title: The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double‐blind, placebo‐controlled trial Effect of tibolone on markers of cardiovascular disease risk in postmenopausal women undergoing hemodialysis: a pilot study. Serially increasing change in lipoprotein(a) concentration has predictive value in acute vascular events A randomised placebo controlled trial of the effects of tibolone on blood pressure and lipids in hypertensive women Tibolone: influence on markers of cardiovascular disease. Acute Reduction of Lipoprotein(a) by Tissue‐Type Plasminogen Activator Lipoprotein(a) as a cardiovascular risk factor: current status Lipoprotein(a) as a potential causal genetic risk factor of cardiovascular disease: a rationale for increased efforts to understand its pathophysiology and develop targeted therapies. Comparison of the effects of tibolone and estrogen therapy on hemostasis in surgical menopause: a randomized, double-blind, placebo-controlled study. A 2‐year Study of Lipid and Lipoprotein Changes in Postmenopausal Women With Tibolone and Estrogen‐Progestin Lipoprotein(a) concentrations, isoform size, and risk of type 2 diabetes: a Mendelian randomisation study. Lowering of HDL cholesterol in post-menopausal women by tibolone is not associated with changes in cholesterol efflux capacity or paraoxonase activity. Observational Study on the Efficacy of Tibolone in Counteracting Early Carotid Atherosclerotic Lesions in Postmenopausal Women The effects of tibolone in older postmenopausal women. Inverse association between serum lipoprotein(a) and cerebral hemorrhage in the Japanese population. The influence of 5-year therapy with tibolone on the lipid profile in postmenopausal women with mild hypercholesterolemia Lipid lowering in healthy volunteers treated with multiple doses of MGL-3196, a liver-targeted thyroid hormone receptor-β agonist. Tibolone lowers high density lipoprotein cholesterol by increasing hepatic lipase activity but does not impair cholesterol efflux Effects of either Tibolone or Continuous Combined Transdermal Estradiol with Medroxyprogesterone Acetate on Coagulatory Factors and Lipoprotein(a) in Menopause Testosterone decreases lipoprotein(a) in men.
abstract: Objective To assess the effects of tibolone on climacteric symptoms , endometrium and serum lipid/lipoproteins in postmenopausal women receiving tamoxifen after surgery for breast cancer OBJECTIVE To assess the effect of tibolone on markers of vascular risk in postmenopausal women who were receiving hemodialysis . DESIGN One-year open-label study . SETTING " Zvezdara " University Medical Center , Bel grade , Serbia . PATIENT(S ) Twenty-eight postmenopausal women undergoing chronic hemodialysis . INTERVENTION(S ) Fifteen women received tibolone 2.5 mg three times per week ; 13 other women served as controls . MAIN OUTCOME MEASURE(S ) Mean arterial pressure and weight were measured at baseline and at 6 and 12 months , and blood was collected for insulin , total cholesterol , low-density lipoprotein , high-density lipoprotein , triglycerides , lipoprotein(a ) , high-sensitivity C-reactive protein ( hs-CRP ) , endothelin-1 ( ET-1 ) , vascular endothelial growth factor ( VEGF ) , and markers of renal function . RESULT ( S ) Mean arterial pressure fell in the tibolone but not in the control group at 6 and 12 months versus baseline ( mean [ SD ] : 93 [ 15 ] vs. 105 [ 11 ] mmHg and 94 [ 10 ] vs. 105 [ 11 ] mmHg , respectively ) . Weight , insulin , lipids , lipoprotein(a ) , hs-CRP , ET-1 , VEGF , and renal function remained unchanged within each group , but high-density lipoprotein concentrations fell in the tibolone group after 12 months ( 1.2 [ 0.3 ] vs. 1.6 [ 0.6 ] mmol/L ) . CONCLUSION ( S ) The effects of tibolone on markers of vascular risk in postmenopausal women who are receiving hemodialysis and healthy women appear to differ . This should be taken into account when tailoring menopausal therapies to the specific requirements of each individual Background : Lipoprotein(a ) ( Lp(a ) ) has been regarded in some studies as an independent risk factor of atherosclerotic vascular disease . However , the use of a baseline plasma Lp(a ) concentration as a screening tool for future acute vascular events ( AVE ) is controversial . We therefore investigated whether progressively increasing change in plasma Lp(a ) concentration is associated with the development of AVE . Methods : We investigated prospect i ve analyses of 985 participants ( 464 women and 521 men ) who had either clinical ly evident vascular disease ( VD group , n=443 ) or its risk factor(s ) ( RF group , n=542 ) .  