Kazuhiko Kotani1, Amirhossein Sahebkar2, Corina Serban3, Florina Andrica4, Peter P Toth5, Steven R Jones6, Karam Kostner7, Michael J Blaha6, Seth Martin6, Jacek Rysz8, Stephen Glasser9, Kausik K Ray10, Gerald F Watts11, Dimitri P Mikhailidis12, Maciej Banach13. 1. Department of Clinical Laboratory Medicine, Jichi Medical University, Shimotsuke City, Tochigi, Japan. 2. 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. 3. Department of Functional Sciences, Discipline of Pathophysiology, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania. 4. Faculty of Pharmacy, Discipline of Pharmaceutical Chemistry "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania. 5. Preventive Cardiology, CGH Medical Center, Sterling, IL, USA; The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA. 6. The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA. 7. Mater Hospital, University of Queensland, St Lucia, QLD, Australia. 8. Chair of Nephrology and Hypertension, Medical University of Lodz, Poland. 9. Department of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. 10. Department of Primary Care and Public Health, Imperial College London, London, UK. 11. Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia. 12. Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London, UK. 13. Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland. Electronic address: maciejbanach@aol.co.uk.
Abstract
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. 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.
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. 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.
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