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.

Study Overview

• Status: Suspended
• Conditions: Breast Neoplasms; Vaginitis; Dyspareunia
• Intervention / Treatment: Drug: Testosterone propionate

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Pawtucket, Rhode Island, United States, 02860
      • Memorial Hospital of Rhode Island,
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care, University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Vaginal Testosterone; Daily application of vaginal testosterone for 28 days.

Drug: Testosterone propionate; Testosterone USP micronized powder at a dose of 1mg/gr will be made into a paste with polysorbate 80 NF liquid and will be placed in an emollient cream base. A calibrated applicator will be supplied to measure out doses containing 300mcg of testosterone for daily application. The cream will be applied daily for 28 days. As above if safety and efficacy endpoints are met at this dose a lower dose (150mcg) will be used and if in tun this meets safety and efficacy endpoints a lower dose (75mcg) will be used.; Other Names: Testosterone cream,; topical testosterone,; vaginal testosterone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum estradiol levels	Will evaluate if serum estradiol levels, measured with a high sensitivity assay, increase in women taking aromatase inhibitors for breast cancer after study intervention of 28 days of vaginal testosterone treatment.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptoms of vaginal atrophy	Will evaluate if symptoms of atrophic vaginitis measured on a symptoms questionnaire impove in women taking aromatase inhibitors for breast cancer after study intervention of 28 days of vaginal testosterone treatment.	28 days
Clinical signs of vaginal atrophy.	Will evaluate if clinical signs of vaginal atrophy on gynecologic examination decrease in women taking aromatase inhibitors for breast cancer after study intervention of 28 days of vaginal testosterone treatment.	28 days
pathologic measures of atrophic vaginitis	Will evaluate if pathologic measures of atrophic vaginitis including maturation index and vaginal pH change in women on aromatase inhibitos for breast cancer after study intervention of 28 days of vaginal testosterone treatment.	28 days

Collaborators and Investigators

• Sponsor: University of Vermont
• Investigators: Principal Investigator: Sabrina M Witherby, MD, Memorial Hospital of Rhode Island, Warren Alpert School od Medicine at Brown University; Principal Investigator: Hyman Muss, MD, University of North Carolina; Principal Investigator: Marie Wood, MD, University of Vermont

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Anticipated): December 1, 2010
• Study Completion (Anticipated): January 1, 2011

Study Registration Dates

• First Submitted: May 12, 2010
• First Submitted That Met QC Criteria: May 12, 2010
• First Posted (Estimate): May 13, 2010

Study Record Updates

• Last Update Posted (Estimate): May 13, 2010
• Last Update Submitted That Met QC Criteria: May 12, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: Testosterone; Vaginal administration; Aromatase inhibitors
• Additional Relevant MeSH Terms: Mental Disorders; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Vaginal Diseases; Breast Neoplasms; Vaginitis; Atrophic Vaginitis; Dyspareunia; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: V0606

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No