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CompletedNCT00799617Updated Feb 21, 2019Results posted

The Testosterone Trials in Older Men

A Phase 3 interventional study of AndroGel® (testosterone gel) and Placebo in Andropause, sponsored by University of Pennsylvania. Completed at 12 sites in United States. Open to male participants aged 65 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-02-21.

Sponsored by University of Pennsylvania · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
790
Allocation
Randomized
Ages
65 Years and older
Sex
Male
01

Study summary

The Testosterone Trials are a multi-center set of trials involving 12 clinical sites geographically distributed across the United States.

The primary specific aims are to test the hypotheses that testosterone treatment of elderly men whose serum testosterone concentrations are unequivocally low - and who have symptoms and objectively measured abnormalities in at least one of five areas that could be due to low testosterone (physical or sexual function, vitality, cognition, and anemia) - will result in more favorable changes in those abnormalities than placebo treatment.

Two additional trials have been incorporated into the T Trial. Only men enrolled in the T Trial are eligible to participate in these trials.

  • The Cardiovascular Trial will examine if testosterone treatment results in more favorable changes in cardiovascular risk factors, compared to placebo.
  • The Bone Trial will test the hypothesis that testosterone treatment will increase volumetric trabecular bone mineral density (vBMD) of the lumbar spine as measured by quantitative computed tomography (QCT), compared with placebo treatment.

A Pharmacokinetic (PK) Study is also being conducted within the context of the interventional T Trial. It will examine the variability of the serum testosterone (T) concentration after application of testosterone gel or placebo, four months after the start of treatment.

Read the detailed description

As men get older, they experience many conditions, often together, that eventually result in the inability to perform many activities of daily living, an increased propensity to fall, and decreased independence. These conditions include mobility disability and low vitality. Elderly men also experience increased anemia, metabolic syndrome, decreased sexual function and memory impairment. These conditions likely have multiple causes, but one cause that could contribute to all of them is a low serum testosterone concentration. When young hypogonadal men are treated with testosterone, they experience improvements in sexual function, muscle mass and strength, bone mineral density, sense of well being, and anemia. However, the benefits of testosterone therapy in older men with age-related decline in testosterone concentration are not known and are the subject of this investigation.

Participants will be treated with testosterone or placebo gel for 1 year. The dose will be adjusted in a blinded fashion to achieve a target T level range. Participants will be followed for one additional year following the treatment phase to assess adverse events.

  • Men participating in the Cardiovascular Trial will be assessed for changes in atherosclerotic plaque burden from 0 to 12 months.
  • Men participating in the Bone Trial will be assessed by QCT of the spine and hip, DXA of the spine and hip and clinical fractures at 0 and 12 months.
  • Men participating in the PK Study will attend 3 additional study visits for blood draws at the time of the 4-month assessment.
02

Conditions studied

  • Andropause

Keywords

  • Testosterone
  • Mobility disability
  • Decreased libido
  • Age associated memory impairment
  • Low vitality
  • Anemia
03

In context

Lead sponsor

University of Pennsylvania is the lead sponsor of 1,635 studies on the registry; 239 are open to participants now.

Of its 154 completed or terminated interventional studies of FDA-regulated products, 104 (68%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
65 Years and older
Sexes eligible
Male
Accepts healthy volunteers
Yes

Inclusion criteria

  • Men greater than or equal to 65 years old
  • Total serum testosterone concentration \< 275 and \< 300 ng/dL at 7 -10 AM at each of two screening visits

Exclusion criteria

Exclusion Criteria:

  • Diagnosed prostate cancer, prostatic intraepithelial neoplasia (PIN), prostate nodule or, by the Prostate Cancer Risk Calculator, a >35% risk of having overall prostate cancer or >7% risk of having high grade prostate cancer
  • Severe lower urinary tract symptoms (score of > 19) by the International Prostate Symptom Score questionnaire
  • Hemoglobin \<10 g/dL or >16.0 g/dL
  • Sleep apnea, diagnosed but untreated
  • Alcohol or substance abuse within the past year (based on self report)
  • Angina not controlled by treatment
  • NYHA class III or IV congestive heart failure
  • Myocardial infarction within the previous 3 months before entry
  • Stroke within the previous 3 months before entry
  • Severe pulmonary disease that precludes physical function tests
  • Serum creatinine >2.2 mg/dL; ALT 3x upper limit of normal; hemoglobin A1c >8.5%, TSH > 7.5mIU/L
  • Diagnosis or treatment for cancer within the past 3 years, with the exception of nonmelanotic skin cancer
  • Body mass index (BMI) >37 kg/m2
  • Mini Mental State Exam (MMSE) Score \<24
  • Major psychiatric disorders, including major depression (PHQ-9 score > 14), mania, hypomania, psychosis, schizophrenia or schizoaffective disorders, that are untreated, unstable, have resulted in hospitalization or medication change within the previous three months, or would result in inability to complete the trial efficacy instruments. Subjects whose disorders have been stable while being treated for more than three months are eligible.

  • Use of the following medications within the previous three months:

    • drugs that affect serum testosterone concentration
    • rhGH or megestrol acetate
    • introduction of anti-depressant medication
    • daily use of prednisone for more than two weeks
  • Opiate use within the past three months
  • Skin conditions at the testosterone gel application site, such as ulcer, erosion, lichenification, inflammation, or crust, or generalized skin conditions such as psoriasis or eczema that might affect testosterone absorption or tolerability of the testosterone gel
  • Known skin intolerance to alcohol or allergy to any of the ingredients of testosterone gel

Participants in the T Trial may also enroll in the Cardiovascular and Bone Trials if it is determined that they are eligible based on the specific exclusion criteria.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
790 participants (actual)

Study arms

  • Active comparator
    AndroGel® (testosterone gel)

    The initial dose of AndroGel will be 5.0 g (containing 50 mg of testosterone) once a day. Participants will apply AndroGel once daily to the shoulders, abdomen or upper arms. The serum testosterone concentration will be measured monthly for the first three months, then at months 6, 9 and 12. If the testosterone concentration is not between 500 and 800 ng/dL at any time point, the dose will be either increased by increments of 1.25-2.5 g/day, up to a maximum of 15 g/day or decreased by increments of 1.25-3.75 ng/day. Participants will be taught how to apply the gel and they will be provided with written instructions and precautions. This information will be reviewed at each contact and visit.

    Drug: AndroGel® (testosterone gel)

  • Placebo comparator
    Placebo gel

    Placebo gel is identical to the testosterone gel and is supplied in an identical pump bottle container. It is applied to the shoulders, abdomen or upper arms once a day. Participants will be taught how to apply the gel and they will be provided with written instructions and precautions. This information will be reviewed at each contact and visit.

    Drug: Placebo

Interventions

  • DrugAndroGel® (testosterone gel)

    Testosterone levels will be measured at regular intervals in order to achieve a testosterone level in the desired range.

    Also known as: Testosterone gel

  • DrugPlacebo

    Testosterone levels will be measured at regular intervals.

06

What researchers measure

Primary outcomes

  1. Sexual Function Trial - Change in Psychosexual Daily Questionnaire Question 4 (PDQ-Q4) From Baseline to Month 12

    Baseline score and change in responses to Question 4 of the Psychosexual Daily Questionnaire (PDQ-Q4) from baseline to Month 12. Question 4 asks 12 questions about sexual activity. Scores on the PDQ-Q4 range from 0 to 12, with higher scores indicating more activity. The change is measured form the baseline value to Month 12.

    Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)

  2. Physical Function Trial - The 6-Minute Walk Test - no./Total no. (%)

    The number and percentage of men who increased the distance walked in the 6-Minute Walk Test by at least 50 meters.

    Time frame: 1 year (Number of participants who increased walk distance > or = 50 meters, change from baseline to month 3, 6, 9 and 12)

  3. Vitality Trial - Increase in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score Greater Than or Equal to 4 - no./Total no. (%)

    The number of participants whose score on the FACIT-Fatigue scale increased by at least 4 points. Scores on the FACIT- Fatigue scale range from 0 to 52, with higher scores indicating less fatigue.

    Time frame: 1 year (Number of participants who increased FACIT-Fatigue score > or = to 4, change from baseline to month 3, 6, 9 and 12)

  4. Cardiovascular Trial - Assess Impact of Testosterone Treatment in Older Men on Noncalcified Plaque Volume

    Non-calcified coronary artery plaque volume, mm3, as determined by coronary computed tomographic angiography (CTA), mean difference in change from baseline to month 12

    Time frame: 1 year (change in plaque volume measurement from baseline to month 12)

  5. Bone Trial - Volumetric Bone Mineral Density (BMD) of Spine Trabecular Bone by Quantitative Computed Tomography (QCT) in Older Men With Low Testosterone

    Volumetric Bone Mineral Density (BMD) of spine trabecular bone as measured by QCT, mg/cm3, the calculated change in measurement from baseline to Month 12

    Time frame: 1 year (QCT measurement of BMD change between baseline and month 12)

  6. Cognitive Function Trial - Delayed Paragraph Recall Wechsler Memory Scale Revised Logical Memory II (WMS-R LMII)

    Baseline score and change in score of the Wechsler Memory Scale Revised Logical Memory II (WMS-R LMII) test of Delayed Paragraph Recall, at baseline, Month 6 and Month 12. The WMS-R LM II involves a delayed paragraph recall activity scored in two components, each ranging from 0-25. The final score is the sum of each component, therefore falling in the range 0-50. WMS-R LM II scores were treated as continuous with change compared between treatment arms using linear random effects models adjusting for several factors: site, indicator variables of participation in each primary efficacy trial, baseline testosterone concentration (\<200), age (≤ 75), use of anti-depressants, use of PDE-inhibitors, baseline WMSR, categorical education, and version of the WMSR.

