Randomized, double-masked, 2-year comparison of tibolone with 17beta-estradiol and norethindrone acetate in preventing postmenopausal bone loss.
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 > or = -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.
Roux
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Centre d'Evaluation des Maladies Osseuses, Département de Rhumatologie, Hôpital Cochin, Université René Descartes, Paris, France. christian.roux@cch.ap-hop-paris.fr
Pelissier
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Fechtenbaum
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Loiseau-Peres
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Benhamou
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CL
D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D001940:Breast; D002118:Calcium / Q000627:therapeutic use; D004311:Double-Blind Method; D004958:Estradiol / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae; D008875:Middle Aged; D009640:Norethindrone / Q000009:adverse effects / Q000627:therapeutic use*; D009652:Norpregnenes / Q000009:adverse effects / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010146:Pain / Q000139:chemically induced; D045167:Progesterone Congeners / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D014592:Uterine Hemorrhage / Q000139:chemically induced
D000726:Androgen Antagonists; D009652:Norpregnenes; D045167:Progesterone Congeners; D004958:Estradiol; C027385:tibolone; D002118:Calcium; D009640:Norethindrone