Androgen Effects in HIV-infected Women

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00095212
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 25
• Location: 1
• Arms: 2
• Duration (Months): 53
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Androgen deficiency in HIV-infected women is associated with sarcopenia and may cause critical reductions in physical functioning and reduced bone density. The effects of long-term androgen therapy on lean body mass, bone density and other clinical endpoints including quality of life, functional status and neurocognitive function in HIV-infected women are not known.

Condition or Disease	Intervention/Treatment	Phase
HIV Infection	Drug: 1 Transdermal Testosterone (Patch); Drug: 2 Placebo Patch	N/A

Detailed Description

We will perform an 18-month randomized, double-blinded, placebo-controlled study among relatively androgen deficient women with HIV, to determine the effects of testosterone administration on lean body mass. The administered dose will be 300 micrograms twice a week vs. identical placebo in the form of a transdermal preparation. Secondary endpoints include effects on bone density, quality of life, neurocognitive function and menstrual function. Open label administration at 300 micrograms twice a week will be initiated for 12 months in all subjects following the randomized portion of the study. Assuming a 15% dropout rate and 25 randomized patients, the probability is 80 percent that the study will detect a treatment difference at a two sided 5.000 percent significance level, if the true difference between the treatments is 2.7 kg. This is based on the assumption that the standard deviation of the response variable, lean body mass by DEXA, is 2.3 kg, as was shown by Choi et al1 over 12 weeks in HIV-infected women at the same dose of 300 ug 2x/week.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Androgen Effects in HIV-infected Women
• Study Start Date: Sep 1, 2004
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Transdermal Testosterone (Patch) 300 micrograms applied twice a week	Drug: 1 Transdermal Testosterone (Patch); 300 micrograms twice a week
Placebo Comparator: 2 Placebo Patch (identical in appearance) placebo patch (0 micrograms of testosterone)applied twice a week	Drug: 2 Placebo Patch; Placebo patch (0 micrograms of testosterone) applied twice a week

Outcome Measures

Primary Outcome Measures

1. Lean Body Mass [Baseline (time 0) to 18 months]

   Represents change in measure from baseline to 18 months. 18 month mean and standard error of the mean for lean body mass measured by dual energy absorptiometry (DEXA)scan.

Secondary Outcome Measures

1. Bone Mineral Density of the Hip [Baseline (time 0) to 18 months]

   Represents change in measure from baseline to 18 months. 18 month mean and standard error of the mean for bone mineral density of the hip measured by dual energy absorptiometry (DEXA)scan.

2. Quality of Life/Depression: Becks Depression Inventory [Baseline (time 0) to 18 months]

   Represents change in the mean score from baseline to 18 months. Depression was evaluated with the Beck's Depression Inventory (BDI). The BDI is a 21-item self-report instrument used to assess the presence and severity of symptoms of depression. A Total score in the range of 0-13 is considered minimal, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.

3. Quality of Life/Sexual Function: Brief Index of Sexual Function (BISF-W) Domain 7: Problems Affecting Sexual Function [Baseline (time 0) to 18 months]

   Represents change in measure from baseline to 18 months. The BISF is 22 items with seven domains: Thoughts and Desires, Arousal, Frequency of Sexual Activity, Receptivity/Initiation, Pleasure, Relationship Satisfaction, and Problems Affecting Sexual Function. Data from Domain 7: Problems Affecting Sexual Function is reported. The score range for this domain is -16 to 75,a higher score indicates greater sexual function.

4. Safety: Number of Subjects Reporting a Skin Reaction to the Patch [Baseline (time 0) to 18 months]

   Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant.

5. Safety: Number of Subjects Reporting a Change in Hair Pattern (Increased Hair on Chin, Upper Lip, Chest, Abdomen, Fore Arms, and Legs) [Baseline (time 0) to 18 months]

   Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant.

6. Safety: Number of Subjects Reporting Acne [Baseline (time 0) to 18 months]

   Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant.

7. Safety: Number of Subjects Reporting a Change in Menstrual Status (Reported More Than One Period in 1 Month or Missed a Period During a Monthly Cycle) [Baseline (time 0) to 18 months]

   Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant.