Blood sample s were taken from all participants every six months to measure inflammatory markers such as Lp(a ) and C-reactive protein during a 10-year follow-up period . Results : During the follow-up , 223 new cases of myocardial infa rct ion , stroke , and peripheral arterial disease were identified . In the RF group , the relative risk of positive ∆ Lp(a ) for predicting AVE was 4.36 ( 95 % confidence interval [ CI ] 1.76 - 10.85 ; P=0.002 ) . In the VD group , the relative risk of positive ∆ Lp(a ) for predicting AVE was 6.35 ( 95 % CI 3.68 - 10.97 ; P<0.001 ) . Conclusions : These results suggest that a progressively increasing change in Lp(a ) concentration has a highly significant predictive value in AVE in both the VD and the RF groups The effects of hormone replacement therapy in hypertensive women are controversial . This r and omised placebo controlled trial assessed the effect of tibolone 2.5 mg on blood pressure and fasting plasma lipids in 29 hypertensive postmenopausal women over 6 months using a 2:1 r and omisation to tibolone . The primary clinical end-point was mean office blood pressure . At 6 months systolic blood pressure declined by 5.30 ± 2.87 % vs4.94 ± 3.37 % whilst diastolic blood pressure declined 5.38 ± 2.65 % vs 0.85 ± 3.69 % on tibolone and placebo respectively . These differences were not statistically significant . Triglycerides decreased by 33.3 ± 6.1 % vs 7.6 ± 7.9 % ( P < 0.01 ) and high-density lipoprotein (hdl)-cholesterol by 21.7 ± 3.8 % vs2.4 ± 2.6 % ( P < 0.01 ) with tibolone as opposed to placebo . no significant differences were observed in total cholesterol , low-density lipoprotein (ldl)-cholesterol and lipoprotein ( a ) . fibrinogen levels were reduced by 13.6 ± 6.8 % on tibolone compared to a 19.3 ± 15.4 % rise ( P < 0.05 ) on placebo . this study suggests that tibolone has no deleterious effect on blood pressure in women with hypertension but has contrasting effects on biochemical risk factors . large-scale studies are required to determine the overall effect of tibolone on cardiovascular morbidity and mortality Tibolone , a synthetic steroid with estrogenic , and rogenic , and progestogenic properties relieves climacteric symptoms and prevents postmenopausal bone loss . The influence of tibolone treatment on coagulation , fibrinolysis , and lipid metabolism was investigated in 91 healthy late postmenopausal women . They were r and omly assigned in a double-blind , placebo-controlled 2-year study to receive either tibolone 1.25 mg ( n = 36 , 29 completed ) or 2.5 mg ( n = 35 , 28 completed ) or placebo ( n = 20 , 13 completed ) . The biochemical markers of lipid metabolism , fibrinolysis , and coagulation were measured every 3 months . In both tibolone groups a similar ( approximately 30 % ) decrease in high density lipoprotein cholesterol and a corresponding lowering of apolipoprotein A-1 ( P < 0.001 ) was detected . Also serum total cholesterol and triglycerides were reduced ( approximately 15 % ; P < 0.01 ) , whereas low density lipoprotein cholesterol , apolipoprotein B , and lipoprotein(a ) were unaffected by tibolone . The two dose levels of tibolone result ed in a similar , marked lowering ( approximately 30 % ) of tissue plasminogen activator and plasminogen activator inhibitor activity as compared with placebo ( P < 0.001 ) . Plasminogen increased ( approximately 15 % ; P < 0.001 ) in both groups . Fibrinogen was lowered ( P < 0.01 ) in the low-dose group , and antithrombin III remained unchanged . The overall effect on hemostatic factors of the present doses of tibolone in healthy , late postmenopausal women tends towards increased fibrinolysis and unchanged coagulation . This may be beneficial and might theoretically counterbalance the potentially negative effect of the decrease in high density lipoprotein cholesterol Background Lipoprotein(a ) [ Lp(a ) ] is a low density lipoprotein-like particle whose apolipoprotein B ( apo B ) moiety is disulfide-linked to apo(a ) , a plasminogen-like inhibitor of fibrinolysis in vitro . We hypothesized that plasma concentrations of Lp(a ) are acutely affected by intravenous tissue-type plasminogen activator ( t-PA ) . Methods and Results Patients with unstable angina were r and omized to receive either intravenous t-PA ( n = 15 ) or placebo ( n = 11 ) . Two-way ANOVA using repeated measures revealed a significant effect of t-PA on concentrations of Lp(a ) ( p=0.026 ) . There was a 48 % fall in Lp(a ) from baseline concentrations in the t-PA group at 12 hours ( p=0.031 ) but not at 72 hours . Lp(a ) in the placebo group was unchanged . Conclusions We conclude that t-PA produces a sharp and substantial but reversible reduction in plasma Lp(a ) . These data suggest that Lp(a ) concentration is not as static in vivo as had been believed and might be acutely modifiable through some mechanism that induces its removal from the freely circulating state Aims The aims of the study were , first , to critically evaluate lipoprotein(a ) [ Lp(a ) ] as a cardiovascular risk factor and , second , to advise on screening for elevated plasma Lp(a ) , on desirable levels , and on therapeutic strategies . Methods and results The robust and specific association between elevated Lp(a ) levels and increased cardiovascular disease (CVD)/coronary heart disease ( CHD ) risk , together with recent genetic findings , indicates that elevated Lp(a ) , like elevated LDL-cholesterol , is causally related to premature CVD/CHD . The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels . Mechanistically , elevated Lp(a ) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a ) resembles both plasminogen and plasmin but has no fibrinolytic activity , or may accelerate atherosclerosis because , like LDL , the Lp(a ) particle is cholesterol-rich , or both . We advise that Lp(a ) be measured once , using an isoform-insensitive assay , in subjects at intermediate or high CVD/CHD risk with premature CVD , familial hypercholesterolaemia , a family history of premature CVD and /or elevated Lp(a ) , recurrent CVD despite statin treatment , ≥3 % 10-year risk of fatal CVD according to European guidelines , and /or ≥10 % 10-year risk of fatal + non-fatal CHD according to US guidelines . As a secondary priority after LDL-cholesterol reduction , we recommend a desirable level for Lp(a ) < 80th percentile ( less than ∼50 mg/dL ) . Treatment should primarily be niacin 1–3 g/day , as a meta- analysis of r and omized , controlled intervention trials demonstrates reduced CVD  by niacin treatment . In extreme cases , LDL-apheresis is efficacious in removing Lp(a ) . Conclusion We recommend screening for elevated Lp(a ) in those at intermediate or high CVD/CHD risk , a desirable level < 50 mg/dL as a function of global cardiovascular risk , and use of niacin for Lp(a ) and CVD/CHD risk reduction Recent published studies have provided increasing evidence that lipoprotein(a ) [ Lp(a ) ] may be a potential causal , genetic , independent risk factor for cardiovascular disease ( CVD ) . Lp(a ) levels > 25 mg/dl are present in ∼30 % of Caucasians and 60 % to 70 % of Blacks . Lp(a ) is composed of apolipoprotein B-100 and apolipoprotein ( a ) [ ( apo(a ) ] . Circulating Lp(a ) levels are primarily influenced by the LPA gene without significant dietary or environmental effects , mediating CVD risk throughout the patient 's lifetime . Recent clinical outcomes studies , meta-analyses , and Mendelian r and omization studies , in which r and omization of Lp(a ) levels is achieved through the r and om assortment of LPA gene variants thereby removing confounders , have shown that genetically determined Lp(a ) levels are continuously and linearly related to risk of CVD . Currently , Lp(a ) pathophysiology is not fully understood , and specifically targeted therapies to lower Lp(a ) are not available . We provide a rationale for increased basic and clinical investigational efforts to further underst and Lp(a ) pathophysiology and assess whether reducing Lp(a ) levels minimizes CVD risk . First , a detailed underst and ing of Lp(a ) synthesis and clearance has not been realized . Second , several mechanisms of atherogenicity are known to varying extent , but the relative contributions of each are not known . Lp(a ) may be