Tibolone Decreases Fracture, Breast Cancer, but Doubles Stroke Risk

Results of a randomized trial show that tibolone (Livial, Organon), approved for treatment of menopausal symptoms, has positive effects on fracture, breast cancer, and possibly colon cancer in women with osteoporosis over the age of 60 years but more than doubled the risk for stroke.

The drug is not currently approved in the United States but is approved in 90 countries to treat menopausal symptoms and in 45 countries to treat osteoporosis.

Results of the study, called the Long-Term Intervention on Fractures with Tibolone (LIFT) trial, are published in the August 14 issue of the New England Journal of Medicine. The trial was supported by Organon.

In an interview, first author Steven R. Cummings, MD, from the San Francisco Coordinating Center and the California Pacific Medical Center Research Institute at the University of California, San Francisco, said that for women in their 50s using the drug for menopausal symptoms, it is probably safe and beneficial. However, he said, "women shouldn't start it or continue it if they're say, 65 or older, and should not start or continue it if they have strong risk factors for stroke such as diabetes or high blood pressure."

Tibolone, a synthetic selective tissue estrogenic activity regulator (STEAR), has estrogenic, progestogenic, and androgenic effects, the authors write. Although it is known to prevent bone loss, its effects on fractures, breast cancer, and cardiovascular disease are uncertain.

In the LIFT trial, 4538 women between the ages of 60 and 85 years were randomized to receive 1.25 mg daily of tibolone or placebo. All had a bone-mineral density 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 a vertebral fracture. Annual spine radiographs were used to assess vertebral fracture, the primary outcome of the trial, and rates of cardiovascular events and cancer were adjudicated by expert panels.

The study was halted in February 2006 on the recommendation of the data and safety monitoring board when the increased risk for stroke became clear.

During a median of 34 months of treatment, women taking tibolone had a decreased risk for vertebral and nonvertebral fracture, particularly among those who had already had a fracture, as well as breast and colon cancer. However, women on tibolone also had an increase in the absolute risk for stroke of 2.3 per 1000 person-years and a more than doubling in the relative hazard of stroke. There was also a trend to a higher incidence of endometrial cancer in women with a uterus