Breast Cancer, Aromatase Inhibitor Therapy, and Sexual Functioning: The Effects of Vaginal Testosterone Therapy

• Sponsor: Creighton University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01697345
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 2.9
• Patients Per Site Per Month: 4.1

Study Details

Study Description

Brief Summary

It is well documented that women who have breast cancer may experience a decrease in quality of life and sexual functioning due to side effects from adjuvant endocrine therapy, typically aromatase inhibitors (AIs). Women taking AIs are more likely to report unpleasant urogenital and vaginal symptoms due to the physiologic suppression of estradiol. This treatment can impair sexual functioning and cause a decreased sexual health quality of life.

At the present time, there are no Food and Drug Administration (FDA) approved medications for the vulvovaginal or sexual side effects related to the use of AIs. The lack of treatment options is concerning because the number of women diagnosed with breast cancer continues to increase; their longevity, also, continues to increase with the use of newer adjuvant chemotherapies. Local health care practitioners have observed that the benefits of vaginal testosterone for sexual health in breast cancer survivors are similar to the benefits of vaginal estrogen in women without breast cancer.

The purpose of this study is to evaluate the impact of using a daily compounded vaginal testosterone cream for 4 weeks (28 days) on breast cancer survivor's reported experience of vulvovaginal symptoms accompanying the use of AIs and their associated quality of life and sexual functioning.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Vaginal Dryness; Dyspareunia; Sexual Health Quality of Life	Drug: Testosterone	Early Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Breast Cancer, Aromatase Inhibitor Therapy, and Sexual Functioning: A Pilot Study on the Effects of Vaginal Testosterone Therapy
• Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Vaginal Testosterone Testosterone USP micronized powder supplied by Medisca Pharmacy will be compounded by Precision Compounding pharmacy as testosterone 0.3% per 0.5 milliliters (mL) in pharmabase cream. The compounded testosterone vaginal cream will be supplied in pre-filled syringes and each 0.5 mL dose will deliver 300 mcg of testosterone daily. The cream will be applied to the vaginal opening once daily for four weeks (28 days).

Drug: Testosterone

Outcome Measures

Primary Outcome Measures

1. Total Female Sexual Function Index (FSFI) Score [Baseline, 4 weeks]

   The Female Sexual Function Index (FSFI) questionnaire was administered to participants prior to starting vaginal testosterone therapy and the survey was repeated after using the study drug for 4 weeks. The participants served as their own controls. The FSFI assesses six domains of sexual functioning (desire, arousal, lubrication, orgasm, satisfaction, and pain) over the past 4 weeks. The sum of all domain scores equals the total FSFI score. The total FSFI score ranges from 2-36 and a total FSFI score < 26.5 suggests female sexual dysfunction.

2. FSFI Desire Domain [Baseline, 4 weeks]

   The desire score is calculated by adding the individual scores from the desire domain (question #1 and #2) and multiplying the sum by the domain factor of 0.6. The domain score for desire ranges from 1.2 (minimum) to 6 (maximum) and a higher value represents a better outcome.

3. FSFI Arousal Domain [Baseline, 4 weeks]

   The arousal score is calculated by adding the individual scores from the arousal domain (question #3, #4, #5, #6) and multiplying the sum by the domain factor of 0.3. The arousal domain score ranges from 0 (minimum) to 6 (maximum)and a higher value represents a better outcome.

4. FSFI Lubrication Domain [Baseline, 4 weeks]

   The lubrication score is calculated by adding the individual scores from the lubrication domain (question #7, #8, #9, #10) and multiplying the sum by the domain factor of 0.3. The domain score for lubrication ranges from 0 (minimum) to 6 (maximum) and a higher value represents a better outcome.

5. FSFI Orgasm Domain [Baseline, 4 weeks]

   The orgasm score is calculated by adding the individual scores from the orgasm domain (question #11, #12, #13) and multiplying the sum by the domain factor of 0.4. The domain score for orgasm ranges from 0 (minimum) to 6 (maximum) and a higher value represents a better outcome.

