Effects Of Tibolone Research Articles

Tibolone improves depression in women through the menopause transition: A double-blind randomized controlled trial of adjunctive tibolone

BackgroundMany women with no past psychiatric history experience severe mood symptoms for the first time in their life during the menopausal transition, with debilitating long-term consequences. Women with a history of depression can experience a relapse or worsening of symptoms during the menopause transition. Traditional antidepressants, SSRIs or SNRIs, are commonly prescribed as the first line response. However, such treatment has shown only small improvements with side effects. Hormone therapies directly targeting the perimenopausal fluctuations in reproductive hormonal systems such as tibolone, have significant potential to treat perimenopausal depression. Our study investigated the use of adjunctive tibolone, selective tissue estrogenic activity regulator, to treat de-novo or relapsing depression occurring during the menopause transition period. MethodsWomen who were going through the menopause transition with depressive symptoms were invited to participate in a double-blind, 12 week randomized control trial with two arms: tibolone (2.5 mg oral/day) or oral placebo (NCT01470092). Forty-four women met inclusion/exclusion criteria; 22 were randomized to tibolone and 22 were randomized to oral placebo. Symptoms were measured with the ‘Montgomery- Asberg depression rating scale’ (MADRS) as the primary outcome measure. Latent growth curve analysis was used to assess the MADRS scores change over time. ResultsParticipants in the tibolone group demonstrated a significant improvement in depression scores, as compared to the placebo group, without any significant side effects. LimitationsThis trial only monitored tibolone's effects over 12 weeks. Future research should be conducted over an extended timeframe and explore whether the benefits of tibolone extend to other symptoms of perimenopausal depression. ConclusionsThe use of hormone therapies such as tibolone provide exciting innovations for the treatment of depression during the menopause transition.

The Synthetic Steroid Tibolone Decreases Reactive Gliosis and Neuronal Death in the Cerebral Cortex of Female Mice After a Stab Wound Injury.

Previous studies have shown that estradiol reduces reactive gliosis after a stab wound injury in the cerebral cortex. Since the therapeutic use of estradiol is limited by its peripheral hormonal effects, it is of interest to determine whether synthetic estrogenic compounds with tissue-specific actions regulate reactive gliosis. Tibolone is a synthetic steroid that is widely used for the treatment of climacteric symptoms and/or the prevention of osteoporosis. In this study, we have assessed the effect of tibolone on reactive gliosis in the cerebral cortex after a stab wound brain injury in ovariectomized adult female mice. By 7days after brain injury, tibolone reduced the number of glial fibrillary acidic protein (GFAP) immunoreactive astrocytes, the number of ionized calcium binding adaptor molecule 1 (Iba1) immunoreactive microglia, and the number of microglial cells with a reactive phenotype in comparison to vehicle-injected animals. These effects on gliosis were associated with a reduction in neuronal loss in the proximity to the wound, suggesting that tibolone exerts beneficial homeostatic actions in the cerebral cortex after an acute brain injury.

Effect of tibolone pretreatment on kinases and phosphatases that regulate the expression and phosphorylation of Tau in the hippocampus of rats exposed to ozone.

Oxidative stress (OS) is a key process in the development of many neurodegenerative diseases, memory disorders, and other pathological processes related to aging. Tibolone (TIB), a synthetic hormone used as a treatment for menopausal symptoms, decreases lipoperoxidation levels, prevents memory impairment and learning disability caused by ozone (O3) exposure. However, it is not clear if TIB could prevent the increase in phosphorylation induced by oxidative stress of the microtubule-associated protein Tau. In this study, the effects of TIB at different times of administration on the phosphorylation of Tau, the activation of glycogen synthase kinase-3β (GSK3β), and the inactivation of Akt and phosphatases PP2A and PTEN induced by O3 exposure were assessed in adult male Wistar rats. Rats were divided into 10 groups: control group (ozone-free air plus vehicle [C]), control + TIB group (ozone-free air plus TIB 1 mg/kg [C + TIB]); 7, 15, 30, and 60 days of ozone exposure groups [O3] and 7, 15, 30, and 60 days of TIB 1 mg/kg before ozone exposure groups [O3 + TIB]. The effects of O3 exposure and TIB administration were assessed by western blot analysis of total and phosphorylated Tau, GSK3β, Akt, PP2A, and PTEN proteins and oxidative stress marker nitrotyrosine, and superoxide dismutase activity and lipid peroxidation of malondialdehyde by two different spectrophotometric methods (Marklund and TBARS, respectively). We observed that O3 exposure increases Tau phosphorylation, which is correlated with decreased PP2A and PTEN protein levels, diminished Akt protein levels, and increased GSK3β protein levels in the hippocampus of adult male rats. The effects of O3 exposure were prevented by the long-term treatment (over 15 days) with TIB. Malondialdehyde and nitrotyrosine levels increased from 15 to 60 days of exposure to O3 in comparison to C group, and superoxide dismutase activity decreased. Furthermore, TIB administration limited the changes induced by O3 exposure. Our results suggest a beneficial use of hormone replacement therapy with TIB to prevent neurodegeneration caused by O3 exposure in rats.