atherothrombotic through its low-density lipoprotein moiety , but also through apo(a ) , including its ability to be retained in the vessel wall and mediate pro-inflammatory and proapoptotic effects including those potentiated by its content of oxidized phospholipids , and antifibrinolytic effects . Finally , development of specific Lp(a)-lowering agents to potently lower Lp(a ) will allow testing of mechanistic hypotheses in animal models and the design of r and omized clinical trials to assess reduction in CVD . A convergence of academic , scientific , pharmaceutical , and National Institutes of Health priorities and efforts can make this a reality in the next decade OBJECTIVE To examine the effects of unopposed estrogen ( E ) and tibolone therapy on coagulation and natural anticoagulant systems in surgical menopause . DESIGN A r and omized , double-blind , placebo-controlled study . SETTING University hospital clinic in Turkey . PATIENT(S ) Ninety healthy surgically postmenopausal women . INTERVENTION(S ) Ninety surgically postmenopausal women were r and omized into three groups : unopposed conjugated ET ( 0.625 mg/d , group 1 ) , tibolone ( 2.5 mg/d , group 2 ) , and identical tablets of placebo ( group 3 ) . MAIN OUTCOME MEASURE(S ) Effects on parameters in the clotting cascade at baseline and after 24 weeks of treatment . RESULT ( S ) After 6 months , fibrinogen , lipoprotein ( a ) , and factor VIIa were decreased , and activated partial thromboplastin time was increased significantly in the ET group compared with in the placebo group . However , tibolone significantly decreased only the serum levels of factor VIIa and factor IX and prolonged the activated partial thromboplastin time , compared with placebo group . In addition , conjugated ET caused a significantly greater decrease in serum fibrinogen level than did tibolone . CONCLUSION ( S ) Neither E nor tibolone therapy led to activation of coagulation in the surgically menopausal women . Both preparations changed the overall hemostatic balance to a more fibrinolytic state Objective To assess changes in lipid-lipoprotein profile in postmenopausal women taking tibolone and estrogenprogestin  , compared with untreated controls . Methods Sixty-three women were r and omized to take a combined estrogen-progestin preparation ( n = 31 ) or tibolone ( n = 32 ) , and 50 other women acted as controls . Fasting lipid-lipoprotein levels were measured over 96 weeks . Results The controls , who were older and postmenopausal longer than the therapy subjects , exhibited significant decreases in total ( P < .05 ) and low-density lipoprotein ( LDL ) ( P < .001 ) cholesterol and increases in triglyceride ( P < .05 ) and lipoprotein ( a ) ( P < .001 ) over the 96-week period of study . Lipoprotein ( a ) also decreased significantly in both treated groups ( P < .001 ) . Total and LDL cholesterol decreased and triglyceride increased in the estrogenprogestin group , but , compared with controls , these changes were not significant . Total cholesterol decreased in the tibolone group , although decreases in low- and particularly high-density lipoprotein ( HDL ) ( P < .001 ) cholesterol and parallel decreases in apolipoprotein A1 ( P < .001 ) and B ( P < .01 ) were also observed . There was evidence of a reversion phenomenon in apolipoproteins A1 and B in all groups , and in lipoprotein ( a ) with tibolone . Conclusion Some changes accompanying tibolone may be favorable and may counter its adverse effect on HDL cholesterol . Lowering of lipoprotein ( a ) was the only significant change found with estrogen-progestin BACKGROUND Low concentrations of lipoprotein(a )  in plasma are associated with increased risk of type 2 diabetes , but whether this association is causal is unclear . Variations in the LPA gene affect lipoprotein(a ) isoform size and concentrations in plasma . We therefore did a Mendelian r and omisation study to investigate whether large isoform size , low concentrations in plasma , or both , are causally associated with type 2 diabetes . METHODS We assessed data for adults from the Danish general population enrolled in the Copenhagen City Heart Study and the Copenhagen General Population Study , with and without type 2 diabetes . Eligible participants had data for  lipoprotein(a ) concentrations in plasma , LPA kringle IV type 2 ( KIV-2 ) sums of repeats ( affecting both isoform size and plasma concentrations ) , and carrier status for the LPA single-nucleotide polymorphism rs10455872 ( mainly affecting concentrations in plasma ) . FINDINGS 77,901 individuals had lipoprotein(a ) data , of whom 28,567 ( 36·7 % ) had all three measurements .  