6. FSFI Satisfaction Domain [Baseline, 4 weeks]

   The satisfaction score is calculated by adding the individual scores from the satisfaction domain (question #14, #15, #16) and multiplying the sum by the domain factor of 0.4. The satisfaction domain score ranges from 0.8 (minimum) to 6 (maximum) and a higher value represents a better outcome.

7. FSFI Pain Domain [Baseline, 4 weeks]

   The score for pain is calculated by adding the individual scores from the pain domain (question #17, #18, #19) and multiplying the sum by the domain factor of 0.4. The domain score for pain ranges from 0 (minimum) to 6 (maximum) and a higher value represents a better outcome.

Secondary Outcome Measures

1. Number of Participants Who Continued Vaginal Testosterone Upon Completion of the Study [After 4 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women with breast cancer

• Currently taking an aromatase inhibitor (AI)

• Age > 50 years of age

• Postmenopausal, or two years since last menstrual cycle

• Urogenital/vulvovaginal symptoms such as vaginal dryness and pain with intercourse

• Changes in sexual health quality of life/sexual functioning since starting AI therapy

Exclusion Criteria:

• The use of other treatments for breast cancer such as chemotherapy or radiation within the past 12 months

• A known sensitivity to medications containing testosterone

• The use of exogenous hormone replacement therapy (HRT) in the past three months, including systemic and local estrogen or testosterone therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nebraska Cancer Specialists/Midwest Cancer Center - Legacy	Omaha	Nebraska	United States	68130

Sponsors and Collaborators

• Creighton University

Investigators

• Principal Investigator: Melissa A Dahir, DNP, Creighton University
• Study Chair: Dianne Travers-Gustafson, PhD, Creighton University
• Study Director: Robert Langdon, MD, Nebraska Cancer Specialists

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Melissa Dahir, Principal Investigator, Creighton University
• ClinicalTrials.gov Identifier: NCT01697345
• Other Study ID Numbers: MelissaDahir
• First Posted: Oct 2, 2012
• Last Update Posted: Jan 24, 2014
• Last Verified: Dec 1, 2013

• Keywords provided by Melissa Dahir, Principal Investigator, Creighton University: Vaginal Testosterone; Vaginal atrophy; Female Sexual Dysfunction; Aromatase Inhibitors
• Additional relevant MeSH terms: Breast Neoplasms; Dyspareunia; Testosterone

Study Results

Participant Flow

Recruitment Details	Participants were prospectively recruited from Nebraska Cancer Specialists in Omaha, NE, between January 11, 2013, and April 23, 2013.
Pre-assignment Detail	During the first study visit, the the PI procured a vaginal swab because women with suppressed estrogen levels have an increased risk for infection. Also, in the clinical setting, the PI has observed that women who develop a yeast or bacterial infection while using vaginal testosterone frequently report symptoms of vaginal burning or irritation.

