Timing and dosage of and adherence to hormone replacement therapy and fracture risk in women with menopausal syndrome in Taiwan: a nested case-control study

Abstract Objective To investigate the association between hormone replacement therapy (HRT) and the risk of bone fracture in menopausal women in Taiwan. Study design The longitudinal, population-based, nested case-control study in Taiwan involved 5269 women aged > 45 years with fractures and 21,076 matched randomly selected controls without fractures. A conditional logistic regression model of analysis was employed. Main outcome measures The association between the risk of bone fracture and various HRT-related parameters, including the timing, dosage, and adherence, was investigated. Results Women with menopausal syndrome were protected from fractures when they received hormone drugs at high cumulative defined daily doses (DDDs) (Cumulative DDDs≥360) (odds ratio [OR]: 0.90, 95 % confidence interval [CI]: 0.82−0.99) and when their adherence was high (over 0.5) (OR: 0.70, 95 % CI: 0.60−0.82). The risk of fracture also decreased with high cumulative DDDs and high adherence combined (OR: 0.71, 95 % CI: 058−0.86). Subgroup analyses suggested that estrogen-containing regimens showed a protective effect against fractures at high cumulative DDDs or when adherence was high. Similar results were also observed with progestogen-containing regimens. Past exposure to an estrogen-containing regimen showed a protective effect against fractures when adherence was high. Past exposure to a progestogen-containing regimen showed a protective effect against fractures at high cumulative DDDs and when adherence was high. Conclusions The results indicate that past exposure to estrogen-containing or progestogen-containing regimens exerts protective effects against bone fracture. These effects increased with higher cumulative DDDs and with adherence in a dose-dependent manner.