Advancing Postmenopausal Preventive Therapy

Atherosclerosis Intervention With Novel Tissue Selective Estrogen Complex Therapy

Advancing Postmenopausal Preventive Therapy (APPT) is a randomized, double-blinded, placebo-controlled trial designed to determine the effects of tissue selective estrogen complex (TSEC) therapy on the progression of subclinical atherosclerosis and cognitive decline in 360 healthy postmenopausal women.

To conduct a double-blinded, placebo-controlled trial to determine the effects of TSEC therapy on the progression of subclinical atherosclerosis in healthy postmenopausal women. A total of 360 postmenopausal women with a uterus who are within 6 years of menopause and 45-59 years of age and without clinical cardiovascular disease and diabetes mellitus will be randomized to Bazedoxifene/Conjugated Equine Estrogen (BZA 20 mg/CE 0.45 mg) or placebo. Recruitment will occur over 3 years and the treatment period will be up to 3 years depending on when an individual is randomized. Rate of change in carotid artery intima-media thickness (CIMT) determined from the distal common carotid artery (CCA) far wall intima-media thickness (IMT) in computer image processed B mode ultrasonograms will be the primary trial endpoint. Arterial stiffness measured from the CCA (same location as CIMT) in computer image processed B mode ultrasonograms will be the secondary trial endpoint. Three composite cognitive measures will be used to test for randomized treatment group differences in cognition; each composite will be considered as co-endpoints.

Inclusion Criteria:

• Women with a serum estradiol level <30 pg/ml and cessation of regular menses >6 months who are <6 years postmenopausal and 45-59 years old.

Exclusion Criteria:

• Women with a hysterectomy
• Clinical signs, symptoms or personal history of cardiovascular disease
• Diabetes mellitus or fasting serum glucose >126 mg/dL
• Life threatening illness with prognosis <5 years
• Cirrhosis or liver disease
• History of deep vein thrombosis or pulmonary embolism
• History of breast cancer
• Current use of postmenopausal hormone replacement therapy (HRT) within 1 month of randomization
• Uncontrolled hypertension (>180/>110 mmHg)*
• Plasma triglyceride levels >500 mg/dL
• Serum creatinine >2.0 mg/dL