Arm/Group Title	Vaginal Testosterone
Arm/Group Description	Testosterone USP micronized powder supplied by Medisca Pharmacy will be compounded by Precision Compounding pharmacy as testosterone 0.3% per 0.5 milliliters (mL) in pharmabase cream. The compounded testosterone vaginal cream will be supplied in pre-filled syringes and each 0.5 mL dose will deliver 300 mcg of testosterone daily. The cream will be applied to the vaginal opening once daily for four weeks (28 days).
Period Title: Overall Study
STARTED	13
COMPLETED	12
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Vaginal Testosterone
Arm/Group Description	Testosterone USP micronized powder supplied by Medisca Pharmacy will be compounded by Precision Compounding pharmacy as testosterone 0.3% per 0.5 milliliters (mL) in pharmabase cream. The compounded testosterone vaginal cream will be supplied in pre-filled syringes and each 0.5 mL dose will deliver 300 mcg of testosterone daily. The cream will be applied to the vaginal opening once daily for four weeks (28 days).
Overall Participants	12
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.67 (6.095)
Sex: Female, Male (Count of Participants)
Female	12 100%
Male	0 0%
Marital Status (Number) [Number]
Married	12 100%
Not Married	0 0%
Length of Marriage (participants) [Number]
0-5 years	1 8.3%
6-10 years	0 0%
11-15 years	0 0%
16-20 years	0 0%
21-25 years	5 41.7%
26-30 years	1 8.3%
31-35 years	2 16.7%
36-40 years	2 16.7%
41-50 years	0 0%
51-55 years	1 8.3%
Highest Level of Education (Number) [Number]
High school degree	3 25%
Associate's degree	3 25%
Bachelor's degree	4 33.3%
Master's degree	2 16.7%
Oophorectomy (Number) [Number]
Yes	4 33.3%
No	8 66.7%
Estrogen-receptor (ER) Status (Number) [Number]
ER+	11 91.7%
ER-	1 8.3%
Progesterone-receptor (PR) Status (Number) [Number]
PR+	10 83.3%
PR-	2 16.7%
Human Epidermal Growth Factor Receptor 2 (HER2) Status (Number) [Number]
HER2+	1 8.3%
HER2-	11 91.7%
Aromatase Inhibitor (Number) [Number]
anastrozole (Arimidex)	11 91.7%
letrozole (Femara)	1 8.3%
exemestane (Aromasin)	0 0%
Vaginal Swab Test (Number) [Number]
No vaginal infection	9 75%
Gardnerella vaginalis	3 25%
Candidiasis species	0 0%
Sexually Active Prior to Study (Number) [Number]
Yes	7 58.3%
No	5 41.7%
Sexually Active During Study (Number) [Number]
Yes	11 91.7%
No	1 8.3%

Outcome Measures

1. Primary Outcome

Title	Total Female Sexual Function Index (FSFI) Score
Description	The Female Sexual Function Index (FSFI) questionnaire was administered to participants prior to starting vaginal testosterone therapy and the survey was repeated after using the study drug for 4 weeks. The participants served as their own controls. The FSFI assesses six domains of sexual functioning (desire, arousal, lubrication, orgasm, satisfaction, and pain) over the past 4 weeks. The sum of all domain scores equals the total FSFI score. The total FSFI score ranges from 2-36 and a total FSFI score < 26.5 suggests female sexual dysfunction.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FSFI Total Score (Pretest)	FSFI Total Score (Postteset)
Arm/Group Description	Administered to participants prior to starting vaginal testosterone therapy.	Testosterone USP micronized powder supplied by Medisca Pharmacy was compounded by Precision Compounding pharmacy as testosterone 0.3% per 0.5 milliliters (mL) in pharmabase cream. The compounded testosterone vaginal cream was supplied in pre-filled syringes and each 0.5 mL dose delivered 300 mcg of testosterone daily. The cream was applied to the vaginal opening once daily for four weeks (28 days).
Measure Participants	12	12
Mean (Standard Deviation) [units on a scale]	8.691 (3.803)	18.783 (7.050)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FSFI Total Score (Pretest), FSFI Total Score (Postteset)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0005
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.092
	Confidence Interval	(2-Sided) 95%; -13.928 to -6.256
	Parameter Dispersion	Type: Standard Deviation; Value: 6.0378
	Estimation Comments

2. Primary Outcome

Title	FSFI Desire Domain
Description	The desire score is calculated by adding the individual scores from the desire domain (question #1 and #2) and multiplying the sum by the domain factor of 0.6. The domain score for desire ranges from 1.2 (minimum) to 6 (maximum) and a higher value represents a better outcome.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FSFI Desire Domain Score (Pretest)	FSFI Desire Domain Score (Posttest)
Arm/Group Description	Administered to participants prior to starting vaginal testosterone therapy.	Testosterone USP micronized powder supplied by Medisca Pharmacy was compounded by Precision Compounding pharmacy as testosterone 0.3% per 0.5 milliliters (mL) in pharmabase cream. The compounded testosterone vaginal cream was supplied in pre-filled syringes and each 0.5 mL dose delivered 300 mcg of testosterone daily. The cream was applied to the vaginal opening once daily for four weeks (28 days).
Measure Participants	12	12
Mean (Standard Deviation) [units on a scale]	1.350 (0.373)	2.650 (0.866)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FSFI Total Score (Pretest), FSFI Total Score (Postteset)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0005
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.30
	Confidence Interval	(2-Sided) 95%; -1.859 to -0.741
	Parameter Dispersion	Type: Standard Deviation; Value: 0.880
	Estimation Comments