Effect of tibolone on the survival of early stage cervical adenocarcinoma patients

ObjectiveGynecologic oncologists are uncertain about the safety of tibolone application in cervical adenocarcinoma (AC) patients. This study examined the possible adverse effects of tibolone on the survival of cervical AC patients.MethodsMedical records of 70 cervical AC patients with International Federation of Gynecology and Obstetrics stages IA to IB were reviewed. A bilateral salpingo-oophorectomy was performed in all patients, and survival outcomes between tibolone users (n=38) and non-users (n=32) were compared.ResultsA comparison of the tibolone users with non-users revealed similar clinicopathological variables. Progression-free survival (P=0.34) and overall survival (P=0.22) were similar in the users and non-users. The risks of progression (hazard ratio [HR], 1.71; 95% confidence interval [CI], 0.46–6.37; P=0.43) and death (HR, 1.59; 95% CI, 0.06–45.66; P=0.79) were also similar in both groups.ConclusionTibolone has no adverse effect on the survival of cervical AC patients and can be administered safely to this population. These findings may be helpful in improving the quality of life of cervical AC patients.

Effects of tibolone on fibrinogen and antithrombin III: A systematic review and meta-analysis of controlled trials

Tibolone is a synthetic steroid with estrogenic, androgenic and progestogenic activity, but the evidence regarding its effects on fibrinogen and antithrombin III (ATIII) has not been conclusive. We assessed the impact of tibolone on fibrinogen and ATIII through a systematic review and meta-analysis of available randomized controlled trials (RCTs). The search included PUBMED, Web of Science, Scopus, and Google Scholar (up to January 31st, 2016) to identify controlled clinical studies investigating the effects of oral tibolone treatment on fibrinogen and ATIII. Overall, the impact of tibolone on plasma fibrinogen concentrations was reported in 10 trials comprising 11 treatment arms. Meta-analysis did not suggest a significant reduction of fibrinogen levels following treatment with tibolone (WMD: −5.38%, 95% CI: −11.92, +1.16, p=0.107). This result was robust in the sensitivity analysis and not influenced after omitting each of the included studies from meta-analysis. When the studies were categorized according to the duration of treatment, there was no effect in the subsets of trials lasting either <12months (WMD: −7.64%, 95% CI: −16.58, +1.29, p=0.094) or ≥12months (WMD: −0.62%, 95% CI: −8.40, +7.17, p=0.876). With regard to ATIII, there was no change following treatment with tibolone (WMD: +0.74%, 95% CI: −1.44, +2.93, p=0.505) and this effect was robust in sensitivity analysis. There was no differential effect of tibolone on plasma ATIII concentrations in trials with either <12months (WMD: +2.26%, 95% CI: −3.14, +7.66, p=0.411) or≥12months (WMD: +0.06%, 95% CI: −1.16, +1.28, p=0.926) duration. Consistent with the results of subgroup analysis, meta-regression did not suggest any significant association between the changes in plasma concentrations of fibrinogen (slope: +0.40; 95% CI: −0.39, +1.19; p=0.317) and ATIII (slope: −0.17; 95% CI: −0.54, +0.20; p=0.374) with duration of treatment. In conclusion, meta-analysis did not suggest a significant reduction of fibrinogen and ATIII levels following treatment with tibolone.

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

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.

Short-term and long-term effects of tibolone in postmenopausal women.

Short-term and long-term effects of tibolone in postmenopausal women.

