Tibolone as Hormonal Therapy and Neuroprotective Agent

Tibolone (TIB), a selective tissue estrogenic activity regulator (STEAR) in clinical use by postmenopausal women, activates hormonal receptors in a tissue-specific manner. Estrogenic activity is present mostly in the brain, vagina, and bone, while the inactive forms predominate in the endometrium and breast. Conflicting literature on TIB’s actions has been observed. While it has benefits for vasomotor symptoms, bone demineralization, and sexual health, a higher relative risk of hormone-sensitive cancer has been reported. In the brain, TIB can improve mood and cognition, neuroinflammation, and reactive gliosis. This review aims to discuss the systemic effects of TIB on peri- and post-menopausal women and its role in the brain. We suggest that TIB is a hormonal therapy with promising neuroprotective properties. In menopause, women experience changes in their body (e.g., lipid metabolism), and these are associated with alterations in mood, muscle mass, memory, and cognition.Hormonal therapy with estradiol and progestins have shown promising results in the brain but undesired actions in other organs.Weight gain in women under hormonal therapy is the most common complaint in clinics and dysregulation of lipid metabolism is a hallmark of menopause.Tibolone, a selective tissue estrogenic activity regulator, shows remarkable results in regulating lipid metabolism in postmenopausal women, but induces possible detrimental effects in women’s bodies.Tibolone use is associated with increased risk of developing breast cancer and vaginal bleeding and conflicting outcomes for the uterus and ovary are noted.The estrogenic activity of tibolone in the brain induces protective signaling in neurons and glial cells by attenuating mitochondrial dysfunction, neuroglobin upregulation, and nuclear translocation of NF-κB.