Trial Information

BACKGROUND:

The results of many studies indicate that estrogen replacement therapy (ERT) reduces the
risk of coronary heart disease (CHD) in postmenopausal women. However, less than 9 percent
of these women choose to take ERT because of unwanted side effects and concerns about
increased risk of cancer associated with ERT. Therefore, alternative therapies are needed.

The isoflavonoids found in soy protein (specifically genistein) have many properties that
may reduce the risk of coronary heart disease. These include favorable effects on plasma
lipids and coronary artery vasomotion. Furthermore, genistein is a tyrosine kinase (TK)
inhibitor with inhibitory effects on thrombin activity and TK receptor-linked mitogens that
may be associated with atherogenesis and neointimal formation after angioplasty.

DESIGN NARRATIVE:

Randomized, double-blind, placebo-controlled. The women were randomized into one of three
groups: placebo, conjugated equine estrogens, or soy supplementation. Primary endpoints were
the impact on menopausal complaints such as hot flushes, mood lability, anxiety, sleep
disturbances; effects on plasma lipids and lipoproteins, including lipoprotein (a); effects
on vaginal bleeding and endometrial proliferation; changes in health-related quality of
life. Secondary endpoints included: assessment of the impact of these interventions on the
progression of carotid artery intimal medial wall thickening as assessed by B-mode
ultrasonography; bone density and bone turnover; additional measures to monitor the
compliance and safety of the intervention such as mammography, anticipated or known side
effects of hormone replacement therapy, blood levels of genistein, and clinical outcomes
such as hospitalizations, physician visits, and symptoms. The study ended in December,
1998.

The study was a subproject within a program project on coronary atherosclerosis in females,
primarily monkeys. Dr. Thomas B. Clarkson was the P.I. The subproject dollars were
estimated based on the CRISP dollars assigned to the study which were approximately 12
percent of the total program project dollars and were broken down as follows: FY 1996 -
219,254; FY 1997 - $217,000; FY 1998 - $221,000.