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TAP: Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception

Sponsor
Boston University (Other)
Overall Status
Completed
CT.gov ID
NCT00351819
Collaborator
(none)
84
Enrollment
1
Location
2
Arms
79
Duration (Months)
1.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Naturally occurring opiates (endorphins) decrease testosterone levels by inhibiting the synthesis of gonadotropin releasing hormone (GnRH) and also inhibiting testosterone synthesis by the testes. Similarly, men with addiction to narcotics and those on exogenous opioids for pain control have decreased serum testosterone levels. Indeed, these men complain of decreased libido, erectile dysfunction and impaired quality of life. Animal studies have shown that gonadectomy results in a decrease in pain threshold in rats and repletion of testosterone elevates that threshold. These observations suggest that testosterone may possess analgesic properties. Hence, the investigators hypothesize that hypogonadism developing in men on opioids results in an increased sensitivity to pain and requirement of higher doses of opioids. In this study, the investigators plan to administer testosterone to men with opioid-induced hypogonadism and evaluate their pain perception, pain sensitivity in response to noxious stimuli and changes in the requirement of opioids in response to testosterone administration.

Hypothesis:

Testosterone replacement in men with opioid-induced hypogonadism will improve pain tolerance, pain perception and quality of life.

Specific aims:

  1. To evaluate the effects of testosterone replacement on pain sensitivity, pain tolerance, and pain modulation in men with opioid-induced hypogonadism.

  2. To determine the effects of testosterone replacement on health-related quality of life.

  3. To determine whether testosterone replacement in hypogonadal men induces changes in the dosage requirements of opioid medications for pain control.

To accomplish our specific aims, the investigators propose a randomized, double blind, placebo-controlled, parallel arm study in which hypogonadal men with non-cancer chronic back pain syndrome on chronic opioids and low testosterone levels (<300 ng/dl) will be randomized to exogenous testosterone replacement therapy vs placebo. Our primary outcome is change in pain tolerance using various external painful stimuli. Secondary outcomes are change in pain sensitivity and modulation, quality of life and opioid requirements.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
84 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception in Men With Chronic Pain Syndrome
Study Start Date :
Apr 1, 2006
Actual Primary Completion Date :
Nov 1, 2012
Actual Study Completion Date :
Nov 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Androgel (testosterone gel)

Testosterone replacement therapy

Drug: AndroGel
5g gel, applied once daily to the upper arms, upper back or shoulders.
Other Names:
  • testosterone gel

    		•
    Placebo Comparator: Placebo

    Placebo gel

    Other: Placebo
    5g gel, applied once daily to the upper arms, upper back or shoulders.

    Outcome Measures

    Primary Outcome Measures

    1. Brief Pain Inventory (BPI) at Week 14 [Week14 after intervention]

      BPI is a self-administered questionnaire that measuring chronic pain. BPI gives two main scores: a pain severity score and a pain interference score. The pain severity score assesses the severity of pain on a continuous scale from 0 (no pain) to 10 (severe pain). The pain interference score corresponds to the item on pain interference, ranging from 0 (does not interfere) to 10(completely interferes). The total score is the sum of the pain severity score and pain interference score, ranging from 0(no pain) to 20 (severe and completely interfered pain).

    2. Algometer-induced Pressure Pain at Week 14 [Week 14 after intervention]

      A digital pressure algometer at the trapezius muscle and the metacarpophalangeal joint of the thumb was used to measure pressure pain thresholds. Higher values represent a better tolerance of pressure pain.

    3. Weighted Pinprick Stimulator-induced Mechanical Pain at Week 14 [Week 14 after intervention]

      Weighted pinprick stimulators are used to assess mechanical pain. Lower values represent better tolerance of pain.

    4. Ice Water-induced Cold Pain and Its After-sensation at Week 14 [Week 14 after intervention]

      Cold-pressor tests measure cold-induced pain and its sensation. Time was measured when a participant reached pain tolerance in cold water and after sensation. Higher values of time in Cold pain tolerance and lower values of time in Cold pain after-sensation (30 seconds) represent better tolerance of pain.

