What are the benefits and harms of tibolone in women with osteoporosis?

For every 1000 women treated for 1 year with tibolone, there will be approximately 9 fewer vertebral fractures, 7 fewer nonvertebral fractures, 2 fewer breast cancers, 1 fewer colon cancer, 2 more strokes, and 1 additional endometrial cancer. Although the authors recommend that tibolone not be used in women older than 70 years or in those who have risk factors for stroke, it is hard to see a compelling advantage of this drug for any group of women since bisphosphonates provide a safer way to prevent fracture. (LOE = 1b)

Cummings SR, Ettinger B, Delmas P, et al, for the LIFT Trial Investigators. The effects of tibolone in older postmenopausal women. N Engl J Med 2008;359(7):697-708.  [PMID:18703472]

Randomized controlled trial (double-blinded)

Industry

Uncertain

Outpatient (any)

Tibolone is a progestin analog used for hormone replacement therapy in postmenopausal women. In this industry-sponsored study, 4538 women between the ages of 60 years and 85 years were randomized to receive tibolone 1.25 mg once daily or placebo. All had a T score of less than -2.5 at the hip or lumbar spine, or a T score of less than -2.0 with radiologic evidence of vertebral fracture. The researchers excluded women with a T score of less than -4.0 or a clinical vertebral fracture within the past year; recent cancer; a history of thromboembolic disease; or recent use of estrogen, a selective estrogen receptor modulator, or bisphosphonates. Groups were balanced at the start of the study and analysis was by modified intention to treat. The median follow-up was 34 months; the study was terminated early because of an absolute increase in the risk of stroke in women receiving tibolone (2.3 per 1000 person-years; 95% CI, 0.4 - 4.2). The risk was greater among women 70 years and older (absolute risk difference = 3.1 per 1000 person-years). There were no differences between groups regarding the risk of coronary artery disease or thromboembolic disease. Women receiving tibolone were less likely to develop invasive breast cancer (0.9 vs 2.8 per 1000 person-years; P = .02) or colon cancer (0.6 vs 1.9 per 1000 person years; P = .04). Women in the tibolone group experienced more adverse effects and were much more likely to require endometrial biopsy during the study period (499 vs 136 women). Four women in the tibolone group developed endometrial cancer, compared with none in the placebo group. The tibolone users were less likely to have new vertebral fractures (10.9 vs 19.6 person years; P< .001) and nonvertebral fractures (19.5 vs 26.3 per 1000 person years; P = .01). Falls were 25% less frequent in the tibolone group,