Tibolone protects astrocytic cells from glucose deprivation through a mechanism involving estrogen receptor beta and the upregulation of neuroglobin expression

Tibolone, a synthetic steroid used for the prevention of osteoporosis and the treatment of climacteric symptoms in post-menopausal women, may exert tissue selective estrogenic actions acting on estrogen receptors (ERs). We previously showed that tibolone protects human T98G astroglial cells against glucose deprivation (GD). In this study we have explored whether the protective effect of tibolone on these cells is mediated by ERs. Experimental studies showed that both ERα and ERβ were involved in the protection by tibolone on GD cells, being ERβ preferentially involved on these actions over ERα. Tibolone increased viability of GD cells by a mechanism fully blocked by an ERβ antagonist and partially blocked by an ERα antagonist. Furthermore, ERβ inhibition prevented the effect of tibolone on nuclear fragmentation, ROS and mitochondrial membrane potential in GD cells. The protective effect of tibolone was mediated by neuroglobin. Tibolone upregulated neuroglobin in T98G cells and primary mouse astrocytes by a mechanism involving ERβ and neuroglobin silencing prevented the protective action of tibolone on GD cells. In summary, tibolone protects T98G cells by a mechanism involving ERβ and the upregulation of neuroglobin.

Relationship Between Breast Density and Selective Estrogen-Receptor Modulators, Aromatase Inhibitors, Physical Activity, and Diet: A Systematic Review.

Background Lower breast density (BD) is associated with lower risk of breast cancer and may serve as a biomarker for the efficacy of chemopreventive strategies. This review explores parameters that are thought to be associated with lower BD. We conducted a systematic review of articles published to date using the PRISMA strategy. Articles that assessed change in BD with estrogen-receptor modulators (tamoxifene [TAM], raloxifene [RLX], and tibolone) and aromatase inhibitors (AIs), as well as cross-sectional and longitudinal studies (LSs) that assessed association between BD and physical activity (PA) or diet were reviewed. Results Ten studies assessed change in BD with TAM; all reported TAM-mediated BD decreases. Change in BD with RLX was assessed by 11 studies; 3 reported a reduction in BD. Effect of tibolone was assessed by 5 RCTs; only 1 reported change in BD. AI-mediated BD reduction was reported by 3 out of 10 studies. The association between PA and BD was assessed by 21 studies; 4 reported an inverse association. The relationship between diet and BD was assessed in 34 studies. All studies on calcium and vitamin D as well as vegetable intake reported an inverse association with BD in premenopausal women. Two RCTs demonstrated BD reduction with a low-fat, high-carbohydrate intervention. Conclusion TAM induces BD reduction; however, the effect of RLX, tibolone, and AIs on BD is unclear. Although data on association between diet and BD in adulthood are contradictory, intake of vegetables, vitamin D, and calcium appear to be associated with lower BD in premenopausal women.

Beneficial Effects of Tibolone on Sexual Dys-function in Women with Premature Ovarian Failure (POF)

Introduction: Premature Ovarian Failure (POF) is cessation of ovarian functions before the age of 40 years old with consequent cessation of menstruation. Objective of study: The aim of this study was to evaluate the association between Premature Ovarian Failure and sexual dysfunctions and outcome of management with tibolone. Patients and Methods: Thirty-one women with Premature Ovarian Failure seen at the outpatient clinic of Maternity Hospital were enrolled into the study with 31 healthy women as control group. The instrument of data collection included two types of questionnaires to assess the effect of Premature Ovarian Failure on sexuality. All the women with POF had oral tibolone 2.5 mg for at least one year and the second questionnaire and the profiles were repeated. Results: Of the 31 women with POF that presented with sexual dysfunction (SD), 27 (87.1%) complained of one or more SD domains such as reduced frequency of coitus, dyspareunia, vaginal dryness, reduced libido and general sexual satisfaction (P < 0.01), amenorrhea (P < 0.01) and hot flashes compared to 5 (16.1%) control women (P < 0.01). Administration of tibolone was associated with significant increase in frequency of coitus, reduced dyspareunia and vaginal dryness, increase libido and general satisfaction and happiness. Reduction of sexual dysfunction was predicated on the estrogenic, progestogenic and androgenic metabolite of tibolone through the reduction of serum level of FSH and LH and increased levels of estrogen and testosterone (P < 0.01). Tibolone had no adverse effect on serum lipid profile. Conclusion: Premature Ovarian Failure is associated with sexual dysfunction. Tibolone provides an effective means of treating sexual dysfunction caused by Premature Ovarian Failure.