    Secondary Outcome Measures

    1. Sexual Functioning as Assessed by International Index of Erectile Function (IIEF) at Week 14 [Week14 after intervention]

      IIEF is a validated, 15-item questionnaire that assesses 5 domains of sexual function: erectile function (range 1-30), orgasmic function (range 0-10), sexual desire (range 2-10), intercourse satisfaction (range 0-15), and overall sexual satisfaction (range 2-10). Each question was answered on a 6-point or 5-point scale from 0/1 to 5 (best) with a total possible score (sum of 5 domains) range of 5 to 75 with higher scores representing better function.

    2. Health Quality of Life (QoL) as Assessed by Short Form 36 (SF-36) at Week 14 [Week 14 after intervention]

      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.

    3. Pain Catastrophizing Scale (PCS) at Week 14 [Values at week 14 after intervention]

      PCS questionnaire measures self-assessment of pain catastrophizing. This questionnaire consists of 13 items on past painful experiences and rate on 5-point scales ranging from 0 (not at all) to 4 (all the time). The PCS yields three subscale scores assessing rumination (range 0-16), magnification (range 0-12), helplessness (range 0-24), and a composite score (sum of three domains, ranging 0-52). Higher score represents worse painful experiences.

    Other Outcome Measures

    1. Total Testosterone Values at Week 14 [Week 14 after intervention]

      Total testosterone was measured in a CDC-certified laboratory using an LC-MS/MS method with a sensitivity of 2 ng/dL.

    2. Free Testosterone Values at Week 14 [Week 14 after intervention]

      Free testosterone was calculated using a law of mass action equation.

    3. Sex Hormone Binding Globulin (SHBG) at Week 14 [Week 14 after intervention]

      Sex hormone binding globulin was measured using immunofluorometric assays, with limits of quantification of 2.5 nmol/L.

    4. Luteinizing Hormone Values at Week 14 [Week 14 after intervention]

      Luteinizing hormone was measured using immunofluorometric assays, with limits of quantification of 0.05 U/L.

    5. Inflammatory Cytokines at Week 14 [Week 14 after intervention]

      The pathophysiology of pain is measured by the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-Alpha).

    6. Body Composition at Week 14 [Week 14 after intervention]

      Body composition was measured using dual-energy X-ray absorptiometry scan.

    7. Lipid Profile at Week 14 [Week 14 after intervention]

      Serum total cholesterol, triglycerides and high-density lipoprotein (HDL) cholesterol levels were measured by enzymatic assays and standardized to the CDC using the Lipid Research Clinic protocol. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation.

    8. HbA1c at Week 14 [Week 14 after intervention]

    9. Glucose Level in Oral Glucose Tolerance Test (OGTT) at Week 14 [Week 14 after intervention]

      All participants underwent 75-g oral glucose tolerance test (OGTT) after a 12-h fast, The plasma glucose level were analyzed at baseline and at 60 and 120 min after glucose loading.

    10. Insulin Level in Oral Glucose Tolerance Test (OGTT) at Week 14 [Values at week 14 after intervention]

      All participants underwent 75-g oral glucose tolerance test (OGTT) after a 12-h fast, The insulin level were analyzed at baseline and at 60 and 120 min after glucose loading.

    11. HOMA IR Score at Week 14 [Week 14 after intervention]

      Insulin resistance was calculated using the homeostatic model assessment (HOMA) index: glucose * insulin / 22.5.

    12. Adiponectin at Week 14 [Week 14 after intervention]

      Total adiponectin was measured using an RIA kit with an interassay CV of 6.9-9.3% and an intra-assay CV of 1.8-6.2% (Millipore).

    13. Leptin at Week 14 [Week 14 after intervention]

      Leptin levels were measured using ELISA with an interassay CV of 2.6% to 6.2% and in intra-assay CV of 2.6% to 4.6% (Millipore, Billerica, MA, USA).

