title: Tibolone decreases Lipoprotein(a) levels in postmenopausal women: A systematic review and meta-analysis of 12 studies with 1009 patients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Laboratory Medicine, Jichi Medical University, Shimotsuke City, Tochigi, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kotani
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
authors.affiliation: Department of Functional Sciences, Discipline of Pathophysiology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania.
authors.forename: Corina
authors.initials: C
authors.lastname: Serban
authors.affiliation: Faculty of Pharmacy, Discipline of Pharmaceutical Chemistry "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania.
authors.forename: Florina
authors.initials: F
authors.lastname: Andrica
authors.affiliation: Preventive Cardiology, CGH Medical Center, Sterling, IL, USA; The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Toth
authors.affiliation: The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Jones
authors.affiliation: Mater Hospital, University of Queensland, St Lucia, QLD, Australia.
authors.forename: Karam
authors.initials: K
authors.lastname: Kostner
authors.affiliation: The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Blaha
authors.affiliation: The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA.
authors.forename: Seth
authors.initials: S
authors.lastname: Martin
authors.affiliation: Chair of Nephrology and Hypertension, Medical University of Lodz, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Rysz
authors.affiliation: Department of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Glasser
authors.affiliation: Department of Primary Care and Public Health, Imperial College London, London, UK.
authors.forename: Kausik K
authors.initials: KK
authors.lastname: Ray
authors.affiliation: Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.affiliation: Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK.
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis
authors.affiliation: Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland. Electronic address: maciejbanach@aol.co.uk.
authors.forename: Maciej
authors.initials: M
authors.lastname: Banach
mesh_terms: D000368:Aged; D018849:Controlled Clinical Trials as Topic; D005260:Female; D006801:Humans; D016013:Likelihood Functions; D017270:Lipoprotein(a) / Q000037:antagonists & inhibitors / Q000097:blood*; D008875:Middle Aged; D009652:Norpregnenes / Q000627:therapeutic use*; D017698:Postmenopause / Q000097:blood*; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D017270:Lipoprotein(a); D009652:Norpregnenes; C027385:tibolone
keywords: Cardiovascular disease; Cardiovascular risk; Lipoprotein(a); Tibolone