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CONTEXT: Evidence is limited on the effects of different patterns of use of postmenopausal hormone therapy on fracture incidence and particularly on the effects of ceasing use. OBJECTIVE: To investigate the effect of different patterns of hormone therapy use on fracture incidence. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 138,737 postmenopausal women aged 50 to 69 years recruited from the UK general population in 1996-1998 (the Million Women Study) and followed up for 1.9 to 3.9 years (average, 2.8 years) for fracture incidence. MAIN OUTCOME MEASURE: Adjusted relative risk (RR) for incident fracture (except fracture of the fingers, toes, and ribs) in hormone therapy users compared with never users at baseline. RESULTS: A total of 5197 women (3.7%) reported 1 or more fractures, 79% resulting from falls. Current users of hormone therapy at baseline had a significantly reduced incidence of fracture (RR, 0.62; 95% confidence interval [CI], 0.58-0.66; P<.001). This protection was evident soon after hormone therapy began, and the RR decreased with increasing duration of use (P =.001). Among current users at baseline the RR of fracture did not vary significantly according to whether estrogen-only, estrogen-progestin, or other types of hormones were used (RR [95% CI], 0.64 [0.58-0.71], 0.58 [0.53-0.64], and 0.67 [0.56-0.80], respectively; P =.19), nor did it vary significantly according to estrogen dose or estrogen or progestin constituents. The RR associated with current use of hormone therapy did not vary significantly according to 11 personal characteristics of study participants, including their age at menopause, body mass index, and physical activity. Past users of hormone therapy at baseline experienced no significant protection against fractures (RR, 1.07; 95% CI, 0.99-1.15); incidence rates returned to those of never-users within about a year of ceasing use. CONCLUSIONS: All types of hormone therapy studied confer substantial protection against fracture while they are used. This protection appears rapidly after use commences and wears off rapidly after use ceases. The older women are, the greater is their absolute reduction in fracture incidence while using hormone therapy.

Original publication




Journal article



Publication Date





2212 - 2220


Aged, Estrogen Replacement Therapy, Female, Fractures, Bone, Humans, Incidence, Middle Aged, Postmenopause, Risk