AndropausePhase 3NCT00799617

The Testosterone Trials in Older Men

A Phase 3 study testing AndroGel® (testosterone gel) in people with Andropause, run by University of Pennsylvania at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 65 years and older, men onlyHealthy volunteers can take part
Conditions the study is for: Andropause
What is being tested?: AndroGel® (testosterone gel)
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 790 participants
Where: 12 sitesUnited States
Study dates: Nov 2009to Dec 2018
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 65 years and older
Men only
Healthy volunteers accepted
Older adult

Who may be able to join

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

Who cannot join

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

Show all 24Show fewer

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.

Trial locations and contacts

12 sites in 1 country.

City, postcode or hospital

12 sites in 1 country

United States12 sites

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

Other trials in United States

About this study

Official title: Randomized, Placebo-controlled, Double-blind Study of Seven Coordinated Testosterone Treatment Trials in Older Men

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.

Conditions: Andropause
Being tested: AndroGel® (testosterone gel), Placebo
Keywords: Testosterone, Mobility disability, Decreased libido, Age associated memory impairment, Low vitality, Anemia
Medical subject headings: Anemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AndroGel® (testosterone gel)Drug
Also called Testosterone gel
Testosterone levels will be measured at regular intervals in order to achieve a testosterone level in the desired range.
PlaceboDrug
Testosterone levels will be measured at regular intervals.

Study groups in NCT00799617
Study group	Role	What they receive
AndroGel® (testosterone gel)	Active comparator	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. Receives: Drug: AndroGel® (testosterone gel)
Placebo gel	Placebo comparator	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. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 1 year (change from baseline to month 3, 6, 9 and 12)
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.
Measured: 1 year (Number of participants who increased walk distance > or = 50 meters, change from baseline to month 3, 6, 9 and 12)
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.
Measured: 1 year (Number of participants who increased FACIT-Fatigue score > or = to 4, change from baseline to month 3, 6, 9 and 12)
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
Measured: 1 year (change in plaque volume measurement from baseline to month 12)
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
Measured: 1 year (QCT measurement of BMD change between baseline and month 12)
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.
Measured: 1 year (change from baseline to month 6 and month 12)
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.
Measured: 1 year (change in hemoglobin g/dL from baseline to month 3, 6, 9 and 12)

Secondary outcomes (30)

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.
Measured: 1 year (change from baseline to month 3, 6, 9 and 12)
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.
Measured: 1 year (change from baseline to month 3, 6, 9 and 12)
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
Measured: 1 year (change from baseline to month 3, 6, 9 and 12)
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.
Measured: 1 year (change from baseline to month 3, 6, 9 and 12)
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.
Measured: 1 year (change from baseline to month 3, 6, 9 and 12)
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.
Measured: 1 year (change from baseline to month 3, 6, 9 and 12)
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.
Measured: 1 year (change from baseline to month 3, 6, 9 and 12)
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.
Measured: 1 year (change from baseline to month 3, 6, 9 and 12)
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.
Measured: 1 year (change from baseline to month 3, 6, 9 and 12)
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.
Measured: 1 year (change from baseline to month 3, 6, 9 and 12)
Cardiovascular Trial - Total Plaque Volume Change From Baseline
Total plaque volume,mm3 measured by coronary computed tomographic angiography
Measured: 1 year (change from baseline to month 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).
Measured: 1 year (change from baseline to month 12)
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)
Measured: 1 year (baseline to month 12)
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)
Measured: 1 year (baseline to month 12)
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)
Measured: 1 year (baseline to month 12)
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)
Measured: 1 year (baseline to month 12)
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)
Measured: 1 year (baseline to month 12)
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)
Measured: 1 year (baseline to month 12)
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)
Measured: 1 year (baseline to month 12)
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)
Measured: 1 year (baseline to month 12)
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)
Measured: 1 year (baseline to month 12)
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)
Measured: 1 year (baseline to month 12)
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)
Measured: 1 year (baseline to month 12)
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)
Measured: 1 year (baseline to month 12)
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)
Measured: 1 year (baseline to month 12)
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)
Measured: 1 year (baseline to month 12)
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.
Measured: 1 year (baseline to month 6 and month 12)
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.
Measured: 1 year (baseline to month 6 to month 12)
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.
Measured: 1 year (baseline to month 6 to month 12)
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.
Measured: 1 year (baseline to month 12)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2009Dec 2018