Migraine during perimenopause.

Migraine affects the female sex to a greater extent than the male, with a female:male ratio of 3:1. Hormonal fluctuations during the reproductive life may influence migraine occurrence and intensity, both in a positive or negative way. Many women experience migraine approaching menopause, but the trend of migraine symptoms may vary according to the different stages of the perimenopause. If a woman is already a migraineur subject, the attacks often worsen during both the early and late phases of menopausal transition, whereas an onset of migraine is quite rare[1]. According to some authors, women with premenstrual syndrome (PMS) before menopause have an increased prevalence of migraine in late menopausal transition, and a subsequent reduction of the attacks in postmenopause[2]. The presence of PMS can be considered one of the predictors of migraine trend during the menopausal transition, since women with PMS are more sensitive to hormonal fluctuations and more prone to develop moderate to severe menopausal symptoms[3]. Hormone replacement therapy (HRT) can be used during the late premenopausal phase and the first years of postmenopause in order to counteract climacteric symptoms[4]. The effect of HRT on migraine has been investigated, either in its role of provoking or preventing the attacks. HRT should be administered continuously, without intervals, to avoid sudden estrogen deprivation and the consequent possible onset of migraine[5]. Treatment with estradiol-based gels and transdermal patches is preferable to oral formulation as it maintains constant serum hormone levels. In contrast to guidelines on the use of estroprogestinic contraceptives, migraine with aura is not an absolute contraindication to HRT when the way of administration is topical with a low dose of natural estrogens. If the aura recurs or worsens, HRT should be in any case discontinued[6]. When the effect of tibolone versus continuous combined HRT regimen in migraine is compared, a significant reduction in the hours with pain-limiting daily activities and of the amount of analgesics intake can be observed, even if there is no reduction of the days with migraine[7]. Natural menopause is associated with a lower incidence of migraine as compared with surgical menopause[8]; data on migraine prevalence in relation to the type of surgical procedure are till now unclear and contradictory[9].

Effect of tibolone on dendritic spine density in the rat hippocampus

IntroductionOestrogen deficiency produces oxidative stress (OS) and changes in hippocampal neurons and also reduces the density of dendritic spines (DS). These alterations affect the plastic response of the hippocampus. Oestrogen replacement therapy reverses these effects, but it remains to be seen whether the same changes are produced by tibolone (TB). The aim of this study was to test the neuroprotective effects of long-term oral TB treatment and its ability to reverse DS pruning in pyramidal neurons (PN) of hippocampal area CA1. MethodsYoung Sprague-Dawley rats were distributed in 3 groups: a control group in proestrus (Pro) and two ovariectomised groups (Ovx), of which one was provided with a daily TB dose (1mg/kg), OvxTB and the other with vehicle (OvxV), for 40 days in both cases. We analysed lipid peroxidation and DS density in 3 segments of apical dendrites from PNs in hippocampal area CA1. ResultsTB did not reduce lipid peroxidation but it did reverse the spine pruning in CA1 pyramidal neurons of the hippocampus which had been caused by ovariectomy. ConclusionsOestrogen replacement therapy for ovariectomy-induced oestrogen deficiency has a protective effect on synaptic plasticity in the hippocampus.

Tibolone decreases Lipoprotein(a) levels in postmenopausal women: A systematic review and meta-analysis of 12 studies with 1009 patients.

Circulating lipoprotein (a) (Lp(a)) is a recognized risk factor for cardiovascular disease (CVD). Tibolone, a synthetic steroid, may lower Lp(a) levels; however, evidence of the effects of tibolone on Lp(a) still remain to be defined. Therefore, we investigated the effects of tibolone treatment on circulating Lp(a) levels in postmenopausal women. The search included PUBMED, Web of Science, Scopus, and Google Scholar (up to January 31st, 2015) to identify controlled clinical studies investigating the effects of oral tibolone treatment on Lp(a) levels in postmenopausal women. Random-effects meta-regression was performed using unrestricted maximum likelihood method for the association between calculated weighted mean difference (WMD) and potential moderators. Meta-analysis of data from 12 trials (16 treatment arms) suggested a significant reduction of Lp(a) levels following tibolone treatment (WMD: -25.28%, 95% confidence interval [CI]: -36.50, -14.06; p < 0.001). This result was robust in the sensitivity analysis and its significance was not influenced after omitting each of the included studies from the meta-analysis. When the studies were categorized according to the tibolone dose, there were consistent significant reductions of Lp(a) in the subsets of studies with doses <2.5 mg/day (WMD: -17.00%, 95%CI: -30.22, -3.77; p < 0.012) and 2.5 mg/day (WMD: -29.18%, 95%CI: -45.02, -13.33; p < 0.001). Likewise, there were similar reductions in the subsets of trials with follow-up either <24 months (WMD: -26.79%, 95%CI: -38.40, -15.17; p < 0.001) or ≥24 months (WMD: -23.10%, 95%CI: -40.17, -6.03; p = 0.008). This meta-analysis shows that oral tibolone treatment significantly lowers circulating Lp(a) levels in postmenopausal women. Further studies are warranted to explore the mechanism of this effect and the potential value and place of tibolone or its analogues in the treatment of elevated Lp(a) in individuals at risk of CVD.

