Effect of hormone therapy on the risk of bone fractures: a systematic review and meta-analysis of randomized controlled trials

Objective:The aim of this study was to investigate the association between hormone therapy (HT) use and the development of bone fractures.Methods:Using terms related to HT and fractures, we searched PubMed, Embase, and the Cochrane library for randomized controlled trials on HT and the associated risk of fractures published before August 2014. Two evaluators independently selected studies on the basis of predetermined selection criteria, and 28 studies were included in the meta-analysis. Summary estimates were obtained using fixed- or random-effects models as appropriate.Results:A total of 28 studies included 33,426 participants and 2,516 fractures cases. The overall relative risk of HT was 0.74 (95% confidence interval [CI] 0.69-0.80) for total fractures, 0.72 (95% CI 0.53-0.98) for hip fractures, and 0.63 (95% CI 0.44-0.91) for vertebral fractures. In subgroup analyses, women of an age less than 60 years had lower risk of total fractures compared with women of an age more than 60 years (P=0.003). Estradiol led to greater decrease in the risk of total fractures compared with conjugated equine estrogens (P=0.01). There is greater reduction in total fracture risk in trials of follow-up less than 36 months than that of follow-up more than 36 months (P=0.003). No increase in the incidence of total cancer events but an increase in the incidence of thrombus was found to be associated with HT.Conclusions:HT is associated with a reduced risk of total, hip, and vertebral fractures, with a possible attenuation of this protection effect after it is stopped or when it is begun after 60 years. However, there may be an increase in the incidence of thrombus formation associated with HT.