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| Name | Class |
|---|---|
| Solvay Pharmaceuticals | INDUSTRY |
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As men grow older, their testosterone levels decrease with age. One-third of men, 70 years of age or older, have low testosterone levels. It is known that short-term testosterone replacement is safe, and can increase muscle strength and physical function, but the risks of long-term testosterone replacement in older men with low testosterone levels are incompletely understood.
Atherosclerosis is characterized by thickening of the artery walls, and the narrowing of the blood vessels as cholesterol is deposited in the lining of the arteries. It is the major cause of cardiovascular disease including ischemic heart disease (heart attacks) and stroke. Although, historically, there has been a widespread perception that higher levels of testosterone might increase the risk of atherosclerosis, the evidence from research does not support this. In observational studies, higher testosterone levels have been correlated with more favorable cardiovascular risk factors, and supplementation with testosterone to bring older men into the normal range for healthy younger men appears to improve several cardiovascular risk factors, and may slow the progression of atherosclerosis.
The primary purpose of this study is to look at the effects of testosterone replacement on the progression of atherosclerosis in older men. This study is also being done to find out whether replacement with testosterone in older men with low testosterone levels improves their health-related quality of life.
Although short-term administration of testosterone in replacement doses is relatively safe, the risks of long-term testosterone administration in older men remain poorly understood. The two major areas of concern include the potential for increased risk of atherosclerotic heart disease and exacerbation of a pre-existing, subclinical prostate cancer. There is a widespread perception that testosterone supplementation adversely affects plasma lipoprotein profile and increases the risk of atherosclerotic heart disease; this premise is not supported by data. Thus, the long-term consequences of testosterone supplementation on the risk of atherosclerosis progression remain unknown. While supraphysiological doses of testosterone and non-aromatizable androgens frequently employed by body-builders undoubtedly decrease plasma high density lipoprotein (HDL)-cholesterol levels, physiologic testosterone replacement in older men has been associated with only a modest or no decrease in plasma HDL-cholesterol. Cross-sectional studies of middle-aged men find a direct, rather than an inverse, relationship between serum testosterone levels and plasma HDL-cholesterol concentrations as well as an inverse correlation between serum testosterone levels and visceral fat volume. Testosterone supplementation of middle-aged men with truncal obesity is associated with a reduction in visceral fat volume, serum glucose concentration, blood pressure, and an improvement in insulin sensitivity. All of these changes are associated with lower risk for atherosclerosis. These data suggest that serum testosterone levels in the range that is mid-normal for healthy young men are consistent with an optimal cardiovascular risk profile at any age, and that testosterone concentrations either above or below the physiologic male range may increase the risk of atherosclerotic heart disease. Studies in a low density lipoprotein (LDL)-receptor deficient mice provide compelling evidence that testosterone retards early atherogenesis, and that testosterone effects on atherogenesis are mediated through its conversion to estradiol by the action of aromatase enzyme that is expressed in the vessel wall. The effects of testosterone replacement on cardiovascular risk in humans have never been directly examined. Therefore, the primary objective of this study is to examine directly the effects of testosterone replacement on atherosclerosis progression in men by measuring common carotid artery intima-media thickness (CCA IMT) and coronary artery calcification (CAC) by multidetector computed tomography (MDCT), two independent measurements of generalized atherosclerosis.
The second objective of this study is to determine whether physiologic testosterone replacement of older men with low testosterone levels improves health-related quality of life. Aging-associated decline in physical, sexual, and cognitive functions contributes to diminished quality of life in older men. Although the pathophysiology of impairment in each of these subdomains of health-related quality of life is complex and multifactorial, one correctable cause of the diminished quality of life in older men is the decrease in serum testosterone concentrations. Total and free testosterone (T) levels decline with advancing age in normal men, with a significant number of men meeting usual criteria for hypogonadism by the sixth to seventh decades. Spontaneous and experimentally-induced androgen-deficiency in young men is associated with decreased muscle mass and strength and impaired sexual function. Because loss of muscle mass and function contributes to diminished health-related quality of life (HRQOL) in older men, anabolic therapies such as testosterone that increase muscle mass and strength, would be expected to improve physical function. In older men with low testosterone levels, testosterone might also improve sexual function and marital interaction. A growing body of literature suggests that testosterone impacts neuronal functioning and may affect cognitive performance. Because physical, sexual, and cognitive functions are important determinants of health-related quality of life, testosterone replacement of older men with low testosterone levels would be expected to improve general health perceptions.
