A systematic review of the skeletal effects of estrogen therapy in postmenopausal women. I. An assessment of the quality of randomized trials published between 1977 and 1995

Purpose To examine the quality of published randomized controlled trials of the effects of estrogen treatment on fracture risk and measures of bone mass. Data sources Articles on estrogen treatment for osteoporosis published between 1977 and 1995 were identified by searching Medline and Excerpta Medica databases and bibliographies of original papers and published reviews. Study selection Studies selected were randomized controlled trials of the efficacy of estrogens in preventing loss of bone mass or fractures in postmenopausal women. Data extraction Data extraction and quality assessment were performed in duplicate, with assistance of a manual. Raters were blinded as to authors and their affiliations and the publication details. Results Of 99 eligible randomized controlled trials published between 1977 and 1995, eight included no extractable data, and 23 contained results that were published in duplicate. Total quality scores increased over time, but this was accounted for by improvements only in the measurement technologies used to estimate bone mineral content or density. There was no improvement in the quality of randomization methods, the extent to which withdrawals were accounted for, or in the baseline comparability of treated and control patients. Neither sample sizes nor durations of follow-up increased over time. Conclusions This body of literature fails to address whether estrogen therapy reduces fracture rates, and does not allow for comparison of the effects of different active therapies on change in bone density. Although there were improvements in the techniques for estimating bone mass and delivering estrogen treatment, the studies published in the 1990s were no more informative for making clinical or policy decisions than those published in the 1970s.