    Time frame: 1 year (change from baseline to month 6 and month 12)

  7. Anemia Trial - Effect of Testosterone on Hemoglobin Levels - Unexplained Anemia

    Proportion of men age 65 years or older with unexplained anemia who increased their hemoglobin level by 1.0 g/dL from baseline. Values are No. (%) for dichotomous outcomes. Dichotomous hemoglobin response is an increase of 1 g/dL or more from baseline.

    Time frame: 1 year (change in hemoglobin g/dL from baseline to month 3, 6, 9 and 12)

Secondary outcomes

  1. Sexual Function Trial - Sexual Desire Domain

    Baseline score and the changes in the score of the sexual-desire domain of the Derogatis Interview for Sexual Functioning in Men-II (DISF-M-II), from baseline to Month 12. Scores on the (DISF-M-II) range from 0 to 33, with higher scores indicating greater sexual desire.

    Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)

  2. Sexual Function Trial - Erectile Function

    Baseline score and the change in score on the International Index of Erectile Function (IIEF) from baseline to Month 12. Scores on the IIEF range from 0-30, with higher scores indicating better function.

    Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)

  3. Physical Function Trial - 6 Minute Walk Test - Total Walking Distance in Meters

    Baseline score and the change in distance walked in the 6-Minute Walking Test in meters from baseline to Month 12

    Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)

  4. Physical Function Trial - The Physical Function Domain (PF-10) of the SF-36 - no./Total no. (%)

    The number of participants whose score on the physical-function domain (PF-10; range, 0 to 100, with higher scores indicating better function) of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) increased by at least 8 points from baseline to Month 12.

    Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)

  5. Physical Function Trial - PF 10 Overall Score

    Baseline score and the change in score on the physical-function scale (PF-10) of the Medical Outcomes Study 36-Item Short Form Health Survey range from 0 to 100, with higher scores indicating better function. Scores were measured as the change from baseline to Month 12.

    Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)

  6. Vitality Trial - FACIT Fatigue Overall Score

    Baseline score and change in the FACIT- Fatigue score from baseline to Month 12. Scores on the Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue scale range from 0 to 52, with higher scores indicating less fatigue.

    Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)

  7. Vitality Trial - SF-36 Score

    Baseline score and change in the SF-36 Vitality Score from baseline to Month 12 Scores on the vitality scale of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) range from 0 to 100, with higher scores indicating less fatigue.

    Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)

  8. Vitality Trial - Change in the Positive Affect Score of the Positive and Negative Affect Scales (PANAS) From Baseline to Month 12.

    Baseline score and change in the total positive affect score of the Positive and Negative Affect Scales (PANAS) from baseline to Month 12. Scores for positive affect and for negative affect on the Positive and Negative Affect Schedule (PANAS) scales range from 5 to 50, with higher scores indicating a greater intensity of the affect.

    Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)

  9. Vitality Trial - Change in the Total Negative Affect Score of the Positive and Negative Affect Scales (PANAS) From Baseline to Month 12

    Baseline score and change in the total negative affect score of the Positive and Negative Affect Scales (PANAS) from baseline to Month 12. Scores for positive affect and for negative affect on the Positive and Negative Affect Schedule (PANAS) scales range from 5 to 50, with higher scores indicating a greater intensity of the affect.

    Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)

  10. Vitality Trial - Patient Health Questionnaire 9 (PHQ-9) Change in Overall Score

    Baseline score and change in score in the Patient Health Questionnaire 9 (PHQ-9) from baseline to Month 12. Scores on the Patient Health Questionnaire 9 (PHQ-9) depression scale range from 0 to 27, with higher scores indicating greater intensity of depressive symptoms.

    Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)

  11. Cardiovascular Trial - Total Plaque Volume Change From Baseline

    Total plaque volume,mm3 measured by coronary computed tomographic angiography

    Time frame: 1 year (change from baseline to month 12)

  12. Cardiovascular Trial - Coronary Artery Calcium Score, Agatston Units Change From Baseline

    Coronary artery calcium score in Agatston units (range of 0 to \>400 Agatston units), with higher values indicating more severe atherosclerosis).

    Time frame: 1 year (change from baseline to month 12)

  13. Bone Trial - Volumetric Bone Mineral Density (BMD) of Spine Peripheral Bone by Quantitative Computed Tomography (QCT)

    Spine peripheral bone as measured by QCT, mg/cm3 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

    Time frame: 1 year (baseline to month 12)

  14. Bone Trial - Volumetric Bone Mineral Density (BMD) of Spine Whole Bone by Quantitative Computed Tomography (QCT)

    Spine whole bone as measured by QCT, mg/cm3 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

    Time frame: 1 year (baseline to month 12)

  15. Bone Trial - Volumetric Bone Mineral Density (BMD) of Hip Trabecular Bone by Quantitative Computed Tomography (QCT)

    Hip trabecular bone as measured by QCT, mg/cm3 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

    Time frame: 1 year (baseline to month 12)

  16. Bone Trial - Volumetric Bone Mineral Density (BMD) of Hip Peripheral Bone by Quantitative Computed Tomography (QCT)

    Hip peripheral bone as measured by QCT, mg/cm3 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

    Time frame: 1 year (baseline to month 12)

  17. Bone Trial - Volumetric Bone Mineral Density (BMD) of Hip Whole Bone by Quantitative Computed Tomography (QCT)

    Hip whole bone as measured by QCT, mg/cm3 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

    Time frame: 1 year (baseline to month 12)

  18. Bone Trial - Bone Strength of Spine Whole Bone by Finite Element Analysis, N

    Spine whole bone (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

    Time frame: 1 year (baseline to month 12)

  19. Bone Trial - Bone Strength of Spine Trabecular Bone by Finite Element Analysis, N

    Spine trabecular bone (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

    Time frame: 1 year (baseline to month 12)

  20. Bone Trial - Bone Strength of Spine Peripheral Bone by Finite Element Analysis, N

    Spine peripheral bone (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

    Time frame: 1 year (baseline to month 12)

  21. Bone Trial - Bone Strength of Hip Whole Bone by Finite Element Analysis, N

    Hip whole bone (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

    Time frame: 1 year (baseline to month 12)

  22. Bone Trial - Bone Strength of Hip Trabecular Bone by Finite Element Analysis, N

    Hip trabecular bone (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

    Time frame: 1 year (baseline to month 12)

  23. Bone Trial - Bone Strength of Hip Peripheral Bone by Finite Element Analysis, N

    Hip peripheral bone (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

    Time frame: 1 year (baseline to month 12)

  24. Bone Trial - Area Bone Mineral Density (BMD) of Lumbar Spine by Dual-energy X-ray Absorptiometry (DXA)

    Lumbar spine as measured by DXA, g/cm2 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

    Time frame: 1 year (baseline to month 12)

  25. Bone Trial - Area Bone Mineral Density (BMD) of Total Hip by Dual-energy X-ray Absorptiometry (DXA)

    Total hip as measured by DXA, g/cm2 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

    Time frame: 1 year (baseline to month 12)

  26. Bone Trial - Area Bone Mineral Density (BMD) of Femoral Neck by Dual-energy X-ray Absorptiometry (DXA)

    Femoral neck as measured by DXA, g/cm2 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

    Time frame: 1 year (baseline to month 12)

  27. Cognitive Function Trial - Visual Memory - Benton Visual Retention Test (BVRT)

    Baseline score and mean change in score in the Visual Memory Using the Benton Visual Retention Test (BVRT) from baseline, Month 6 and Month 12. The BVRT measures short term visual memory and visuo-constructional abilities and was administered and scored according to standard procedures. Each of 10 designs was presented one at a time for 10 seconds, and immediately after the design was withdrawn, the participant was instructed to draw it from memory on a blank sheet of paper. The score was the total number of figures with errors and ranged from 0 to 26. Scores were inverted to 0 to -26 so that higher scores would reflect better performance. Change in BVRT scores from baseline are treated as continuous and compared between AAMI Androgel and placebo subjects using linear random effects models adjusting for balancing factors as described in the primary analysis.

    Time frame: 1 year (baseline to month 6 and month 12)

  28. Cognitive Function Trial - Spatial Ability Card Rotation Test (CRT)

    Baseline score and change in score in the Spatial Ability Using the Card Rotation Test at baseline, Month 6 and Month 12. Change in performance on the Card Rotations Test will be analyzed using linear random effects models adjusting for baseline performance, balancing factors, education, and test version. The test consists of a series of 10 primary figures, each of which has 8 corresponding secondary figures. Subjects are asked to determine which of the secondary figures is the same as the corresponding primary figure, and the score is taken as the number of figures answered correctly minus the number of figures answered incorrectly. The maximum score is 80 for subjects who answer all items correctly.