First posted1 Dec 2008 (estimated)
Study startNov 2009
Primary completionJul 2014
Study completionDec 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (15)Papers the sponsor has linked to this study.
Other trials for AndropauseStudies of the same condition, open and under way.
More trials run by University of PennsylvaniaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 790 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00799617
Sponsor's protocol ID: U01AG030644
Other IDs: R01AG037679
Status last verified: Feb 2019
First submitted: 26 Nov 2008
Last updated: 21 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Lee H, Hwang EC, Oh CK, Lee S, Yu HS, Lim JS, Kim HW, Walsh T, Kim MH, Jung JH, Dahm P. Testosterone replacement in men with sexual dysfunction. Cochrane Database Syst Rev. 2024 Jan 15;1(1):CD013071. doi: 10.1002/14651858.CD013071.pub2.
PubMed 38224135
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.
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.
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.
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

Study at a glance

From the registry record, last updated by the sponsor on 21 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized, Placebo-controlled, Double-blind Study of Seven Coordinated Testosterone Treatment Trials in Older Men
ClinicalTrials.gov ID: NCT00799617
Acronym / sponsor ID: U01AG030644
Conditions: Andropause
Keywords: Testosterone, Mobility disability, Decreased libido, Age associated memory impairment, Low vitality, Anemia
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 790 participants (actual)
Lead sponsor: University of PennsylvaniaUniversity, hospital or other
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
Study start: Nov 2009
Primary completion: Jul 2014 (actual)
Study completion: Dec 2018 (actual)
First posted: 1 Dec 2008 (estimated)
Results: Posted 28 Aug 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

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.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
AndroGel® (testosterone gel)	Active comparator	Drug: 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.
Placebo gel	Placebo comparator	Drug: PlaceboPlacebo 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.

Who may qualify

Ages: 65 years and older
Sex: Male only
Healthy volunteers: Accepted
Age groups: Older adult

Key inclusion criteria (2 listed)

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

Key exclusion criteria (24 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AndroGel® (testosterone gel)Also: Testosterone gelTestosterone levels will be measured at regular intervals in order to achieve a testosterone level in the desired range.	Drug	AndroGel® (testosterone gel)
PlaceboTestosterone levels will be measured at regular intervals.	Drug	Placebo gel

Primary outcome

Sexual Function Trial - Change in Psychosexual Daily Questionnaire Question 4 (PDQ-Q4) From Baseline to Month 12
Time frame: 1 year (change from baseline to month 3, 6, 9 and 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.
Physical Function Trial - The 6-Minute Walk Test - no./Total no. (%)
Time frame: 1 year (Number of participants who increased walk distance > or = 50 meters, change from baseline to month 3, 6, 9 and 12)
The number and percentage of men who increased the distance walked in the 6-Minute Walk Test by at least 50 meters.
Vitality Trial - Increase in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score Greater Than or Equal to 4 - no./Total no. (%)
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)
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.
Cardiovascular Trial - Assess Impact of Testosterone Treatment in Older Men on Noncalcified Plaque Volume
Time frame: 1 year (change in plaque volume measurement from baseline to month 12)
Non-calcified coronary artery plaque volume, mm3, as determined by coronary computed tomographic angiography (CTA), mean difference in change from baseline to month 12
Bone Trial - Volumetric Bone Mineral Density (BMD) of Spine Trabecular Bone by Quantitative Computed Tomography (QCT) in Older Men With Low Testosterone
Time frame: 1 year (QCT measurement of BMD change between baseline and month 12)
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
Cognitive Function Trial - Delayed Paragraph Recall Wechsler Memory Scale Revised Logical Memory II (WMS-R LMII)
Time frame: 1 year (change from baseline to month 6 and month 12)
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.
Anemia Trial - Effect of Testosterone on Hemoglobin Levels - Unexplained Anemia
Time frame: 1 year (change in hemoglobin g/dL from baseline to month 3, 6, 9 and 12)
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.