Efeitos da tibolona sobre o parênquima mamário: estudo experimental

To assess the effect of tibolone on mammary tissue of castrated rats over 3 different periods of time. Sixty virgin female Wistar rats were submitted to oophorectomy. Twenty-one days after surgery, with hypoestrogenism confirmed, the experimental rats were randomly assigned to six groups: Tibolone 1 (n=10) received tibolone 1 mg/day for 23 days, tibolone 2 (n=10) for 59 days and tibolone 3 (n=10) for 118 days. The groups control 1 (n=8), control 2 (n=7) and control 2 (n=10) received distilled water for 23, 59 and 118 days, respectively. After treatment, all six pairs of mammary glands were removed and stained with hematoxylin and eosin (HE) for histological analysis after euthanasia. The histological parameters evaluated were: epithelial cell proliferation and secretory activity. The variables were analyzed statistically, with the level of significance set at 0.05. Histological changes were observed in 20/55 rats, mild epithelial hyperplasia in 7/55, moderate epithelial hyperplasia in 5/55, alveolar-nodular hyperplasia in 7/55, atypia without epithelial proliferation in 1/55, and no cases of severe epithelial hyperplasia were found. Secretory activity was observed in 31/55 rats. The secretory activity was significantly higher in the tibolone groups compared to control at all the time points assessed (p=0,001). The histological changes were did not show significance when the control and tibolone groups were compared. The time of exposure to tibolone did not show significance when the three different periods of evaluation were compared. No relation between histological modification and tibolone treatment was verified after short-, medium- and long-term treatment.

Effects of tibolone and its metabolites on prolactin and insulin-like growth factor binding protein-1 expression in human endometrial stromal cells

The effects of the postmenopausal replacement steroid tibolone and its 3α-, 3β-OH and Δ-4 tibolone metabolites were evaluated on progesterone receptor-mediated classic decidualization markers insulin-like growth factor binding protein-1 (IGFBP-1) and prolactin expression in human endometrial stromal cells (HESCs). Supernatants of conditioned medium or erxtracted RNA from experimental cell incubations of confluent HESCs were subjected to ELISAs, Western blot analysis and RT/PCR, and results were statisically assesed. Over 21 days, specific ELISAs observed linear increases in secreted IGFBP-1 and prolactin levels elicited by tibolone and its metabolites. Cultured HESCs were refractory to E2 and dexamethasone, whereas tibolone and each metabolite exceeded medroxyprogesterone acetate in significantly elevating IGFBP-1 and prolactin output. Anti-progestins eliminated IGFBP-1 and prolactin induction by tibolone and its metabolites. Immunoblotting and RT/PCR confirmed ELISA results. These observations of IGFBP-1 and prolactin expression: (a) indicate the relevance of cultured HESCs in evaluating the chronic effects of tibolone administration to women; (b) are consistent with PR-mediated endometrial atrophy and protection against endometrial bleeding despite the persistence of circulating ER-binding, but not PR-binding metabolites following tibolone administration to women.

