Tibolone as Hormonal Therapy and Neuroprotective Agent

Río, Juan Pablo del; Molina, Santiago; Hidalgo-Lanussa, Oscar; García‐Segura, Luis M.; Barreto, George E.

doi:10.1016/j.tem.2020.04.007

Cited by 35 publications

(26 citation statements)

References 158 publications

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“…[ 20 ] The relatively better performance of TIB with respect to management of depression as observed in the present study could be attributed to its strong estrogenic effect. [ 21 ] Anxiety symptoms scores using HAM-A showed a significant decline of 56% in TIB group at the end of 12 weeks ( P < 0.001**). Some previous studies have reported improvement in anxiety with TIB.…”

Section: Discussionmentioning

confidence: 99%

Comparative safety and efficacy of tibolone and escitalopram in postmenopausal women

Raj

Sharma

Garg

et al. 2021

Industrial Psychiatry Journal

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Background: A high prevalence of psychiatric disorders, particularly depressive and anxiety disorders among women is observed through the postmenopausal stage. Aim: The aim of this study is to compare the safety and efficacy of tibolone (TIB) and escitalopram (ESCIT) in postmenopausal women (PMW). Materials and Methods: It was an interventional, open-label, hospital-based, follow-up study conducted on 60 PMW with the diagnosis of depression as per the Diagnostic and Statistical Manual of Mental Disorder-5 criteria. Patients were divided into two groups of 30 each, i.e. Group I (TIB-2.5 mg/day) and Group II (ESCIT-10–20 mg/day). The primary outcome was assessed for change in climacteric symptom scores on Greene's Climacteric Scale (GCS), severity of depression and anxiety on Hamilton Rating Scale for Depression (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A), and sexual functioning on Arizona Sexual Experience Scale (ASEX). The secondary outcome of well-being was assessed on World Health Organization Quality of life (QOL)-BREF. All the observations were carried out from baseline and at 2, 4, 8, and 12 weeks. Results: Both the groups showed significant improvement in climacteric and depressive symptoms. However, at the 8th and 12th weeks, mean ± standard deviation scores were significantly lower in Group I (GCS score - 24.80 ± 4.92, 20.30 ± 3.56; HAM-D score - 16.57 ± 5.83, 10.2 ± 5.67) compared to Group II (GCS score - 27.27 ± 5.83 and 23.33 ± 5.70, HAM-D score - 19.97 ± 7.98 and 16.17 ± 10.11). No significant difference between the groups was seen for anxiety on HAM-A scores. Only in Group I, there was significant improvement in ASEX scores. QoL in Group I had shown significant improvement in physical and psychological domain compared to Group II at different time interval, i.e. 4th and 8th week onward. In Group I, Alternative Dispute Resolution was reported to be 23.3%, whereas it was 56.7% in Group II. However, none were serious to warrant discontinuation. Conclusion: TIB was better than ESCIT in improving depression, climacteric symptoms, and physical and psychological domain of QoL with an additional benefit of restoring sexual functioning.

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Section: Discussionmentioning

confidence: 99%

Comparative safety and efficacy of tibolone and escitalopram in postmenopausal women

Raj

Sharma

Garg

et al. 2021

Industrial Psychiatry Journal

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“…The damage caused by pal has been reported to trigger an inflammatory response in astrocytes and is associated with harmful mechanisms such as oxidative stress, ER stress, and autophagic defects [ 16 , 63 ]. In this sense, it has also been reported that tibolone exerts protective functions against inflammation in experimental neuronal models [ 27 ]. Furthermore, the findings of this study agree with literature reports with astrocytes treated with 1 mM pal for 24 h with no ROS production [ 101 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, multiple studies have used estrogen-like compounds as alternatives to obtain therapeutic agents as potential treatments for different NDs [ 23 ]. Among these, tibolone, a synthetic steroid, has attracted attention because it shows beneficial effects in acute and chronic NDs [ 24 , 25 , 26 , 27 ], and as hormonal therapy for postmenopausal women. Tibolone may exert estrogenic actions in the brain while inducing progestogenic and androgenic effects in the uterus, endometrium, and breast due to its capacity of being metabolized in different compounds generating a specific response in different tissues [ 26 , 28 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Tibolone Pre-Treatment Ameliorates the Dysregulation of Protein Translation and Transport Generated by Palmitic Acid-Induced Lipotoxicity in Human Astrocytes: A Label-Free MS-Based Proteomics and Network Analysis