    14. C-reactive Protein (CRP) at Week 14 [Week 14 after intervention]

      High-sensitivity C-reactive protein (Alpco Diagnostics) was measured using a high-sensitivity sandwich ELISA with an intra-assay CV of 5.6%

    15. Insomnia Severity Index (ISI) at Week 14 [Week 14 after intervention]

      ISI is comprised of 7 items assesses a participant's perception of insomnia. Each item is rated on a 5-point scale from 0 (none) to 4 (very severe). Scores from the questions are summed to assign a total score ranging from 0 to 28, where higher score represents worse insomnia problem.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 100 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Men

    • Age 18 years and older

    • Non-cancer chronic pain

    • Serum total testosterone level <350 ng/dl

    • Consumption of at least 20 mg of hydrocodone (or analgesic equivalent of another opioid) for at least 4 weeks

    • Absence of hospitalization in the past 2 months

    • No acute illness in the past 2 months

    • No current anabolic therapy (growth hormone, DHEA, etc)

    • No current use or consumption in the past 2 months of melatonin

    • Normal prostate exam

    • Normal PSA level

    Exclusion Criteria:

    • Cancer-related chronic pain

    • Liver enzymes > 3 times upper limit of normal

    • Serum creatinine > 2 times upper limit of normal

    • Neurological disease

    • Active psychiatric illness

    • Any addictive drug use

    • Alcoholism (>3 drinks/day)

    • Patients currently receiving melatonin or anabolic agents

    • Hospitalization in the past 2 months

    • Acute illness in the past 2 months

    • Consumption of < 20 mg of hydrocodone (or analgesic equivalent of another opioid)

    • Severe BPH

    • PSA > 4.0 ng/ml

    • Prostate cancer

    • Breast cancer

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Brigham and Women's Hospital Boston Massachusetts United States 02115

    Sponsors and Collaborators

    • Boston University

    Investigators

    • Principal Investigator: Shehzad Basaria, MD, Brigham and Women's Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Shehzad Basaria, ASSOCIATE PROFESSOR, Brigham and Women's Hospital
    ClinicalTrials.gov Identifier:
    NCT00351819
    Other Study ID Numbers:
    • H-27995
    First Posted:
    Jul 13, 2006
    Last Update Posted:
    Jun 28, 2017
    Last Verified:
    May 1, 2017
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Shehzad Basaria, ASSOCIATE PROFESSOR, Brigham and Women's Hospital
    Testosterone
    Pain
    Opioid
    Hypogonadism
    Additional relevant MeSH terms:
    Hypogonadism
    Testosterone

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Period Title: Overall Study
    STARTED 43 41
    COMPLETED 36 29
    NOT COMPLETED 7 12

