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, 2017, 8630764

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


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

Rodolfo Pinto-Almazán et al. Biomed Res Int.


Hormone replacement therapy (HRT) increases the risk of endometrial and breast cancer. A strategy to reduce this incidence is the use of tibolone (TIB). The aim of this paper was to address the effects of TIB on the central nervous system (CNS). For the present review, MEDLINE (via PubMed), LILACS (via BIREME), Ovid Global Health, SCOPUS, Scielo, and PsycINFO (ProQuest Research Library) electronic databases were searched for the results of controlled clinical trials on peri- and postmenopausal women published from 1990 to September 2016. Also, this paper reviews experimental studies performed to analyze neuroprotective effects, cognitive deficits, neuroplasticity, oxidative stress, and stroke using TIB. Although there are few studies on the effect of this hormone in the CNS, it has been reported that TIB decreases lipid peroxidation levels and improves memory and learning. TIB has important neuroprotective effects that could prevent the risk of neurodegenerative diseases in postmenopausal women as well as the benefits of HRT in counteracting hot flashes, improving mood, and libido. Some reports have found that TIB delays cognitive impairment in various models of neuronal damage. It also modifies brain plasticity since it acts as an endocrine modulator regulating neurotransmitters, Tau phosphorylation, and decreasing neuronal death. Finally, its antioxidant effects have also been reported in different animal models.

Conflict of interest statement

The authors declare no conflict of interests regarding the publication of this paper.


Figure 1
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 Δ4-tibolone (produced from them or directly from TIB). Hydroxysteroid dehydrogenase metabolites α and β have a high affinity for ER, while Δ4-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].
Figure 2
Figure 2
Clinical and experimental approaches of TIB in the central nervous system. Climacteric symptoms: vasomotor symptoms, mood, and well-being. ↑: increase; ↓: decrease (see [, , , , –, –, –67]).

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