Study Criteria Intervention Primary outcome Results
Testosterone gel
vs
Placebo
for physical function
in men ≥ 65 years

NEJM
2016

PubMed abstract
Main inclusion criteria:
  • ≥ 65 years of age
  • Serum testosterone < 275 ng/dl
  • Self-reported difficulty walking or climbing stairs and a gait speed of less than 1.2 m per second on the 6-minute walk test
Main exclusion criteria:
  • History of prostate cancer or high-risk for prostate cancer
  • BPH symptoms (IPSS score > 19)
  • MI or stroke within previous 3 months
  • SBP > 160; DBP > 100
  • NYHA III or IV heart failure

  • Average age was 72 years
  • Average baseline testosterone level was 234 ng/dl
  • Average BMI was 31
Group 1 (191 patients) - AndroGel 1% starting at 5g once daily and titrated to a normal range for a 19 - 40 year old male

Group 2 (196 patients) - placebo gel once daily
  • Treatment period was for 1 year
  • Testosterone levels were checked at 1, 2, 3, 6, and 9 months
The primary outcome was the percentage of men who increased the distance walked in the 6-minute walk test by at least 50 meters

Primary outcome:
  • Group 1 - 20%, Group 2 - 12% (at 12 months)
  • Adjusted odds ratio of achieving primary outcome - 1.42, 95%CI [0.83 - 2.45], p=0.20, nonsignificant

  • Median free testosterone level at the end of the study in Group 1 was ∼ 150 pg/ml

Study Criteria Intervention Primary outcome Results
Testosterone gel
vs
Placebo
for vitality
in men ≥ 65 years

NEJM
2016

PubMed abstract
Main inclusion criteria:
  • ≥ 65 years of age
  • Serum testosterone < 275 ng/dl
  • Self-reported low vitality and a score of less than 40 on the Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue scale (range, 0 to 52, with higher scores indicating less fatigue)
Main exclusion criteria:
  • History of prostate cancer or high-risk for prostate cancer
  • BPH symptoms (IPSS score > 19)
  • MI or stroke within previous 3 months
  • SBP > 160; DBP > 100
  • NYHA III or IV heart failure

  • Average age was 72 years
  • Average baseline testosterone level was 234 ng/dl
  • Average BMI was 31
Group 1 (236 patients) - AndroGel 1% starting at 5g once daily and titrated to a normal range for a 19 - 40 year old male

Group 2 (238 patients) - placebo gel once daily
  • Treatment period was for 1 year
  • Testosterone levels were checked at 1, 2, 3, 6, and 9 months
The primary outcome was the percentage of men whose score on the FACIT–Fatigue scale increased by at least 4 points

Primary outcome:
  • Group 1 - 72.4%, Group 2 - 62.8% (at 12 months)
  • Adjusted odds ratio of achieving primary outcome - 1.23, 95%CI [0.83 - 1.84], p=0.30, nonsignificant

  • Median free testosterone level at the end of the study in Group 1 was ∼ 150 pg/ml

Study Criteria Intervention Primary outcome Results
Testosterone
vs
Placebo
for leg strength
in men ≥ 65 years

NEJM
2010

PubMed abstract
Main inclusion criteria:
  • ≥ 65 years of age
  • Serum testosterone 100 - 350 ng/dl or free testosterone < 50 pg/ml
  • Limitations in mobility
Main exclusion criteria:
  • Heart attack within 3 months of enrollment
  • NYHA III or IV heart failure
  • PSA > 4 ng/ml
  • Hematocrit > 48%
  • BMI > 40

  • Average age was 74 years
  • Average baseline testosterone level was 243 ng/dl
  • Average BMI was 30
Group 1 (106 patients) - 10g of gel containing 100 mg of testosterone (Testim 1%) once daily for 6 months

Group 2 (103 patients) - placebo gel once daily for 6 months

Dose was adjusted as needed 2 weeks after randomization based on testosterone level
The primary efficacy outcome was the change from baseline in maximal voluntary muscle strength in a leg-press exercise.