Astrocytes mediate the neuroprotective effects of Tibolone following brain injury

Event Abstract Back to Event Astrocytes mediate the neuroprotective effects of Tibolone following brain injury Marcos Ávila-Rodriguez1, Luis M. Garcia-Segura2 and George E. Barreto1* 1 Pontificia Universidad Javeriana, Colombia 2 Instituto Cajal, CSIC, Spain Recently, astrocytes have become a key central player in mediating important functions in the brain. These physiological processes include neurotransmitter recycling, energy management, metabolic shuttle, immune sensing, K+ buffer, antioxidant supply and release of neurotrophic factors and gliotransmitters. These astrocytic roles are somehow altered upon brain injury, therefore strategies aimed at better protecting astrocytes are an essential asset to maintain brain homeostasis. In this context, estrogenic compounds, such as Tibolone, have attracted attention for their beneficial effects in acute and chronic degenerative diseases. Tibolone may act through binding to estrogen, androgen or progesterone receptors and exert protective effects by reducing astrocytes cell death and oxidative stress signaling mechanisms. Although Tibolone has a multifactorial effect in the brain, its mechanisms of action are not completely understood. In this work, we highlight the role of Tibolone in brain protection upon damage, how astrocytes might mediate part of its neuroprotective actions and discuss the effects of Tibolone in diminishing the harmful consequences of a metabolic insult and energy failure in the setting of a pathological event. Figure 1 References Avila-Rodriguez M, Garcia-Segura LM, Cabezas R, Torrente D, Capani F, Gonzalez J, Barreto GE. Tibolone protects T98G cells from glucose deprivation. J Steroid Biochem Mol Biol., 2014, In Press. Barreto G , Santos-Galindo M, Diz-Cháves Y, Pernía O, Carrero P, Azcoitia I, Garcia-Segura LM. Selective Estrogen Receptor Modulators decrease reactive astrogliosis in the injured brain: Effects of aging and prolonged depletion of ovarian hormones. Endocrinology 150(11):5010-5, 2009. Barreto G, Veiga S, Azcoitia I, Garcia-Segura LM, Garcia-Ovejero D. Testosterone decreases reactive astroglia and reactive microglia after brain injury in male rats: role of its metabolites, oestradiol and dihydrotestosterone. Eur J Neurosci. 25(10):3039-46, 2007. Barreto GE, Santos-Galindo M, Garcia-Segura LM. Selective estrogen receptor modulators regulate reactive microglia after penetrating brain injury. Front Aging Neurosci, 6:132, 2014. Avila MF, Cabezas M, Torrente D, Gonzalez J, Morales L, Alvarez L, Capani F, Barreto GE. Novel interactions of GRP78: UPR and estrogen responses in the brain. Cell Biol Int, 37:521-532, 2013. Barreto GE , González J, Torres Y, Morales L. Astrocyte-neuronal crosstalk: Implications for neuroprotection from brain injury. Neurosc Res, 71(2):107-13, 2011. Keywords: tibolone, Astrocytes, Brain Injuries, Neuroprotection, energy failure Conference: Latin-American School on glial cells in the diseased brain (IBRO), Bogotá, Colombia, 13 Jul - 17 Jul, 2015. Presentation Type: Oral Presentation Topic: Traumatic and Cerebrovascular diseases Citation: Ávila-Rodriguez M, Garcia-Segura LM and Barreto G (2015). Astrocytes mediate the neuroprotective effects of Tibolone following brain injury. Conference Abstract: Latin-American School on glial cells in the diseased brain (IBRO). doi: 10.3389/conf.fncel.2015.35.00002 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Feb 2015; Published Online: 16 May 2015. * Correspondence: Prof. George E. Barreto, Pontificia Universidad Javeriana, Bogotá, Colombia, gesbarreto@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Marcos Ávila-Rodriguez Luis M Garcia-Segura George E. Barreto Google Marcos Ávila-Rodriguez Luis M Garcia-Segura George E. Barreto Google Scholar Marcos Ávila-Rodriguez Luis M Garcia-Segura George E. Barreto PubMed Marcos Ávila-Rodriguez Luis M Garcia-Segura George E. Barreto Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Changes in serum calcium and vitamin D3 levels after tibolone treatment and their correlations with health-related quality of life

ObjectiveTo assess the effects of tibolone on serum calcium and vitamin D3 levels, the effects on health-related quality of life (HRQOL), and the relationship between these variables. MethodsAn open-label, prospective, parallel-arm study was conducted at S.C. Das Memorial Medical and Research Center, Kolkata, India, between July 2012, and June 2013. Women aged 34–55years were eligible when they were experiencing surgical menopause and were symptomatic. Group A comprised patients who chose to receive tibolone (2.5mg daily for 6months) and group B comprised those who refused treatment. At baseline and 6months, body mass index (BMI), serum calcium and vitamin D3 levels and HRQOL were assessed. ResultsOf 79 participants, 53 were in group A and 26 in group B. After 6months, BMI had increased significantly in both groups. The vitamin D3 level had increased significantly from baseline in group A (P=0.02), and was higher than that in group B (P=0.01). HRQOL had also improved significantly from baseline in group A (P=0.001), and was significantly better than that in group B (P<0.001). In group A, a significant correlation was found between HRQOL improvement and vitamin D3 levels (P<0.001). ConclusionTibolone significantly increases the serum vitamin D3 level and improves HRQOL in menopausal women.Clinical Trial Registry India: CTRI/2012/06/002752.

