Breast cancer tibolone

A subsequent large epidemiologic study found a greater risk for breast cancer with combined estrogen-progestogen use, as well as increased risk for estrogen-only therapy and tibolone, but selection bias was found in the study population. 

The Million Women Study reported that current use of hormone therapy increased breast cancer risk and breast cancer mortality. Increased incidence was observed for estrogen only, estrogen plus progestogen, and for tibolone. 

Studies and reviews sponsored by the manufacturer of tibolone have over many decades argued that, as one reviewer puts it, tibolone may provide a safer alternative to traditional hormone replacement therapy , but even this review adds that the impact of tibolone on the risk of breast cancer or cardiovascular and thromboembolic events is not well defined (2). Bearing in mind that these are precisely the questions that have cast a shadow over other forms of hormone replacement therapy, this is a serious defect in the evidence about the drug s safety it is possible that the extent of use of tibolone has been insufficient to provide well-documented answers. 

Despite the still uncertain adverse effects profile of tibolone, it continues to be used in relieving the hot flushes caused by anti-estrogen therapy, and does so in doses that cause no additional problems. In a further double-blind, placebo-controlled study of oral tibolone 2.5 mg/day in 70 postmenopausal women taking tamoxifen after breast cancer surgery tibolone reduced the severity of hot flushes and perhaps also their incidence (3). 

A 2-year randomized controlled study in 90 women compared the effects of oral tibolone doses of 1.25 mg/day and 2.5 mg/day on bone loss in the early postmenopausal period all took calcium 1000 mg/day. Vertebral and femoral bone density rose in both treated groups but fell in the control group, and bone turnover markers (urinary excretion of hydroxyproline/creatinine and plasma osteocalcin concentrations) were similarly affected favorably in the treated groups, as was the incidence of hot flushes/ flashes (5). Studies such as this still leave open the question of the advisability of continuing tibolone treatment over a longer period. While tibolone has indeed been shown to benefit mineral bone density, few data are available to show whether it lowers fracture incidence nor is it clear whether there is a link between tibolone and breast cancer (6). 

Kroiss R, Fentiman IS, Helmond FA, Rymer J, Foidart JM, Bundred N, Mol-Arts M, Kubista E. The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer a randomised, double-blind, placebo-con-trolled trial. BJOG 2005 112 228-33. 

Tibolone has combined estrogenic, progestogenic, and androgenic activity. Its effects depend on metabolism and activation in peripheral tissues. Tibolone has beneficial effects on mood and hbido and improves menopausal symptoms and vaginal atrophy. It protects against bone loss and reduces the risk of vertebral fractures. It reduces total cholesterol, triglyceride, lipoprotein (a), and, unfortunately, high-density lipoprotein concentrations. It may increase cardiovascular risk, breast cancer risk, and endometrial cancer risk. 

Tibolone (Livial) is widely used in treatment of vasomotor symptoms and prevention of osteoporosis. The parent compound itself is devoid of activity, but it is metabolized in a tissue-selective manner to three metabolites that have predominantly estrogenic, progestogenic, and androgenic activities. The drug appears to increase bone mineral density and decrease vasomotor symptoms without stimulating the endometrium, but its effects on fractures, breast cancer, and long-term outcomes remain to be established. 

Cardiovascular In some cases tibolone prevents bone loss in elderly subjects, although after 40 years of use some questions regarding its clinical role remain unanswered. In a randomized study in the US, in which 4538 older women took either tibolone 1.25 mg/day or placebo, tibolone reduced the risk of vertebral fractures and of breast cancer. However, there was an increased risk of stroke (relative hazard = 2.19 95% Cl = 1.14, 4.23) the study was stopped after a mean treatment period of 34 months at the recommendation of the data and safety monitoring board [83. There were no significant differences between the two groups in the risks of either coronary heart disease or venous thromboembolism. 

Kenemans P, Hundred NJ, Foidart JM, Kubista E, von Schoultz B, Sismondi P, Vassilopoulou-Sellin R, Yip CH, Egberts J, Mol-Arts M, Mulder R, van Os S, Beckmann MW. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms a double-blind, randomised, non-inferiority trial. Lancet Oncol 2009 10 135-46. 

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