Notelovitz 2002.
| Methods | Stated purpose: to determine the lowest effective dose of an oestradiol transdermal delivery system for preventing bone loss in postmenopausal women Stratification: not described Unblinding: not described No. of women screened for eligibility: not stated No. randomised: 355 (0.025 mg dose: 89; 0.05 mg dose: 90; 0.075 mg dose: 89; placebo: 87) No. analysed: 355 (data imputed for losses to follow‐up) Losses to follow‐up: 34 (9.6%) Adherence to treatment: 125 drop‐outs: 125 (35%) did not complete 2 years' treatment (88 in active treatment arms, 37 in placebo arm). One participant was withdrawn for failure to adhere to the treatment schedule. Overall level of adherence to treatment in women who continued with their allocated treatment is not described. Analysis by intention to treat: yes No. of centres: 22 Years of recruitment: not stated Design: parallel Funding: Proctor and Gamble Pharmaceuticals | |
| Participants |
Included Postmenopausal, non‐osteoporotic, ambulatory women younger than 70 years of age who had had a hysterectomy, with or without bilateral oophorectomy, at least 12 months earlier. Postmenopausal status documented by serum oestrogen < 23 picograms/mL and FSH serum levels > 40 mlU/mL. Non‐osteoporotic status defined by dual energy x‐ray absorptiometry (DXA) minimum T‐score of ‐2.5 Excluded Participants who had received oral oestrogens within 2 months of enrolment, or who had contraindications to oestrogen therapy or history of oestrogen intolerance, women with clinically significant systemic or psychiatric disorders; history of cancer (other than basal cell carcinoma in remission or uterine cancer treated by hysterectomy); history of osteomalacia, hyperparathyroidism or untreated hyperthyroidism, abnormal serum lipids, creatinine or liver enzymes; use of medications within 3 months of enrolment that could modify BMD, radiographic abnormalities of the lumbar spine on anterior/posterior or lateral view, which would preclude precise DXA measurements Mean age: not stated Age range: not stated Means of recruitment: not stated Baseline equality of treatment groups: yes Country: USA |
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| Interventions | HT arm: 2 patches, delivering daily dose of oestradiol: 0.025 mg, 0.05 mg or 0.075 mg Control arm: 2 placebo patches Duration: 2 years (26 cycles) | |
| Outcomes | Breast cancer (regular mammograms) Fractures | |
| Notes | Power calculation: not mentioned | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Not described |
| Allocation concealment (selection bias) | Unclear risk | Not described |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 34 (9.6%) losses to follow‐up. Analysed by intention to treat |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | States double‐blinded, double‐dummy |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | States double‐blinded, double‐dummy; "hard" outcomes |
| Selective reporting (reporting bias) | Low risk | All expected outcomes reported |
| Other bias | Low risk | No apparent source of other bias |