Disease relevance of tibolone

• In conclusion, tibolone can be regarded as an alternative to conventional HRT to prevent postmenopausal bone loss [1].
• We conclude that 16 months of tibolone treatment prevents ovariectomy-induced deterioration of axial and peripheral skeleton and preserves cortical and trabecular bone strength by reducing bone resorption [2].
• Progestogenic effects of tibolone on human endometrial cancer cells [3].
• Because nitric oxide (NO) is a key regulator of vascular tone and atherogenesis, we studied its regulation by tibolone and its metabolites on human endothelial cells [4].
• After adjustment for confounding factors, an increased risk of breast cancer was found for the current use of estrogen only (RR = 1.96; 95% CI = 1.16-3.35), for the combined use of estrogen and progestin (RR = 2.70; 95% CI = 1.96-3.73) and for current users of tibolone (RR = 4.27; 95% CI = 1.74-10.51) compared to the never use of HRT [5].

Psychiatry related information on tibolone

• Women treated with tibolone report significant reductions in vaginal dryness and dyspareunia, effects that may be secondary to both estrogenic and androgenic actions [6].
• CONCLUSIONS: Spine BMD increased significantly in response to tibolone irrespective of physical activity participation [7].
• Maximal isometric strength of knee flexors was determined in 23 of the tibolone group, 26 of the oestrogen group and 12 of the no therapy group [8].
• Based on the evidence available, the panel proposed a number of subgroups of postmenopausal women with vasomotor symptoms in whom tibolone might have added value; these included women with sexual dysfunction, mood disorders, fibroids and urogenital complaints, as well as those with breast tenderness or high mammographic breast density with EPT use [9].
• At the end of the 6-month follow-up period, the QoL was better in the tibolone group in the area of mental health [10].

High impact information on tibolone

• In postmenopausal women, tibolone prevents bone loss without stimulating the endometrium [11].
• This suggests a major involvement of the estrogen receptor in the action of tibolone on bone metabolism [11].
• Treatment with tibolone prevented ovariectomy-induced bone loss in peripheral (femur and tibia) and axial (L1-L2 and L4) skeleton [2].
• Tibolone, a synthetic steroid with simultaneous weak estrogenic, androgenic, and progestational activity, which does not stimulate endometrial proliferation, has recently been proposed for the treatment of climacteric symptoms [1].
• Prevention of postmenopausal bone loss using tibolone or conventional peroral or transdermal hormone replacement therapy with 17beta-estradiol and dydrogesterone [1].

Chemical compound and disease context of tibolone

• In conclusion, treatment with tibolone for 4 weeks prevented OVX-induced bone loss by suppressing both bone resorption and bone turnover in a similar way as EE2 [12].
• Tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic properties relieves climacteric symptoms and prevents postmenopausal bone loss [13].
• Hormonal environment in the induction of breast cancer in castrated rats using dimethylbenzanthracene: influence of the presence or absence of ovarian activity and of treatment with estradiol, tibolone, and raloxifene [14].
• The hormone replacement therapy drug tibolone acts very similar to medroxyprogesterone acetate in an estrogen-and progesterone-responsive endometrial cancer cell line [15].
• Use of leuprolide acetate plus tibolone in the treatment of severe premenstrual syndrome [16].

Biological context of tibolone

• To compare the efficacy of conventional oral and transdermal HRT with that of tibolone in the prevention of postmenopausal bone loss, 140 postmenopausal women (age, 52 +/- 0.6 years; median duration of menopause, 3 years) were enrolled in an open 2-year study [1].
• In a separate group of patients (four pairs + one post biopsy) on concurrent treatment with tibolone, there was no significant increase in the osteon density, cortical porosity, median canal diameter, or the markers of bone formation and resorption [17].
• The results revealed a steady and equal increase in bone mineral density in both tibolone groups at the bone sites studied [18].
• The apoptosis network was stimulated by the progestagenic properties of tibolone; in contrast, the estrogenic effect of tibolone suppressed the apoptosis network [19].
• The objective was to compare the effects of L-HT and tibolone on lipid profile, vasodilation, and factors associated with inflammation and haemostasis [20].