8. Neurocognitive Function: Hopkins Verbal Learning Test-revised,"Total Recall" Z Score Represents Change in Z Score From Baseline to 18 Months. [Baseline (time 0) to 18 months]

   This test assesses verbal learning and memory. Subjects are given a list of 12 words and asked to repeat as many words as they can recall during 3 separate trials. The Total Recall Z score is calculated based on the sum of total correct responses for Trials 1,2,& 3. A Z score of 0 equals the 50 percentile, a Z score of 1 is 1 standard deviation above the mean and a Z score of -1 is 1 standard deviation below the mean. The lowest and highest T scores for the HVLT-R are ≤20 and ≥80. This correlates to lowest and highest Z scores of ≤ -3.0 and ≥3.0. A lower Z score is indicative of poor recall.

9. Strength: Total Knee Flexion Performed Via Quantitative Muscle Function Testing. [Baseline (time 0) to 18 months]

   Represents change in isometric force (measured in kilograms) from baseline to 18 months. Peak isometric force of total knee flexion and extension were measured on the best of 2 repetitions for which subjects held a maximum contraction for 5 seconds.

10. Strength: Total Knee Extension Performed Via Quantitative Muscle Function Testing. [Baseline (time 0) to 18 months]

    Represents change in isometric force (measured in kilograms) from baseline to 18 months. Peak isometric force of total knee flexion and extension were measured on the best of 2 repetitions for which subjects held a maximum contraction for 5 seconds.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female 18 - 55

• BMI less than or equal to 26

• HIV-infected

• Androgen deficient, with free testosterone < 3 pg/mL

• Stable antiretroviral regimen for 3 months prior to study

• Tubal ligation, hysterectomy, or verbalized understanding of appropriate barrier contraception methods. Subjects will be counseled in appropriate barrier contraception methods and the counseling will be documented.

Exclusion Criteria:

• Use of anabolic agent, including testosterone, GH or other preparations within 3 months of the study.

• Use of megestrol acetate within 3 months of the study

• Use of estrogen or any preparation known to affect bone density or bone turnover.This includes oral contraceptives, depo provera or combined progesterone-estrogen injections, and transdermal contraceptive patches.

• Pregnant or breast-feeding

• Hgb < 9.0 mg/dL

• Current participation in another research study conducted by this investigator or past participation in the DHEA study funded by the same grant as this protocol.

• Creatinine > 1.5 mg/dL

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mass General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00095212
• Other Study ID Numbers: DK54167 (completed); R01DK054167
• First Posted: Nov 2, 2004
• Last Update Posted: Apr 14, 2010
• Last Verified: Apr 1, 2010

• Keywords provided by , ,: HIV; women; androgen; Treatment Experienced
• Additional relevant MeSH terms: HIV Infections; Testosterone

Study Results

Participant Flow

Recruitment Details	Recruitment began in August, 2004 and continued through October, 2006. Subjects were recruited via poster advertisement at community health centers, hospitals, and AIDS Service Organizations, as well as newspaper advertisement and provider referral.
Pre-assignment Detail	Prior to randomization at the baseline visit, each subject's doctor was contacted to confirm safety of study enrollment. Subjects age 40 and older were required to have a mammogram performed within one year of study enrollment and provide results. Eligible subjects completed a pregnancy test at each visit and were excluded for a positive test.

Arm/Group Title	Transdermal Testosterone (Patch)	Placebo Patch (Identical in Appearance)
Arm/Group Description	300 micrograms applied twice a week	placebo patch (0 micrograms of testosterone)applied twice a week
Period Title: Overall Study
STARTED	13	12
COMPLETED	12	9
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Transdermal Testosterone (Patch)	Placebo Patch (Identical in Appearance)	Total
Arm/Group Description	300 micrograms applied twice a week	placebo patch (0 micrograms of testosterone)applied twice a week	Total of all reporting groups
Overall Participants	13	12	25
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 100%	12 100%	25 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45 (2)	43 (1)	44 (1)
Sex: Female, Male (Count of Participants)
Female	13 100%	12 100%	25 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	13 100%	12 100%	25 100%

Outcome Measures

1. Primary Outcome

Title	Lean Body Mass
Description	Represents change in measure from baseline to 18 months. 18 month mean and standard error of the mean for lean body mass measured by dual energy absorptiometry (DEXA)scan.
Time Frame	Baseline (time 0) to 18 months

Outcome Measure Data

Analysis Population Description

Responses at 9 and 18 months were pooled as the post treatment repeated measures. All data were included in the analysis, including 9 month data from the 4 subjects who discontinued after the 9 month visit.