The aging of humans is a recent evolutionary event. Of the thousand generations of men and women who have lived on this planet, only the humans of the last two generations could have hoped to live past the age of 50. The population is getting proportionally older. The number of people 85 years of age and older today is substantially greater than at the beginning of the 20th century. Advancing age is associated with decreased muscle mass and strength, and impairment of physical, sexual, and cognitive functions. Diminished muscle mass and strength increases the risk of falls, disability and poor quality of life. Age-related impairment of sexual and cognitive functions also contributes to overall reduction in quality of life. Testosterone replacement, by improving some aspects of physical, sexual and cognitive functions, would be expected to improve health-related quality of life.
Previous studies have established that testosterone replacement in older men with low testosterone levels increases muscle mass and strength. However, lack of information in two areas has prevented formulation of general recommendations about wider use of testosterone replacement in older men. First, the effectiveness of testosterone in improving physical function, quality of life, and other health-related outcomes has not been demonstrated. Second, while there is agreement that short-term administration of testosterone in replacement doses is safe, the long-term risks of testosterone supplementation in older men remain unknown. The areas of major concern are the risks of prostate cancer and heart disease. Because of the high prevalence, even small increases in the incidence rates of atherosclerotic heart disease associated with testosterone supplementation will have significant impact on overall morbidity and mortality, and health care costs. The study will evaluate one important aspect of the long-term safety of testosterone administration by directly examining its effects on the rate of progression of atherosclerosis. If the study demonstrates that testosterone retards atherosclerosis progression, then that would provide one additional reason for testosterone supplementation of older men with low testosterone levels. If the study demonstrates a neutral effect of testosterone on atherosclerosis progression, that information would also be reassuring and useful to regulatory agencies. This study will establish the efficacy of testosterone replacement in improving physical, sexual and cognitive functions that are major determinants of health-related quality of life in older men.
In spite of the paucity of efficacy and safety data, the sales of testosterone and other androgenic products have witnessed explosive growth because of increased media attention and public interest. During the summer of 2000, testosterone-related stories were on the cover of Time, Newsweek, New York Times, and Los Angeles Times. The prescription sales of testosterone that had been growing at 25-30% annual rate since 1993, almost doubled in the year 2000, and have cumulatively increased 500% since 1993 (Source: IMS Sales Data, provided by Reed Selby, Marketing Director for ALZA Corporation). The growing testosterone use in older men, without a clear understanding of its benefits or long-term risks, has raised concern among regulatory agencies. The proposed study by providing definitive information on the effects of testosterone replacement on several measures of efficacy and safety in older men would facilitate an analysis of its risk:benefit ratio.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Testosterone | Active Comparator | Participants received 7.5 g of 1% testosterone gel to achieve a nominal delivery of 75 mg testosterone daily for 3 years. Dose adjustments were made by an unblinded observer. (Serum testosterone level measured on treatment day 15 was measured in a sample sent separately to the laboratory such that the results were reported directly to unblinded physician, who then communicated the decision about dose adjustment (or not) directly to the research pharmacist through e-mail.) |
|
| Placebo | Placebo Comparator | Participants received placebo-matching testosterone gel daily for 3 years. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Testosterone Gel (Androgel) | Drug | 7.5 g of 1% testosterone gel to achieve a nominal delivery of 75 mg testosterone daily for 3 years |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Common Carotid Artery Intima-Media Thickness (IMT) | B-mode carotid artery images for IMT were acquired from the far wall of the distal centimeter of the right carotid artery with high-resolution ultrasound equipment. IMT is used as a predictor of the incidence of cardiovascular events. An increase in the IMT thickness is associated with a higher incidence of cardiovascular events. Less thickening is best. Change is expressed in millimeters (mm). | Baseline and Month 36 |
| Change From Baseline in Coronary Artery Calcium Score | A multiple detector computed tomography (MDCT) scan was performed. Proximal coronary arteries were visualized, and at least 30 consecutive images were obtained at 3-mm intervals. Coronary calcium was defined as a plaque of at least 3 contiguous pixels (area, 1.02 mm^2) with a density of more than 130 Hounsfield units.The lesion score was calculated by multiplying lesion area by a density factor derived from Hounsfield units. The Agatston method was used to determine the total calcium score by summing the lesion scores from the left main, left anterior descending, circumflex, and right coronary arteries. The Agatston score is the measure of calcification in arteries expressed on continuous scale with "0" value (better) indicating no calcification and score above 400 (worse) indicating high calcification. There is no upper limit for this measure. A positive change from baseline indicates a worsening. | Baseline and Month 36 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Lipid Profiles | Laboratory tests included in the lipid profile were Total Cholesterol, High Density Lipoprotein-Cholesterol (HDL-C), Low Density Lipoprotein-Cholesterol (LDL-C) and Triglycerides.Lower values for Total Cholesterol, LDL-C are better and a negative change from Baseline indicates improvement. Higher values for HDL-C are better and a positive change from Baseline indicates improvement. |