    Time frame: 1 year (baseline to month 6 to month 12)

  29. Cognitive Function Trial - Executive Function - Trail Making Test B - A

    Baseline score and change in score in Executive Function as Measured by Trail-Making Test (TMT) B - A, at baseline, Month 6 and Month 12. Change in performance on the Trail Making Test was analyzed using linear random effects models adjusting for baseline performance, balancing factors, education, and test version. Participants are required to connect a set of numbers (Part A) or alternating letters and numbers (Part B) in sequential order. The score for each part is the total time (in seconds) to complete both parts. The outcome analyzed will be the total time for Trails B minus the total time for Trails A to provide a measure of working memory, adjusted for attention and processing speed. Higher scores reflect lower executive function.

    Time frame: 1 year (baseline to month 6 to month 12)

  30. Anemia Trial - Effect of Testosterone on Hemoglobin Levels - Unexplained Anemia - Hemoglobin (Continuous)

    Proportion of men age 65 years or older with unexplained anemia who increased their hemoglobin level by 1.0 gm/dL from baseline. Values are means (SDs) for continuous outcomes.

    Time frame: 1 year (baseline to month 12)

07

Results

Posted Aug 28, 2017

Participant flow

Main Testosterone Trial
Participant flow — Main Testosterone Trial
MilestoneAndroGel® (Testosterone Gel)Placebo Gel
Started395395
Completed376374
Not completed1921
Withdrew: Randomized in error11
Withdrew: Lost to follow-up1820
Sexual Funtion Trial
Participant flow — Sexual Funtion Trial
MilestoneAndroGel® (Testosterone Gel)Placebo Gel
Started234236
Completed218215
Not completed1621
Withdrew: Lost to follow-up1214
Withdrew: No baseline data47
Physical Function Trial
Participant flow — Physical Function Trial
MilestoneAndroGel® (Testosterone Gel)Placebo Gel
Started191196
Completed185185
Not completed611
Withdrew: Lost to follow-up611
Vitality Trial
Participant flow — Vitality Trial
MilestoneAndroGel® (Testosterone Gel)Placebo Gel
Started236238
Completed229216
Not completed722
Withdrew: Lost to follow-up722
Cardiovascular Trial
Participant flow — Cardiovascular Trial
MilestoneAndroGel® (Testosterone Gel)Placebo Gel
Started8882
Completed7365
Not completed1517
Withdrew: Month 12 scan not available1515
Withdrew: Baseline scan not analyzable02
Bone Trial
Participant flow — Bone Trial
MilestoneAndroGel® (Testosterone Gel)Placebo Gel
Started110101
Completed10485
Not completed616
Withdrew: Month 12 scan not available616
Cognitive Function Trial
Participant flow — Cognitive Function Trial
MilestoneAndroGel® (Testosterone Gel)Placebo Gel
Started247246
Completed247245
Not completed01
Withdrew: Lost to follow-up01
Anemia Trial
Participant flow — Anemia Trial
MilestoneAndroGel® (Testosterone Gel)Placebo Gel
Started2735
Completed2432
Not completed33
Withdrew: Withdrawal by subject33

Outcome measures

PrimarySexual Function Trial - Change in Psychosexual Daily Questionnaire Question 4 (PDQ-Q4) From Baseline to Month 12

Baseline score and change in responses to Question 4 of the Psychosexual Daily Questionnaire (PDQ-Q4) from baseline to Month 12. Question 4 asks 12 questions about sexual activity. Scores on the PDQ-Q4 range from 0 to 12, with higher scores indicating more activity. The change is measured form the baseline value to Month 12.

Time frame:
1 year (change from baseline to month 3, 6, 9 and 12)
Reported as:
Mean · units on the PDQ-Q4 scale
Sexual Function Trial - Change in Psychosexual Daily Questionnaire Question 4 (PDQ-Q4) From Baseline to Month 12
units on the PDQ-Q4 scaleAndroGel® (Testosterone Gel)Placebo Gel
Baseline Score1.4 ± 1.31.4 ± 1.3
Change at Month 30.6 ± 1.30.1 ± 1.1
Change at Month 60.6 ± 1.5-0.1 ± 1.2
Change at Month 90.5 ± 1.5-0.1 ± 1.2
Change at Month 120.2 ± 1.6-0.1 ± 1.4
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = <0.001 (The p value for the treatment effect was determined with the use of a linear mixed model with a random effect for participant.) · Mean difference (net): 0.58 · 95% CI 0.38 to 0.78Adjustment for balancing factors: baseline testosterone, age, site, trial participation, use of antidepressants, use of PDE5 inhibitors
PrimaryPhysical Function Trial - The 6-Minute Walk Test - no./Total no. (%)

The number and percentage of men who increased the distance walked in the 6-Minute Walk Test by at least 50 meters.

Time frame:
1 year (Number of participants who increased walk distance > or = 50 meters, change from baseline to month 3, 6, 9 and 12)
Reported as:
Count of participants · Participants
Physical Function Trial - The 6-Minute Walk Test - no./Total no. (%)
ParticipantsAndroGel® (Testosterone Gel)Placebo Gel
Month 32014
Month 62423
Month 92822
Month 123520
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = 0.20 (The P value for the treatment effect was determined with the use of a logistic mixed model with a random effect for participant for dichotomous outcomes and a linear mixed model with a random effect for participant for continuous outcomes.) · Odds ratio (or): 1.42 · 95% CI 0.83 to 2.45
PrimaryVitality Trial - Increase in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score Greater Than or Equal to 4 - no./Total no. (%)

The number of participants whose score on the FACIT-Fatigue scale increased by at least 4 points. Scores on the FACIT- Fatigue scale range from 0 to 52, with higher scores indicating less fatigue.

Time frame:
1 year (Number of participants who increased FACIT-Fatigue score > or = to 4, change from baseline to month 3, 6, 9 and 12)
Reported as:
Count of participants · Participants
Vitality Trial - Increase in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score Greater Than or Equal to 4 - no./Total no. (%)
ParticipantsAndroGel® (Testosterone Gel)Placebo Gel
Month 3148138
Month 6144126
Month 9148127
Month 12147120
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = 0.30 (The p value for the treatment effect was determined with the use of a logistic mixed model with a random effect for participant for dichotomous outcomes and a linear mixed model with a random effect for participant for continuous outcomes.) · Odds ratio (or): 1.23 · 95% CI 0.83 to 1.84
PrimaryCardiovascular Trial - Assess Impact of Testosterone Treatment in Older Men on Noncalcified Plaque Volume

Non-calcified coronary artery plaque volume, mm3, as determined by coronary computed tomographic angiography (CTA), mean difference in change from baseline to month 12

Time frame:
1 year (change in plaque volume measurement from baseline to month 12)
Reported as:
Mean · mm^3
Cardiovascular Trial - Assess Impact of Testosterone Treatment in Older Men on Noncalcified Plaque Volume
mm^3AndroGel® (Testosterone Gel)Placebo Gel
Cardiovascular Trial - Assess Impact of Testosterone Treatment in Older Men on Noncalcified Plaque Volume54 (12 to 97)14 (-29 to 56)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = .003 (Determined by a linear mixed model with all balancing factors and baseline outcome value as covariates and a random effect for participant.) · Mean difference (final values): 41 · 95% CI 14 to 67Mean difference in change from baseline for participants assigned to testosterone v. placebo, with adjustment for balancing factors: baseline testosterone, age, site, trial participation, use of antidepressants, PDE5 inhibitors, baseline outcome.
PrimaryBone Trial - Volumetric Bone Mineral Density (BMD) of Spine Trabecular Bone by Quantitative Computed Tomography (QCT) in Older Men With Low Testosterone

Volumetric Bone Mineral Density (BMD) of spine trabecular bone as measured by QCT, mg/cm3, the calculated change in measurement from baseline to Month 12

Time frame:
1 year (QCT measurement of BMD change between baseline and month 12)
Reported as:
Mean · mg/cm^3
Bone Trial - Volumetric Bone Mineral Density (BMD) of Spine Trabecular Bone by Quantitative Computed Tomography (QCT) in Older Men With Low Testosterone
mg/cm^3AndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Volumetric Bone Mineral Density (BMD) of Spine Trabecular Bone by Quantitative Computed Tomography (QCT) in Older Men With Low Testosterone7.5 (4.8 to 10.3)0.8 (-1.9 to 3.4)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = <.001 (Treatment effect is the mean difference in the change from baseline between testosterone and placebo arms.The P-Value for the significance of the treatment effect was determined by multivariable linear regression adjusted for balancing factors.) · Mean difference (final values): 6.8 · 95% CI 4.8 to 8.7
PrimaryCognitive Function Trial - Delayed Paragraph Recall Wechsler Memory Scale Revised Logical Memory II (WMS-R LMII)

Baseline score and change in score of the Wechsler Memory Scale Revised Logical Memory II (WMS-R LMII) test of Delayed Paragraph Recall, at baseline, Month 6 and Month 12. The WMS-R LM II involves a delayed paragraph recall activity scored in two components, each ranging from 0-25. The final score is the sum of each component, therefore falling in the range 0-50. WMS-R LM II scores were treated as continuous with change compared between treatment arms using linear random effects models adjusting for several factors: site, indicator variables of participation in each primary efficacy trial, baseline testosterone concentration (\<200), age (≤ 75), use of anti-depressants, use of PDE-inhibitors, baseline WMSR, categorical education, and version of the WMSR.

