The effect of hormone replacement therapy and tibolone on lipoprotein (a) concentrations in postmenopausal women: A systematic review and meta-analysis

Objective: Data on the effect of hormone replacement therapy (HRT) and tibolone on lipoprotein (a) [Lp(a)], an independent risk factor for cardiovascular disease, are heterogeneous and conflicting. Studies of the effect of HRT and tibolone on Lp(a) concentrations in post-menopausal women are reviewed in this meta-analysis. Design and methods: MEDLINE, Scopus, EMBASE and Cochrane databases were searched (up to February 10, 2017). Two researchers identified randomized controlled studies and extracted data. Potential controversies were resolved by a third reviewer. Results: In 24 eligible studies, HRT caused a significant reduction in Lp(a) concentrations compared with placebo or no treatment [mean relative difference: −20.35%, 95% Confidence Interval (CI): −25.33% to −15.37%, p < 0.0001], with significant heterogeneity between studies (I2 = 98.5%), but without evidence of publication bias. No significant effect was found for tibolone (n = 7) (mean relative difference: −23.84%, 95% CI: −63.43% to 15.74%, p = 0.238) (I2 = 98.7%, but without publication bias). Oral estrogen caused a greater reduction in Lp(a) concentrations than transdermal estrogen (n = 10) (mean relative difference: 37.66%, 95% CI: 16.84% to 58.48%, p < 0.0001), with significant heterogeneity between studies (I2 = 99%), but no evidence of publication bias. No difference was observed when continuous was compared with cyclical HRT, conventional with low-dose estrogen, and estrogen monotherapy with estrogen combined with progestogen. No difference was observed between HRT and tibolone regarding their effect on Lp(a). Conclusions: HRT significantly decreases Lp(a) concentrations, with oral being more effective than transdermal estradiol. The type of HRT, dose of estrogen and addition of progestogen do not seem to modify the Lp(a)-lowering effect of HRT