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Inclusion Criteria:
Exclusion Criteria:
epilepsy, multiple sclerosis, human immunodeficiency virus (HIV), Parkinson's disease, stroke
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| Name | Affiliation | Role |
|---|---|---|
| Shalender Bhasin, MD | Boston University / Boston Medical Center, Boston, MA | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kronos Longevity Research Institute | Phoenix | Arizona | 85016 | United States | ||
| Charles R. Drew University of Medicine and Science |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29373734 | Derived | Huang G, Pencina KM, Li Z, Basaria S, Bhasin S, Travison TG, Storer TW, Harman SM, Tsitouras P. Long-Term Testosterone Administration on Insulin Sensitivity in Older Men With Low or Low-Normal Testosterone Levels. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1678-1685. doi: 10.1210/jc.2017-02545. | |
| 28981994 | Derived |
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| ID | Title | Description |
|---|---|---|
| FG000 | Testosterone | Participants received 7.5 g of 1% testosterone gel to achieve a nominal delivery of 75 mg testosterone daily for 3 years. Dose adjustments were made by an unblinded observer. (Serum testosterone level measured on treatment day 15 was measured in a sample sent separately to the laboratory such that the results were reported directly to unblinded physician, who then communicated the decision about dose adjustment (or not) directly to the research pharmacist through e-mail.) |
| FG001 | Placebo | Participants received placebo-matching testosterone gel daily for 3 years. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intent-to-treat Population included all randomized participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Testosterone | Participants received 7.5 g of 1% testosterone gel to achieve a nominal delivery of 75 mg testosterone daily for 3 years. Dose adjustments were made by an unblinded observer. (Serum testosterone level measured on treatment day 15 was measured in a sample sent separately to the laboratory such that the results were reported directly to unblinded physician, who then communicated the decision about dose adjustment (or not) directly to the research pharmacist through e-mail.) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Common Carotid Artery Intima-Media Thickness (IMT) | B-mode carotid artery images for IMT were acquired from the far wall of the distal centimeter of the right carotid artery with high-resolution ultrasound equipment. IMT is used as a predictor of the incidence of cardiovascular events. An increase in the IMT thickness is associated with a higher incidence of cardiovascular events. Less thickening is best. Change is expressed in millimeters (mm). | All participants from the Intent-to-treat population, all randomized and treated participants, with data available at the given time-point. | Posted | Mean | Standard Deviation | mm | Baseline and Month 36 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Testosterone | Participants received 7.5 g of 1% testosterone gel to achieve a nominal delivery of 75 mg testosterone daily for 3 years. Dose adjustments were made by an unblinded observer. (Serum testosterone level measured on treatment day 15 was measured in a sample sent separately to the laboratory such that the results were reported directly to unblinded physician, who then communicated the decision about dose adjustment (or not) directly to the research pharmacist through e-mail.) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | General disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated Prostate-Specific Antigen (PSA) | Investigations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Shalendar Bhasin, MD | Brigham and Women's Hospital | Sbhasin@partners.org |
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| ID | Term |
|---|---|
| D007006 | Hypogonadism |
| D050197 | Atherosclerosis |
| D006331 | Heart Diseases |
| D014652 | Vascular Diseases |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
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| ID | Term |
|---|---|
| D013739 | Testosterone |
| ID | Term |
|---|---|
| D000737 | Androstenols |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 |
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| Placebo | Drug | Placebo-matching testosterone gel daily for 3 years |
|
| Baseline and Month 36 |
| Changes in Biomarkers of Inflammation | Three years |
| Changes in Blood Pressure | Three years |
| Change From Baseline in Complex Figure (Immediate) and Complex Figure (Delayed) | Cognitive Function was assessed by Complex Figure (Immediate) and (Delayed). The Complex Figure Test consists of three tasks: copy, immediate recall, and delayed recall. Participants were presented with a complex design and then asked to draw the same figure. Subsequently, they were instructed to draw what they remembered immediately, and after a 30 minute delay. Scoring was based on the number of correct items for a total possible score of 0 (worst) to 36 (Best). A positive change from Baseline indicates improvement. A negative change from Baseline indicates a worsening. | Baseline and Month 36 |
| Change From Baseline in Paragraph Recall Test (Delayed) | Cognitive Function was assessed by the Paragraph Recall Test (Delayed). In the Paragraph Recall Test, participants were read two short paragraphs and asked to recall them immediately and after a 30 minute delay, using the exact words that were read aloud. Scoring was based on the number of items correctly recalled. More items correctly recalled is best and a positive change from Baseline indicates improvement. | Baseline and Month 36 |
| Change From Baseline in the Buschke Selective Reminding Test (Delayed) | Cognitive function was assessed by the Buschke Selective Reminding Test. In the Buschke Selective Reminding Test, participants were read 12 words and asked to recall as many words as possible. Subsequent trials included only those words that were not recalled in the preceding trial. Individuals were also asked to recall the list 30 minutes later. To assess phonemic and category fluency, participants were asked to name as many items from a given category as possible in 1 minute. Higher number of correct items is best and a positive change from Baseline indicates improvement. | Baseline and Month 36 |