Time frame:
1 year (change from baseline to month 6 and month 12)
Reported as:
Mean · percentage of change in test score
Cognitive Function Trial - Delayed Paragraph Recall Wechsler Memory Scale Revised Logical Memory II (WMS-R LMII)
percentage of change in test scoreAndroGel® (Testosterone Gel)Placebo Gel
Baseline Score14.0 (13.2 to 14.8)14.4 (13.6 to 15.2)
Change at Month 61.1 (-0.1 to 2.3)1.1 (-0.1 to 2.3)
Change at Month 121.3 (0.1 to 2.5)1.4 (0.3 to 2.6)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = .88 (The estimated difference and P-value were determined by a linear mixed-model with a random effect for participants using outcomes at month 6 and month 12.) · Mean difference (net): -0.07 · 95% CI -0.92 to 0.79
PrimaryAnemia Trial - Effect of Testosterone on Hemoglobin Levels - Unexplained Anemia

Proportion of men age 65 years or older with unexplained anemia who increased their hemoglobin level by 1.0 g/dL from baseline. Values are No. (%) for dichotomous outcomes. Dichotomous hemoglobin response is an increase of 1 g/dL or more from baseline.

Time frame:
1 year (change in hemoglobin g/dL from baseline to month 3, 6, 9 and 12)
Reported as:
Count of participants · Participants
Anemia Trial - Effect of Testosterone on Hemoglobin Levels - Unexplained Anemia
ParticipantsAndroGel® (Testosterone Gel)Placebo Gel
Month 364
Month 683
Month 9152
Month 12134
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = .002 (The P-value for the significance of the treatment effect was determined by a logistic mixed model with a random intercept for participant.) · Odds ratio (or): 31.5 · 95% CI 3.7 to 277.8The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors.
SecondarySexual Function Trial - Sexual Desire Domain

Baseline score and the changes in the score of the sexual-desire domain of the Derogatis Interview for Sexual Functioning in Men-II (DISF-M-II), from baseline to Month 12. Scores on the (DISF-M-II) range from 0 to 33, with higher scores indicating greater sexual desire.

Time frame:
1 year (change from baseline to month 3, 6, 9 and 12)
Reported as:
Mean · Score on the DISF-M-II scale
Sexual Function Trial - Sexual Desire Domain
Score on the DISF-M-II scaleAndroGel® (Testosterone Gel)Placebo Gel
Baseline Score11.9 ± 6.711.6 ± 6.6
Change at Month 33.5 ± 6.30.7 ± 5.8
Change at Month 63.5 ± 6.00.8 ± 5.6
Change at Month 94.0 ± 7.40.9 ± 5.5
Change at Month 122.6 ± 6.50.0 ± 5.0
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = <0.001 (The p value for the treatment effect was determined with the use of a linear mixed model with a random effect for participant.) · Mean difference (net): 2.93 · 95% CI 2.13 to 3.74Adjustment for balancing factors: baseline testosterone, age, site, trial participation, use of antidepressants, use of PDE5 inhibitors
SecondarySexual Function Trial - Erectile Function

Baseline score and the change in score on the International Index of Erectile Function (IIEF) from baseline to Month 12. Scores on the IIEF range from 0-30, with higher scores indicating better function.

Time frame:
1 year (change from baseline to month 3, 6, 9 and 12)
Reported as:
Mean · Score on the IIEF test scale
Sexual Function Trial - Erectile Function
Score on the IIEF test scaleAndroGel® (Testosterone Gel)Placebo Gel
Baseline Score8.0 ± 8.27.7 ± 8.2
Change at Month 33.4 ± 6.11.0 ± 5.3
Change at Month 63.3 ± 6.50.5 ± 6.1
Change at Month 93.4 ± 6.90.5 ± 7.1
Change at Month 123.1 ± 6.91.0 ± 6.0
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = <0.001 (The p value for the treatment effect was determined with the use of a linear mixed model with a random effect for participant.) · Median difference (net): 2.64 · 95% CI 1.68 to 3.61Adjustment for balancing factors: baseline testosterone, age, site, trial participation, use of antidepressants, use of PDE5 inhibitors
SecondaryPhysical Function Trial - 6 Minute Walk Test - Total Walking Distance in Meters

Baseline score and the change in distance walked in the 6-Minute Walking Test in meters from baseline to Month 12

Time frame:
1 year (change from baseline to month 3, 6, 9 and 12)
Reported as:
Mean · meters
Physical Function Trial - 6 Minute Walk Test - Total Walking Distance in Meters
metersAndroGel® (Testosterone Gel)Placebo Gel
Baseline Score347.7 ± 69.1344.9 ± 68.5
Change at Month 310.2 ± 35.84.6 ± 35.2
Change at Month 68.2 ± 41.57.8 ± 41.4
Change at Month 95.3 ± 50.33.2 ± 52.4
Change at Month 1214.3 ± 45.95.5 ± 46.4
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = 0.28 (The P value for the treatment effect was determined with the use of a logistic mixed model with a random effect for participant for dichotomous outcomes and a linear mixed model with a random effect for participant for continuous outcomes.) · Mean difference (final values): 4.09 · 95% CI -3.00 to 11.18
SecondaryPhysical Function Trial - The Physical Function Domain (PF-10) of the SF-36 - no./Total no. (%)

The number of participants whose score on the physical-function domain (PF-10; range, 0 to 100, with higher scores indicating better function) of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) increased by at least 8 points from baseline to Month 12.

Time frame:
1 year (change from baseline to month 3, 6, 9 and 12)
Reported as:
Count of participants · Participants
Physical Function Trial - The Physical Function Domain (PF-10) of the SF-36 - no./Total no. (%)
ParticipantsAndroGel® (Testosterone Gel)Placebo Gel
Month 37759
Month 67273
Month 97760
Month 126658
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = 0.15 (The P value for the treatment effect was determined with the use of a logistic mixed model with a random effect for participant for dichotomous outcomes and a linear mixed model with a random effect for participant for continuous outcomes.) · Odds ratio (or): 1.34 · 95% CI 0.90 to 2.00
SecondaryPhysical Function Trial - PF 10 Overall Score

Baseline score and the change in score on the physical-function scale (PF-10) of the Medical Outcomes Study 36-Item Short Form Health Survey range from 0 to 100, with higher scores indicating better function. Scores were measured as the change from baseline to Month 12.

Time frame:
1 year (change from baseline to month 3, 6, 9 and 12)
Reported as:
Mean · Score on the PF-10 test scale
Physical Function Trial - PF 10 Overall Score
Score on the PF-10 test scaleAndroGel® (Testosterone Gel)Placebo Gel
Baseline Score65.4 ± 20.064.8 ± 21.3
Change at Month 35.6 ± 15.24.2 ± 13.7
Change at Month 66.5 ± 16.74.8 ± 17.0
Change at Month 95.9 ± 19.43.3 ± 18.9
Change at Month 125.8 ± 17.52.4 ± 17.3
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = 0.03 (The P value for the treatment effect was determined with the use of a logistic mixed model with a random effect for participant for dichotomous outcomes and a linear mixed model with a random effect for participant for continuous outcomes.) · Mean difference (net): 2.75 · 95% CI 0.20 to 5.29
SecondaryVitality Trial - FACIT Fatigue Overall Score

Baseline score and change in the FACIT- Fatigue score from baseline to Month 12. Scores on the Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue scale range from 0 to 52, with higher scores indicating less fatigue.

Time frame:
1 year (change from baseline to month 3, 6, 9 and 12)
Reported as:
Mean · Score on the FACIT- Fatigue test scale
Vitality Trial - FACIT Fatigue Overall Score
Score on the FACIT- Fatigue test scaleAndroGel® (Testosterone Gel)Placebo Gel
Baseline Score31.6 ± 6.431.3 ± 6.4
Change at Month 37.8 ± 8.47.2 ± 8.8
Change at Month 67.4 ± 9.15.9 ± 9.2
Change at Month 98.6 ± 9.17.2 ± 9.2
Change at Month 128.0 ± 8.46.7 ± 9.4
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = 0.06 (The p value for the treatment effect was determined with the use of a logistic mixed model with a random effect for participant for dichotomous outcomes and a linear mixed model with a random effect for participant for continuous outcomes.) · Mean difference (net): 1.21 · 95% CI -0.04 to 2.46
SecondaryVitality Trial - SF-36 Score

Baseline score and change in the SF-36 Vitality Score from baseline to Month 12 Scores on the vitality scale of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) range from 0 to 100, with higher scores indicating less fatigue.

Time frame:
1 year (change from baseline to month 3, 6, 9 and 12)
Reported as:
Mean · Score on the SF-36 vitality scale
Vitality Trial - SF-36 Score
Score on the SF-36 vitality scaleAndroGel® (Testosterone Gel)Placebo Gel
Baseline Score50.6 ± 13.849.4 ± 12.6
Change at Month 37.4 ± 13.65.9 ± 11.1
Change at Month 67.2 ± 14.64.5 ± 11.2
Change at Month 98.4 ± 14.45.7 ± 12.3
Change at Month 128.2 ± 15.36.1 ± 13.8
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = 0.03 (The p value for the treatment effect was determined with the use of a logistic mixed model with a random effect for participant for dichotomous outcomes and a linear mixed model with a random effect for participant for continuous outcomes.) · Mean difference (net): 2.41 · 95% CI 0.31 to 4.50
SecondaryVitality Trial - Change in the Positive Affect Score of the Positive and Negative Affect Scales (PANAS) From Baseline to Month 12.