Arm/Group Title	Transdermal Testosterone (Patch)	Placebo Patch (Identical in Appearance)
Arm/Group Description	300 micrograms applied twice a week	placebo patch (0 micrograms of testosterone)applied twice a week
Measure Participants	13	12
Mean (Standard Error) [kilograms]	1.8 (0.5)	0.8 (0.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transdermal Testosterone (Patch), Placebo Patch (Identical in Appearance)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	longitudinal linear mixed effects model
	Comments

2. Secondary Outcome

Title	Bone Mineral Density of the Hip
Description	Represents change in measure from baseline to 18 months. 18 month mean and standard error of the mean for bone mineral density of the hip measured by dual energy absorptiometry (DEXA)scan.
Time Frame	Baseline (time 0) to 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transdermal Testosterone (Patch)	Placebo Patch (Identical in Appearance)
Arm/Group Description	300 micrograms applied twice a week	placebo patch (0 micrograms of testosterone)applied twice a week
Measure Participants	13	12
Mean (Standard Error) [grams per centimeter squared]	0.01 (0.01)	-0.01 (0.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transdermal Testosterone (Patch), Placebo Patch (Identical in Appearance)
	Comments	The study was powered at 80% to detect a significant treatment difference of 2.7 kg in lean body mass between the two groups with 25 randomized patients and a 15% assumed dropout rate, using a two sided 5.0 percent significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Longitudinal linear mixed effects model
	Comments

3. Secondary Outcome

Title	Quality of Life/Depression: Becks Depression Inventory
Description	Represents change in the mean score from baseline to 18 months. Depression was evaluated with the Beck's Depression Inventory (BDI). The BDI is a 21-item self-report instrument used to assess the presence and severity of symptoms of depression. A Total score in the range of 0-13 is considered minimal, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.
Time Frame	Baseline (time 0) to 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transdermal Testosterone (Patch)	Placebo Patch (Identical in Appearance)
Arm/Group Description	300 micrograms applied twice a week	placebo patch (0 micrograms of testosterone)applied twice a week
Measure Participants	13	12
Mean (Standard Error) [Units on a scale]	-6.8 (2.2)	-1.9 (3.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transdermal Testosterone (Patch), Placebo Patch (Identical in Appearance)
	Comments	The study was powered at 80% to detect a significant treatment difference of 2.7 kg in lean body mass between the two groups with 25 randomized patients and a 15% assumed dropout rate, using a two sided 5.0 percent significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Longitudinal mixed methods model
	Comments

4. Secondary Outcome

Title	Quality of Life/Sexual Function: Brief Index of Sexual Function (BISF-W) Domain 7: Problems Affecting Sexual Function
Description	Represents change in measure from baseline to 18 months. The BISF is 22 items with seven domains: Thoughts and Desires, Arousal, Frequency of Sexual Activity, Receptivity/Initiation, Pleasure, Relationship Satisfaction, and Problems Affecting Sexual Function. Data from Domain 7: Problems Affecting Sexual Function is reported. The score range for this domain is -16 to 75,a higher score indicates greater sexual function.
Time Frame	Baseline (time 0) to 18 months

Outcome Measure Data

Analysis Population Description

data not available for all subjects as some did not wish to complete the questionnaire

Arm/Group Title	Transdermal Testosterone (Patch)	Placebo Patch (Identical in Appearance)
Arm/Group Description	300 micrograms applied twice a week	placebo patch (0 micrograms of testosterone)applied twice a week
Measure Participants	9	7
Mean (Standard Error) [Units on a scale]	-1.8 (0.8)	0.5 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transdermal Testosterone (Patch), Placebo Patch (Identical in Appearance)
	Comments	The study was powered at 80% to detect a significant treatment difference of 2.7 kg in lean body mass between the two groups with 25 randomized patients and a 15% assumed dropout rate, using a two sided 5.0 percent significance level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Longitudinal mixed methods model
	Comments