| Change From Baseline in the Verbal Fluency Test | Cognitive function was assessed by the Verbal Fluency Test. Participants were asked to name as many letters from a given category as possible in 1 minute. Higher number of letters is best and a positive change from Baseline indicates improvement. | Baseline and Month 36 |
| Change From Baseline in the Category Fluency Test | Cognitive function was assessed by the Category Fluency Test. Participants were asked to name as many items from a given category as possible. Higher number of items named is best and a positive change from Baseline indicates improvement. | Baseline and Month 36 |
| Change From Baseline in the Stroop Interference Test | Cognitive function was assessed by the Stroop Interference Test. In the Stroop Interference Test, participants were presented with a word list of colors printed in ink of a color different from how the printed word read. Participants were instructed to read aloud the color of the ink in which a word was printed, while not verbalizing the word itself. The time in seconds that the items were correctly identified was recorded. Less time is better and a negative change from Baseline indicates improvement. | Baseline and Month 36 |
| Change From Baseline in the Trail Making Test B | Cognitive function was assessed by the Trail Making Test B. Trail Making Test B involved participants connecting numbers (1-13) and letters (A-L) alternately (1-A, 2-B, etc) on a piece of paper as quickly as possible. Scores represent the time it takes the participant to complete the test. Less time is best and a negative change from Baseline indicates improvement. A positive change from Baseline indicates a worsening. | Baseline and Month 36 |
| Change From Baseline in Chest Press Strength and Leg Press Strength | Maximal voluntary strength of the lower and upper extremities was assessed using the one repetition maximum (1-RM) method for the seated leg press and chest press exercises. Participants were positioned with standardized seat position and foot placement that allowed 90° of knee flexion for the leg press exercise. Seat height and handle position was standardized for the chest press. Participants were familiarized with the exercises, practiced the technique and completed a 5-minute warm-up. The 1-RM procedure consisted of a warm up set with 5 to 8 repetitions at a resistance set to about 50% of the participant's estimated 1-RM and progressed with increasing loads interspersed with standardized rest periods until the participant was able to perform only one full-range-of-motion repetition. | Baseline and Month 36 |
| Change From Baseline in Unloaded Stair Climb Power and Loaded Stair Climb Power | Physical Function was evaluated using two tests of stair climb power using an indoor 12-step staircase. One test consisted of ascending the 12-steps as rapidly as possible without running (unloaded stair climb) while the second test required participants to carry a load equivalent to 20% of their baseline body weight evenly distributed in two canvas tote bags (loaded stair climb). Time to ascend the stairs was measured electronically with a digital clock and switch mats placed at the base of the steps and on the 12th step. Power in watts is calculated by the following: [body weight (kilograms) * distance (meters)/ (time/60)] /6.12. A negative change from Baseline indicates improvement. | Baseline and Month 36 |
| Change in Sexual Function as Assessed by the International Index of Erectile Function (IIEF) | IIEF is a validated, 15-item questionnaire that assesses 5 domains of sexual function: erectile function (6 questions), orgasmic function (2 questions), sexual desire (2 questions), intercourse satisfaction (3 questions), and overall sexual satisfaction (2 questions). Each question was answered on a 5-point scale from 1 to 5 (best) with a total possible score range of 0 to 75 with higher scores representing better function. A positive change from Baseline indicates improvement. | Baseline and Month 36 |
| Change in Health Quality of Life (QoL) as Assessed by Short Form 36 (SF-36) | The SF-36 measures 8 domains of the QoL: physical function, bodily pain, vitality, role limitations due to physical problems, general health perceptions, emotional well-being, social function, and role limitations due to emotional problems. Each domain is scored separately from 0 to 100 with higher scores representing better health-related QoL. The Overall Score is the average of the individual domain scores. A negative change from Baseline indicates improvement. | Baseline and Month 36 |
| Los Angeles |
| California |
| 90059 |
| United States |
| Boston University / Boston Medical Center | Boston | Massachusetts | 02118 | United States |
| Bhasin S, Travison TG, O'Brien L, MacKrell J, Krishnan V, Ouyang H, Pencina K, Basaria S. Contributors to the substantial variation in on-treatment testosterone levels in men receiving transdermal testosterone gels in randomized trials. Andrology. 2018 Jan;6(1):151-157. doi: 10.1111/andr.12428. Epub 2017 Oct 5. |
| 27992261 | Derived | Gagliano-Juca T, Icli TB, Pencina KM, Li Z, Tapper J, Huang G, Travison TG, Tsitouras P, Harman SM, Storer TW, Bhasin S, Basaria S. Effects of Testosterone Replacement on Electrocardiographic Parameters in Men: Findings From Two Randomized Trials. J Clin Endocrinol Metab. 2017 May 1;102(5):1478-1485. doi: 10.1210/jc.2016-3669. |
| 27754805 | Derived | Storer TW, Basaria S, Traustadottir T, Harman SM, Pencina K, Li Z, Travison TG, Miciek R, Tsitouras P, Hally K, Huang G, Bhasin S. Effects of Testosterone Supplementation for 3 Years on Muscle Performance and Physical Function in Older Men. J Clin Endocrinol Metab. 2017 Feb 1;102(2):583-593. doi: 10.1210/jc.2016-2771. |
| 27377542 | Derived | Huang G, Wharton W, Bhasin S, Harman SM, Pencina KM, Tsitouras P, Li Z, Hally KA, Asthana S, Storer TW, Basaria S. Effects of long-term testosterone administration on cognition in older men with low or low-to-normal testosterone concentrations: a prespecified secondary analysis of data from the randomised, double-blind, placebo-controlled TEAAM trial. Lancet Diabetes Endocrinol. 2016 Aug;4(8):657-665. doi: 10.1016/S2213-8587(16)30102-4. Epub 2016 Jul 1. |