    Baseline Characteristics

    Arm/Group Title Androgel (Testosterone Gel) Placebo Total
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders. Total of all reporting groups
    Overall Participants 36 29 65
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    48
    (9)
    50
    (6)
    49
    (8)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    36
    100%
    29
    100%
    65
    100%
    Region of Enrollment (participants) [Number]
    United States
    36
    100%
    29
    100%
    65
    100%
    Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m2]
    32.0
    (7.0)
    33.4
    (8.0)
    32.6
    (7.4)
    Opioid dose (morphine equivalent) (mg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg]
    114
    (176)
    76
    (139)
    97
    (161)
    Time on opioids (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    54
    (48)
    40
    (54)
    48
    (50)
    Total testosterone (ng/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [ng/dL]
    221
    (87)
    237
    (97)
    228
    (91)
    Free testosterone (pg/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pg/mL]
    44.1
    (22.6)
    43.6
    (19.3)
    43.9
    (21.0)
    Sex hormone binding globulin (nmol/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [nmol/L]
    39.3
    (31.4)
    37.7
    (14.5)
    38.6
    (25.2)
    Luteinizing hormone (U/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [U/L]
    2.8
    (1.9)
    3.8
    (2.4)
    3.2
    (2.2)
    TNF-Alpha (pg/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pg/mL]
    1.8
    (0.6)
    2.2
    (2.7)
    2.0
    (1.9)
    IL-6 (pg/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pg/mL]
    2.6
    (2.8)
    2.8
    (2.9)
    2.7
    (2.8)
    Hemoglobin (g/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [g/dL]
    15
    14
    15
    Hematocrit (%) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [%]
    44
    43
    43
    Brief Pain Inventory (BPI) questionnaire (units on a scale) [Mean (Standard Deviation) ]
    Total
    11.5
    (3.2)
    10.4
    (3.1)
    11.0
    (3.2)
    Severity
    5.7
    (1.5)
    5.5
    (1.7)
    5.6
    (1.6)
    Interference
    5.8
    (2.2)
    4.9
    (1.8)
    5.4
    (2.1)
    Algometer-induced pressure pain (kPa/cm2) [Mean (Standard Deviation) ]
    Trapezius
    341
    (116)
    353
    (197)
    347
    (157)
    Thumb
    369
    (125)
    383
    (185)
    375
    (155)
    Weighted pinprick stimulator-induced mechanical pain (watt) [Mean (Standard Deviation) ]
    First stimulus
    12.0
    (13.0)
    8.0
    (7.4)
    10.2
    (11.0)
    10th stimulus
    27.0
    (20.6)
    18.6
    (19.5)
    23.2
    (20.4)
    Ice water-induced cold pain and its after-sensation (seconds) [Mean (Standard Deviation) ]
    Cold pain tolerance
    40.1
    (33.4)
    53.3
    (51.3)
    46.1
    (42.7)
    Cold pain after sensation: 30s
    16.7
    (19.2)
    13.8
    (18.0)
    15.4
    (18.5)
    Sexual Function as assessed by International Index of Erectile Function (IIEF) (units on a scale) [Mean (Standard Deviation) ]
    Total score
    44.6
    (19.0)
    41.1
    (21.7)
    43.0
    (20.2)
    Erectile function
    18.8
    (9.2)
    16.8
    (10.6)
    17.9
    (9.8)
    Orgasmic function
    6.5
    (3.5)
    6.1
    (3.6)
    6.3
    (3.6)
    Sexual desire
    5.5
    (2.5)
    6.2
    (2.1)
    5.8
    (2.3)
    Intercourse satisfaction
    8.2
    (4.6)
    7.1
    (5.6)
    7.7
    (5.1)
    Overall satisfaction
    4.9