Low concentrations of lipoprotein(a ) in plasma were associated with risk of type 2 diabetes , with adjusted odds ratios of 1·26 ( 1·09 - 1·45 ) , 1·17 ( 1·01 - 1·36 ) , 1·04 ( 0·90 - 1·21 ) , and 1·05 ( 95 % CI 0·90 - 1·22 ) , respectively , for quintiles 1 - 4 , compared with quintile 5 concentrations . High KIV-2 sums of repeats were associated with risk of type 2 diabetes ( adjusted odds ratio 1·16 , 95 % CI 1·05 - 1·28 ) for KIV-2 quintile 5 versus quintiles 1 - 4 combined . Being a carrier of rs10455872 did not affect risk of type 2 diabetes . For a halving of lipoprotein(a ) concentrations , the instrumental variable estimate of the causal odds ratio for type 2 diabetes was 1·15 ( 95 % CI 1·05 - 1·27 ) for KIV-2 sum of repeats and 0·99 ( 0·95 - 1·03 ) for rs10455872 genotype . INTERPRETATION Low lipoprotein(a ) concentrations alone seem not to be causally associated with type 2 diabetes , but a causal association for large lipoprotein(a ) isoform size can not be excluded . FUNDING Danish Heart Foundation , Danish Council for Independent Research -Medical Sciences , IMK Almene Fund , and Johan and Lise Boserup 's Fund Low HDL cholesterol increases the risk of coronary heart disease . Treatment of postmenopausal women with tibolone  lowers  HDL cholesterol . We eluci date d the consequences of this unwanted side effect in a r and omized , double-blind study , where 12 women received 2.5 mg tibolone per day and 6 women , placebo .  Blood sample s were collected on days -1 ( i.e. baseline ) , 28 , 56 , and 84 for the analysis of various parameters of lipid metabolism and HDL function . Compared to placebo , treatment with tibolone led to statistically significant decreases of HDL cholesterol ( -22 % to -32 % ) , apoA-I ( -14 % to -22 % ) , and HDL subclass LpA-I ( -30 % to -40 % ) but to no significant changes in apoA-II and HDL subclass LpA-I , A-II . These changes were not associated with statistically significant changes in the activity of plasma to release 3H-cholesterol from radiolabeled fibroblasts or in the serum activity of the anti-oxidative enzyme paraoxonase/arylesterase . There were no significant changes in either serum levels of triglycerides , LDL cholesterol , apoB , and leptin , or in LDL size . We conclude that changes in insulin do not contribute to the lowering of HDL cholesterol by tibolone . Despite decreased HDL cholesterol , putatively anti-atherogenic activities of HDL remained unchanged Objective : To study whether tibolone affects lipid profile and diffused intima media thickness ( IMT ) of the common carotid arteries ( CCA ) in postmenopausal women ( PMW ) . Methods : Twenty-two PMW and 20 premenopausal women participated in the study . The PMW were r and omly divided into 11 women who did not receive any treatment and 11 women who received tibolone ( 2.5 mg once a day ) . Results : After 6 months the treated women had lipoprotein(a ) ( Lpa ) , total-cholesterol ( total-C ) , and LDL-cholesterol ( LDL-C ) levels lower than before , while in the non-treated women Lpa was increased . The IMT of CCA was unmodified in the treated women , whereas it increased in non-treated women . Conclusions : This preliminary study suggests that a 6-month tibolone treatment could counteract the increase of the IMT of CCA observed in untreated PMW BACKGROUND Tibolone has estrogenic , progestogenic , and and rogenic effects . Although tibolone prevents bone loss , its effects on fractures , breast cancer , and cardiovascular disease are uncertain . METHODS In this r and omized study , we assigned 4538 women , who were between the ages of 60 and 85 years and had a bone mineral density T score of -2.5 or less at the hip or spine or a T score of -2.0 or less and radiologic evidence of a vertebral fracture , to receive once-daily tibolone ( at a dose of 1.25 mg ) or placebo . Annual spine radiographs were used to assess for vertebral fracture . Rates of cardiovascular events and breast