| 26262795 | Derived | Basaria S, Harman SM, Travison TG, Hodis H, Tsitouras P, Budoff M, Pencina KM, Vita J, Dzekov C, Mazer NA, Coviello AD, Knapp PE, Hally K, Pinjic E, Yan M, Storer TW, Bhasin S. Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone Levels: A Randomized Clinical Trial. JAMA. 2015 Aug 11;314(6):570-81. doi: 10.1001/jama.2015.8881. |
| Death |
|
| Elevated Hematocrit |
|
| Rash |
|
| Elevated Prostate Specific Antigen |
|
| Stroke |
|
| Myocardial Infarction |
|
| Lower Urinary Tract Symptoms |
|
| Cognitive Impairment |
|
| Pancreatic Cancer |
|
| Sleep Apnea |
|
| Shoulder Pain |
|
| Inappropriate Behaviour with Staff |
|
| Nonadherence |
|
| Enrolled in Another Study |
|
| Major Depression |
|
| Lung Cancer |
|
| Elevated IPSS Score |
|
| Retroperitoneal Cancer |
|
| Mastodynia and Gynecomastia |
|
| Mood Swings and Irritability |
|
| Bradycardia |
|
| Itchy Swollen Eyes |
|
| Recurrent Melanoma |
|
| BG001 | Placebo | Participants received placebo-matching testosterone gel daily for 3 years. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Placebo | Participants received placebo-matching testosterone gel daily for 3 years. |
|
|
| Primary | Change From Baseline in Coronary Artery Calcium Score | A multiple detector computed tomography (MDCT) scan was performed. Proximal coronary arteries were visualized, and at least 30 consecutive images were obtained at 3-mm intervals. Coronary calcium was defined as a plaque of at least 3 contiguous pixels (area, 1.02 mm^2) with a density of more than 130 Hounsfield units.The lesion score was calculated by multiplying lesion area by a density factor derived from Hounsfield units. The Agatston method was used to determine the total calcium score by summing the lesion scores from the left main, left anterior descending, circumflex, and right coronary arteries. The Agatston score is the measure of calcification in arteries expressed on continuous scale with "0" value (better) indicating no calcification and score above 400 (worse) indicating high calcification. There is no upper limit for this measure. A positive change from baseline indicates a worsening. | All participants from the Intent-to-treat population, all randomized and treated participants, with data available at the given time-point. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Month 36 |
|
|
|
| Secondary | Change From Baseline in Lipid Profiles | Laboratory tests included in the lipid profile were Total Cholesterol, High Density Lipoprotein-Cholesterol (HDL-C), Low Density Lipoprotein-Cholesterol (LDL-C) and Triglycerides.Lower values for Total Cholesterol, LDL-C are better and a negative change from Baseline indicates improvement. Higher values for HDL-C are better and a positive change from Baseline indicates improvement. | All participants from the Intent-to-treat population, all randomized and treated participants, with data available at the given time-point. | Posted | Mean | Standard Deviation | mg/dL | Baseline and Month 36 |
|
|
|
| Secondary | Changes in Biomarkers of Inflammation | No analysis was performed. No funds were left to cover the costs of the assays for inflammation biomarkers. | Posted | Three years |
|
|
| Secondary | Changes in Blood Pressure | No analysis was performed. Although blood pressure measurements were standardized within a trial site, there is a possibility that measurement techniques might have varied across the three trial sites over the trial's long duration. For this reason we decided not to include blood pressure data in the results. | Posted | Three years |
|
|
| Secondary | Change From Baseline in Complex Figure (Immediate) and Complex Figure (Delayed) | Cognitive Function was assessed by Complex Figure (Immediate) and (Delayed). The Complex Figure Test consists of three tasks: copy, immediate recall, and delayed recall. Participants were presented with a complex design and then asked to draw the same figure. Subsequently, they were instructed to draw what they remembered immediately, and after a 30 minute delay. Scoring was based on the number of correct items for a total possible score of 0 (worst) to 36 (Best). A positive change from Baseline indicates improvement. A negative change from Baseline indicates a worsening. | All participants from the Intent-to-treat population, all randomized and treated participants, with cognitive baseline data and data available at the given time-point. | Posted | Mean | Standard Deviation | correct items | Baseline and Month 36 |
|
|
|
| Secondary | Change From Baseline in Paragraph Recall Test (Delayed) | Cognitive Function was assessed by the Paragraph Recall Test (Delayed). In the Paragraph Recall Test, participants were read two short paragraphs and asked to recall them immediately and after a 30 minute delay, using the exact words that were read aloud. Scoring was based on the number of items correctly recalled. More items correctly recalled is best and a positive change from Baseline indicates improvement. | All participants from the Intent-to-treat population, all randomized and treated participants, with cognitive baseline data and data available at the given time-point. | Posted | Mean | Standard Deviation | correct items | Baseline and Month 36 |
|
|
|
| Secondary | Change From Baseline in the Buschke Selective Reminding Test (Delayed) | Cognitive function was assessed by the Buschke Selective Reminding Test. In the Buschke Selective Reminding Test, participants were read 12 words and asked to recall as many words as possible. Subsequent trials included only those words that were not recalled in the preceding trial. Individuals were also asked to recall the list 30 minutes later. To assess phonemic and category fluency, participants were asked to name as many items from a given category as possible in 1 minute. Higher number of correct items is best and a positive change from Baseline indicates improvement. | All participants from the Intent-to-treat population, all randomized and treated participants, with cognitive baseline data and data available at the given time-point. | Posted | Mean | Standard Deviation | correct items | Baseline and Month 36 |
|
|
|
