Advancing Postmenopausal Preventive Therapy (APPT)

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.

Randomization randomly determined with key to treatment groups maintained by a single individual in the data coordinating center (DCC); study product masked with matching placebo.

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.

Arterial stiffness measured from the CCA (same location as CIMT) in computer image processed B mode ultrasonograms.

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