5. Secondary Outcome

Title	Safety: Number of Subjects Reporting a Skin Reaction to the Patch
Description	Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant.
Time Frame	Baseline (time 0) to 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transdermal Testosterone (Patch)	Placebo Patch (Identical in Appearance)
Arm/Group Description	300 micrograms applied twice a week	placebo patch (0 micrograms of testosterone)applied twice a week
Measure Participants	13	12
Number [participants]	4 30.8%	1 8.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transdermal Testosterone (Patch), Placebo Patch (Identical in Appearance)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	Chi-squared
	Comments

6. Secondary Outcome

Title	Safety: Number of Subjects Reporting a Change in Hair Pattern (Increased Hair on Chin, Upper Lip, Chest, Abdomen, Fore Arms, and Legs)
Description	Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant.
Time Frame	Baseline (time 0) to 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transdermal Testosterone (Patch)	Placebo Patch (Identical in Appearance)
Arm/Group Description	300 micrograms applied twice a week	placebo patch (0 micrograms of testosterone)applied twice a week
Measure Participants	13	12
Number [participants]	2 15.4%	4 33.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transdermal Testosterone (Patch), Placebo Patch (Identical in Appearance)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments
	Method	Chi-squared
	Comments

7. Secondary Outcome

Title	Safety: Number of Subjects Reporting Acne
Description	Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant.
Time Frame	Baseline (time 0) to 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transdermal Testosterone (Patch)	Placebo Patch (Identical in Appearance)
Arm/Group Description	300 micrograms applied twice a week	placebo patch (0 micrograms of testosterone)applied twice a week
Measure Participants	13	12
Number [participants]	4 30.8%	3 25%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transdermal Testosterone (Patch), Placebo Patch (Identical in Appearance)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments
	Method	Chi-squared
	Comments

8. Secondary Outcome

Title	Safety: Number of Subjects Reporting a Change in Menstrual Status (Reported More Than One Period in 1 Month or Missed a Period During a Monthly Cycle)
Description	Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant.
Time Frame	Baseline (time 0) to 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transdermal Testosterone (Patch)	Placebo Patch (Identical in Appearance)
Arm/Group Description	300 micrograms applied twice a week	placebo patch (0 micrograms of testosterone)applied twice a week
Measure Participants	13	12
Number [participants]	6 46.2%	9 75%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transdermal Testosterone (Patch), Placebo Patch (Identical in Appearance)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	Chi-squared
	Comments

9. Secondary Outcome

Title	Neurocognitive Function: Hopkins Verbal Learning Test-revised,"Total Recall" Z Score Represents Change in Z Score From Baseline to 18 Months.
Description	This test assesses verbal learning and memory. Subjects are given a list of 12 words and asked to repeat as many words as they can recall during 3 separate trials. The Total Recall Z score is calculated based on the sum of total correct responses for Trials 1,2,& 3. A Z score of 0 equals the 50 percentile, a Z score of 1 is 1 standard deviation above the mean and a Z score of -1 is 1 standard deviation below the mean. The lowest and highest T scores for the HVLT-R are ≤20 and ≥80. This correlates to lowest and highest Z scores of ≤ -3.0 and ≥3.0. A lower Z score is indicative of poor recall.
Time Frame	Baseline (time 0) to 18 months

Outcome Measure Data

Analysis Population Description

data not available for all subjects as some did not wish to complete the testing

Arm/Group Title	Transdermal Testosterone (Patch)	Placebo Patch (Identical in Appearance)
Arm/Group Description	300 micrograms applied twice a week	placebo patch (0 micrograms of testosterone)applied twice a week
Measure Participants	12	7
Mean (Standard Error) [Units on a scale]	-0.21 (0.41)	0.50 (0.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transdermal Testosterone (Patch), Placebo Patch (Identical in Appearance)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	t-test, 2 sided
	Comments

10. Secondary Outcome

Title	Strength: Total Knee Flexion Performed Via Quantitative Muscle Function Testing.
Description	Represents change in isometric force (measured in kilograms) from baseline to 18 months. Peak isometric force of total knee flexion and extension were measured on the best of 2 repetitions for which subjects held a maximum contraction for 5 seconds.
Time Frame	Baseline (time 0) to 18 months

Outcome Measure Data

Analysis Population Description

data not available for all subjects due to malfunctioning equipment at some sessions, and some subjects did not wish to complete testing.