cancer were adjudicated by expert panels . RESULTS During a median of 34 months of treatment , the tibolone group , as compared with the placebo group , had a decreased risk of vertebral fracture , with 70 cases versus 126 cases per 1000 person-years ( relative hazard , 0.55 ; 95 % confidence interval [ CI ] , 0.41 to 0.74 ; P<0.001 ) , and a decreased risk of nonvertebral fracture , with 122 cases versus 166 cases per 1000 person-years ( relative hazard , 0.74 ; 95 % CI , 0.58 to 0.93 ; P=0.01 ) . The tibolone group also had a decreased risk of invasive breast cancer ( relative hazard , 0.32 ; 95 % CI , 0.13 to 0.80 ; P=0.02 ) and colon cancer ( relative hazard , 0.31 ; 95 % CI , 0.10 to 0.96 ; P=0.04 ) . However , the tibolone group had an increased risk of stroke ( relative hazard , 2.19 ; 95 % CI , 1.14 to 4.23 ; P=0.02 ) , for which the study was stopped in February 2006 at the recommendation of the data and safety monitoring board . There were no significant differences in the risk of either coronary heart disease or venous thromboembolism between the two groups . CONCLUSIONS Tibolone reduced the risk of fracture and breast cancer and possibly colon cancer but increased the risk of stroke in older women with osteoporosis . ( Clinical Trials.gov number , NCT00519857 . INTRODUCTION Although lipoprotein(a ) ( Lp(a ) ) is involved in cardiometabolic disease processes , the association between serum Lp(a ) and stroke and /or its subtypes has not yet been eluci date d among Japanese people . This study investigated the association between Lp(a ) and the incidence of stroke and /or its subtypes in the general Japanese population . MATERIAL S AND METHODS This population -based prospect i ve cohort study included 10,494 community-dwelling participants ( 4,030 males/6,464 females ) . The incidence of stroke and its subtypes was the primary outcome . The subjects were divided into tertiles based on their Lp(a ) levels , and the risk of all stroke and stroke subtypes was examined using Cox 's proportional hazard model . RESULTS A total of 393 subjects ( 199 males and 194 females ) with stroke were identified during a follow-up duration of 10.7years . The multivariate-adjusted hazard ratios for all stroke events were 0.55 ( 95 % confidence interval : 0.38 - 0.81 ) and 0.69 ( 0.49 - 0.99 ) in the 2nd ( 9 - 19mg/dl ) and 3rd tertiles ( ≥20mg/dl ) of Lp(a ) in reference to the 1st tertile ( < 9mg/dl ) in males , and 0.85 ( 0.59 - 1.24 ) and 0.76 ( 0.52 - 1.11 ) in 2nd ( 10 - 22mg/dl ) and 3rd tertiles ( ≥23mg/dl ) of Lp(a ) in reference to the 1st tertile ( < 10mg/dl ) in females . The multivariate-adjusted hazard ratios for cerebral hemorrhage were 0.26 ( 0.10 - 0.67 ) and 0.34 ( 0.15 - 0.76 ) in the 2nd and 3rd tertiles of Lp(a ) in reference to the 1st tertile in males , and were 0.48 ( 0.23 - 1.04 ) and 0.44 ( 0.21 - 0.96 ) in the 2nd and 3rd tertiles of Lp(a ) in females . CONCLUSIONS Lp(a ) was associated with the incidence of cerebral hemorrhage in the general Japanese population , particularly among males , while a similar trend was seen among females . A low Lp(a ) level may be a marker of the risk of cerebral hemorrhage in this population Our objective was to investigate the effects of 5-year therapy with tibolone on the lipid profile in postmenopausal women with mild hypercholesterolemia ( total cholesterol , 241 ± 7 mg/dl ; LDL cholesterol , 153 ± 9 mg/dl ) . Eighty-two patients were divided into two groups . Group A ( 53 women ) received 2.5 mg of tibolone per day . Group B ( 29 women ) received no tibolone . Total , low- and high-density lipoprotein cholesterol and lipoprotein(a ) were found to be decreased in the tibolone group , by 17.7 % , 32 % , 15.5 % and 12 % , respectively ( p < 0.01 ) throughout the 5-year treatment , while triglycerides showed no significant change . The lipid profile in the control group remained at its initial values . Menopausal symptoms disappeared in the treatment group within the first 5 months , whereas they deteriorated in the control group during the first 2 years . Although a few unwanted side-effects on hormonedependent tissues were observed ( including vaginal spotting in 11.3 % and febrile hemorrhagic cystic mastopathy in 3.8 % ) long-term therapy with tibolone seemed to be well tolerated , and