30 secondary outcomes

Sexual Function Trial - Sexual Desire Domain
Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)
Sexual Function Trial - Erectile Function
Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)
Physical Function Trial - 6 Minute Walk Test - Total Walking Distance in Meters
Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)
Physical Function Trial - The Physical Function Domain (PF-10) of the SF-36 - no./Total no. (%)
Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)
Physical Function Trial - PF 10 Overall Score
Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)
Vitality Trial - FACIT Fatigue Overall Score
Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)
Vitality Trial - SF-36 Score
Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)
Vitality Trial - Change in the Positive Affect Score of the Positive and Negative Affect Scales (PANAS) From Baseline to Month 12.
Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)
Vitality Trial - Change in the Total Negative Affect Score of the Positive and Negative Affect Scales (PANAS) From Baseline to Month 12
Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)
Vitality Trial - Patient Health Questionnaire 9 (PHQ-9) Change in Overall Score
Time frame: 1 year (change from baseline to month 3, 6, 9 and 12)
Cardiovascular Trial - Total Plaque Volume Change From Baseline
Time frame: 1 year (change from baseline to month 12)
Cardiovascular Trial - Coronary Artery Calcium Score, Agatston Units Change From Baseline
Time frame: 1 year (change from baseline to month 12)
Bone Trial - Volumetric Bone Mineral Density (BMD) of Spine Peripheral Bone by Quantitative Computed Tomography (QCT)
Time frame: 1 year (baseline to month 12)
Bone Trial - Volumetric Bone Mineral Density (BMD) of Spine Whole Bone by Quantitative Computed Tomography (QCT)
Time frame: 1 year (baseline to month 12)
Bone Trial - Volumetric Bone Mineral Density (BMD) of Hip Trabecular Bone by Quantitative Computed Tomography (QCT)
Time frame: 1 year (baseline to month 12)
Bone Trial - Volumetric Bone Mineral Density (BMD) of Hip Peripheral Bone by Quantitative Computed Tomography (QCT)
Time frame: 1 year (baseline to month 12)
Bone Trial - Volumetric Bone Mineral Density (BMD) of Hip Whole Bone by Quantitative Computed Tomography (QCT)
Time frame: 1 year (baseline to month 12)
Bone Trial - Bone Strength of Spine Whole Bone by Finite Element Analysis, N
Time frame: 1 year (baseline to month 12)
Bone Trial - Bone Strength of Spine Trabecular Bone by Finite Element Analysis, N
Time frame: 1 year (baseline to month 12)
Bone Trial - Bone Strength of Spine Peripheral Bone by Finite Element Analysis, N
Time frame: 1 year (baseline to month 12)
Bone Trial - Bone Strength of Hip Whole Bone by Finite Element Analysis, N
Time frame: 1 year (baseline to month 12)
Bone Trial - Bone Strength of Hip Trabecular Bone by Finite Element Analysis, N
Time frame: 1 year (baseline to month 12)
Bone Trial - Bone Strength of Hip Peripheral Bone by Finite Element Analysis, N
Time frame: 1 year (baseline to month 12)
Bone Trial - Area Bone Mineral Density (BMD) of Lumbar Spine by Dual-energy X-ray Absorptiometry (DXA)
Time frame: 1 year (baseline to month 12)
Bone Trial - Area Bone Mineral Density (BMD) of Total Hip by Dual-energy X-ray Absorptiometry (DXA)
Time frame: 1 year (baseline to month 12)
Bone Trial - Area Bone Mineral Density (BMD) of Femoral Neck by Dual-energy X-ray Absorptiometry (DXA)
Time frame: 1 year (baseline to month 12)
Cognitive Function Trial - Visual Memory - Benton Visual Retention Test (BVRT)
Time frame: 1 year (baseline to month 6 and month 12)
Cognitive Function Trial - Spatial Ability Card Rotation Test (CRT)
Time frame: 1 year (baseline to month 6 to month 12)
Cognitive Function Trial - Executive Function - Trail Making Test B - A
Time frame: 1 year (baseline to month 6 to month 12)
Anemia Trial - Effect of Testosterone on Hemoglobin Levels - Unexplained Anemia - Hemoglobin (Continuous)
Time frame: 1 year (baseline to month 12)

Results and safety

Results posted to the registry on 28 Aug 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AndroGel® (Testosterone Gel)	395	376
Placebo Gel	395	374

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

Time frame: 1 year (change from baseline to month 3, 6, 9 and 12). Mean (Standard Deviation). Unit: units on the PDQ-Q4 scale

