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
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
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.
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.
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.