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Tibolone reduced the risk for fractures, breast and colon cancers
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Though older women with osteoporosis may have a lower risk for fractures, breast and colon cancers when taking tibolone, their risk for stroke may be increased, according to recent data.
Researchers from the San Francisco Coordinating Center and other sites in the United States and Europe conducted a randomized study to determine the effects of tibolone on fractures, cancer and cardiovascular disease risk.
Women with a hip or spine BMD T score of –2.5 or less or with a T score of –2.0 or less and radiologic evidence of a vertebral fracture (n=4,538) were randomly assigned to once-daily tibolone (1.25 mg) or placebo. The women were between the ages of 60 and 85 years.
Compared with placebo, women in the tibolone group had a lower risk for vertebral fracture at a median of 34 months (126 vs. 70 cases per 1,000 person-years; P<.001). The risk for nonvertebral fracture was also lower in the tibolone group, compared with placebo (122 vs. 166 cases; P=.01).
Women in the tibolone group had a decreased risk for invasive breast (relative hazard=0.32; P=.02) and colon cancers (relative hazard=0.31; P=.04).
The researchers reported an increased risk for stroke among patients in the tibolone group (relative hazard=2.19; P=.02), which caused the data and safety monitoring board to close the trial early in February 2006.
Risk for coronary heart disease and venous thromboembolism were similar between both groups. – by Stacey L. Adams
N Engl J Med. 2008;359:697-708.
The risk for stroke seems to be a common theme among the various estrogens and estrogen look-alikes. Blood clots are clearly a feature of these medications as therapy, but it’s hard to understand why. Blood clots are not a feature of the vast majority of healthy premenopausal women who are clearly estrogen replete but they are a recognized complication in some premenopausal women on contraceptives. There is a lot of evidence that this is in some manner mediated by Factor V Leiden, a genetic variant of factor V in the coagulation cascade. This cannot be the whole story because the strokes that were reported in the article were both ischemic and hemorrhagic.
In essence, there’s no great surprise in the new tibolone data. Tibolone has been in use in more than 70 countries worldwide for at least 20 years, but has not been approved by the FDA for use in the United States. I cannot recall whether such approval has been sought to date.
Based on what we’re hearing, estrogen when given to the right person at the right time is fine — the benefits are substantial. The downside is that the side effects, when they happen, can be devastating. Before beginning such therapy we can find out who might be at greatest risk. In terms of breast cancer, we can check for a family history of breast cancer or look at BRCA. I think the same is probably true for clotting. The burning question is, how much information do you need to get from a woman before you start her on appropriate therapy? This is something that’s been asked in the literature for a long time.
On the benefit side it is clear that nothing seems as effective as estrogen at preventing hot flashes. We are also seeing that almost every one of the possible therapies (estrogen, raloxifene, tibolone) seems to be protective against heart disease if started early enough post-menopause. The same appears to be the case for prevention of postmenopausal bone loss, where again, the earlier therapy is started, the more evident the protection. So, the benefits are important and they’re much more prevalent than the side effects; the side effects are just disastrous when they happen.
As with all medications — the lowest effective dose in the right patient for the most appropriate length of time. If only there was a formula to determine that for all classes of medication.
– Michael Kleerekoper, MD, FACP
Endocrine Today Editorial Board member