A Randomized Controlled Trial

OSTEOPOROSIS IS A MAJOR cause of disability and excess mortality in older women. Estrogen therapy has been used for treatment and prevention of osteoporosis; however, many older women are reluctant to use it because of adverse effects. Recent data from the Women’s Health Initiative demonstrated that postmenopausal women who took hormone therapy for approximately 7 years had decreased hip fracture risk; however, the dose and preparation of hormone therapy used in the study also increased the risk of breast cancer, heart disease, stroke, and deep venous thrombosis. Previous studies demonstrated that a conventional dose of estrogen therapy (1.0 mg/d of 17 estradiol or 0.625 mg/d of conjugated equine estrogen [CEE]) reduced bone turnover and bone loss and was associated with reduced fracture incidence in older women. Moreover, half the conventional hormone therapy dose (0.3 mg/d of CEE and 2.5 mg/d of medroxyprogesterone acetate [MPA] or 0.5 mg/d of 17 -estradiol) decreased bone turnover and increased bone mass in older women when taken with adequate doses of calcium and vitamin D. We previously demonstrated that 0.25 mg/d of 17 -estradiol decreased markers of bone turnover to the same degree as 0.5 mg/d or 1.0 mg/d of 17 -estradiol with an adverse effect profile that was equivalent to placebo. We designed this study to determine the long-term effects on bone and overall safety of treatment with 0.25 mg/d of 17 -estradiol in older women.