Katherine M. Newton, Ph.D. - US grants

DESCRIPTION: (Adapted from Investigator's Abstract) Diabetes imposes a tremendous burden of morbidity and mortality on postmenopausal women. It is associated with a three- to nine-fold increase in risk of myocardial infarction (MI), an eight-fold increase in risk of peripheral vascular disease, and a threefold increase in risk for cardiovascular mortality. Observational studies indicate that hormone replacement therapy (HRT) reduces the risk of coronary heart disease (CHD) in postmenopausal women by 50 percent, while the effect of HRT on lower extremity peripheral arterial disease is unknown. The effects of HRT on CHD in women with diabetes have not been evaluated. The purpose of this case-cohort study is to examine the association between postmenopausal HRT (estrogen alone or with progestin) and CHD (nonfatal MI and fatal CHD) in postmenopausal women with Type II diabetes. Secondary outcomes include lower extremity amputations and all-cause mortality. The investigators state that a unique opportunity is available to conduct this study due to automated databases at Group Health Cooperative, a health maintenance organization in western Washington with over 500,000 members, including approximately 7,000 women with Type II diabetes. Women aged 45 to 80, with incident or prevalent Type II diabetes between 1986 and 1990, will be identified using criteria established for an ongoing study on management and outcomes in diabetics. From this cohort an age-stratified random sample of 1,500 women will be selected for the sub-cohort. These women plus those with the outcomes of interest (nonfatal MI and fatal CHD; lower extremity amputations; or death between cohort entry and September, 1998 [8 to 12 years follow-up]) will comprise the analytic cohort. Medical records will be reviewed to confirm eligibility and outcomes as well as to collect data on medical history, demographic characteristics and confounding variables. HRT use will be determined from computerized pharmacy records. Data will be analyzed using descriptive statistics, categorical survival methods, and Cox regression, applying methods specific to the case-cohort study design. The investigators state that this study will extend knowledge regarding the safety and efficacy of HRT in a subgroup of women at high risk for cardiovascular complications.

DESCRIPTION: (Adapted from Investigator's Abstract) Hormone replacement therapy (HRT: estrogen and progestin) remains the treatment of choice for women with vasomotor symptoms, and long-term HRT has been recommended for prevention purposes. The demand for alternatives to HRT, and the availability and use of over-the-counter products including dietary phytoestrogen supplements and naturopathic medicines, has grown dramatically. Few of these products have faced the rigors of randomized trials and none have been tested to evaluate their effects on long-term outcomes. The purpose of this four-year randomized controlled trial is to evaluate the efficacy and safety of three alternative approaches utilizing phytoestrogens to treat vasomotor symptoms in peri- and postmenopausal women. The treatments were chosen because of the scientific evidence supporting a possible benefit, the availability of products with adequate quality control their frequency of use in naturopathic medicine, and our ability to blind participants to the intervention. The five proposed treatment arms are as follow: 1) esterified estrogen and micronized progesterone: 9) a single herbal product, black cohosh; 3) a multibotanical preparation; 4) a combination regimen that includes the same multibotanical preparation plus soy diet counseling; and 5) placebo. The primary aim is to compare the effects of three alternative treatments, HRT, and placebo on the frequency and intensity of vasomotor symptoms measured by The Wiklund Menopause Symptom Checklist and a daily Vasomotor Symptom Diary. The secondary aims are to compare the effects of three alternative treatments, HRT, and placebo on the following: 1) vaginal cytology (vaginal maturation index); 2) serum lipids (total cholesterol, HDL and LDL cholesterol, triglycerides); 3) bone mineral density (hip and spine dual energy x-ray absorptiometry scan); 4) glucose metabolism (insulin, fasting blood glucose); and 5) coagulation factors (fibrinogen, PAI-1). The hypotheses are that compared to placebo the three alternative treatments tested in this study will have the following effects: reduce frequency of hot flashes and night sweats, improve vaginal maturation and decrease vagina atrophy as measured by maturation index, lower total cholesterol and LDL with no effect on HDL, reduce the rate of decline in bone mineral density (BMD), and have no effect on glucose metabolism or clotting factors. To accomplish the specific aims the investigators propose to do the following: 1) recruit and randomize 400 peri- and post-menopausal women to one of five treatment arms for one year; 2) collect measurements of primary and secondary outcomes at baseline, three, six, and 12 months; and 3) compare changes in outcomes in the groups taking alternative treatments to those in the HRT and placebo groups.