Tibolone decreases Lipoprotein(a) levels in postmenopausal women: A systematic review and meta-analysis of 12 studies with 1009 patients

•Circulating Lp(a) is a recognized risk factor for cardiovascular disease (CVD).•Tibolone may lower Lp(a), however, evidence of this effect remains to be confirmed.•Meta-analysis suggests a significant Lp(a) reduction following tibolone (by 25.28%).•Further studies are warranted to explore the mechanism of this effect.•A place of tibolone in individuals at CVD risk needs to be further investigated.

IntroductionCirculating 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.MethodsThe 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.ResultsMeta-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).ConclusionsThis 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.