Breast Cancer, Dyspareunia, Sexual Health Quality of Life, Vaginal Dryness
Conditions
Keywords
Vaginal Testosterone, Vaginal atrophy, Female Sexual Dysfunction, Aromatase Inhibitors
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.
Interventions
DRUGTestosterone
Sponsors
Creighton University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
50 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants Who Continued Vaginal Testosterone Upon Completion of the Study | After 4 weeks |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Vaginal Testosterone |
|---|---|
| Age, Continuous | 59.67 Years STANDARD_DEVIATION 6.095 |
| Aromatase Inhibitor anastrozole (Arimidex) | 11 Participants |
| Aromatase Inhibitor exemestane (Aromasin) | 0 Participants |
| Aromatase Inhibitor letrozole (Femara) | 1 Participants |
| Estrogen-receptor (ER) Status ER- | 1 Participants |
| Estrogen-receptor (ER) Status ER+ | 11 Participants |
| Highest Level of Education Associate's degree | 3 Participants |
| Highest Level of Education Bachelor's degree | 4 Participants |
| Highest Level of Education High school degree | 3 Participants |
| Highest Level of Education Master's degree | 2 Participants |
| Human Epidermal Growth Factor Receptor 2 (HER2) Status HER2- | 11 Participants |
| Human Epidermal Growth Factor Receptor 2 (HER2) Status HER2+ | 1 Participants |
| Length of Marriage 0-5 years | 1 participants |
| Length of Marriage 11-15 years | 0 participants |
| Length of Marriage 16-20 years | 0 participants |
| Length of Marriage 21-25 years | 5 participants |
| Length of Marriage 26-30 years | 1 participants |
| Length of Marriage 31-35 years | 2 participants |
| Length of Marriage 36-40 years | 2 participants |
| Length of Marriage 41-50 years | 0 participants |
| Length of Marriage 51-55 years | 1 participants |
| Length of Marriage 6-10 years | 0 participants |
| Marital Status Married | 12 Participants |
| Marital Status Not Married | 0 Participants |
| Oophorectomy No | 8 Participants |
| Oophorectomy Yes | 4 Participants |
| Progesterone-receptor (PR) Status PR- | 2 Participants |
| Progesterone-receptor (PR) Status PR+ | 10 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 0 Participants |
| Sexually Active During Study No | 1 Participants |
| Sexually Active During Study Yes | 11 Participants |
| Sexually Active Prior to Study No | 5 Participants |
| Sexually Active Prior to Study Yes | 7 Participants |
| Vaginal Swab Test Candidiasis species | 0 Participants |
| Vaginal Swab Test Gardnerella vaginalis | 3 Participants |
| Vaginal Swab Test No vaginal infection | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
FSFI Arousal Domain
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSFI Total Score (Pretest) | FSFI Arousal Domain | 1.200 units on a scale | Standard Deviation 0.677 |
| FSFI Total Score (Postteset) | FSFI Arousal Domain | 2.825 units on a scale | Standard Deviation 1.256 |
p-value: 0.00295% CI: [-2.495, -0.755]t-test, 2 sided
Primary
FSFI Desire Domain
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSFI Total Score (Pretest) | FSFI Desire Domain | 1.350 units on a scale | Standard Deviation 0.373 |
| FSFI Total Score (Postteset) | FSFI Desire Domain | 2.650 units on a scale | Standard Deviation 0.866 |
p-value: <0.000595% CI: [-1.859, -0.741]t-test, 2 sided
Primary
FSFI Lubrication Domain
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSFI Total Score (Pretest) | FSFI Lubrication Domain | 1.175 units on a scale | Standard Deviation 0.62 |
| FSFI Total Score (Postteset) | FSFI Lubrication Domain | 2.675 units on a scale | Standard Deviation 1.929 |
p-value: 0.01895% CI: [-2.692, -0.308]t-test, 2 sided
Primary
FSFI Orgasm Domain
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSFI Total Score (Pretest) | FSFI Orgasm Domain | 1.733 units on a scale | Standard Deviation 1.767 |
| FSFI Total Score (Postteset) | FSFI Orgasm Domain | 2.933 units on a scale | Standard Deviation 2.049 |
p-value: 0.00595% CI: [-1.9508, -0.4492]t-test, 2 sided
Primary
FSFI Pain Domain
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSFI Total Score (Pretest) | FSFI Pain Domain | 0.933 units on a scale | Standard Deviation 0.875 |
| FSFI Total Score (Postteset) | FSFI Pain Domain | 3.500 units on a scale | Standard Deviation 2.276 |
p-value: <0.000595% CI: [-3.706, -1.428]t-test, 2 sided
Primary
FSFI Satisfaction Domain
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSFI Total Score (Pretest) | FSFI Satisfaction Domain | 2.300 units on a scale | Standard Deviation 1.311 |
| FSFI Total Score (Postteset) | FSFI Satisfaction Domain | 4.200 units on a scale | Standard Deviation 1.293 |
p-value: 0.00195% CI: [-2.761, -1.039]t-test, 2 sided
Primary
Total Female Sexual Function Index (FSFI) Score
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSFI Total Score (Pretest) | Total Female Sexual Function Index (FSFI) Score | 8.691 units on a scale | Standard Deviation 3.803 |
| FSFI Total Score (Postteset) | Total Female Sexual Function Index (FSFI) Score | 18.783 units on a scale | Standard Deviation 7.05 |
p-value: <0.000595% CI: [-13.928, -6.256]t-test, 2 sided
Secondary
Number of Participants Who Continued Vaginal Testosterone Upon Completion of the Study
Time frame: After 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FSFI Total Score (Pretest) | Number of Participants Who Continued Vaginal Testosterone Upon Completion of the Study | 11 participants |
| FSFI Total Score (Postteset) | Number of Participants Who Continued Vaginal Testosterone Upon Completion of the Study | 1 participants |