Anatomical context of tibolone

• Hence, tibolone may induce antivasoocclusive actions and protect women against coronary artery disease [21].
• In the present study an endometrial carcinoma cell line (Ishikawa PRAB-36) was used to investigate the progestogenic properties of tibolone and its metabolites [3].
• Tibolone activates nitric oxide synthesis in human endothelial cells [4].
• Because abnormal growth of smooth muscle cells (SMCs) is a prerequisite for coronary artery disease, here we investigated the effects of tibolone on SMC growth [21].
• The effect of tibolone on fat mass, fat-free mass, and total body water in postmenopausal women [22].

Associations of tibolone with other chemical compounds

• Upon measuring the expression of two progesterone-regulated genes (fibronectin and IGF-binding protein-3), tibolone, the Delta(4) isomer and medroxyprogesterone acetate showed similar gene expression regulation [3].
• Effect of tibolone on glucose and lipid metabolism in postmenopausal women [23].
• Samples obtained from postmenopausal women treated with different doses of cyclic or continuous hormone replacement therapy (HRT) with an estrogen analog (tibolone) or with a bisphosphonate (ibandronate) were measured in the Serum CrossLaps One Step ELISA at baseline and at various time points during therapy [24].
• Estrogen withdrawal increased (p < 0.01) and concomitant tibolone treatment decreased (p < 0.05) the overall mean bone density [25].
• Women with risk factors for osteoporosis or cardiovascular disease were allocated either to tibolone (n = 56) or raloxifene (n = 48) therapy [26].

Gene context of tibolone

• Furthermore, strong substrate inhibition was observed for the AKR1C2 catalyzed reduction of tibolone [27].
• RESULTS: E2, tibolone, 3alpha-hydroxytibolone, and 3beta-hydroxytibolone increased both VEGF 121 and 165 mRNA compared with the control [28].
• In primary hepatocytes (which express AKR1C1-AKR1C4), time-dependent reduction of tibolone into 3beta- and 3alpha-hydroxytibolone was observed again in a 4:1 ratio [29].
• In HepG2 cell cytosol and intact cells (which do not express AKR1C4), tibolone was exclusively reduced to 3beta-hydroxytibolone and was blocked by the AKR1C1-AKR1C3 inhibitor flufenamic acid [29].
• Liver pool (n=5) SULT activities measured with tibolone substrates reflected COS-1 expressed SULT2A1 and SULT1E1 activities [30].

Analytical, diagnostic and therapeutic context of tibolone

• The groups were tibolone [two doses were used, 0.05 mg/kg (LoTib) and 0.2 mg/kg (HiTib)], CEE (0.042 mg/kg), CEE (0.042 mg/kg) plus MPA (0.167 mg/kg given continuously), and a control group given no treatment for 2 yr [31].
• Significant differential effects of lower doses of hormone therapy or tibolone on markers of cardiovascular disease in post-menopausal women: a randomized, double-blind, crossover study [20].
• METHODS AND RESULTS: The OPAL study was a three-arm, randomized, placebo-controlled, double-blind study to determine the effect of tibolone (2.5 mg daily) and of CEE/MPA (0.625/2.5 mg daily) over 3 years on progression of carotid intima-media thickness (CIMT) in 866 healthy post-menopausal women [32].
• In conclusion, within 2 yr of treatment, tibolone increases bone mass in the spine and prevents bone loss in the forearm in late postmenopausal women determined by densitometry and several biochemical parameters of bone turnover [18].
• At baseline and after 3 months of tibolone administration (2.5 mg/day), glucose metabolism was evaluated in each subject using both an oral glucose tolerance test (75 g) and the minimal model method of a frequently sampled intravenous glucose tolerance test [23].

References