Baseline score and change in the total positive affect score of the Positive and Negative Affect Scales (PANAS) from baseline to Month 12. Scores for positive affect and for negative affect on the Positive and Negative Affect Schedule (PANAS) scales range from 5 to 50, with higher scores indicating a greater intensity of the affect.

Time frame:
1 year (change from baseline to month 3, 6, 9 and 12)
Reported as:
Mean · Score on the PANAS test scale
Vitality Trial - Change in the Positive Affect Score of the Positive and Negative Affect Scales (PANAS) From Baseline to Month 12.
Score on the PANAS test scaleAndroGel® (Testosterone Gel)Placebo Gel
Baseline Score15.3 ± 3.215.4 ± 3.5
Change at Month 30.7 ± 3.20.3 ± 3.3
Change at Month 60.9 ± 3.80.0 ± 3.3
Change at Month 90.9 ± 3.40.4 ± 3.4
Change at Month 120.7 ± 3.90.2 ± 3.2
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = 0.04 (The p value for the treatment effect was determined with the use of a logistic mixed model with a random effect for participant for dichotomous outcomes and a linear mixed model with a random effect for participant for continuous outcomes.) · Mean difference (net): 0.47 · 95% CI 0.02 to 0.92
SecondaryVitality Trial - Change in the Total Negative Affect Score of the Positive and Negative Affect Scales (PANAS) From Baseline to Month 12

Baseline score and change in the total negative affect score of the Positive and Negative Affect Scales (PANAS) from baseline to Month 12. Scores for positive affect and for negative affect on the Positive and Negative Affect Schedule (PANAS) scales range from 5 to 50, with higher scores indicating a greater intensity of the affect.

Time frame:
1 year (change from baseline to month 3, 6, 9 and 12)
Reported as:
Mean · Score on the PANAS test scale
Vitality Trial - Change in the Total Negative Affect Score of the Positive and Negative Affect Scales (PANAS) From Baseline to Month 12
Score on the PANAS test scaleAndroGel® (Testosterone Gel)Placebo Gel
Baseline Score7.5 ± 2.77.4 ± 2.8
Change at Month 3-0.2 ± 2.50.3 ± 2.4
Change at Month 6-0.4 ± 2.40.4 ± 2.6
Change at Month 9-0.2 ± 2.3-0.1 ± 2.6
Change at Month 12-0.6 ± 2.1-0.1 ± 2.6
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Treatment Effect · p = <0.001 (The p value for the treatment effect was determined with the use of a logistic mixed model with a random effect for participant for dichotomous outcomes and a linear mixed model with a random effect for participant for continuous outcomes.) · Mean difference (net): -0.49 · 95% CI -0.79 to -0.19
SecondaryVitality Trial - Patient Health Questionnaire 9 (PHQ-9) Change in Overall Score

Baseline score and change in score in the Patient Health Questionnaire 9 (PHQ-9) from baseline to Month 12. Scores on the Patient Health Questionnaire 9 (PHQ-9) depression scale range from 0 to 27, with higher scores indicating greater intensity of depressive symptoms.

Time frame:
1 year (change from baseline to month 3, 6, 9 and 12)
Reported as:
Mean · Score on the PHQ-9 test scale
Vitality Trial - Patient Health Questionnaire 9 (PHQ-9) Change in Overall Score
Score on the PHQ-9 test scaleAndroGel® (Testosterone Gel)Placebo Gel
Baseline Score6.6 ± 4.06.6 ± 4.0
Change at Month 3-1.3 ± 3.8-0.8 ± 3.5
Change at Month 6-1.7 ± 3.8-0.5 ± 3.7
Change at Month 9-1.9 ± 4.0-1.2 ± 4.2
Change at Month 12-1.8 ± 3.7-1.1 ± 3.8
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Treatment Effect · p = 0.004 (The p value for the treatment effect was determined with the use of a logistic mixed model with a random effect for participant for dichotomous outcomes and a linear mixed model with a random effect for participant for continuous outcomes.) · Mean difference (net): -0.72 · 95% CI -1.20 to -0.23
SecondaryCardiovascular Trial - Total Plaque Volume Change From Baseline

Total plaque volume,mm3 measured by coronary computed tomographic angiography

Time frame:
1 year (change from baseline to month 12)
Reported as:
Mean · mm^3
Cardiovascular Trial - Total Plaque Volume Change From Baseline
mm^3AndroGel® (Testosterone Gel)Placebo Gel
Cardiovascular Trial - Total Plaque Volume Change From Baseline75 (22 to 128)28 (-24 to 81)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = .006 (Determined by linear mixed model with all balancing factors and baseline outcome value as covariates and a random effect for participant.) · Mean difference (final values): 47 · 95% CI 13 to 80Mean difference in change from baseline for participants assigned to testosterone v. placebo, with adjustment for balancing factors: baseline testosterone, age, site, trial participation, use of antidepressants, PDE5 inhibitors, baseline outcome.
SecondaryCardiovascular Trial - Coronary Artery Calcium Score, Agatston Units Change From Baseline

Coronary artery calcium score in Agatston units (range of 0 to \>400 Agatston units), with higher values indicating more severe atherosclerosis).

Time frame:
1 year (change from baseline to month 12)
Reported as:
Least squares mean · Agatston units
Cardiovascular Trial - Coronary Artery Calcium Score, Agatston Units Change From Baseline
Agatston unitsAndroGel® (Testosterone Gel)Placebo Gel
Cardiovascular Trial - Coronary Artery Calcium Score, Agatston Units Change From Baseline64 (-19 to 146)91 (7 to 174)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = .31 (Determined by a linear mixed model with all balancing factors and baseline outcome value as covariates and a random effect for participant.) · Mean difference (final values): -27 · 95% CI -80 to 26Mean difference in change from baseline for participants assigned to testosterone v. placebo, with adjustment for balancing factors: baseline testosterone, age, site, trial participation, use of antidepressants, PDE5 inhibitors, baseline outcome.
SecondaryBone Trial - Volumetric Bone Mineral Density (BMD) of Spine Peripheral Bone by Quantitative Computed Tomography (QCT)

Spine peripheral bone as measured by QCT, mg/cm3 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · percentage of change
Bone Trial - Volumetric Bone Mineral Density (BMD) of Spine Peripheral Bone by Quantitative Computed Tomography (QCT)
percentage of changeAndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Volumetric Bone Mineral Density (BMD) of Spine Peripheral Bone by Quantitative Computed Tomography (QCT)4.0 (2.9 to 5.2)1.1 (0.0 to 2.2)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = <.001 (Treatment effect is the mean difference in the change from baseline between testosterone and placebo arms. The P-Value for the significance of the treatment effect was determined by multivariable linear regression adjusted for balancing factors.) · Mean difference (final values): 2.9 · 95% CI 2.1 to 3.7
SecondaryBone Trial - Volumetric Bone Mineral Density (BMD) of Spine Whole Bone by Quantitative Computed Tomography (QCT)

Spine whole bone as measured by QCT, mg/cm3 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · percentage of change
Bone Trial - Volumetric Bone Mineral Density (BMD) of Spine Whole Bone by Quantitative Computed Tomography (QCT)
percentage of changeAndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Volumetric Bone Mineral Density (BMD) of Spine Whole Bone by Quantitative Computed Tomography (QCT)5.5 (4.0 to 6.9)1.2 (-0.2 to 2.6)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = <.001 (Treatment effect is the mean difference in the change from baseline between testosterone and placebo arms. The P-Value for the significance of the treatment effect was determined by multivariable linear regression adjusted for balancing factors.) · Mean difference (final values): 4.2 · 95% CI 3.2 to 5.3
SecondaryBone Trial - Volumetric Bone Mineral Density (BMD) of Hip Trabecular Bone by Quantitative Computed Tomography (QCT)

Hip trabecular bone as measured by QCT, mg/cm3 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · percentage of change
Bone Trial - Volumetric Bone Mineral Density (BMD) of Hip Trabecular Bone by Quantitative Computed Tomography (QCT)
percentage of changeAndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Volumetric Bone Mineral Density (BMD) of Hip Trabecular Bone by Quantitative Computed Tomography (QCT)1.6 (0.8 to 2.4)0.1 (-0.6 to 0.9)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = <.001 (Treatment effect is the mean difference in the change from baseline between testosterone and placebo arms. The P-Value for the significance of the treatment effect was determined by multivariable linear regression adjusted for balancing factors.) · Median difference (final values): 1.5 · 95% CI 0.9 to 2.0
SecondaryBone Trial - Volumetric Bone Mineral Density (BMD) of Hip Peripheral Bone by Quantitative Computed Tomography (QCT)

Hip peripheral bone as measured by QCT, mg/cm3 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · percentage of change
Bone Trial - Volumetric Bone Mineral Density (BMD) of Hip Peripheral Bone by Quantitative Computed Tomography (QCT)
percentage of changeAndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Volumetric Bone Mineral Density (BMD) of Hip Peripheral Bone by Quantitative Computed Tomography (QCT)1.6 (0.9 to 2.3)0.7 (-0.0 to 1.4)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = <.001 (Treatment effect is the mean difference in the change from baseline between testosterone and placebo arms. The P-Value for the significance of the treatment effect was determined by multivariable linear regression adjusted for balancing factors.) · Mean difference (final values): 1.0 · 95% CI 0.5 to 1.5
SecondaryBone Trial - Volumetric Bone Mineral Density (BMD) of Hip Whole Bone by Quantitative Computed Tomography (QCT)