    (2.5)
    5.0
    (2.9)
    4.9
    (2.7)
    Health Quality of Life (QoL) as assessed by Short Form 36 (SF-36) (units on a scale) [Mean (Standard Deviation) ]
    Physical functioning
    41
    (22)
    38
    (25)
    39
    (23)
    Bodily pain
    56
    (15)
    55
    (17)
    56
    (16)
    Role limitations due to physical health problems
    10
    (24)
    18
    (31)
    13
    (27)
    Role limitations due to emotional problems
    39
    (45)
    40
    (45)
    39
    (44)
    Emotional well-being
    60
    (16)
    59
    (17)
    60
    (16)
    Social functioning
    53
    (13)
    54
    (15)
    54
    (14)
    Energry/fatigue
    37
    (18)
    37
    (18)
    37
    (18)
    General health perceptions
    54
    (14)
    51
    (14)
    52
    (14)
    Body composition measured by dual energy x-ray absorptiometry (kg) [Mean (Standard Deviation) ]
    Lean mass
    57.4
    (7.8)
    60.1
    (6.9)
    58.6
    (7.5)
    Fat mass
    27.0
    (9.7)
    26.8
    (9.5)
    26.9
    (9.5)
    Total mass
    84.4
    (16.1)
    86.8
    (13.8)
    85.5
    (15.0)
    Appendicular lean mass
    27.4
    (4.0)
    28.6
    (4.2)
    27.9
    (4.1)
    Appendicular fat mass
    11.7
    (4.9)
    11.9
    (5.1)
    11.8
    (5.0)
    Appendicular total mass
    38.3
    (7.8)
    39.4
    (7.0)
    38.8
    (7.4)
    Lipid profile (mmol/L) [Mean (Standard Deviation) ]
    Total cholesterol
    4.6
    (1.1)
    5.2
    (1.2)
    4.9
    (1.2)
    LDL
    2.8
    (1.0)
    3.2
    (0.9)
    3.0
    (1.0)
    HDL
    1.0
    (0.3)
    1.1
    (0.4)
    1.0
    (0.3)
    Triglycerides
    2.0
    (1.6)
    2.0
    (1.2)
    2.0
    (1.4)
    HbA1c (percentage of glycossylated hemoglobin) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage of glycossylated hemoglobin]
    5.7
    (0.01)
    6.2
    (0.02)
    5.9
    (0.01)
    Glucose levels in OGTT (mmol/L) [Mean (Standard Deviation) ]
    Fasting glucose
    5.2
    (0.7)
    5.6
    (2.6)
    5.3
    (1.8)
    OGTT 1-h glucose
    8.4
    (2.9)
    8.0
    (2.8)
    8.2
    (2.8)
    OGTT 2-h glucose
    6.5
    (1.9)
    6.0
    (2.0)
    6.3
    (1.9)
    Insulin levels in OGTT (pmol/L) [Mean (Standard Deviation) ]
    Fasting insulin
    64
    (66)
    100
    (174)
    80
    (126)
    OGTT 1-h insulin
    300
    (306)
    416
    (325)
    351
    (317)
    OGTT 2-h insulin
    246
    (242)
    311
    (293)
    275
    (266)
    HOMA IR (HOMA IR score) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [HOMA IR score]
    2.1
    (2.1)
    3.3
    (5.8)
    2.6
    (4.2)
    Adiponectin (ug/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [ug/mL]
    4.9
    (2.7)
    4.5
    (1.7)
    4.7
    (2.3)
    Leptin (ug/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [ug/L]
    16
    (12)
    18
    (17)
    17
    (14)
    C-reactive protein (mg/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/L]
    3.1
    (3.5)
    2.7
    (2.3)
    2.9
    (3.0)
    Pain catastrophizing scale (PCS) (units on a scale) [Mean (Standard Deviation) ]
    Composite score
    26
    (11)
    27
    (11)
    27
    (11)
    Rumination score
    9.5
    (4.0)
    9.6
    (3.0)
    9.5
    (3.6)
    Magnification score
    4.7
    (3.2)
    5.1
    (2.9)
    4.9
    (3.1)
    Helplessness score
    11.5
    (5.3)
    11.6
    (5.1)
    11.6
    (5.2)
    Insomnia severity index (ISI) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    11.9
    (4.7)
    11.6
    (4.4)
    11.8
    (4.5)