| Secondary | Change From Baseline in the Verbal Fluency Test | Cognitive function was assessed by the Verbal Fluency Test. Participants were asked to name as many letters from a given category as possible in 1 minute. Higher number of letters is best and a positive change from Baseline indicates improvement. | All participants from the Intent-to-treat population, all randomized and treated participants, with cognitive baseline data and data available at the given time-point. | Posted | Mean | Standard Deviation | letters | Baseline and Month 36 |
|
|
|
| Secondary | Change From Baseline in the Category Fluency Test | Cognitive function was assessed by the Category Fluency Test. Participants were asked to name as many items from a given category as possible. Higher number of items named is best and a positive change from Baseline indicates improvement. | All participants from the Intent-to-treat population, all randomized and treated participants, with cognitive baseline data and data available at the given time-point. | Posted | Mean | Standard Deviation | items | Baseline and Month 36 |
|
|
|
| Secondary | Change From Baseline in the Stroop Interference Test | Cognitive function was assessed by the Stroop Interference Test. In the Stroop Interference Test, participants were presented with a word list of colors printed in ink of a color different from how the printed word read. Participants were instructed to read aloud the color of the ink in which a word was printed, while not verbalizing the word itself. The time in seconds that the items were correctly identified was recorded. Less time is better and a negative change from Baseline indicates improvement. | All participants from the Intent-to-treat population, all randomized and treated participants, with cognitive baseline data and data available at the given time-point. | Posted | Mean | Standard Deviation | seconds | Baseline and Month 36 |
|
|
|
| Secondary | Change From Baseline in the Trail Making Test B | Cognitive function was assessed by the Trail Making Test B. Trail Making Test B involved participants connecting numbers (1-13) and letters (A-L) alternately (1-A, 2-B, etc) on a piece of paper as quickly as possible. Scores represent the time it takes the participant to complete the test. Less time is best and a negative change from Baseline indicates improvement. A positive change from Baseline indicates a worsening. | All participants from the Intent-to-treat population, all randomized and treated participants, with cognitive baseline data and data available at the given time-point. | Posted | Mean | Standard Deviation | seconds | Baseline and Month 36 |
|
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| Secondary | Change From Baseline in Chest Press Strength and Leg Press Strength | Maximal voluntary strength of the lower and upper extremities was assessed using the one repetition maximum (1-RM) method for the seated leg press and chest press exercises. Participants were positioned with standardized seat position and foot placement that allowed 90° of knee flexion for the leg press exercise. Seat height and handle position was standardized for the chest press. Participants were familiarized with the exercises, practiced the technique and completed a 5-minute warm-up. The 1-RM procedure consisted of a warm up set with 5 to 8 repetitions at a resistance set to about 50% of the participant's estimated 1-RM and progressed with increasing loads interspersed with standardized rest periods until the participant was able to perform only one full-range-of-motion repetition. | All participants from the Intent-to-treat population, all randomized and treated participants, with baseline physical function data and data available at the given time-point. | Posted | Mean | Standard Deviation | newton | Baseline and Month 36 |
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| Secondary | Change From Baseline in Unloaded Stair Climb Power and Loaded Stair Climb Power | Physical Function was evaluated using two tests of stair climb power using an indoor 12-step staircase. One test consisted of ascending the 12-steps as rapidly as possible without running (unloaded stair climb) while the second test required participants to carry a load equivalent to 20% of their baseline body weight evenly distributed in two canvas tote bags (loaded stair climb). Time to ascend the stairs was measured electronically with a digital clock and switch mats placed at the base of the steps and on the 12th step. Power in watts is calculated by the following: [body weight (kilograms) * distance (meters)/ (time/60)] /6.12. A negative change from Baseline indicates improvement. | All participants from the Intent-to-treat population, all randomized and treated participants, with baseline physical function data and data available at the given time-point. | Posted | Mean | Standard Deviation | watts | Baseline and Month 36 |
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| Secondary | Change in Sexual Function as Assessed by the International Index of Erectile Function (IIEF) | IIEF is a validated, 15-item questionnaire that assesses 5 domains of sexual function: erectile function (6 questions), orgasmic function (2 questions), sexual desire (2 questions), intercourse satisfaction (3 questions), and overall sexual satisfaction (2 questions). Each question was answered on a 5-point scale from 1 to 5 (best) with a total possible score range of 0 to 75 with higher scores representing better function. A positive change from Baseline indicates improvement. | All participants from the Intent-to-treat population, all randomized and treated participants, with data available at the given time-point. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Month 36 |
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| Secondary | Change in Health Quality of Life (QoL) as Assessed by Short Form 36 (SF-36) | The SF-36 measures 8 domains of the QoL: physical function, bodily pain, vitality, role limitations due to physical problems, general health perceptions, emotional well-being, social function, and role limitations due to emotional problems. Each domain is scored separately from 0 to 100 with higher scores representing better health-related QoL. The Overall Score is the average of the individual domain scores. A negative change from Baseline indicates improvement. | All participants from the Intent-to-treat population, all randomized and treated participants, with data available at the given time-point. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Month 36 |
