Ultralow-Dose Micronized 17β-Estradiol and Bone Density and Bone Metabolism in Older Women: A Randomized Controlled Trial

CONTEXT Estrogen therapy is known to prevent osteoporosis, but studies have shown that conventional doses increase adverse events. Whether lower doses, one quarter of standard treatment, prevent bone loss is not known. OBJECTIVE To examine the effect of 3 years of treatment with 0.25 mg/d of micronized 17β-estradiol on bone mineral density (BMD) and bone turnover in healthy older postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-controlled trial conducted from July 24, 1998, through June 14, 2002, at a university general clinical research center in the United States. Healthy, community-dwelling women (N = 167) who were older than 65 years at enrollment. INTERVENTION Dosage of 0.25 mg/d of micronized 17β-estradiol (n = 83) or placebo (n = 84); all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months. MAIN OUTCOME MEASURES The BMD of the hip, spine, wrist, and total body measured annually for 3 years. Serum and urine biochemical markers of bone resorption and formation and sex hormones were measured at baseline, 3 months, and during years 1 and 3 of treatment. RESULTS Mean BMD increased at all sites for participants taking low-dose estrogen (17β-estradiol) compared with placebo (P