Tibolone is a synthetic steroid that possesses weak estrogenic, progestational and androgenic properties [1]. The selective local metabolism of Tibolone into the Δ4 metabolite, which has progestogenic properties, prevents endometrial proliferation and negates the requirement for the addition of a progestogen [2]. Tibolone has been widely used in various animal models to alleviate vascular dilation and constriction and to improve the functions of the urinary and reproductive systems[3].
In vitro, Tibolone treatment for 48 hours significantly inhibited the proliferation of MCF-7 cells, with an IC50 value of 0.019μM[4]. Treatment of cells with 10nM Tibolone for 24 hours significantly reduced glucose deprivation-induced cell death in T98G cells and maintained cell morphology, while reducing nuclear fragmentation[5]. Treatment with 10nM Tibolone for 24 hours can reduce the cytotoxicity of 2mM palmitic acid on normal human astrocytes (NHAs) and decrease the loss of cardiolipin[6].
In vivo, Tibolone treatment via oral administration at a dose of 0.04mg/kg/day for 15 days significantly reduced the mean arterial pressure of renal vascular hypertension rats after ovary removal (OVX), albeit lowering total cholesterol and high-density lipoprotein (HDL) cholesterol levels[7]. Oral administration of 1mg/day of Tibolone for three consecutive months can enhance the bone integration process of intramedullary titanium implants in OVX rats, preventing the decline in bone mineral density (BMD) and weight gain after OVX [8].
References:
[1] Albertazzi P, Di Micco R, Zanardi E. Tibolone: a review[J]. Maturitas, 1998, 30(3): 295-305.
[2] Kenemans P, Speroff L, International Tibolone Consensus Group. Tibolone: clinical recommendations and practical guidelines: a report of the International Tibolone Consensus Group[J]. Maturitas, 2005, 51(1): 21-28.
[3] Del Río J P, Molina S, Hidalgo-Lanussa O, et al. Tibolone as hormonal therapy and neuroprotective agent[J]. Trends in Endocrinology & Metabolism, 2020, 31(10): 742-759.
[4] Sookvanichsilp N, Boonleang C, Sookvanichsilp N. Alendronate, raloxifene and tibolone inhibit the proliferation-stimulating activity of 17 (beta)-estradiol in MCF-7 cells[J]. 2005.
[5] Rodriguez M Á, Garcia-Segura L M, Cabezas R, et al. Tibolone protects T98G cells from glucose deprivation[J]. The Journal of steroid biochemistry and molecular biology, 2014, 144: 294-303.
[6] Martin-Jiménez C, González J, Vesga D, et al. Tibolone ameliorates the lipotoxic effect of palmitic acid in normal human astrocytes[J]. Neurotoxicity research, 2020, 38(3): 585-595.
[7] Gilglioni E H, Campos L B, Oliveira M C, et al. Beneficial effects of tibolone on blood pressure and liver redox status in ovariectomized rats with renovascular hypertension[J]. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 2013, 68(5): 510-520.
[8] Apostu D, Lucaciu O, Mester A, et al. Tibolone, alendronate, and simvastatin enhance implant osseointegration in a preclinical in vivo model[J]. Clinical oral implants research, 2020, 31(7): 655-668.
Tibolone是一种合成类固醇，具有弱雌激素、孕激素及雄激素活性[1]。Tibolone在局部的特异性代谢过程会转化为具有孕激素作用的Δ4代谢产物，这一过程能够抑制子宫内膜的增生，并且无需再额外添加孕激素[2]。Tibolone已广泛应用于多种动物模型中，用于改善血管舒缩功能及泌尿生殖系统功能[3]。
在体外，Tibolone处理48小时可显著抑制MCF-7细胞增殖，IC50值为0.019μM[4]。使用10nM的Tibolone处理T98G细胞24小时，能显著减轻葡萄糖剥夺诱导的细胞死亡，维持细胞形态并减少核碎裂[5]。以10nM的Tibolone处理正常人星形胶质细胞(NHAs)24小时，可减轻棕榈酸诱导的细胞毒性，减少心磷脂损失[6]。
在体内，卵巢切除（OVX）的肾血管性高血压大鼠每日口服0.04mg/kg/day剂量的Tibolone，连续15天，可显著降低平均动脉压，且总胆固醇和高密度脂蛋白胆固醇水平也有所下降[7]。连续三个月每日口服1mg/day剂量的Tibolone，能增强OVX大鼠髓内钛植入体的骨整合过程，防止OVX后骨密度下降及体重增加[8]。