Hip whole bone as measured by QCT, mg/cm3 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · percentage of change
Bone Trial - Volumetric Bone Mineral Density (BMD) of Hip Whole Bone by Quantitative Computed Tomography (QCT)
percentage of changeAndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Volumetric Bone Mineral Density (BMD) of Hip Whole Bone by Quantitative Computed Tomography (QCT)1.7 (1.0 to 2.4)0.4 (-0.2 to 1.1)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = <.001 · Mean difference (final values): 1.3 · 95% CI 0.8 to 1.7
SecondaryBone Trial - Bone Strength of Spine Whole Bone by Finite Element Analysis, N

Spine whole bone (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · percentage of change
Bone Trial - Bone Strength of Spine Whole Bone by Finite Element Analysis, N
percentage of changeAndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Bone Strength of Spine Whole Bone by Finite Element Analysis, N9.0 (6.4 to 11.6)1.9 (-0.6 to 4.4)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = <.001 (Treatment effect is the mean difference in the change from baseline between testosterone and placebo arms. The P-Value for the significance of the treatment effect was determined by multivariable linear regression adjusted for balancing factors.) · Mean difference (final values): 7.1 · 95% CI 5.3 to 809
SecondaryBone Trial - Bone Strength of Spine Trabecular Bone by Finite Element Analysis, N

Spine trabecular bone (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · percentage of change
Bone Trial - Bone Strength of Spine Trabecular Bone by Finite Element Analysis, N
percentage of changeAndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Bone Strength of Spine Trabecular Bone by Finite Element Analysis, N10.8 (7.4 to 14.3)2.4 (-1.0 to 5.7)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = <.001 (Treatment effect is the mean difference in the change from baseline between testosterone and placebo arms. The P-Value for the significance of the treatment effect was determined by multivariable linear regression adjusted for balancing factors.) · Mean difference (final values): 8.5 · 95% CI 6.0 to 10.9
SecondaryBone Trial - Bone Strength of Spine Peripheral Bone by Finite Element Analysis, N

Spine peripheral bone (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · percentage of change
Bone Trial - Bone Strength of Spine Peripheral Bone by Finite Element Analysis, N
percentage of changeAndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Bone Strength of Spine Peripheral Bone by Finite Element Analysis, N7.2 (5.2 to 9.2)1.5 (-0.5 to 3.4)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = <.001 (Treatment effect is the mean difference in the change from baseline between testosterone and placebo arms. The P-Value for the significance of the treatment effect was determined by multivariable linear regression adjusted for balancing factors.) · Mean difference (final values): 5.7 · 95% CI 4.3 to 7.2
SecondaryBone Trial - Bone Strength of Hip Whole Bone by Finite Element Analysis, N

Hip whole bone (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · percentage of change
Bone Trial - Bone Strength of Hip Whole Bone by Finite Element Analysis, N
percentage of changeAndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Bone Strength of Hip Whole Bone by Finite Element Analysis, N2.5 (1.4 to 3.5)0.6 (-0.4 to 1.7)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = <.001 (Treatment effect is the mean difference in the change from baseline between testosterone and placebo arms. The P-Value for the significance of the treatment effect was determined by multivariable linear regression adjusted for balancing factors.) · Mean difference (final values): 1.8 · 95% CI 1.1 to 2.6
SecondaryBone Trial - Bone Strength of Hip Trabecular Bone by Finite Element Analysis, N

Hip trabecular bone (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · percentage of change
Bone Trial - Bone Strength of Hip Trabecular Bone by Finite Element Analysis, N
percentage of changeAndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Bone Strength of Hip Trabecular Bone by Finite Element Analysis, N1.5 (0.5 to 2.5)0.5 (-0.5 to 1.5)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = .005 (Treatment effect is the mean difference in the change from baseline between testosterone and placebo arms. The P-Value for the significance of the treatment effect was determined by multivariable linear regression adjusted for balancing factors.) · Mean difference (final values): 1.0 · 95% CI 0.3 to 1.7
SecondaryBone Trial - Bone Strength of Hip Peripheral Bone by Finite Element Analysis, N

Hip peripheral bone (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · percentage of change
Bone Trial - Bone Strength of Hip Peripheral Bone by Finite Element Analysis, N
percentage of changeAndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Bone Strength of Hip Peripheral Bone by Finite Element Analysis, N1.4 (0.7 to 2.0)0.4 (-0.3 to 1.0)
Statistical analysis
  • AndroGel® (Testosterone Gel) · Regression, Linear · p = <.001 (Treatment effect is the mean difference in the change from baseline between testosterone and placebo arms. The P-Value for the significance of the treatment effect was determined by multivariable linear regression adjusted for balancing factors.) · Mean difference (final values): 1.0 · 95% CI 0.5 to 1.4
SecondaryBone Trial - Area Bone Mineral Density (BMD) of Lumbar Spine by Dual-energy X-ray Absorptiometry (DXA)

Lumbar spine as measured by DXA, g/cm2 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · percentage of change
Bone Trial - Area Bone Mineral Density (BMD) of Lumbar Spine by Dual-energy X-ray Absorptiometry (DXA)
percentage of changeAndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Area Bone Mineral Density (BMD) of Lumbar Spine by Dual-energy X-ray Absorptiometry (DXA)3.3 (2.01 to 4.56)2.1 (0.87 to 3.36)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = .01 (Treatment effect is the mean difference in the change from baseline between testosterone and placebo arms. The P-Value for the significance of the treatment effect was determined by multivariable linear regression adjusted for balancing factors.) · Mean difference (final values): 1.2 · 95% CI 0.25 to 2.09
SecondaryBone Trial - Area Bone Mineral Density (BMD) of Total Hip by Dual-energy X-ray Absorptiometry (DXA)

Total hip as measured by DXA, g/cm2 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · percentage of change
Bone Trial - Area Bone Mineral Density (BMD) of Total Hip by Dual-energy X-ray Absorptiometry (DXA)
percentage of changeAndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Area Bone Mineral Density (BMD) of Total Hip by Dual-energy X-ray Absorptiometry (DXA)1.2 (0.19 to 2.17)0.5 (-0.45 to 1.46)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = .052 (Treatment effect is the mean difference in the change from baseline between testosterone and placebo arms. The P-Value for the significance of the treatment effect was determined by multivariable linear regression adjusted for balancing factors.) · Mean difference (final values): .07 · 95% CI -0.01 to 1.36
SecondaryBone Trial - Area Bone Mineral Density (BMD) of Femoral Neck by Dual-energy X-ray Absorptiometry (DXA)

Femoral neck as measured by DXA, g/cm2 (within-arm mean percent change between baseline and month 12 adjusted for balancing factors)

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · percentage of change
Bone Trial - Area Bone Mineral Density (BMD) of Femoral Neck by Dual-energy X-ray Absorptiometry (DXA)
percentage of changeAndroGel® (Testosterone Gel)Placebo Gel
Bone Trial - Area Bone Mineral Density (BMD) of Femoral Neck by Dual-energy X-ray Absorptiometry (DXA)1.5 (0.02 to 2.97)0.9 (-0.49 to 2.35)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Regression, Linear · p = 0.27 (Treatment effect is the mean difference in the change from baseline between testosterone and placebo arms. The P-Value for the significance of the treatment effect was determined by multivariable linear regression adjusted for balancing factors.) · Mean difference (final values): 0.56 · 95% CI -0.45 to 1.58
SecondaryCognitive Function Trial - Visual Memory - Benton Visual Retention Test (BVRT)

Baseline score and mean change in score in the Visual Memory Using the Benton Visual Retention Test (BVRT) from baseline, Month 6 and Month 12. The BVRT measures short term visual memory and visuo-constructional abilities and was administered and scored according to standard procedures. Each of 10 designs was presented one at a time for 10 seconds, and immediately after the design was withdrawn, the participant was instructed to draw it from memory on a blank sheet of paper. The score was the total number of figures with errors and ranged from 0 to 26. Scores were inverted to 0 to -26 so that higher scores would reflect better performance. Change in BVRT scores from baseline are treated as continuous and compared between AAMI Androgel and placebo subjects using linear random effects models adjusting for balancing factors as described in the primary analysis.

Time frame:
1 year (baseline to month 6 and month 12)
Reported as:
Mean · Score on the BVRT test scale
Cognitive Function Trial - Visual Memory - Benton Visual Retention Test (BVRT)
Score on the BVRT test scaleAndroGel® (Testosterone Gel)Placebo Gel
Baseline Score-8.2 (-8.6 to -7.8)-8.2 (-8.6 to -7.8)
Change at Month 60.2 (-0.4 to 0.9)0.3 (-0.3 to 1.0)
Change at Month 120.3 (-0.4 to 0.9)0.7 (0.0 to 1.4)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = .24 (The estimated difference and P-value were determined by a linear mixed-model with a random effect for participants using outcomes at month 6 and month 12.) · Mean difference (final values): -0.28 · 95% CI -0.76 to 0.19The difference is the mean difference in the change from baseline to 6 months to 12 months in participants allocated to testosterone vs placebo adjusted for balancing factors.
SecondaryCognitive Function Trial - Spatial Ability Card Rotation Test (CRT)

Baseline score and change in score in the Spatial Ability Using the Card Rotation Test at baseline, Month 6 and Month 12. Change in performance on the Card Rotations Test will be analyzed using linear random effects models adjusting for baseline performance, balancing factors, education, and test version. The test consists of a series of 10 primary figures, each of which has 8 corresponding secondary figures. Subjects are asked to determine which of the secondary figures is the same as the corresponding primary figure, and the score is taken as the number of figures answered correctly minus the number of figures answered incorrectly. The maximum score is 80 for subjects who answer all items correctly.