  • The study was stopped early because of a higher incidence of cardiovascular events in Group 1 when compared to Group 2 (Group 1 - 23 events, Group 2 - 5 events)
  • Of the 209 randomly assigned men, 129 had completed the 6-month intervention period, and an additional 47 had received the study medication for 12 or more weeks and had undergone at least one outcome assessment after randomization.
  • Average testosterone levels were 574 ng/dl in Group 1



Study Criteria Intervention Primary outcome Results
Testosterone gel
vs
Placebo
for sexual function
in men ≥ 65 years

NEJM
2016

PubMed abstract
Main inclusion criteria:
  • ≥ 65 years of age
  • Serum testosterone < 275 ng/dl
  • Self-reported decreased libido, a score of 20 or less on the sexual-desire domain (range, 0 to 33, with higher scores indicating greater desire) of the Derogatis Interview for Sexual Functioning in Men–II (DISF-M-II), and a partner willing to have intercourse twice a month.
Main exclusion criteria:
  • History of prostate cancer or high-risk for prostate cancer
  • BPH symptoms (IPSS score > 19)
  • MI or stroke within previous 3 months
  • SBP > 160; DBP > 100
  • NYHA III or IV heart failure

  • Average age was 72 years
  • Average baseline testosterone level was 234 ng/dl
  • Average BMI was 31
Group 1 (230 patients) - AndroGel 1% starting at 5g once daily and titrated to a normal range for a 19 - 40 year old male

Group 2 (229 patients) - placebo gel once daily
  • Treatment period was for 1 year
  • Testosterone levels were checked at 1, 2, 3, 6, and 9 months
The primary outcome was the change from baseline in the score for sexual activity (question 4) on the Psychosexual Daily Questionnaire (PDQ-Q4; range, 0 to 12, with higher scores indicating a greater number of activities)

Primary outcome:
  • The average difference in the change from baseline on the PDQ-Q4 score was 0.58 (95%CI [0.38 - 0.78), p<0.001, significant
  • The difference (0.58) equates to a 4.8% improvement on the PDQ-Q4 scale

  • Median free testosterone level at the end of the study in Group 1 was ∼ 150 pg/ml

Study Criteria Intervention Primary outcome Results
Testosterone
vs
Placebo
in men with diabetes

J Clin Endocrinol Metab
2014

PubMed abstract
Main inclusion criteria:
  • Age 35 - 70 years
  • Type 2 diabetes with A1C < 8.5%
  • Serum testosterone 144 - 346 ng/dl
Main exclusion criteria:
  • NYHA III or IV heart failure
  • PSA > 4 ng/ml
  • Hematocrit > 50%
  • CrCl < 30ml/min

  • Average age was 62
  • Average baseline BMI was 32
  • Average baseline testosterone level was 248 ng/dl
  • Average baseline AMS score was 33
  • Average baseline IIEF-5 score was 17.5
Group 1 (45 patients) - Testosterone undecanoate 1000 mg IM at 0, 6, 18, and 30 weeks

Group 2 (43 patients) - Placebo injection

Change after 40 weeks of therapy in constitutional symptoms using the aging male symptoms (AMS) score, sexual desire (question 17 AMS score), and erectile function (International Index of Erectile Function-5)
  • There was no significant difference between the two groups for AMS score and sexual desire (question 17 AMS score)
  • Group 1 had significantly better IIEF-5 scores than Group 2 (p=0.02), but the change in score from baseline for Group 1 was not significant (p=0.20)
  • Average testosterone level was ∼ 418 ng/dl in Group 1 at 40 weeks




Study Criteria Intervention Primary outcome Results
Testosterone
vs
Placebo
in older men

JAMA
2015

PubMed abstract

Main inclusion criteria:
  • Age ≥ 60 years
  • Testosterone level 100 - 400 ng/dl or free testosterone < 50 pg/ml

Main exclusion criteria:
  • BMI > 35
  • SBP > 160 mmHg; DBP > 100 mmHg
  • PSA > 4 ng/ml
  • Hematocrit > 48%

Baseline characteristics:
  • Average age 67.6 years
  • Average BMI 28
  • Average testosterone 307 ng/dl
Group 1 (155 patients) - Testosterone gel 1% titrated to a target level of 500 - 900 ng/dl

Group 2 (151 patients) - Placebo gel

Treatment length was 3 years
Coprimary outcome: the rate of change in distal right common carotid artery intima-media thickness (CIMT) and coronary artery calcium (CAC)

Secondary outcome: sexual function and health-related quality of life
Coprimary outcomes at 3 years:
  • There was no significant difference in rate of change of CIMT between groups (mean difference 0.0002 mm/year; 95%CI [−0.003 to 0.003], p=0.89)
  • There was no significant difference in rate of change of CAC scores between groups (Group 1 - 31.4 units/yr, Group 2 - 41.4 units/year, mean difference 10.8; 95%CI [−45.7 to 24.2 Agatston units], p=0.54)
  • Average testosterone level at 3 years: Group 1 - 565 ng/dl; Group 2 - 330 ng/dl

Secondary outcomes at 3 years:
  • There was no significant difference in erectile function, orgasmic function, sexual desire, and intercourse satisfaction between groups
  • There was no significant difference in quality of life and self-reported physical function between groups