Hormone replacement therapy and risk of hip fracture: population based case-control study

BMJ 1998;316:1858-1863 ( 20 June )

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Hormone replacement therapy and risk of hip fracture: population based case-control study

Editorial by Khaw. Members of the study group are listed at the end of the paper.

Karl Michaëlsson, senior registrar, ^a John A Baron, professor, ^b Bahman Y Farahmand, statistician, ^d Olof Johnell, professor, ^e Cecilia Magnusson, research fellow, ^c Per-Gunnar Persson, reader, ^d Ingemar Persson, reader, ^c Sverker Ljunghall, professor, ^f on behalf of the Swedish Hip Fracture Study Group.

^a Department of Orthopaedics, University Hospital, S-751 85 Uppsala, Sweden, ^b Departments of Medicine and Community and Family Medicine, Dartmouth Medical School, Hanover, New Hampshire, USA, ^c Department of Medical Epidemiology, Karolinska Institute Box 281, S-171 77 Stockholm, Sweden, ^d Department of Epidemiology, Stockholm County Council, 171 76 Stockholm, Sweden, ^e Department of Orthopaedics, Malmö General Hospital, S-205 02 Malmö, Sweden, ^f Department of Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden

Correspondence to: Dr Michaëlsson Karl.Michaelsson{at}ortopedi.uu.se.

Abstract
Objective: To determine the relative risk of hip fracture associated with postmenopausal hormone replacement therapy including the effect of duration and recency of treatment, theaddition of progestins, route of administration, and dose.
Design: Population based case-control study.
Setting: Six counties in Sweden.
Subjects: 1327 women aged 50-81 years with hip fracture and 3262 randomly selected controls.
Main outcome measure: Use of hormone replacement therapy.
Results: Compared with women who had never used hormone replacement therapy, current users had an odds ratio of 0.35(95 % confidence interval 0.24 to 0.53) for hip fracture and former users had an odds ratio of 0.76 (0.57 to 1.01). For every yearof therapy, the overall risk decreased by 6% (3% to 9%): 4% (1%to 8%) for regimens without progestin and 11% (6% to 16%) forthose with progestin. Last use between one and five years previously,with a duration of use more than five years, was associated withan odds ratio of 0.27 (0.08 to 0.94). After five years withouthormone replacement therapy the protective effect was substantiallydiminished ( $-$ 7% to 48%). With current use, an initiation of therapynine or more years after the menopause gave equally strong reductionin risk for hip fracture as an earlier start. Oestrogen treatmentwith skin patches gave similar risk estimates as oral regimens.
Conclusions: Recent use of hormone replacement therapy is required for optimum fracture protection, but therapy canbe started several years after the menopause. The protective effect increases with duration of use, and an oestrogen-sparing effectis achieved when progestins are included in the regimen.

Key messages

Hormone replacement therapy should be continued for long periods for optimal protection of hip fracture
No overall substantial hip fracture protection remains after five years without hormone replacement therapy
Therapy can be initiated several years after menopause without loss of fracture protection
Oral or transdermal therapy are equally effective in reducing the risk of hip fracture
The addition of progestins permits lower doses of oestrogens

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Long term hormone replacement therapy is needed to prevent hip fractures
BMJ 1998 316: 0. [Full Text]

Hormone replacement therapy again: Kay-Tee Khaw
BMJ 1998 316: 1842-1844. [Extract] [Full Text]

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