    Outcome Measures

    1. Primary Outcome
    Title Brief Pain Inventory (BPI) at Week 14
    Description BPI is a self-administered questionnaire that measuring chronic pain. BPI gives two main scores: a pain severity score and a pain interference score. The pain severity score assesses the severity of pain on a continuous scale from 0 (no pain) to 10 (severe pain). The pain interference score corresponds to the item on pain interference, ranging from 0 (does not interfere) to 10(completely interferes). The total score is the sum of the pain severity score and pain interference score, ranging from 0(no pain) to 20 (severe and completely interfered pain).
    Time Frame Week14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 36 29
    Total score
    10.2
    (3.8)
    9.7
    (3.3)
    Severity
    5.3
    (1.7)
    5.1
    (1.6)
    Interference
    5.0
    (2.3)
    4.7
    (1.9)
    2. Primary Outcome
    Title Algometer-induced Pressure Pain at Week 14
    Description A digital pressure algometer at the trapezius muscle and the metacarpophalangeal joint of the thumb was used to measure pressure pain thresholds. Higher values represent a better tolerance of pressure pain.
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 36 29
    Trapezius
    379.4
    (194.7)
    315.9
    (151.6)
    Thumb
    409.7
    (167.9)
    326.4
    (187.3)
    3. Primary Outcome
    Title Weighted Pinprick Stimulator-induced Mechanical Pain at Week 14
    Description Weighted pinprick stimulators are used to assess mechanical pain. Lower values represent better tolerance of pain.
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 36 29
    First Stimulus
    10.9
    (8.4)
    11.7
    (13.2)
    10th Stimulus
    21.9
    (17.4)
    22.2
    (23.5)
    4. Primary Outcome
    Title Ice Water-induced Cold Pain and Its After-sensation at Week 14
    Description Cold-pressor tests measure cold-induced pain and its sensation. Time was measured when a participant reached pain tolerance in cold water and after sensation. Higher values of time in Cold pain tolerance and lower values of time in Cold pain after-sensation (30 seconds) represent better tolerance of pain.
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 36 29
    Cold pain tolenrance
    54.2
    (55.9)
    54.1
    (50.9)
    Cold pain after sensation: 30s
    13.1
    (18.4)
    13.9
    (15.1)
    5. Secondary Outcome
    Title Sexual Functioning as Assessed by International Index of Erectile Function (IIEF) at Week 14
    Description IIEF is a validated, 15-item questionnaire that assesses 5 domains of sexual function: erectile function (range 1-30), orgasmic function (range 0-10), sexual desire (range 2-10), intercourse satisfaction (range 0-15), and overall sexual satisfaction (range 2-10). Each question was answered on a 6-point or 5-point scale from 0/1 to 5 (best) with a total possible score (sum of 5 domains) range of 5 to 75 with higher scores representing better function.
    Time Frame Week14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 36 29
    Total score
    51.3
    (17.5)
    47.1
    (23.1)
    Erectile function
    21.7
    (7.9)
    19.2
    (10.8)
    Orgasmic funcion
    7.7
    (2.9)
    6.4
    (3.4)
    Sexual desire
    6.8
    (2.1)
    6.3
    (2.6)
    Intercourse satisfaction
    9.1
    (5.2)
    9.0
    (5.4)
    Overall satisfaction
    6.1
    (2.5)
    6.1
    (3.1)
    6. Secondary Outcome
    Title Health Quality of Life (QoL) as Assessed by Short Form 36 (SF-36) at Week 14
    Description 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.
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 36 29
    Physical functioning
    42
    (19)
    42
    (24)
    Bodily pain
    62
    (21)
    61
    (17)
    Role limitations due to physical health problems
    23
    (35)
    22
    (29)
    Role limitations due to emotional problems
    56
    (42)
    37
    (43)
    Emotional well-being
    64
    (16)
    63
    (15)
    Social functioning
    57
    (14)
    54
    (13)
    Energy-fatigue
    44
    (17)
    40
    (18)
    General health perceptions
    55
    (12)
    52
    (13)
    7. Secondary Outcome
    Title Pain Catastrophizing Scale (PCS) at Week 14
    Description PCS questionnaire measures self-assessment of pain catastrophizing. This questionnaire consists of 13 items on past painful experiences and rate on 5-point scales ranging from 0 (not at all) to 4 (all the time). The PCS yields three subscale scores assessing rumination (range 0-16), magnification (range 0-12), helplessness (range 0-24), and a composite score (sum of three domains, ranging 0-52). Higher score represents worse painful experiences.
    Time Frame Values at week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 33 29
    Composite score
    20
    (12)
    21
    (10)
    Rumination score
    7.1
    (4.1)
    7.6
    (3.1)
    Magnification score
    3.7
    (2.8)
    4.1
    (2.4)
    Helplessness score
    9.2
    (5.8)
    8.4
    (4.7)
    8. Other Pre-specified Outcome
    Title Total Testosterone Values at Week 14
    Description Total testosterone was measured in a CDC-certified laboratory using an LC-MS/MS method with a sensitivity of 2 ng/dL.
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 33 29
    Mean (Standard Deviation) [ng/dL]
    790
    (544)
    328
    (185)
    9. Other Pre-specified Outcome
    Title Free Testosterone Values at Week 14
    Description Free testosterone was calculated using a law of mass action equation.
