['We wished to appraise the effectiveness of hormone replacement therapy (HRT) in early (< 67 years) and late (> 67 years) post-menopausal women referred to a metabolic outpatient clinic for assessment of their bone status. Because older women often experience side-effects with conventional HRT, a low dose preparation (Estraderm 25) was also compared with conventional HRT (Estraderm 50).', 'Since all patients were symptomatic, the investigation was open and not placebo controlled. Patients were offered HRT and told about the two dosages. If they wished to use HRT, allocation of dosage was made randomly unless there were reasons to use a specific dose.', 'One hundred and ninety-six women were studied over 1 or 2 years with 80 reaching 3 years of treatment. Patients were divided into those under 67 years and those over 67 years at the start of treatment. Each group was further divided into those taking Estraderm 25 and those taking Estraderm 50 with norethisterone if appropriate.', 'Bone mineral density (BMD) was measured (DXA, Hologic) at the lumbar spine and femoral neck at 0 year (196 patients), at 1 year (169 patients), at 2 years (139 patients) and at 3 years (80 patients). Patients losing bone were expressed as those whose 3 year BMD was lower than initial or as those whose BMD at 3 years had fallen by more than twice the coefficient of variation for that site (non-responders).', 'In lumbar spine, BMD increased maximally in the first year in all groups and the gain was maintained after 3 years. The change was similar whether patients were divided by age or dosage. For those on Estraderm 25, mean change after 3 years was 8.1 +/- 6.8% and on Estraderm 50, 9.0 +/- 8.3% (combined 8.7 +/- 7.8%). Only 3.9% of patients were non-responders at the lumbar spine after 3 years. At femoral neck, changes were significant at 3 years only in the Estraderm 25 > 67 years and Estraderm 50 < 67 years groups and averaged 2.3 +/- 5.4% for all patients. At the femoral neck, 10.4% of patients were non-responders after 3 years. Percentage change of BMD over 3 years at lumbar spine correlated with that at the femoral neck (r = 0.56). Percentage change of BMD at lumbar spine over 3 years correlated with menopausal age (r = 0.295). No relation was found between dosage of Estraderm/kg body weight and response of BMD at either site.'] Are low and conventional dose transdermal oestradiol equally effective at preventing bone loss in spine and femur at all post-menopausal ages?