3. Primary Outcome

Title	FSFI Arousal Domain
Description	The arousal score is calculated by adding the individual scores from the arousal domain (question #3, #4, #5, #6) and multiplying the sum by the domain factor of 0.3. The arousal domain score ranges from 0 (minimum) to 6 (maximum)and a higher value represents a better outcome.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FSFI Arousal Domain Score (Pretest)	FSFI Arousal Domain Score (Posttest)
Arm/Group Description	Administered to participants prior to starting vaginal testosterone therapy.	Testosterone USP micronized powder supplied by Medisca Pharmacy was compounded by Precision Compounding pharmacy as testosterone 0.3% per 0.5 milliliters (mL) in pharmabase cream. The compounded testosterone vaginal cream was supplied in pre-filled syringes and each 0.5 mL dose delivered 300 mcg of testosterone daily. The cream was applied to the vaginal opening once daily for four weeks (28 days).
Measure Participants	12	12
Mean (Standard Deviation) [units on a scale]	1.200 (0.677)	2.825 (1.256)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FSFI Total Score (Pretest), FSFI Total Score (Postteset)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-1.625
	Confidence Interval	(2-Sided) 95%; -2.495 to -0.755
	Parameter Dispersion	Type: Standard Deviation; Value: 1.369
	Estimation Comments

4. Primary Outcome

Title	FSFI Lubrication Domain
Description	The lubrication score is calculated by adding the individual scores from the lubrication domain (question #7, #8, #9, #10) and multiplying the sum by the domain factor of 0.3. The domain score for lubrication ranges from 0 (minimum) to 6 (maximum) and a higher value represents a better outcome.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FSFI Lubrication Domain Score (Pretest)	FSFI Lubrication Domain Score (Posttest)
Arm/Group Description	Administered to participants prior to starting vaginal testosterone therapy.	Testosterone USP micronized powder supplied by Medisca Pharmacy was compounded by Precision Compounding pharmacy as testosterone 0.3% per 0.5 milliliters (mL) in pharmabase cream. The compounded testosterone vaginal cream was supplied in pre-filled syringes and each 0.5 mL dose delivered 300 mcg of testosterone daily. The cream was applied to the vaginal opening once daily for four weeks (28 days).
Measure Participants	12	12
Mean (Standard Deviation) [units on a scale]	1.175 (0.620)	2.675 (1.929)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FSFI Total Score (Pretest), FSFI Total Score (Postteset)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.500
	Confidence Interval	(2-Sided) 95%; -2.692 to -0.308
	Parameter Dispersion	Type: Standard Deviation; Value: 1.876
	Estimation Comments

5. Primary Outcome

Title	FSFI Orgasm Domain
Description	The orgasm score is calculated by adding the individual scores from the orgasm domain (question #11, #12, #13) and multiplying the sum by the domain factor of 0.4. The domain score for orgasm ranges from 0 (minimum) to 6 (maximum) and a higher value represents a better outcome.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FSFI Orgasm Domain Score (Pretest)	FSFI Orgasm Domain Score (Posttest)
Arm/Group Description	Administered to participants prior to starting vaginal testosterone therapy.	Testosterone USP micronized powder supplied by Medisca Pharmacy was compounded by Precision Compounding pharmacy as testosterone 0.3% per 0.5 milliliters (mL) in pharmabase cream. The compounded testosterone vaginal cream was supplied in pre-filled syringes and each 0.5 mL dose delivered 300 mcg of testosterone daily. The cream was applied to the vaginal opening once daily for four weeks (28 days).
Measure Participants	12	12
Mean (Standard Deviation) [units on a scale]	1.733 (1.767)	2.933 (2.049)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FSFI Total Score (Pretest), FSFI Total Score (Postteset)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.20000
	Confidence Interval	(2-Sided) 95%; -1.95080 to -.44920
	Parameter Dispersion	Type: Standard Deviation; Value: 1.18168
	Estimation Comments

