laboratory values in spite of lack of clinical manifestations, in the investigator's opinion
* Suspected lack of the patient's compliance
* Hypersensitivity to the active substance
B: Inclusion Criteria:

* Age 60 years or greater
* Hypogonadism, Testosterone 100-400 ng/dl or Free Testosterone \< 50 pg/ml
* Generally good health
* At least 8 years of primary school education
* Able to pass screening test for dementia
* Able to give informed consent

Exclusion Criteria:

* Testosterone level \< 100 ng/dl (these individuals will be referred for evaluation of severe hypogonadism)
* Use of testosterone or other androgens \[dehydroepiandrosterone (DHEA), Androstenedione\] in last year
* Use of growth hormone in the last year
* Current alcohol of drug dependence \[Alcohol Use Disorders Identification Test (AUDIT) Score \> 8\]
* Diseases known to affect gonadal function
* Medications known to affect gonadal function eg. anticonvulsants, glucocorticoids such as prednisone
* Prostate cancer, breast cancer
* Any cancer that may limit life expectancy to less than 5 years
* Limiting neuromuscular, joint or bone disease
* History of stroke with residual neurologic deficit
* Neurologic condition that would impair cognitive function including:

epilepsy, multiple sclerosis, human immunodeficiency virus (HIV), Parkinson's disease, stroke

* Psychiatric disorder in the last year meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSMIV) Axis 1 criteria
* Use of psychotropic medicine for at least 6 months
* Dementia as assessed by (Telephone Interview for Cognitive Status modified score less than 31)
* Severe symptoms of benign prostatic hyperplasia (BPH) (American Urological Association symptom index score greater than 21)
* Prostate nodule or induration of digital rectal exam (DRE)
* Prostate specific antigen (PSA) greater than 4 unless participant has had a negative transrectal biopsy within last 3 months
* Limiting heart disease in including New York (NY) Class III or IV - congestive heart failure, unstable angina, or myocardial infarction (MI) in last 3 months
* Liver function tests \[aspartate aminotransferase (AST) and alanine aminotransferase(ALT)\] greater than 3 times the upper limit of the reference range
* Serum creatinine (Cr) greater than 2.5 mg/dl
* Hematocrit greater than 48%
* Hemoglobin (Hb)A1c greater than 9.0%
* Untreated thyroid disease
* Uncontrolled hypertension (systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg)
* Body mass index (BMI greater than 35 kg/m2)
* Untreated severe obstructive sleep apnea
* Development of electrocardiogram (EKG) changes consistent with myocardial ischemia or changes in blood pressure during cardiopulmonary exercise testing will be excluded from testing of muscle strength and physical function.
C: 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
D: Inclusion Criteria:

* Men, 40-70 years of age, in a stable relationship, with mild to moderate erectile dysfunction for at least 6 months; defined as an IIEF-EF domain score between 11 and 25 (mild to moderate ED)
* Neutral or extremely dissatisfied with one's sex life
* Presence of androgen deficiency defined as serum total testosterone level less than 300 ng/dL (measured by LC-MS/MS) and/or free testosterone level (measured by equilibrium dialysis) less than 50 pg/ml.
* Able to understand the nature of the study and provide written, informed consent

Exclusion Criteria:

* Contraindication for use of testosterone, e.g., history of prostate or breast cancer
* benign prostatic hyperplasia with AUA/IPSS symptom scores of 21 or greater
* erythrocytosis (hematocrit \>50% at baseline)
* untreated, severe sleep apnea
* serum PSA levels \>4 ug/L will be excluded unless they have had a urologic evaluation in the past three months to exclude prostate cancer.
* Contraindication for use of sildenafil, e.g., symptomatic coronary artery disease taking long-acting or short-acting nitrate drugs on a regular basis.
* Symptomatic postural hypotension
* Congestive heart failure with class III or IV symptoms
* History of myocardial infarction or stroke within the past six months
* Primary diagnosis of another sexual disorder such as premature ejaculation
* AST, ALT, alkaline phosphatase elevation greater than three times the upper limit of normal, creatinine greater than 2 mg/dL.
* Currently taking testosterone or oral androgen precursors; unless willing to discontinue their use for 4 weeks (oral precursors or transdermal testosterone patch or gel) or 6 weeks (if injectable testosterone) before the initial screen visit.
* Currently taking medications that affect androgen metabolism, action, or clearance (dilantin, phenobarbital, aldactone, flutamide, finasteride).
* Uncontrolled diabetes mellitus or diabetes mellitus, e.g., if their baseline hemoglobin A1C is less than 8.5%.
* Structural abnormalities of the penis, including Peyronie's disease, will be excluded.
* Men who are taking medications for erectile dysfunction, including sildenafil, must stop using these medications for at least 4 weeks before starting Visit 2.
* DSM-IV criteria for an Axis I psychiatric disorder within the past year, including depression; use of psychotropic medication for at least six months, or dementia is also an exclusion.

Answer: B