Hormonal Tibolone

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. 

Palomba S, Affinito P, Di Carlo C, Bifulco G, Nappi C (1999) Longterm administration of tibolone plus gonadotropin-releasing hormone agonist for treatment of uterine leiomyomas effectiveness and effects on vasomotor symptoms, bone mass, and lipid profile. Fertil Steril 72 889-895... 

Another approach to the study of the effects of hormone replacement therapy on the breast is to examine breast density, using mammography and the Wolfe classification. In a randomized study of 166 menopausal women, using this technique, there was increased breast density after 6 months of treatment eight times more commonly in those who took estradiol and norethisterone acetate than in those who took tibolone (186). The significance of this increased density is not clear, but it should for the present be regarded as undesirable,... 

Lundstrom E, Christow A, Kersemaekers W, Svane G, Azavedo E, Soderqvist G, Mol-Arts M, Barkfeldt J, von Schoultz B. Effects of tibolone and continuous combined hormone replacement therapy on mammographic breast density. Am J Obstet Gynecol 2002 186(4) 717-22. 

Tibolone is an agonist at estrogen and progestogen receptors, with weak androgenic activity. It is given as an alternative to hormone replacement therapy, without added progestogen, and has been in use for some 30 years to treat bone loss in post-menopausal women. Some long-term studies (for example over 10 years) appear to have confirmed its safety and relative freedom from adverse effects (1). In particular there is little or no increase in thrombotic events and the incidence of breast tenderness is low. 

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. 

Two patients taking oral anticoagulants developed excessive anticoagulant activity shortly after they had begun to take a course of tibolone (7). This seems to be a specific interaction, apparently similar to that seen with more potent estrogens, and the dose of anticoagulant may need to be reduced when tibolone is taken the problem did not seem to arise consistently with other hormone replacement formulations. 

Swegle JM, Kelly MW. Tibolone a unique version of hormone replacement therapy. Ann Pharmacother... 

Hormone replacement therapy (HRT), including tibolone, is not recommended for postmenopausal women over the age of 50 years unless other treatments for osteoporosis are contraindicated or not tolerated (MHRA, 2005). 

El-Hajj Fuleihan G. Tibolone and the promise of ideal hormone-replacement therapy. N Engl J Med 2008 359 753-5. 

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