Time frame:
1 year (baseline to month 6 to month 12)
Reported as:
Mean · Score on the CRT test scale
Cognitive Function Trial - Spatial Ability Card Rotation Test (CRT)
Score on the CRT test scaleAndroGel® (Testosterone Gel)Placebo Gel
Baseline Score28.7 (26.9 to 30.5)30.0 (28.1 to 31.8)
Change at Month 60.6 (-1.9 to 30.)0.2 (-2.3 to 2.7)
Change at Month 120.6 (-1.8 to 3.1)1.2 (-1.3 to 3.7)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = .89 (The estimated difference and P-value were determined by a linear mixed-model with a random effect for participants using outcomes at month 6 and month 12.) · Mean difference (net): -0.12 · 95% CI -1.89 to 1.65The difference is the mean difference in the change from baseline to 6 months to 12 months in participants allocated to testosterone vs placebo adjusted for balancing factors.
SecondaryCognitive Function Trial - Executive Function - Trail Making Test B - A

Baseline score and change in score in Executive Function as Measured by Trail-Making Test (TMT) B - A, at baseline, Month 6 and Month 12. Change in performance on the Trail Making Test was analyzed using linear random effects models adjusting for baseline performance, balancing factors, education, and test version. Participants are required to connect a set of numbers (Part A) or alternating letters and numbers (Part B) in sequential order. The score for each part is the total time (in seconds) to complete both parts. The outcome analyzed will be the total time for Trails B minus the total time for Trails A to provide a measure of working memory, adjusted for attention and processing speed. Higher scores reflect lower executive function.

Time frame:
1 year (baseline to month 6 to month 12)
Reported as:
Mean · Score on the Trail Making Test scale
Cognitive Function Trial - Executive Function - Trail Making Test B - A
Score on the Trail Making Test scaleAndroGel® (Testosterone Gel)Placebo Gel
Baseline Score86.4 (78.3 to 94.6)76.7 (69.9 to 83.5)
Change at Month 6-2.1 (-12.4 to 8.2)1.8 (-8.6 to 12.2)
Change at Month 12-0.0 (-10.3 to 10.3)7.1 (-3.3 to 17.5)
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = .14 (The estimated difference and P-value were determined by a linear mixed-model with a random effect for participants using outcomes at month 6 and month 12.) · Mean difference (net): -5.51 · 95% CI -12.91 to 1.88The difference is the mean difference in the change from baseline to 6 months to 12 months in participants allocated to testosterone vs placebo adjusted for balancing factors.
SecondaryAnemia Trial - Effect of Testosterone on Hemoglobin Levels - Unexplained Anemia - Hemoglobin (Continuous)

Proportion of men age 65 years or older with unexplained anemia who increased their hemoglobin level by 1.0 gm/dL from baseline. Values are means (SDs) for continuous outcomes.

Time frame:
1 year (baseline to month 12)
Reported as:
Mean · proportion of participants
Anemia Trial - Effect of Testosterone on Hemoglobin Levels - Unexplained Anemia - Hemoglobin (Continuous)
proportion of participantsAndroGel® (Testosterone Gel)Placebo Gel
Anemia Trial - Effect of Testosterone on Hemoglobin Levels - Unexplained Anemia - Hemoglobin (Continuous)0.9 ± 1.40.2 ± 0.8
Statistical analysis
  • AndroGel® (Testosterone Gel) vs Placebo Gel · Mixed Models Analysis · p = <.001 (The P-value for the significance of the treatment effect was determined by a linear mixed model for continuous outcomes with a random intercept for participant.) · Mean difference (net): 0.83 · 95% CI 0.48 to 1.39Intent-to-treat analysis by a linear mixed effects model adjusted for balancing factors.

Adverse events

Collected over Adverse events were identified during study visits in the First (Treatment) Year, and by phone interview during the Second (Observation) Year.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
AndroGel® (Testosterone Gel)—183/394 (46.4%)343/394 (87.1%)
Placebo Gel—176/394 (44.7%)341/394 (86.5%)
Most frequent serious events
Showing 10 of 17
Most frequent serious events
EventAndroGel® (Testosterone Gel)Placebo Gel
Cardiac disordersCardiac disorders35/39434/394
Infections and infestationsInfections and infestations29/39421/394
Musculoskeletal and connective tissue disordersMusculoskeletal and connective tissue disorders22/39419/394
Nervous system disordersNervous system disorders16/39422/394
Respiratory disordersRespiratory, thoracic and mediastinal disorders9/39417/394
Neoplasms benign, malignant and unspecifiedNeoplasms benign, malignant and unspecified (incl cysts and polyps)15/39412/394
General disordersGeneral disorders12/39414/394
Injury, poisoning and procedural complicationsInjury, poisoning and procedural complications9/39411/394
Gastrointestinal disordersGastrointestinal disorders10/3947/394
Vascular disordersVascular disorders10/3947/394
Most frequent other events
Showing 10 of 18
Most frequent other events
EventAndroGel® (Testosterone Gel)Placebo Gel
Musculoskeletal and connective tissue disordersMusculoskeletal and connective tissue disorders145/394155/394
Infections and infestationsInfections and infestations152/394145/394
Injury poisoning and procedural complicationsInjury, poisoning and procedural complications87/39489/394
Skin and subcutaneous tissue disordersSkin and subcutaneous tissue disorders88/39452/394
Nervous system disordersNervous system disorders75/39478/394
General disorders and administration site conditionsGeneral disorders74/39475/394
Respiratory, thoracic and mediastinal disordersRespiratory, thoracic and mediastinal disorders74/39467/394
Gastrointestinal disordersGastrointestinal disorders65/39471/394
Reproductive system and breast disordersReproductive system and breast disorders49/39419/394
Cardiac disordersCardiac disorders45/39445/394

Baseline characteristics

Two participants were randomized in error, one in each arm of the study.

Age, Continuous
Age, Continuous(years)AndroGel® (Testosterone Gel)Placebo GelTotal
Main Testosterone Trial72.3 ± 5.872.1 ± 5.772.2 ± 5.8
Cardiovascular Trial70.5 ± 5.772.0 ± 5.771.2 ± 5.7
Bone Trial72.3 ± 6.372.4 ± 5.572.4 ± 5.9
Cognitive Function Trial72.3 ± 5.872.8 ± 6.172.6 ± 5.9
Anemia Trial74.8 ± 6.075.6 ± 7.575.2 ± 6.8
Sex: Female, Male
Sex: Female, Male(Participants)AndroGel® (Testosterone Gel)Placebo GelTotal
Female000
Male394394788
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)AndroGel® (Testosterone Gel)Placebo GelTotal
Hispanic or Latino181028
Not Hispanic or Latino375384759
Unknown or Not Reported101
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)AndroGel® (Testosterone Gel)Placebo GelTotal
Race — Caucasian348350698
Race — African-American212041
Race — Other252449
08

Study locations

12 sites
  • University of Alabama at Birmingham
    Birmingham, Alabama 35294, United States
  • University of California San Diego
    La Jolla, California 92093, United States
  • Center for Men's Health LA BioMed at Harbor-UCLA Medical Center
    Torrance, California 90501, United States
  • Yale University
    New Haven, Connecticut 06520, United States
  • University of Florida
    Gainesville, Florida 32611, United States
  • Northwestern University
    Chicago, Illinois 60208, United States
  • Boston University
    Boston, Massachusetts 02215, United States
  • University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • Albert Einstein College of Medicine
    Bronx, New York 10461, United States
  • University of Pittsburgh
    Pittsburgh, Pennsylvania 15261, United States
  • Baylor College of Medicine
    Houston, Texas 76798, United States
  • VA Puget Sound Health Care System
    Seattle, Washington 98108, United States
09

