The effect of low dose micronized 17 beta-estradiol on bone turnover, sex hormone levels, and side effects in older women: A randomized, double blind, placebo-controlled study

The purpose of this study was to examine the effects of three doses (0.25, 0.5, and 1.0 mg/day) of micronized 17 beta -estradiol on bone turn over, se x hormone levels, and side effects compared with placebo in healthy older w omen. The study design was randomized, double blind, and placebo controlled . The setting was a university clinical research center. Healthy, community -living women over 65 yr of age participated in the study. The main outcome measures mere serum and urinary biochemical markers of bone resorption and formation at baseline, 6 and 12 weeks on treatment, and 6 and 12 weeks off treatment. Markers of bone resorption were N-telopeptides of type I collag en, C-telopeptides of type I collagen, and total deoxypyridinoline cross-li nks; formation markers were bone alkaline phosphatase, osteocalcin, and N-t erminal procollagen peptides. We also measured serum estradiol, estrone, an d sex hormone-binding globulin levels at baseline, 12 weeks on treatment, a nd 12 weeks posttreatment. All markers of bone resorption significantly decreased at 12 weeks on treat ment compared with placebo and returned toward baseline at 12 weeks posttre atment. Two markers of bone formation, bone alkaline phosphatase and N-term inal procollagen peptides, significantly decreased 12 weeks posttreatment, but the decrease in osteocalcin varied with time and estrogen dose. Based o n equivalence testing, the response of markers of bone turnover to therapy with 0.25 mg/day was similar to that seen with 1.0 mg/day. Serum estradiol increased compared with baseline in all treatment groups and compared with placebo in the two higher dose groups. Breast tenderness, bleeding, and end ometrial changes were significantly less frequent in the 0.25 md day and pl acebo groups compared with the higher dose groups. We conclude that low dose of estrogen (0.25 mg/day 17 beta -estradiol) redu ced bone turnover to a similar degree as that seen with usual replacement t herapy (1.0 mg/day 17 beta -estradiol), but had a side effect profile simil ar to that of placebo. In our study additional increases in estradiol level s, as seen with 0.5 and 1.0 mg/day 17 beta -estradiol treatment, resulted i n more side effects without evidence of additional benefit to bone. Those d ata suggest that 0.25 mg/day 17 beta -estradiol may be an effective and tol erable agent for the treatment of osteoporosis in older women.