Vaginal Testosterone Cream For Atrophic Vaginitis in Women Taking Aromatase Inhibitors for Breast Cancer.
Vaginal Testosterone Cream For Atrophic Vaginitis in Women Taking Aromatase Inhibitors for Breast Cancer.
Atrophic vaginitis is a condition in which the skin lining of the vagina and labia becomes
 thin and symptoms develop including vaginal itching, vaginal discomfort and dyspareunia.
 These can significantly affect women's comfort, sexuality and quality of life.

 Treatment for this condition includes estrogen given in pill form, commonly known as hormone
 replacement therapy and local estrogen treatments, such as vaginal estrogen creams and
 topical vaginal lubricants. Unfortunately, systemic estrogen is contraindicated in many women
 with breast cancer. Some providers also feel that women who are taking aromatase inhibitors
 for their breast cancer should also not use local estrogens as several small studies suggest
 that these treatments might effect estrogen levels and thus might change how effective the
 aromatase inhibitors are. If these women choose not to use any form of estrogen therapy there
 symptoms may not be well controlled with other treatments.

 The investigators hypothesize that a vaginal testosterone cream might be a safe and effective
 alternative treatment for these women. This small study is intended to test the hypothesis
 that testosterone cream will not increase estrogen (estradiol) levels and that it will
 improve the symptoms of atrophic vaginitis including vaginal dryness, vaginal itching and
 pain with intercourse.

 The investigators will enroll women in the trial who are taking an aromatase inhibitor and
 have the symptoms mentioned above. They will receive a testosterone cream which will be
 applied vaginally once a day for 28 days. If good results are found with a prespecified dose
 of testosterone, a lower dose will be tested in the next group of women enrolled.
Atrophic vaginitis is a condition in which the skin lining of the vagina and labia becomes
 thin, usually due to a decreased estrogen state - such as menopause. Symptoms of atrophic
 vaginitis include vaginal itching, vaginal discomfort and dyspareunia and can significantly
 affect women's comfort, sexuality and quality of life.

 Treatment for this condition includes estrogen given in pill form, commonly known as hormone
 replacement therapy and local estrogen treatments, such as vaginal estrogen creams and
 topical vaginal lubricants. Unfortunately, systemic estrogen is contraindicated in many women
 with breast cancer. Some providers also feel that women who are taking aromatase inhibitors
 for their breast cancer should also not use local estrogens as several small studies suggest
 that these treatments might effect estrogen levels and thus might change how effective the
 aromatase inhibitors are. If these women choose not to use any form of estrogen therapy there
 symptoms may not be well controlled with other treatments.

 The investigators hypothesize that a vaginal testosterone cream might be a safe and effective
 alternative treatment for these women. This small study is intended to test the hypothesis
 that testosterone cream will not increase estrogen (estradiol) levels and that it will
 improve the symptoms of atrophic vaginitis including vaginal dryness, vaginal itching and
 pain with intercourse.

 The investigators will enroll women in the trial who are taking an aromatase inhibitor and
 have the symptoms mentioned above. They will receive a testosterone cream which will be
 applied vaginally once a day for 28 days. If good results are found with a prespecified dose
 of testosterone, a lower dose will be tested in the next group of women enrolled.

 Objectives:

 PRIMARY OBJECTIVE:

 1.1. Does topical testosterone cream affect serum estradiol levels in women taking aromatase
 inhibitors for breast cancer?

 SECONDARY OBJECTIVES:

 1.2. Can atrophic vaginitis and resultant symptoms of vaginal dryness, itching and
 dyspareunia in women taking aromatase inhibitors for the treatment of breast cancer be
 improved with a topical testosterone cream?

 1.3. Does topical testosterone cream affect physical findings, pH and cytologic changes in
 atrophic vaginitis?

 Schema:

 Intervention - Subjects will apply a testosterone cream to the vaginal area daily for one
 month (28 days).

 Evaluation - Before and after the study intervention participants will have testosterone and
 high-sensitivity estradiol tested. They will complete a questionnaire on symptoms of atrophic
 vaginitis and have a gynecologic examination (with visual, speculum, pH and sample of vaginal
 epithelial cells.)

 Endpoints - Serum estradiol levels Improvement in symptoms of atrophic vaginitis, as measured
 by questionnaire. Atrophic vaginitis as measured by gynecological examination (including pH
 and cytology to assess maturation index).
Inclusion Criteria:

 -  Histologically or cytologically confirmed breast cancer (any stage).

 -  Currently be using an aromatase inhibitor (anastrazole, exemestane or letrozole) for
 primary or adjuvant breast cancer treatment.

 -  Must have complaints of vaginal itching, vaginal dryness and/or dyspareunia.

 -  Not undergoing active chemotherapeutic or radiotherapeutic treatment

 -  Age >18 years

 -  Life expectancy of greater than 2 months.

 -  CALGB (ZUBROD) performance status <3.

 -  Post-menopausal - defined by absence of menses for at least 12 months and/or an FSH
 >25. Not post-menopausal as a function of medications intended to suppress ovarian
 function, such as gonadotropin releasing hormone agonists. Surgically post-menopausal
 subject eligible.

 -  The effects of topical testosterone cream on the developing human fetus at the
 recommended therapeutic dose are unknown. For this study only post-menopausal women
 are included and all women of child-bearing potential are excluded. Should a woman
 become pregnant or suspect she is pregnant while participating in this study, she
 should inform her treating physician immediately.

 Exclusion Criteria:

 -  Patients who have not recovered from adverse events due to chemotherapeutic agents
 administered more than 4 weeks earlier.

 -  History of allergic reactions attributed to compounds of similar chemical or biologic
 composition to testosterone or the emollient delivery cream used in the study.

 -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
 arrhythmia, or psychiatric illness/social situations that would limit compliance with
 study requirements.

 -  Pregnant women and women who are breast-feeding are excluded from this study because
 it is limited to post-menopausal women.