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

Recruitment & Eligibility

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

Study & Design

Primary Outcome Measures

Name	Time	Method
Immunohistochemistry (IHC) Proliferative Effects Measurement	4 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Mean Gene Expression Intensity After 4 Weeks of Either 0.5 or 2 mg Estrace Compared to Placebo.	4 weeks

Recruitment & Eligibility