Arm/Group Title	Transdermal Testosterone (Patch)	Placebo Patch (Identical in Appearance)
Arm/Group Description	300 micrograms applied twice a week	placebo patch (0 micrograms of testosterone)applied twice a week
Measure Participants	11	8
Mean (Standard Error) [kilograms]	28.5 (11.0)	11.0 (4.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transdermal Testosterone (Patch), Placebo Patch (Identical in Appearance)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments
	Method	t-test, 2 sided
	Comments

11. Secondary Outcome

Title	Strength: Total Knee Extension Performed Via Quantitative Muscle Function Testing.
Description	Represents change in isometric force (measured in kilograms) from baseline to 18 months. Peak isometric force of total knee flexion and extension were measured on the best of 2 repetitions for which subjects held a maximum contraction for 5 seconds.
Time Frame	Baseline (time 0) to 18 months

Outcome Measure Data

Analysis Population Description

data not available for all subjects due to malfunctioning equipment at some sessions, and some subjects did not wish to complete testing.

Arm/Group Title	Transdermal Testosterone (Patch)	Placebo Patch (Identical in Appearance)
Arm/Group Description	300 micrograms applied twice a week	placebo patch (0 micrograms of testosterone)applied twice a week
Measure Participants	11	9
Mean (Standard Error) [kilograms]	28.0 (7.6)	26.9 (10.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Transdermal Testosterone (Patch), Placebo Patch (Identical in Appearance)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Adverse events were collected over an 18 month period
Adverse Event Reporting Description	Subjects were seen every 6 weeks at which time a physical exam was performed, and subjects reported adverse events and/or safety concerns to the investigator.
Arm/Group Title	Transdermal Testosterone (Patch)		Placebo Patch (Identical in Appearance)
Arm/Group Description	300 micrograms applied twice a week		placebo patch (0 micrograms of testosterone)applied twice a week
All Cause Mortality
	Transdermal Testosterone (Patch)		Placebo Patch (Identical in Appearance)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Transdermal Testosterone (Patch)		Placebo Patch (Identical in Appearance)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/13 (7.7%)		1/12 (8.3%)
Gastrointestinal disorders
Appendectomy	1/13 (7.7%)	1	0/12 (0%)	0
Reproductive system and breast disorders
ovarian cyst	0/13 (0%)	0	1/12 (8.3%)	1
uterine fibroid	0/13 (0%)	0	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	Transdermal Testosterone (Patch)		Placebo Patch (Identical in Appearance)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/13 (69.2%)		6/12 (50%)
Ear and labyrinth disorders
otitis externa	0/13 (0%)	0	1/12 (8.3%)	1
Infections and infestations
sinusitis	1/13 (7.7%)	1	0/12 (0%)	0
herpes zoster	1/13 (7.7%)	1	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
arthralgia	1/13 (7.7%)	1	1/12 (8.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
simple renal cyst	0/13 (0%)	0	1/12 (8.3%)	1
Nervous system disorders
peripheral neuropathy	1/13 (7.7%)	1	0/12 (0%)	0
vertigo	1/13 (7.7%)	1	0/12 (0%)	0
Pregnancy, puerperium and perinatal conditions
candidiasis of the vagina	0/13 (0%)	0	1/12 (8.3%)	1
Psychiatric disorders
insomnia	0/13 (0%)	0	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
pneumonia	2/13 (15.4%)	2	0/12 (0%)	0
bronchitis	1/13 (7.7%)	1	0/12 (0%)	0
Surgical and medical procedures
excision of bunion	0/13 (0%)	0	1/12 (8.3%)	1
elective mammoplasty	1/13 (7.7%)	1	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.