SummaryOBJECTIVEAlthough there is evidence from cross‐sectional studies that percutaneous oestrogen administration protects against menopausal bone loss, few longitudinal data are available. We have examined the effect of 3 years' treatment with percutaneous oestradiol on total body calcium, spinal trabecular bone mineral density and radial bone mineral content in post‐menopausal women.DESIGNand PATIENTS Twenty‐nine post‐menopausal women, aged 37–55 years, who had undergone hysterectomy and had experienced the onset of menopausal symptoms within the previous 2 years, were studied before and for 3 years during hormone replacement with oestradiol implants, given at approximately 6‐monthly intervals.MEASUREMENTSTotal body calcium was measured by prompt gamma neutron activation analysis, spinal trabecular bone mineral density by quantitative computed tomography and radial bone mineral content by single‐photon absorptiometry.RESULTSThere was a significant increase in the mean total body calcium, spinal trabecular bone mineral density and radial bone mineral content over the 3 years of the study. The mean (± SEM) percentage change per annum was +2 4% (±0.8) for total body calcium (P<0 01), + 3.3% (±0.6) for spinal trabecular bone mineral density (P<0.001) and +12% (± 0.6) for radial bone mineral content (P<0 05).CONCLUSIONSPercutaneous oestradiol replacement therapy prevents menopausal bone loss and is associated with a sustained and significant increase in total body calcium, spinal trabecular bone mineral density and radial bone mineral content over a 3‐year treatment period. Oestradiol implants thus have skeletal effects comparable to those of oral or tra