A Clinical Study to Evaluate the Effects of Estrogen in Healthy Postmenopausal Women

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to examine the effect of two different dose levels of estrogen or placebo in healthy postmenopausal women by measuring the changes in hormone levels and examining the changes in the uterine lining (endometrium).

Official Title
-----------------
A Randomized Clinical Trial to Evaluate the Effects of Estrogen on Uterine Endometrium in Healthy Postmenopausal Women

Conditions
-----------------
Postmenopausal Symptoms

Intervention / Treatment
-----------------
* Drug: Comparator: Estrace 0.5 mg
* Drug: Comparator: Estrace 2 mg
* Drug: Comparator: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient is a healthy postmenopausal woman less than or equal to 65 years of age with onset of menopause less than or equal to 10 years prior to prestudy visit 1 Patient has a uterus and no history of uterine bleeding in the past 3 months Patient has not had a previous endometrial biopsy within the last 4 weeks Patient has had a normal mammogram within the last 11 months Patient has had a normal pap-smear within the past 3 years prior to screening Patient has had a normal transvaginal ultrasound of the endometrium Patient is willing to avoid strenuous physical activity such as strenuous or unaccustomed weight lifting, running, bicycling, etc for the duration of the study Patient agrees to not consume grapefruit products beginning approximately 2 weeks prior to the first dose of study drug and throughout the study Patient agrees to limit daily consumption of alcohol. During the study, daily alcohol consumption should not be more than 2 glasses Patient agrees to limit daily consumption of caffeine. During the study, daily caffeine consumption should not exceed 3 cups of coffee Patient is a non-smoker Exclusion Criteria: Patient is mentally or legally incapacitated Patient has a history of any first degree relatives with breast or endometrial cancer Patient has a history of multiple and/or severe allergies to prescription or non-prescription drugs or food Patient has used any type of estrogen or progesterone preparation unless followed by appropriate wash-out periods Patient has had surgery, donated approximately 500 mL of blood or has participated in another investigational study within the last 4 weeks Patient has a history of deep vein thromboses, coronary artery disease, heart attack or stroke Patient is a current user of illegal drugs Patient has a history of hypersensitivity to estrogen products Patient is unable to refrain from using anti-coagulants

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 17β-estradiol 2.0 milligrams<br>Estrace 2.0 mg tablet | Drug: Comparator: Estrace 2 mg<br>* 2 mg tablets taken once daily for 28 days.<br>* Other names: Estrace;|
| Active Comparator: 17β-estradiol 0.5 milligrams<br>Estrace 0.5 mg tablet | Drug: Comparator: Estrace 0.5 mg<br>* 0.5 mg tablet taken once daily for 28 days<br>* Other names: Estrace;|
| Placebo Comparator: 3<br>Placebo | Drug: Comparator: Placebo<br>* Placebo 0 mg capsule taken once daily for 28 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunohistochemistry (IHC) Proliferative Effects Measurement | Ratio of the total number of positively stained cell nuclei to the total number of cell nuclei. Proliferating endometrial cells express the Ki-67 antigen. The ratio was converted to a percent proliferating cells by taking the number of Ki-67 positive stained nuclei in a given field and dividing by the total number of nuclei in that field and multiplying by 100. At least 5 high power fields were scored in this manner and an aggregate percent Ki-67 positive cells was reported. Square root transformation was taken to make it approximately normally distributed for an ANOVA model to apply. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Gene Expression Intensity After 4 Weeks of Either 0.5 or 2 mg Estrace Compared to Placebo. |  | 4 weeks |