Tibolone : A Selective Tissue Estrogenic Activity Regulator

Tibolone is a STEAR (Selective tissue estrogenic activity regulator) (1). It is a synthetic steroid with tissue selectivity that has progestogenic, some androgenic as well as estrogenic effects. It has been used as an alternative to estrogen replacement therapy in several European countries for almost 2 decades, primarily for the prevention of postmenopausal osteoporosis and treatment of climacteric symptoms. Mechanism of action (2) : Tibolone itself has no biological activity; its effects are the results of the activity of its metabolites on various tissues. After administration, tibolone is quickly metabolized into 3a-hydroxytibolone (3 ß OH-tibolone) and 3 ß-OH-tibolone compounds, which are also present in an inactive, sulfated form. A third compound, the ?4isomer, is formed from tibolone directly or from the 3 ß -OH-metabolites. Tibolone has estrogenic effects on bone and vaginal tissue. In endometrial tissue the ?4-isomer functions as a progestagen, whereas in the brain and liver it has androgenic effects. In breast tissue, the main actions of tibolone are strong inhibition of sulfatase activity and weak inhibition of 17 a -hydroxysteroid dehydrogenase activity, which result in blocking the conversion of estrone sulfate to E2. Tibolone actions are as follows :