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| 24 |
| 155 |
| 33 |
| 155 |
| EG001 | Placebo | Participants received placebo-matching testosterone gel daily for 3 years. | 25 | 151 | 20 | 151 |
| Pulmonary carcinoma complications | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment | Resulting in death |
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| Pancreatic cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment | Resulting in death |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Resulting in death |
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| Angina pectoris | Cardiac disorders | Systematic Assessment |
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| Appendicitis | Infections and infestations | Systematic Assessment |
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| Appendectomy | Surgical and medical procedures | Systematic Assessment |
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| Bacterial septicemia | Infections and infestations | Systematic Assessment |
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| Triple by-pass surgery | Surgical and medical procedures | Systematic Assessment |
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| Coronary artery bypass graft | Surgical and medical procedures | Systematic Assessment |
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| Chest pain | General disorders | Systematic Assessment |
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| Colitis with abscess and fistula | Infections and infestations | Systematic Assessment |
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| Colonic diverticulitis | Gastrointestinal disorders | Systematic Assessment |
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| Complete ankle replacement surgery | Surgical and medical procedures | Systematic Assessment |
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| Congestive heart failure | Cardiac disorders | Systematic Assessment |
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| Congestive heart failure exacerbation | Cardiac disorders | Systematic Assessment |
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| Lung mass | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| E.coli infection | Infections and infestations | Systematic Assessment |
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| Glioma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Hypoglycemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Renal artery stenosis | Renal and urinary disorders | Systematic Assessment |
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| Melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Meningitis not otherwise specified (NOS) | Infections and infestations | Systematic Assessment |
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| Bacteriemia | Infections and infestations | Systematic Assessment |
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| Bladder cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Mugged | Injury, poisoning and procedural complications | Systematic Assessment | Resulted in death |
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| Pulseless electrical activity (PEA) cardiac arrest | Cardiac disorders | Systematic Assessment |
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| Pneumonia | Infections and infestations | Systematic Assessment |
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| Lung cancer reaccurence | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Lung pulmonary nodule | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Slient myocardial infarction | Cardiac disorders | Systematic Assessment |
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| Sinus bradycardia | Cardiac disorders | Systematic Assessment |
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| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Coronary angiogram resulted in 2 occluded vessels | Injury, poisoning and procedural complications | Systematic Assessment |
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| Coronary stent procedure | Surgical and medical procedures | Systematic Assessment |
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| Upper gastrointestinal bleeding | Gastrointestinal disorders | Systematic Assessment |
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| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Acute posterior myocardial infarction | Cardiac disorders | Systematic Assessment |
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| Angioplasty | Surgical and medical procedures | Systematic Assessment |
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| Aspiration pneumonia | Infections and infestations | Systematic Assessment |
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| Bilateral toe gangrene | Infections and infestations | Systematic Assessment |
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| Cellulites on right foot and calf | Infections and infestations | Systematic Assessment |
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| Cerebellar neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Elevated blood pressure | Investigations | Systematic Assessment |
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| Complete left knee replacement surgery | Surgical and medical procedures | Systematic Assessment |
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| Coronary artery disease | Cardiac disorders | Systematic Assessment |
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| Coronary heart disease | Cardiac disorders | Systematic Assessment |
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| Cerebrovascular accident (CVA) | Nervous system disorders | Systematic Assessment |
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| Exertional chest pains | General disorders | Systematic Assessment |
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| Herniated free fragment with right lumbar radiculopathy | Nervous system disorders | Systematic Assessment |