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 33 29
    Mean (Standard Deviation) [pg/mL]
    189
    (152)
    65
    (36)
    10. Other Pre-specified Outcome
    Title Sex Hormone Binding Globulin (SHBG) at Week 14
    Description Sex hormone binding globulin was measured using immunofluorometric assays, with limits of quantification of 2.5 nmol/L.
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 36 29
    Mean (Standard Deviation) [nmol/L]
    34.6
    (18.2)
    35.0
    (14.3)
    11. Other Pre-specified Outcome
    Title Luteinizing Hormone Values at Week 14
    Description Luteinizing hormone was measured using immunofluorometric assays, with limits of quantification of 0.05 U/L.
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 36 29
    Mean (Standard Deviation) [U/L]
    1.6
    (2.2)
    3.5
    (2.3)
    12. Other Pre-specified Outcome
    Title Inflammatory Cytokines at Week 14
    Description The pathophysiology of pain is measured by the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-Alpha).
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 36 29
    IL-6
    2.4
    (2.1)
    2.6
    (2.7)
    TNF-Alpha
    1.9
    (1.0)
    2.1
    (2.4)
    13. Other Pre-specified Outcome
    Title Body Composition at Week 14
    Description Body composition was measured using dual-energy X-ray absorptiometry scan.
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 36 29
    Lean mass
    57.8
    (7.5)
    60.9
    (5.9)
    Fat mass
    25.7
    (8.7)
    27.9
    (9.7)
    Total mass
    83.5
    (14.8)
    88.7
    (12.8)
    Appendicular lean mass
    27.9
    (4.1)
    29.4
    (3.7)
    Appendicular fat mass
    11.4
    (4.7)
    12.1
    (4.7)
    Appendicular total mass
    38.6
    (7.9)
    40.8
    (6.3)
    14. Other Pre-specified Outcome
    Title Lipid Profile at Week 14
    Description Serum total cholesterol, triglycerides and high-density lipoprotein (HDL) cholesterol levels were measured by enzymatic assays and standardized to the CDC using the Lipid Research Clinic protocol. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation.
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 33 27
    Total cholesterol
    4.8
    (1.2)
    5.1
    (1.1)
    LDL
    2.9
    (1.0)
    3.1
    (1.0)
    HDL
    1.0
    (0.4)
    1.1
    (0.4)
    Triglycerides
    1.8
    (1.0)
    1.9
    (1.0)
    15. Other Pre-specified Outcome
    Title HbA1c at Week 14
    Description
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 36 28
    Mean (Standard Deviation) [percentage of glycosylated hemogobin]
    5.7
    (0.01)
    6.1
    (0.01)
    16. Other Pre-specified Outcome
    Title Glucose Level in Oral Glucose Tolerance Test (OGTT) at Week 14
    Description All participants underwent 75-g oral glucose tolerance test (OGTT) after a 12-h fast, The plasma glucose level were analyzed at baseline and at 60 and 120 min after glucose loading.
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 33 25
    Fasting glucose
    5.2
    (1.4)
    5.6
    (1.4)
    OGTT 1-h glucose
    8.0
    (3.4)
    8.3
    (2.4)
    OGTT 2-h glucose
    6.7
    (3.2)
    6.1
    (2.6)
    17. Other Pre-specified Outcome
    Title Insulin Level in Oral Glucose Tolerance Test (OGTT) at Week 14
    Description All participants underwent 75-g oral glucose tolerance test (OGTT) after a 12-h fast, The insulin level were analyzed at baseline and at 60 and 120 min after glucose loading.
    Time Frame Values at week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 33 25
    Fasting insulin
    70
    (88)
    110
    (149)
    OGTT 1-h insulin
    279
    (181)
    407
    (318)
    OGTT 2-h insulin
    231
    (210)
    325
    (275)
    18. Other Pre-specified Outcome
    Title HOMA IR Score at Week 14
    Description Insulin resistance was calculated using the homeostatic model assessment (HOMA) index: glucose * insulin / 22.5.
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 33 25
    Mean (Standard Deviation) [HOMA IR score]
    2.5
    (3.6)
    4.2
    (5.9)
    19. Other Pre-specified Outcome
    Title Adiponectin at Week 14
    Description Total adiponectin was measured using an RIA kit with an interassay CV of 6.9-9.3% and an intra-assay CV of 1.8-6.2% (Millipore).
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 36 28
    Mean (Standard Deviation) [ug/mL]
    4.8
    (3.0)
    4.7
    (2.1)
    20. Other Pre-specified Outcome
    Title Leptin at Week 14
    Description Leptin levels were measured using ELISA with an interassay CV of 2.6% to 6.2% and in intra-assay CV of 2.6% to 4.6% (Millipore, Billerica, MA, USA).
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 35 28
    Mean (Standard Deviation) [ug/L]
    16
    (12)
    21
    (21)
    21. Other Pre-specified Outcome
    Title C-reactive Protein (CRP) at Week 14
    Description High-sensitivity C-reactive protein (Alpco Diagnostics) was measured using a high-sensitivity sandwich ELISA with an intra-assay CV of 5.6%
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 36 28
    Mean (Standard Deviation) [mg/L]
    4.2
    (4.4)
    3.4
    (3.3)
    22. Other Pre-specified Outcome
    Title Insomnia Severity Index (ISI) at Week 14
    Description ISI is comprised of 7 items assesses a participant's perception of insomnia. Each item is rated on a 5-point scale from 0 (none) to 4 (very severe). Scores from the questions are summed to assign a total score ranging from 0 to 28, where higher score represents worse insomnia problem.
    Time Frame Week 14 after intervention