Vesga-Jiménez¹,

Martin-Jimenez²,

Grismaldo

et al. 2022

IJMS

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Excessive accumulation and release of fatty acids (FAs) in adipose and non-adipose tissue are characteristic of obesity and are associated with the leading causes of death worldwide. Chronic exposure to high concentrations of FAs such as palmitic acid (pal) is a risk factor for developing different neurodegenerative diseases (NDs) through several mechanisms. In the brain, astrocytic dysregulation plays an essential role in detrimental processes like metabolic inflammatory state, oxidative stress, endoplasmic reticulum stress, and autophagy impairment. Evidence shows that tibolone, a synthetic steroid, induces neuroprotective effects, but its molecular mechanisms upon exposure to pal remain largely unknown. Due to the capacity of identifying changes in the whole data-set of proteins and their interaction allowing a deeper understanding, we used a proteomic approach on normal human astrocytes under supraphysiological levels of pal as a model to induce cytotoxicity, finding changes of expression in proteins related to translation, transport, autophagy, and apoptosis. Additionally, tibolone pre-treatment showed protective effects by restoring those same pal-altered processes and increasing the expression of proteins from cell survival processes. Interestingly, ARF3 and IPO7 were identified as relevant proteins, presenting a high weight in the protein-protein interaction network and significant differences in expression levels. These proteins are related to transport and translation processes, and their expression was restored by tibolone. This work suggests that the damage caused by pal in astrocytes simultaneously involves different mechanisms that the tibolone can partially revert, making tibolone interesting for further research to understand how to modulate these damages.

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“…Thus, 3α and 3β metabolites preferentially bind to ERs, mainly ERα, while δ4-tibolone binds to AR and PGR [97]. In the nervous system, tibolone exerts neuroprotective actions and promotes cognition [98,99], probably by acting in part over glial cells through the attenuation of the reactive activation of astrocytes and microglia after traumatic brain injury [100], and the regulation of astrocyte phagocytosis of brain cellular debris [101].…”

Section: Role Of Neuroglobin In the Neuroprotective Actions Of Natural And Synthetic Compounds With Estrogenic Activitymentioning

confidence: 99%

Role of Neuroglobin in the Neuroprotective Actions of Estradiol and Estrogenic Compounds

Barreto

McGovern

García‐Segura

2021

Cells

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Estradiol exerts neuroprotective actions that are mediated by the regulation of a variety of signaling pathways and homeostatic molecules. Among these is neuroglobin, which is upregulated by estradiol and translocated to the mitochondria to sustain neuronal and glial cell adaptation to injury. In this paper, we will discuss the role of neuroglobin in the neuroprotective mechanisms elicited by estradiol acting on neurons, astrocytes and microglia. We will also consider the role of neuroglobin in the neuroprotective actions of clinically relevant synthetic steroids, such as tibolone. Finally, the possible contribution of the estrogenic regulation of neuroglobin to the generation of sex differences in brain pathology and the potential application of neuroglobin as therapy against neurological diseases will be examined.

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Tibolone as Hormonal Therapy and Neuroprotective Agent

Cited by 35 publications

References 158 publications

Comparative safety and efficacy of tibolone and escitalopram in postmenopausal women

Comparative safety and efficacy of tibolone and escitalopram in postmenopausal women

Tibolone Pre-Treatment Ameliorates the Dysregulation of Protein Translation and Transport Generated by Palmitic Acid-Induced Lipotoxicity in Human Astrocytes: A Label-Free MS-Based Proteomics and Network Analysis

Role of Neuroglobin in the Neuroprotective Actions of Estradiol and Estrogenic Compounds

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