Tibolone reduces fracture and breast CA risk, increases stroke risk

The Long-Term Intervention on Fractures with Tibolone (LIFT) study demonstrated a reduced risk of vertebral fracture, breast cancer, and possibly colon cancer but a significantly increased risk of stroke in older postmenopausal women treated with tibolone versus those treated with placebo. Results of this study were published in the New England Journal of Medicine.
This randomized, double-blind, placebo-controlled, multinational clinical trial enrolled 4,538 women aged 60 to 85 years who had a bone mineral density (BMD) T score of –2.5 or less at the hip or spine or a T score of –2.0 or less and radiologic evidence of vertebral fracture. Study participants were randomized to receive either tibolone 1.25 mg/d or placebo. Investigators evaluated the risk of vertebral fracture and the rates of cardiovascular events and breast cancer in study participants.
The median treatment duration was 34 months. In February 2006, the trial was terminated early because of an increased risk of stroke; additionally, the effect of tibolone on vertebral fracture risk had met the criteria for halting the trial for efficacy.
In comparison with patients receiving placebo, patients taking tibolone demonstrated an increase in BMD of 4.8 percentage points (95% CI, 4.5–5.2) in the spine and 3.1 percentage points (95% CI, 2.7–3.4) in the femoral neck. The absolute risk of vertebral fracture in tibolone-treated patients was reduced by 8.6 (95% CI, 4.4–12.9) per 1,000 person-years; the relative hazard for vertebral fracture in tibolone-treated patients was 0.55 (95% CI, 0.41–0.74; P<.001) versus placebo. Women who had already experienced a vertebral fracture at baseline demonstrated a greater decrease in absolute risk (20.8 per 1,000 person-y) and a greater decrease in relative hazard (61%) for vertebral fracture compared with patients who had not experienced a vertebral fracture at baseline (decrease in absolute risk, 4.6 per 1,000 person-y; decrease in relative hazard, 31%). The absolute risk of nonvertebral fracture for patients taking tibolone decreased by 6.9 (95% CI, 1.6–12.2) per 1,000 person-years; the relative hazard for nonvertebral fractures in these patients was 0.74 (95% CI, 0.58–0.93; P=.01) versus placebo.
Compared with patients receiving placebo, patients taking tibolone demonstrated a decrease of 1.9 (95% CI, 0.5–3.4) per 1,000 person-years in the absolute incidence of invasive breast cancer; the relative hazard for invasive breast cancer in these patients was 0.32 (95% CI, 0.13–0.80; P=.02) versus placebo. Patients taking tibolone also demonstrated a decrease of 1.3 (95% CI, 0.1–2.6) per 1,000 person-years in the absolute incidence of colon cancer; the relative hazard for colon cancer in these patients was 0.31 (95% CI, 0.10–0.96; P=.04) versus placebo.
The absolute risk of stroke in patients receiving tibolone increased by 2.3 (95% CI, 0.4–4.2) per 1,000 person-years; the relative hazard for stroke in these patients was 2.19 (95% CI, 1.14–4.23; P=.02) versus placebo. The risk of stroke for patients who were aged at least 70 years was 6.6 per 1,000 person-years for patients receiving tibolone and 3.4 per 1,000 person-years for patients receiving placebo; for patients who were aged 60 to 69 years, the risk was 2.8 per 1,000 person-years for tibolone-treated patients and 1.0 per 1,000 person-years for placebo-treated patients.
The LIFT study indicated that the use of tibolone reduces the risk of both vertebral and nonvertebral fractures in older women with osteoporosis, with particular benefit for patients with a history of vertebral fracture. Tibolone also appears to decrease the risk of breast cancer. The study’s authors cautioned that the evidence of increased risk of stroke connected with tibolone use indicates that this agent should generally not be used in patients at risk for stroke or in elderly patients.

Source

Cummings SR, Ettinger B, Delmas PD, et al; for the LIFT Trial Investigators. The effects of tibolone in older postmenopausal women. N Engl J Med. 2008;359:697–708.