Effects of Tibolone on the Central Nervous System: Clinical and Experimental Approaches

Figure 1

Chemical structure of TIB and its metabolites. After oral intake, TIB is metabolized by aldo-keto reductase (AKR) family members, which are a superfamily of NADPH-dependent oxidoreductase enzymes also called hydroxysteroid dehydrogenases (HSD). From this reaction, three different metabolites are originated: 3α-hydroxy tibolone (3α-OH TIB) and 3β-hydroxy tibolone (3β-OH TIB) in their sulfated inactive forms and -tibolone (produced from them or directly from TIB). Hydroxysteroid dehydrogenase metabolites α and β have a high affinity for ER, while -tibolone has an affinity only for PR and AR. The tissue-specific activity of TIB will depend on the interaction of two main physiological mechanisms: biochemical mechanism (TIB metabolism) and genetic mechanism (through the interaction with the steroid receptor). Therefore, the action of TIB will also depend on its metabolism at the targeted organ, as well as the interaction of its metabolites with the receptors to which they bind [24].