Issues concerning the use of hormone replacement therapy and risk of fracture: a population-based, nested case-control study.

AIMS: To investigate the effect of duration, how recently it has been used, and age at start of hormone replacement therapy (HRT) and the risk of bone fracture. METHODS: A population-based, nested case-control study was conducted in Lombardia, Northern Italy. The 78,294 women aged 45-75 years who received at least one HRT prescription during 1998-2000 were followed until 2005. Cases were women who experienced bone fracture during follow-up. Up to six controls were randomly selected for each case from the cohort after matching for age and date of cohort entry. The odds ratio of fracture associated with the use of HRT was estimated by conditional logistic regression. RESULTS: One thousand one hundred and seventy-four cases and 6760 controls were included. Compared with women who took HRT for less than 2 months, those who were treated for more than 20 months had an odds ratio (OR) of 0.80 (95% confidence interval 0.65, 0.99). This risk reduction was still significant among current HRT users (OR 0.71, 95% CI 0.55, 0.90) and in women who began therapy at the age of 55-65 years (OR 0.63, 95% CI 0.42, 0.94) or 65-75 years (OR 0.56, 95% CI 0.32, 0.99). There was no statistical evidence of a protective effect for women who had stopped treatment more than 6 months previously or those who began HRT at the age of 45-55 years. CONCLUSIONS: HRT should be continued for long periods to achieve an optimal protection from fracture. The fracture reducing potential of HRT seems to disappear after a few months without treatment and might mainly act in women who begin therapy at older age.