6. Primary Outcome

Title	FSFI Satisfaction Domain
Description	The satisfaction score is calculated by adding the individual scores from the satisfaction domain (question #14, #15, #16) and multiplying the sum by the domain factor of 0.4. The satisfaction domain score ranges from 0.8 (minimum) to 6 (maximum) and a higher value represents a better outcome.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FSFI Satisfaction Domain Score (Pretest)	FSFI Satisfaction Domain Score (Posttest)
Arm/Group Description	Administered to participants prior to starting vaginal testosterone therapy.	Testosterone USP micronized powder supplied by Medisca Pharmacy was compounded by Precision Compounding pharmacy as testosterone 0.3% per 0.5 milliliters (mL) in pharmabase cream. The compounded testosterone vaginal cream was supplied in pre-filled syringes and each 0.5 mL dose delivered 300 mcg of testosterone daily. The cream was applied to the vaginal opening once daily for four weeks (28 days).
Measure Participants	12	12
Mean (Standard Deviation) [units on a scale]	2.300 (1.311)	4.200 (1.293)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FSFI Total Score (Pretest), FSFI Total Score (Postteset)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.900
	Confidence Interval	(2-Sided) 95%; -2.761 to -1.039
	Parameter Dispersion	Type: Standard Deviation; Value: 1.355
	Estimation Comments

7. Primary Outcome

Title	FSFI Pain Domain
Description	The score for pain is calculated by adding the individual scores from the pain domain (question #17, #18, #19) and multiplying the sum by the domain factor of 0.4. The domain score for pain ranges from 0 (minimum) to 6 (maximum) and a higher value represents a better outcome.
Time Frame	Baseline, 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FSFI Pain Domain Score (Pretest)	FSFI Pain Domain Score (Posttest)
Arm/Group Description	Administered to participants prior to starting vaginal testosterone therapy.	Testosterone USP micronized powder supplied by Medisca Pharmacy was compounded by Precision Compounding pharmacy as testosterone 0.3% per 0.5 milliliters (mL) in pharmabase cream. The compounded testosterone vaginal cream was supplied in pre-filled syringes and each 0.5 mL dose delivered 300 mcg of testosterone daily. The cream was applied to the vaginal opening once daily for four weeks (28 days).
Measure Participants	12	12
Mean (Standard Deviation) [units on a scale]	0.933 (0.875)	3.500 (2.276)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FSFI Total Score (Pretest), FSFI Total Score (Postteset)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0005
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.567
	Confidence Interval	(2-Sided) 95%; -3.706 to -1.428
	Parameter Dispersion	Type: Standard Deviation; Value: 1.793
	Estimation Comments

8. Secondary Outcome

Title	Number of Participants Who Continued Vaginal Testosterone Upon Completion of the Study
Time Frame	After 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Continued Vaginal Testosterone Therapy	Did Not Continue Vaginal Testosterone Therapy
Arm/Group Description	Participants who chose to continue vaginal testosterone therapy upon completion of the study.	Participants who chose not to continue vaginal testosterone upon completion of the study.
Measure Participants	12	12
Number [participants]	11 91.7%	1 NaN

Adverse Events

Arm/Group Title	Vaginal Testosterone
Arm/Group Description	Testosterone USP micronized powder supplied by Medisca Pharmacy will be compounded by Precision Compounding pharmacy as testosterone 0.3% per 0.5 milliliters (mL) in pharmabase cream. The compounded testosterone vaginal cream will be supplied in pre-filled syringes and each 0.5 mL dose will deliver 300 mcg of testosterone daily. The cream will be applied to the vaginal opening once daily for four weeks (28 days).
All Cause Mortality
	Vaginal Testosterone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vaginal Testosterone
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Other (Not Including Serious) Adverse Events
	Vaginal Testosterone
	Affected / at Risk (%)	# Events
Total	0/13 (0%)

Limitations/Caveats

Limitations of this pilot study included the narrow time frame for enrollment, the exclusion of surgically menopausal women under the age of 50, and symptoms of recurrent Gardnerella vaginalis.

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.