Efecto neuroprotector de la tibolona contra el estrés oxidativo inducido por la exposición a ozono

Oxidative stress increases brain lipid peroxidation, memory and motor deficits and progressive neurodegeneration. Tibolone, a treatment for menopausal symptoms, decreases lipid peroxidation levels and improves memory and learning. To study the effect of chronic administration of tibolone on lipid peroxidation, memory and motor deficits in ozone induced oxidative stress. 100 male Wistar adult rats were randomly divided into 10 experimental groups: control (C) was exposed to an airstream for 60 days; C + tibolone, airstream exposure plus 1 mg/kg of tibolone for 60 days; groups 3-6 were exposed to ozone for 7, 15, 30, and 60 days, and groups 7-10 received 1 mg/kg of tibolone treatment by oral gavage for 7, 15, 30 and 60 days and were then exposed to ozone. We determined the effect of tibolone on memory and motor activity. Hippocampus was processed to determine the content of 4-hydroxynonenal and nitrotyrosine by Western blot. Four animals were perfused and processed for analysis of neuronal death. In the hippocampus, administration of 1 mg/kg of tibolone for 30 days prevented increased levels of lipid peroxidation and protein oxidation, whereas after 60 days prevented neuronal death in the CA3 region caused by exposure to ozone. Therefore, tibolone prevents cognitive deficits in short- and long-term memory on the passive avoidance task and prevents a decrease in exploratory behavior and an increase in freezing behavior. Our results indicate a possible neuroprotective role of tibolone as a useful treatment to prevent oxidative stress neurodegeneration.

Effects of tibolone on osteoarthritis in ovariectomized rats: Association with nociceptive pain behaviour

To investigate the role of the synthetic steroid tibolone in the progression of osteoarthritis (OA) and in nociceptive behaviour in an experimental rat model of OA and ovariectomy (OVX)-induced osteoporosis. OA was induced in Wistar rats by anterior cruciate ligament transection (ACLT) of the right knee. Osteoporosis was induced by bilateral OVX. Groups of animals were subjected to ACLT, OVX, sham or OVX + ACLT. In addition, two groups were subjected to OVX + ACLT surgeries and were orally administered 0.1 or 0.5 mg tibolone every other day for 14 consecutive weeks, starting 6 weeks after surgery. Nociceptive behaviours (secondary mechanical allodynia and weight-bearing distribution of the hind paws) were analysed prior to and every 3 weeks after surgery up to 24 weeks. At 24 weeks, histopathological studies were performed on the cartilage and synovial membranes of the knee joints, and bone metabolism was assessed by measuring serum concentrations of calcium, phosphorus and alkaline phosphatase. Rats undergoing ACLT or OVX + ACLT surgeries showed obvious OA changes in the joints. Animals subjected to ACLT + OVX and treated with tibolone had significantly less cartilage degeneration and synovitis and showed improved nociceptive tests compared with animals undergoing ACLT + OVX surgeries alone. OVX increased the severity of the ACLT-induced OA changes. There was a significant increase in serum alkaline phosphatase in the tibolone-treated ACLT + OVX groups. Treatment with tibolone attenuated the development of OA, concomitantly reduced nociception and increased serum alkaline phosphatase in ACLT + OVX rats.

Effects of tibolone on serum calcium and 25-hydroxy vitamin D3 levels and health related quality of life (HRQOL) in postmenopausal (surgical) women

There are growing evidences that vitamin D3 sufficiency is required for optimal health. Objective is to study the effects of 6 months of treatment with Tibolone, as hormone replacement therapy (HRT) on BMI (body mass index), serum calcium and 25-hydroxy vitamin D3 levels, Health related quality of life (HRQOL) in postmenopausal (surgically) women and the relationship between different studied parameters.