Human Reproduction Update, Vol.6, No.5 pp.419-426, 2000
© European Society of Human Reproduction and Embryology 2000; all rights reserved
Prevention of postmenopausal osteoporosis with oestrogen replacement therapy and associated compounds: update on clinical trials since 1995
1 King's College Hospital, Department of Family Planning, London, UK 2 Department of Obstetrics and Gynecology, Lund University, S-22185 Lund, Sweden
To whom correspondence should be addressed at: M. Dören , King's College Hospital, Department of Family Planning, 100 Denmark Hill, London SE5 9RS, UK. Tel: +44 20 7346 5000; Fax: +44 20 7733 2477; e-mail: martina{at}doeren.fsnet.co.uk
Abstract
Hormonal replacement therapy (HRT) is generally regarded as first choice for pharmacological prevention of osteoporosis in women. We reviewed recent studies of HRT regimens and selective oestrogen receptor modulators (SERMs), including controlled trials of at least one-year duration published since 1995 until February 2000 providing data on bone mineral density (BMD) or fractures. Natural and synthetic oestrogens exert a continuum of positive effects on BMD in a dose-dependent, though non-proportional, fashion independent of age and mode of administration. Bone loss may be largely prevented by 25µg transdermal patch oestradiol, 0.3 mg conjugated equine or 0.3 mg esterified oestrogens. Progestogens neither attenuate nor augment the effect of oestrogens; sole use of tibolone prevents bone loss. Both the SERMs, tamoxifen and raloxifene, slightly increase BMD. There are no adequately powered fracture trials for any HRT regimen. Raloxifene 60 mg daily decreases the relative risk of vertebral fractures by at least 30%, as demonstrated by one 3-year fracture study of osteoporotic women. In conclusion, the recommendation to use oestrogen for postmenopausal osteoporosis, given both the lack of fracture trials and the rare trials on long-term use of HRT in (late) postmenopausal women, is not well supported. Fracture trials could overcome shortcomings of the current level of evidence.
Key words: bone mineral density / hormone replacement therapy / prevention of osteoporosis / progestogen / selective oestrogen receptor modulators
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