    Outcome Measure Data

    Analysis Population Description
    All available data expressed as absolute values at week 14.
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    Measure Participants 33 29
    Mean (Standard Deviation) [units on a scale]
    10.8
    (5.2)
    11.1
    (5.1)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Androgel (Testosterone Gel) Placebo
    Arm/Group Description Testosterone replacement therapy Androgel (testosterone gel): 5g gel, applied once daily to the upper arms, upper back or shoulders. Placebo gel Placebo: 5g gel, applied once daily to the upper arms, upper back or shoulders.
    All Cause Mortality
    Androgel (Testosterone Gel) Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Androgel (Testosterone Gel) Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/43 (2.3%) 2/41 (4.9%)
    Gastrointestinal disorders
    Pancreatitis 1/43 (2.3%) 0/41 (0%)
    Surgical and medical procedures
    Knee arthroplasty 0/43 (0%) 1/41 (2.4%)
    Wrist arthrodesis 0/43 (0%) 1/41 (2.4%)
    Other (Not Including Serious) Adverse Events
    Androgel (Testosterone Gel) Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/43 (14%) 5/41 (12.2%)
    General disorders
    Fever 3/43 (7%) 0/41 (0%)
    Nervous system disorders
    Headache 2/43 (4.7%) 3/41 (7.3%)
    Respiratory, thoracic and mediastinal disorders
    Nasal congestion 5/43 (11.6%) 4/41 (9.8%)
    Cough 4/43 (9.3%) 5/41 (12.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Shehzad Basaria
    Organization Brigham and Women's Hospital
    Phone 617-525-9150
    Email sbasaria@partners.org
    Responsible Party:
    Shehzad Basaria, ASSOCIATE PROFESSOR, Brigham and Women's Hospital
    ClinicalTrials.gov Identifier:
    NCT00351819
    Other Study ID Numbers:
    • H-27995
    First Posted:
    Jul 13, 2006
    Last Update Posted:
    Jun 28, 2017
    Last Verified:
    May 1, 2017