Fracture Incidence in Relation to the Pattern of Use of Hormone Therapy in Postmenopausal Women

Abstract

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; PϽ.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, estrogenprogestin, 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.

Effects of Conjugated Equine Estrogen on Risk of Fractures and BMD in Postmenopausal Women With Hysterectomy: Results From the Women's Health Initiative Randomized Trial

“…The relative fracture reduction was similar at the hip, wrist, and vertebrae and for total fractures. These results are consistent with previous observational reports (13)(14)(15)(16) and meta-analyses (17)(18)(19) that suggested that unopposed estrogen therapy reduces bone loss and fractures in postmenopausal women. In addition, these findings are consistent with the findings in the WHI estrogen plus progestin trial previously reported.…”

Predicting risk of osteoporotic fracture in men and women in England and Wales: prospective derivation and validation of QFractureScores

“…Our findings are consistent with those from the Women’s Health Initiative study and other studies 4445 46 The loss of the protective effect of HRT on risk of fracture after stopping treatment is consistent with some46 47 but not other studies 48. Our study is larger than previous studies44 49 and has a longer follow-up 44.…”

“…Our rates of hip fracture were similar to those obtained in other similar general practice databases such as GPRD 5253 54 Our rates tend to be higher than some population based cohorts,25 46 which might be because of some under-ascertainment due to self reported events reported by questionnaire rather than by analysis of data prospectively recorded on the patients’ medical records, as in our study.…”

Hip Fracture Incidence in Relation to Age, Menopausal Status, and Age at Menopause: Prospective Analysis

“…The rapid and substantial impact of menopause on the risk of hip fracture is likely to relate to the large reductions in bone mineral density that occur in the first few years after the menopause [2]–[4], which follow the rapid reductions in circulating levels of estradiol and related hormones occurring at that time. This finding is in keeping with the established protective effect of both endogenous [32] and exogenous estrogens on fracture incidence [26],[27].…”