Randomized, Double-masked, 2-year Comparison of Tibolone with 17β-Estradiol and Norethindrone Acetate in Preventing Postmenopausal Bone Loss

Abstract

In this 2-year, randomized study, we compared the efficacy and tolerability of tibolone 2.5 mg (n= 75), tibolone 1.25 mg (n= 76) and estradiol 2 mg plus norethindrone acetate 1 mg (E₂/NETA; n= 74) for preventing bone loss in postmenopausal women. Bone mineral density (BMD), measured by dual-energy X-ray absorptiometry, and bone remodeling markers were assessed every 6 months. Side-effects were assessed quarterly. After 24 months, the mean increase (± SD) in lumbar spine BMD from baseline was 3.6%± 2.9%, 1.9%± 3.5% and 6.8%± 4.5% in the tibolone 2.5 mg, tibolone 1.25 mg and E₂/NETA groups, respectively. All pairwise differences were significant. The proportion of responders (women with a change from baseline in lumbar spine BMD of ≥−2% after 2 years) was 95.7%, 89.0% and 98.5% with tibolone 2.5 mg, tibolone 1.25 mg and E₂/NETA, respectively. Similar results were obtained for femoral BMD, although the difference between tibolone 2.5 mg and E₂/NETA was not significant at 24 months. Decreases in bone remodeling markers were similar in the three groups. Vaginal bleeding was more common in the E₂/NETA group (33.8%) than with tibolone 2.5 mg (12.0%) or tibolone 1.25 mg (9.2%), as was breast pain (23.0%, 2.7% and 2.6%, respectively). Each treatment effectively prevented bone loss. Overall, tolerability of tibolone was better than with E₂/NETA, because of less frequent vaginal bleeding and breast pain. This may promote long-term adherence.