Effect of 10 years' hormone replacement therapy on bone mineral content in postmenopausal women

The purpose of this study was to investigate the effects of 10 years of hormone replacement therapy (HRT) in postmenopausal women on bone mineral density of the lumbar spine (L-BMD) and bone mineral content of the distal forearm (F-BMC). A total of 151 women were enrolled in the study, 100 of whom were randomized to receive oral HRT (equally divided between a continuous combined and a sequential treatment regimen), with the remaining 51 receiving placebo or no treatment. The study was double-blind for the first 24 months, followed by 8 years of open-label follow-up. Total treatment duration was 10 years. At the end of 10 years, 38% of women randomized to continuous combined HRT remained on therapy compared with 22% of those who had received sequential HRT and 49% of the untreated group. A further 18% of women originally randomized to HRT had switched to other regimens. After 10 years of therapy, L-BMD was found to be significantly higher in HRT-treated women than in those who remained untreated (14.5%; p < 0.001), corresponding to an increase in L-BMD of 13.1% from baseline values on HRT compared with a reduction in L-BMD of 4.7% without therapy. L-BMD increased by 15.9% in women receiving continuous combined therapy compared with 11.1% in those on sequential HRT; however, intergroup differences were not statistically significant. F-BMC decreased by 0.7% over the 10 year period in the HRT treatment groups compared with a reduction of 17.6% in untreated women (p < 0.001). Mean F-BMC was 20.3% higher in women who had received HRT than in those who had not received therapy at the end of the 10 year follow-up. In conclusion, 10 years of treatment with HRT resulted in a substantial increase in L-BMD, with F-BMC also significantly higher in the HRT group than in untreated women. These results confirm that long-term HRT exerts a continuous effect against bone loss in postmenopausal women.