Effect of estrogen plus progestin on risk for biliary tract surgery in postmenopausal women with coronary artery disease. The Heart and Estrogen/progestin Replacement Study.

BACKGROUND: Animal and observational epidemiologic studies have reported that estrogens may increase the risk for gallstones. No major clinical trials have examined the effect of estrogen plus progestin therapy in postmenopausal women on the risk for biliary tract surgery. OBJECTIVE: To determine the effect of estrogen plus progestin on the risk for biliary tract surgery in postmenopausal women with known coronary artery disease. DESIGN: Randomized, double-blind placebo-controlled trial of postmenopausal hormone therapy for coronary heart disease. SETTING: 20 U.S. clinical centers. PARTICIPANTS: 2253 postmenopausal women with a gallbladder, 44 to 79 years of age at baseline, in the Heart and Estrogen/progestin Replacement Study (HERS). INTERVENTION: Conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, daily in one tablet or identical placebo. MEASUREMENTS: Documented biliary tract surgery. RESULTS: A total of 147 women (7%) were hospitalized for biliary tract surgery in HERS. Treatment with estrogen plus progestin resulted in a marginally significant 38% increase in the relative risk for biliary tract surgery (P = 0.05). A small absolute difference in risk suggested that for every 185 women treated with estrogen plus progestin, one additional woman had biliary tract surgery per year. After adjustment for baseline and in-study statin use, the association was attenuated further (P = 0.09). After adjustment for treatment assignment and other variables, increased body mass index, fibric acid use, and a history of nonsurgical gallbladder disease were associated with an increased risk for biliary tract surgery, whereas statin use was associated with a decreased risk (for each comparison, P < 0.05). CONCLUSION: Estrogen plus progestin therapy among postmenopausal women with known coronary disease resulted in a marginally significant increase in the risk for biliary tract surgery.

Relation of life events to blood pressure control in the SHEP pilot trial.

The Systolic Hypertension in the Elderly (SHEP) pilot trial was a five-center study in which 551 persons aged 60 years or older with isolated systolic hypertension were given antihypertensive drugs or placebos in order to determine the effects on blood pressure control and possible side effects of therapy. A life events inventory was administered to the cohort one year into the study. Results of this inventory were then compared to blood pressure and changes in blood pressure in the placebo and active therapy groups. One or more of the life events assessed were present in about 65% of the population. Although the sample was too small to detect very subtle effects, there was no evidence in this study that either individual or groups of life events play a major role in blood pressure regulation of persons with isolated systolic hypertension.

Recruitment of elderly volunteers for a multicenter clinical trial: the SHEP pilot study.

Few large trials have involved the elderly, and little is known about the feasibility of recruiting such participants for study and the validity of inferences drawn from them. This article reviews the recruitment experience of the Systolic Hypertension in the Elderly Program (SHEP) pilot study. That program involved five clinical centers, and contacted approximately 75,000 persons in order to enroll a cohort of 551 individuals over 60 years old isolated systolic hypertension. The enrolled cohort was somewhat older and more highly educated than those screened. Except for deliberate oversampling of blacks and those over 70 years old, the enrolled population resembled the U.S. population, although individuals in the SHEP group were initially healthier, and more likely to have had some college education than those in the general population. There was substantial variation among sites in number of staff hours spent per participant recruited. The SHEP experience indicates that older persons are willing to volunteer for clinical trials research and that problems of inference are probably not any greater for that age group than for any other.