Measure	AndroGel® (Testosterone Gel) n = 230	Placebo Gel n = 229
Baseline Score	1.4 (1.3)	1.4 (1.3)
Change at Month 3	0.6 (1.3)	0.1 (1.1)
Change at Month 6	0.6 (1.5)	-0.1 (1.2)
Change at Month 9	0.5 (1.5)	-0.1 (1.2)
Change at Month 12	0.2 (1.6)	-0.1 (1.4)

AndroGel® (Testosterone Gel) vs Placebo Gel: Mean Difference (Net): 0.58 (95% CI 0.38 to 0.78), p <0.001, Mixed Models Analysis

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

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

Measure	AndroGel® (Testosterone Gel) n = 191	Placebo Gel n = 196
Month 3	20	14
Month 6	24	23
Month 9	28	22
Month 12	35	20

AndroGel® (Testosterone Gel) vs Placebo Gel: Odds Ratio (OR): 1.42 (95% CI 0.83 to 2.45), p = 0.20, Mixed Models Analysis

Population analysed: The number analyzed differs from the overall number due to participant withdrawal or test results that were incomplete.

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

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). Count of participants. Unit: Participants

Measure	AndroGel® (Testosterone Gel) n = 236	Placebo Gel n = 238
Month 3	148	138
Month 6	144	126
Month 9	148	127
Month 12	147	120

AndroGel® (Testosterone Gel) vs Placebo Gel: Odds Ratio (OR): 1.23 (95% CI 0.83 to 1.84), p = 0.30, Mixed Models Analysis

Population analysed: The number analyzed differs from the overall number due to participant withdrawal or test results that were incomplete.

Primary outcome: Cardiovascular Trial - Assess Impact of Testosterone Treatment in Older Men on Noncalcified Plaque Volume

Time frame: 1 year (change in plaque volume measurement from baseline to month 12). Mean (95% Confidence Interval). Unit: mm^3

Measure	AndroGel® (Testosterone Gel) n = 73	Placebo Gel n = 65
Value	54 (12 to 97)	14 (-29 to 56)

AndroGel® (Testosterone Gel) vs Placebo Gel: Mean Difference (Final Values): 41 (95% CI 14 to 67), p = .003, Regression, Linear

Population analysed: Men aged 65 years or \> with an average of 2 serum testosterone levels lower than 275 ng/L and enrolled in the CV Trial of the Testosterone Trials between June 2010 and June 2014.

30 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were identified during study visits in the First (Treatment) Year, and by phone interview during the Second (Observation) Year.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AndroGel® (Testosterone Gel)	183 of 394 (46.4%)	343 of 394 (87.1%)	Not reported
Placebo Gel	176 of 394 (44.7%)	341 of 394 (86.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38224135Lee H, Hwang EC, Oh CK, Lee S, Yu HS, Lim JS, Kim HW, Walsh T, Kim MH, Jung JH, Dahm P. Testosterone replacement in men with sexual dysfunction. Cochrane Database Syst Rev. 2024 Jan 15;1(1):CD013071. doi: 10.1002/14651858.CD013071.pub2.
Derived from this study: PubMed 35041751Stephens-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.
Derived from this study: PubMed 32785689Artz 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.
Derived from this study: PubMed 31784747Shaikh 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.
Derived from this study: PubMed 30366567Bhasin 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.
Derived from this study: PubMed 29253154Mohler 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.
Derived from this study: PubMed 28241356Resnick 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.
Derived from this study: PubMed 28241355Budoff 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.
Derived from this study: PubMed 28241237Roy 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.
Derived from this study: PubMed 28241231Snyder 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.
Derived from this study: PubMed 27355400Cunningham 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.
Derived from this study: PubMed 26886521Snyder 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.
Find out more information about The Testosterone Trial and the list of participating clinical sites.Link provided by the sponsor.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Peter J Snyder, MD principal investigator

University of Pennsylvania

12 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing AndroGel® (testosterone gel) in people with Andropause, run by University of Pennsylvania at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Sexual Function Trial - Change in Psychosexual Daily Questionnaire Question 4 (PDQ-Q4) From Baseline to Month 12 (time frame: 1 year (change from baseline to month 3, 6, 9 and 12)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00799617, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2019.