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| Leg pain | General disorders | Systematic Assessment |
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| Localized prostate adeno-carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | Systematic Assessment |
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| Neoplasm left kidney | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Saphenous vein graft occlusion | Vascular disorders | Systematic Assessment |
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| Pancreatic tumor | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Quadruple by-pass surgery | Surgical and medical procedures | Systematic Assessment |
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| Right hemispheric subacute stroke | Nervous system disorders | Systematic Assessment |
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| Right knee re-placement surgery | Surgical and medical procedures | Systematic Assessment |
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| Second-degree atrioventricular heart block | Cardiac disorders | Systematic Assessment |
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| Dual chamber pace maker placement | Surgical and medical procedures | Systematic Assessment |
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| Upper respiratory infection | Infections and infestations | Systematic Assessment |
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| Elevated hematocrit (HCT) | Investigations | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D002318 | Cardiovascular Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045165 | Testosterone Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| Change at Month 36 |
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| Total Cholesterol, Change at Month 36 |
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| HDL-C, Baseline |
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| HDL-C, Change at Month 36 |
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| LDL-C, Baseline |
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| LDL-C, Change at Month 36 |
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| Triglycerides, Baseline |
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| Triglycerides, Change at Month 36 |
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| Complex Figure:Immediate, Change at Month 36 |
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| Complex Figure:Delayed, Baseline |
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| Complex Figure:Delayed, Change at Month 36 |
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| Paragraph:Delayed, Change at Month 36 |
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| Buschke Total Correct Delayed, Change at Month 36 |
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| Change at Month 36 |
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| Category Fluency, Change at Month 36 |
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| Stroop Interference, Change at Month 36 |
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| Trails B, Change at Month 36 |
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| Chest Press Strength, Change at Month 36 |
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| Leg Press Strength, Baseline |
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| Leg Press Strength, Change at Month 36 |
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| Unloaded Stair Climb Power, Change at Month 36 |
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| Loaded Stair Climb Power, Baseline |
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| Loaded Stair Climb Power, Change at Month 36 |
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| Erectile Function, Change at Month 36 |
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| Orgasmic Function, Baseline |
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| Orgasmic Function, Change at Month 36 |
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| Sexual Desire, Baseline |
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| Sexual Desire, Change at Month 36 |
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| Intercourse Satisfaction, Baseline |
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| Intercourse Satisfaction, Change at Month 36 |
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| Overall Satisfaction, Baseline |
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| Overall Satisfaction, Change at Month 36 |
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| Total Score, Baseline |
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| Total Score, Change at Month 36 |
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| Energy/Fatigue, Change at Month 36 |
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| Emotional Well-Being, Baseline |
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| Emotional Well-Being, Change at Month 36 |
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| Role Limitations/Emotional Problems, Baseline |
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| Role Limitations/Emotional Problems,Change |
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| Social Functioning, Baseline |
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| Social Functioning, Change at Month 36 |
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| Physical Functioning, Baseline |
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| Physical Functioning, Change at Month 36 |
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| Role Limitations/Physical Health, Baseline |
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| Role Limitations,/Physical Health, Change |
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| Pain, Baseline |
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| Pain, Change at Month 36 |
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| General Health, Baseline |
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| General Health, Change at Month 36 |
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| Overall Score, Baseline |
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| Overall Score, Change at Month 36 |
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