Table 2:
Comparison of randomized control trials
| Author/Year | Copenhagen, 198641 | Marin, 199333 | Srinivas-Shankar, 201042 | Behre, 201243 | Brock, 201644 | Snyder, 201616 |
|---|---|---|---|---|---|---|
| Study Size | N=221 | N=31 | N=274 | N=362 | N=558 | N=790 |
| Mean age | 53 years | 58 years | 74 years | 62 years | 55 years | 72 years |
| Inclusion Criteria | Hospitalized men, daily ethanol consumption >50gm for >2 years, cirrhosis diagnosed by liver biopsy within 6 months |
Men age >40 years, abdominal obesity (WHR>0.9), BMI <35, serum total testosterone <20nmol/L (577 ng/dL), stable weight | Men ≥65 years, frailty, low morning total testosterone <345 ng/dL or free T <7.2 ng/dL | Men 50–80 years old, symptomatic hypogonadism, AMS score>36, total testosterone <430 ng/dL, free testosterone < 193 ng/dL | Men ≥18, 2 total testosterone levels <300 ng/dl, symptomatic hypogonadism | Men age >65 years, serum testosterone <275 ng/dL, symptoms of hypogonadism |
| Exclusion Criteria | Malignancy, Hepatitis infection, Klinefelter’s syndrome, unable to cooperate | Prostate enlargement or elevated PSA (>3.0ug/L), diabetes mellitus, hypertension, alcohol abuse | Prostate cancer, IPSS score >21, PSA >4ng/ml, creatinine >180mmol/liter, active liver disease, moderate to severe pad, severe COPD, CHF (NYHA ≥2), angina requiring nitrates, untreated sleep apnea, major psychotic illness, certain medications, stroke, MMSE score <18, active disease of muscle or joint | BMI>35kg/m2, PSA ≥4ng/mL, IPSS≥20, prostate cancer, hematocrit >50%, prolactin >25ng/mL, metallic implants, cytochrome P450 inducing medications, psychiatric disorders, uncontrolled diabetes mellitus, uncontrolled thyroid disorder, HTN, epilepsy, severe cardiac, hepatic, or renal insufficiency | Hemoglobin A1c>11%, BMI >37kg/m2, hematocrit >50%, active cancer, PSA>4ng/mL | History of prostate cancer, high risk of prostate cancer by Prostate Cancer Risk Calculator, an IPSS >19, conditions known to cause hypogonadism, medications that alter testosterone concentration, high cardiovascular risk, severe depression, “other conditions that would affect the interpretation of the results”. |
| Intervention | Micronized-free testosterone (600mg daily) (n=134) vs. placebo (n=87) | Testosterone gel vs. DHT gel vs. placebo gel | Testosterone gel (n=130) vs. placebo gel (n=132) | Testosterone gel (n=183) vs. placebo gel (n=179) | Topical 2% testosterone (n=283) vs. observation (n=275) | Testosterone gel (n=394) vs. placebo gel (n=394) |
| Masking | Double-blind | Double-blind | Double-blind | Double-blind | Open-label | Double-blind |
| Follow Up Duration | 3 years | 9 months | 6 months | 6 months | 6 months | 12 months |
| VTE events | Testosterone = 3 Placebo = 0 | Gel testosterone = 1 Gel DHT= 0 Placebo gel = 0 |
Testosterone = 1 Placebo = 0 | Testosterone = 1 Placebo = 0 | Testosterone = 2 Observation = 0 | Testosterone = 3 Placebo = 2 |
| Random sequence generation | Low ROB | Unclear | Low ROB | Low ROB | Low Risk | Low ROB |
| Allocation concealment | Low ROB | Unclear | Low ROB | Unclear | Unclear | Low ROB |
| Blinding of participants and personnel | Low ROB | Low ROB | Low ROB | Low ROB | High ROB | Low ROB |
| Blinding of outcome assessment | Low ROB | Unclear | Low ROB | Low ROB | Low ROB | Low ROB |
Abbreviations: AMS = Aging Males Symptoms, BMI = body mass index, CHF = congestive heart failure, COPD = chronic obstructive pulmonary disease, DHT = dihydrotestosterone, HTN= hypertension, IPSS = International Prostate Symptom Score, MMSE = Mini Mental Status Examination, Prostate Symptom Score, PSA = prostate antigen, ROB = risk of bias, WHR = waist-hip ratio