Postmenopausal Tibolone Therapy: Biologic Principles and Applied Clinical Practice

Morris Notelovitz, MD, PhD, MB, BCh, FACOG, FRCOG

In This Article


Results from the Women's Health Initiative study suggested that the long-term adverse consequences of hormone therapy (HT) restricted its safe use to the shorter-term management of menopausal symptoms, and possibly, the early prevention of osteoporosis.[1] This conclusion is contrary to experimental and other science-based studies validating the rationale for HT, the large body of supporting clinical and observational trials and the decades of clinical experience.

The reason for this discrepancy is clear; although the menopause is a generic physiologic event, its biology is variable and specific to the individual woman.[2] The distribution and polymorphism of relevant hormone receptors and the genes that control enzymes and other factors regulating their expression and function are the actual biologic determinants of an individual's clinical response to both endogenous and prescribed hormones and to other therapies. The net effect of exogenous therapy (including HT) will further be influenced by the age and health of the individual (and hence the timing of the intervention) plus the dose and the route of administration (and therefore the pharmacokinetics) of the prescribed treatment. In this context, postmenopausal HT is additive to endogenously synthesized estrogen and androgens, and is best regarded as pharmacologic therapy.[2]

Advances in molecular biology have led to the development of newer pharmacologic agents. Drugs can be tailored to meet specific therapeutic objectives while avoiding undesirable side effects. Thus, diminishing function of certain hormone-dependent tissues - such as bone - can be upregulated pharmacologically by compounds that target receptors and enzymes responsible for local estrogen synthesis in bone, and not in other estrogen-dependent tissues, such as the endometrium and breast. Different classes of hormone-modulating drugs have emerged that target the estrogen receptor (SERMS)[3]; the enzymes involved in androgen/estrogen synthesis and metabolism (SEEMS)[4]; or both receptors (estrogen, androgen, progesterone) and related enzymes. Tibolone is a drug that satisfies this latter category.[5] Tibolone has been available for clinical use in Europe and elsewhere for 17 years.

This article briefly reviews the hormonal biology of relevant organs, the modulating pharmacologic effect of tibolone and its clinical utility in the treatment of the symptomatic menopause, and some prevalent postmenopausal conditions: osteoporosis, cardiovascular disease, and breast and endometrial cancer.


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