appeared to have a beneficial effect on the levels of serum lipids MGL-3196 is an oral , liver-targeted selective agonist for the thyroid hormone receptor-β ( THR-β ) that is being developed for the treatment of dyslipidemia . The safety profile and tolerability of THR-β agonist MGL-3196 was assessed in first-in humans studies , including a single ascending dose study ( NCT01367873 ) in which MGL-3196 appeared safe at all doses tested . A two-week multiple dose study was conducted at doses of 5 , 20 , 50 , 80 , 100 , and 200 mg per day in healthy subjects with mildly elevated low density lipoprotein ( LDL ) cholesterol ( > 110 mg/dL ) ( NCT01519531 ) . MGL-3196 was well-tolerated at all doses with no dose-related adverse events or liver enzyme , ECG or vital-sign changes . At the highest dose , there was a reversible reduction of ∼20 % in the level of pro-hormone , free thyroxine ( free T4 ) that was significantly different from placebo ( p < 0.0001 ) that may be explained by increased hepatic metabolism of T4 . There was no change in thyrotropin ( TSH ) or triiodothyronine ( free T3 ) or other evidence of central thyroid axis dysfunction at any dose . Doses ranging from 50 to 200 mg demonstrated highly statistically significant reductions relative to placebo of up to : 30 % for LDL cholesterol ( range , p = 0.05-<0.0001 ) ; 28 % for non- high density lipoprotein ( HDL ) cholesterol ( range , p = 0.027 - 0.0001 ) ; 24 % for Apolipoprotein B ( range , p = 0.008 - 0.0004 ) , and statistical trends of up to 60 % reduction in triglycerides ( TG ) ( range , p = 0.13 - 0.016 ) . The near maximal lipid effects were observed at a dose of 80 mg daily . In summary , in a two-week study in healthy volunteers with mild LDL cholesterol elevation , MGL-3196 appeared safe , was well-tolerated and showed a beneficial effect on lipid parameters objective And rogens and other drugs that reduce plasma concentrations of high density lipoprotein ( HDL ) cholesterol are often considered to be pro‐atherogenic . Tibolone lowers HDL‐cholesterol by 20 % but the clinical significance of this effect is unknown Background / Aim : The aim of this prospect i ve controlled study was to compare the effects of two therapies for menopause on factor VII ( FVII ) and hemostatic variables . Methods : Postmenopausal women were assigned to receive one of the following treatments : transdermal estradiol ( TTS E2 ; 50 μg ) combined in a continuous sequential regimen with oral medroxyprogesterone acetate ( MPA ; 10 mg/day for 12 days ) ( group A ; n = 20 ) , tibolone ( 2.5 mg/day ) ( group B ; n = 21 )  or placebo  ( group C ; n = 19 ) . Sixty women completed the 1-year treatment and underwent follow-up examinations after 3 , 6 and 12 months . Results : TTS E2/MPA induced various changes in procoagulatory factors . At 12 months , fibrinogen , activated FVII ( FVIIa ) and coagulative FVII ( FVIIc ) had increased by 10.7 , 12.9 and 3.7 % , respectively . Among the fibrinolytic factors , plasminogen and α2-antiplasmin increased by 11.3 and 7.2 % , respectively . Lipoprotein(a ) [ Lp(a ) ] and antithrombin III ( ATIII ) did not show any significant variation . Tibolone induced some changes toward a more homogeneous antithrombotic profile . Fibrinogen , FVIIa and FVIIc decreased significantly by 7.5 , 8.1 and 21.3 % , respectively . Plasminogen increased ( by 11.8 % ) and Lp(a ) decreased ( by 28.4 % ) . ATIII was unchanged with tibolone therapy . Conclusion : Our results show that tibolone induces a significant reduction in FVIIc and Lp(a ) and a greater enhancement of factors promoting fibrinolysis than the TTS E2/MPA regimen We administered testosterone , with or without the aromatase inhibitor testolactone , to determine the effects of testosterone and its aromatization to estradiol on Lp(a ) levels in normal men .  Average Lp ( a ) values decreased by 37 % during testosterone alone and by 28 % when testosterone and testolactone were combined , suggesting that testosterone reduces Lp(a ) in men primarily by an and rogenic effect and not by its conversion to estradiol
target: This meta- analysis shows that oral tibolone treatment significantly lowers circulating Lp(a ) levels in postmenopausal women .
background: INTRODUCTION 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 .