References and documents

Publications

  • Stephens-Shields AJ, Snyder PJ, Ellenberg SS, Taylor L, Bhasin S. Relation of Testosterone, Dihydrotestosterone, and Estradiol With Changes in Outcomes Measures in the Testosterone Trials. J Clin Endocrinol Metab. 2022 Apr 19;107(5):1257-1269. doi: 10.1210/clinem/dgac028. PubMed 35041751 ↗
  • Artz AS, Stephens-Shields AJ, Bhasin S, Ellenberg SS, Cohen HJ, Snyder PJ. Markers of Iron Flux during Testosterone-Mediated Erythropoiesis in Older Men with Unexplained or Iron-Deficiency Anemia. J Clin Endocrinol Metab. 2020 Nov 1;105(11):3396-403. doi: 10.1210/clinem/dgaa521. PubMed 32785689 ↗
  • Shaikh K, Ellenberg SS, Nakanishi R, Snyder PJ, Lee J, Wenger NK, Lewis CE, Swerdloff RS, Preston P, Hamal S, Stephens-Sheilds A, Bhasin S, Cherukuri L, Cauley JA, Crandall JP, Cunningham GR, Ensrud KE, Matsumoto AM, Molich ME, Alla VM, Birudaraju D, Nezarat N, Rai K, Almeida S, Roy SK, Sheikh M, Trad G, Budoff MJ. Biomarkers and Noncalcified Coronary Artery Plaque Progression in Older Men Treated With Testosterone. J Clin Endocrinol Metab. 2020 Jul 1;105(7):2142-9. doi: 10.1210/clinem/dgz242. PubMed 31784747 ↗
  • Bhasin S, Ellenberg SS, Storer TW, Basaria S, Pahor M, Stephens-Shields AJ, Cauley JA, Ensrud KE, Farrar JT, Cella D, Matsumoto AM, Cunningham GR, Swerdloff RS, Wang C, Lewis CE, Molitch ME, Barrett-Connor E, Crandall JP, Hou X, Preston P, Cifelli D, Snyder PJ, Gill TM. Effect of testosterone replacement on measures of mobility in older men with mobility limitation and low testosterone concentrations: secondary analyses of the Testosterone Trials. Lancet Diabetes Endocrinol. 2018 Nov;6(11):879-890. doi: 10.1016/S2213-8587(18)30171-2. PubMed 30366567 ↗
  • Mohler ER 3rd, Ellenberg SS, Lewis CE, Wenger NK, Budoff MJ, Lewis MR, Barrett-Connor E, Swerdloff RS, Stephens-Shields A, Bhasin S, Cauley JA, Crandall JP, Cunningham GR, Ensrud KE, Gill TM, Matsumoto AM, Molitch ME, Pahor M, Preston PE, Hou X, Cifelli D, Snyder PJ. The Effect of Testosterone on Cardiovascular Biomarkers in the Testosterone Trials. J Clin Endocrinol Metab. 2018 Feb 1;103(2):681-688. doi: 10.1210/jc.2017-02243. Erratum In: J Clin Endocrinol Metab. 2020 Jan 1;105(1):dgz042. doi: 10.1210/clinem/dgz042. PubMed 29253154 ↗
  • Resnick SM, Matsumoto AM, Stephens-Shields AJ, Ellenberg SS, Gill TM, Shumaker SA, Pleasants DD, Barrett-Connor E, Bhasin S, Cauley JA, Cella D, Crandall JP, Cunningham GR, Ensrud KE, Farrar JT, Lewis CE, Molitch ME, Pahor M, Swerdloff RS, Cifelli D, Anton S, Basaria S, Diem SJ, Wang C, Hou X, Snyder PJ. Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment. JAMA. 2017 Feb 21;317(7):717-727. doi: 10.1001/jama.2016.21044. PubMed 28241356 ↗
  • Budoff MJ, Ellenberg SS, Lewis CE, Mohler ER 3rd, Wenger NK, Bhasin S, Barrett-Connor E, Swerdloff RS, Stephens-Shields A, Cauley JA, Crandall JP, Cunningham GR, Ensrud KE, Gill TM, Matsumoto AM, Molitch ME, Nakanishi R, Nezarat N, Matsumoto S, Hou X, Basaria S, Diem SJ, Wang C, Cifelli D, Snyder PJ. Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone. JAMA. 2017 Feb 21;317(7):708-716. doi: 10.1001/jama.2016.21043. PubMed 28241355 ↗
  • Roy CN, Snyder PJ, Stephens-Shields AJ, Artz AS, Bhasin S, Cohen HJ, Farrar JT, Gill TM, Zeldow B, Cella D, Barrett-Connor E, Cauley JA, Crandall JP, Cunningham GR, Ensrud KE, Lewis CE, Matsumoto AM, Molitch ME, Pahor M, Swerdloff RS, Cifelli D, Hou X, Resnick SM, Walston JD, Anton S, Basaria S, Diem SJ, Wang C, Schrier SL, Ellenberg SS. Association of Testosterone Levels With Anemia in Older Men: A Controlled Clinical Trial. JAMA Intern Med. 2017 Apr 1;177(4):480-490. doi: 10.1001/jamainternmed.2016.9540. Erratum In: JAMA Intern Med. 2019 Mar 1;179(3):457. doi: 10.1001/jamainternmed.2019.0248. JAMA Intern Med. 2021 May 1;181(5):727. doi: 10.1001/jamainternmed.2020.9154. PubMed 28241237 ↗
  • Snyder PJ, Kopperdahl DL, Stephens-Shields AJ, Ellenberg SS, Cauley JA, Ensrud KE, Lewis CE, Barrett-Connor E, Schwartz AV, Lee DC, Bhasin S, Cunningham GR, Gill TM, Matsumoto AM, Swerdloff RS, Basaria S, Diem SJ, Wang C, Hou X, Cifelli D, Dougar D, Zeldow B, Bauer DC, Keaveny TM. Effect of Testosterone Treatment on Volumetric Bone Density and Strength in Older Men With Low Testosterone: A Controlled Clinical Trial. JAMA Intern Med. 2017 Apr 1;177(4):471-479. doi: 10.1001/jamainternmed.2016.9539. Erratum In: JAMA Intern Med. 2017 Apr 1;177(4):600. doi: 10.1001/jamainternmed.2017.0968. JAMA Intern Med. 2019 Mar 1;179(3):457. doi: 10.1001/jamainternmed.2019.0249. PubMed 28241231 ↗
  • Cunningham GR, Stephens-Shields AJ, Rosen RC, Wang C, Bhasin S, Matsumoto AM, Parsons JK, Gill TM, Molitch ME, Farrar JT, Cella D, Barrett-Connor E, Cauley JA, Cifelli D, Crandall JP, Ensrud KE, Gallagher L, Zeldow B, Lewis CE, Pahor M, Swerdloff RS, Hou X, Anton S, Basaria S, Diem SJ, Tabatabaie V, Ellenberg SS, Snyder PJ. Testosterone Treatment and Sexual Function in Older Men With Low Testosterone Levels. J Clin Endocrinol Metab. 2016 Aug;101(8):3096-104. doi: 10.1210/jc.2016-1645. Epub 2016 Jun 29. PubMed 27355400 ↗
  • Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, Gill TM, Barrett-Connor E, Swerdloff RS, Wang C, Ensrud KE, Lewis CE, Farrar JT, Cella D, Rosen RC, Pahor M, Crandall JP, Molitch ME, Cifelli D, Dougar D, Fluharty L, Resnick SM, Storer TW, Anton S, Basaria S, Diem SJ, Hou X, Mohler ER 3rd, Parsons JK, Wenger NK, Zeldow B, Landis JR, Ellenberg SS; Testosterone Trials Investigators. Effects of Testosterone Treatment in Older Men. N Engl J Med. 2016 Feb 18;374(7):611-24. doi: 10.1056/NEJMoa1506119. PubMed 26886521 ↗
  • Abd Alamir M, Ellenberg SS, Swerdloff RS, Wenger NK, Mohler ER 3rd, Lewis CE, Barrett-Conner E, Nakanishi R, Darabian S, Alani A, Matsumoto S, Nezarat N, Snyder PJ, Budoff MJ. The Cardiovascular Trial of the Testosterone Trials: rationale, design, and baseline data of a clinical trial using computed tomographic imaging to assess the progression of coronary atherosclerosis. Coron Artery Dis. 2016 Mar;27(2):95-103. doi: 10.1097/MCA.0000000000000321. PubMed 26554661 ↗
  • Cunningham GR, Stephens-Shields AJ, Rosen RC, Wang C, Ellenberg SS, Matsumoto AM, Bhasin S, Molitch ME, Farrar JT, Cella D, Barrett-Connor E, Cauley JA, Cifelli D, Crandall JP, Ensrud KE, Fluharty L, Gill TM, Lewis CE, Pahor M, Resnick SM, Storer TW, Swerdloff RS, Anton S, Basaria S, Diem S, Tabatabaie V, Hou X, Snyder PJ. Association of sex hormones with sexual function, vitality, and physical function of symptomatic older men with low testosterone levels at baseline in the testosterone trials. J Clin Endocrinol Metab. 2015 Mar;100(3):1146-55. doi: 10.1210/jc.2014-3818. Epub 2014 Dec 30. PubMed 25548978 ↗
  • Meng J, Mostaghel EA, Vakar-Lopez F, Montgomery B, True L, Nelson PS. Testosterone regulates tight junction proteins and influences prostatic autoimmune responses. Horm Cancer. 2011 Jun;2(3):145-56. doi: 10.1007/s12672-010-0063-1. PubMed 21761342 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 21, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00799617
Lead sponsor
University of Pennsylvania
Collaborators
National Institute on Aging (NIA), National Institute of Neurological Disorders and Stroke (NINDS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Heart, Lung, and Blood Institute (NHLBI), Abbott
Responsible party
Sponsor
First posted
Dec 1, 2008
Start date
Nov 2009
Primary completion
Jul 2014
Completion
Dec 2018
Results posted
Aug 28, 2017
Last update
Feb 21, 2019

Study contacts

Peter J Snyder, MD
principal investigator · University of Pennsylvania

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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