Conclusion: Personalized Healthcare
Advances in genomic medicine - diagnostic and pharmacologic - will in the foreseeable future permit a specific and targeted approach to both the prevention and treatment of specific diseases. Central to this ideal is appreciation of the biology and pathophysiology of aging and the multifactorial etiology of age-related diseases such as osteoporosis, cardiovascular disease, and breast cancer.
In this context, it is now apparent that although the menopause is a physiologic event generic to all women, the underlying hormonal biology differs among women, and within individuals, between various organs. These differences contribute to - but do not necessarily cause - alterations in the molecular biology of various tissues that may either promote or prevent disease. Thus, although all women stop menstruating, not all will, for example, develop hormone-related atherothrombosis. Some women experience severe hot flushes while others remain symptom free. These differences are frequently accounted for by polymorphism and/or mutations of genes that control relevant tissue metabolism and organ function. Understanding of the role of normal vs aberrant molecular biology allows for the development of therapies that target mechanisms responsible for specific abnormalities in the otherwise normal process of aging.
Central to this approach is the selective use of hormone therapy (estrogen, androgen, and progesterone) and other drugs that target sex steroid receptors and enzymes. The clinical usage and efficacy (including safety) of these various compounds is governed by differentiating between the role of sex steroid dysfunction as potential risk factors for a given disease, as opposed to factors causing that disease. Clinical caveats include: (1) not all menopausal women are biologically the same (individualization); (2) timing of treatment is critical (prevention vs treatment), and (3) the selected therapy may be beneficial in certain organs but potentially harmful to others. This phenomenon is explained in part by the differences in tissue hormone receptor distribution, the expression of steroid enzymes in various tissues of postmenopausal women, and the pharmacodynamics of the prescribed drug.
For example, tibolone reduces tissue levels of estrogen in breast tissue by inhibiting sulfatase activity, but not in bone cells. Conversely, tibolone does not inhibit aromatase activity and would therefore be ineffective in tissues expressing overactivity of this enzyme. In short, there is no one therapy that is effective or safe for all women.
Time- and age-adjusted interventions will vary with the pathogenesis of various diseases and the goal of therapy (Figure 4); primary prevention (health promotion); secondary intervention (disease prevention); or post-event therapy (curative medicine). Tibolone is effective in the management of menopausal symptoms and in the amelioration of risk factors associated with osteoporosis, CVD, and possibly breast cancer. However, the clinical indication for tibolone use is presently restricted to treatment of the symptomatic menopause. Longer-term clinical trials may confirm the biologic logic of selectively prescribing tibolone based on its mechanistic action in bone, the cardiovascular system, and the breast. The art of medicine is knowing how to interpret data from experimental and other mechanistic studies in light of randomized clinical trials, and the healthcare needs of a given woman at a given point in her life. It is vital that data from population-based studies not get "lost in translation" when applied to individuals.
Editorial support was provided by L.S. Shapiro and A.C. Garcia.Funding information
This work was supported in part by an unrestricted educational grant from NV Organon.
© 2007 Medscape
Cite this: Postmenopausal Tibolone Therapy: Biologic Principles and Applied Clinical Practice - Medscape - Jan 03, 2007.