Methods and Applications of Statistics in Clinical Trials, Volume 1: Concepts, Principles, Trials, and Designs

Chapter 77

Women’s Health Initiative Hormone Therapy Trials

Shari S. Bassuk and JoAnn E. Manson

77.1 Introduction

Once prescribed primarily to treat vasomotor symptoms, postmenopausal hormone therapy (HT) had in recent years been increasingly promoted as a strategy to forestall many chronic diseases that accelerate with aging, including coronary heart disease (CHD), cognitive impairment, and osteoporosis. Indeed, more than two of five postmenopausal women in the United States were taking HT in the year 2001 [1]. The belief that estrogen protected the heart and that women of all ages could benefit was so strong that many clinicians were initiating HT in patients who were 20 to 30 years past the menopausal transition and in women at high risk of CHD. This widespread use was unwarranted given the lack of conclusive data from randomized clinical trials on the balance of risks and benefits of such therapy when used for chronic disease prevention.

77.2 Objectives

Launched in 1991 by the National Institutes of Health, the HT component of the WHI consisted of two randomized, double-blind, placebo-controlled trials in post-menopausal women who were aged 50 to 79 years and generally healthy at baseline. The trials were designed to test the effect of estrogen plus progestin (for women with a uterus) or estrogen alone (for women with hysterectomy) on CHD, breast cancer, osteoporotic fracture, and other health outcomes and whether the possible benefits of treatment would outweigh possible risks. ...