The effect of 17β-estradiol plus norethisterone acetate treatment on lipoprotein (a), atherogenic and anti-atherogenic apolipoproteins levels in postmenopausal women: A meta-analysis of randomized controlled trials

Background and aim: The administration of 178-estradiol plus norethisterone acetate seems to confer women cardioprotection, however, its impact on lipoprotein (a) and apolipoproteins' concentrations remains unclear. Thus, we conducted a meta-analysis of randomized controlled trials (RCTs) to investigate the effect of 178estradiol plus norethisterone acetate treatment on lipoprotein (a) and apolipoproteins' values in females. Methods: We systematically searched four databases (PubMed/MEDLINE, Scopus, Embase, and Web of Science) to identify relevant publications published until March 9th, 2022. No language restrictions were applied. The random-effects model (the DerSimonian and Laird methods) was employed to calculate the weighted mean difference (WMD).Results: The administration of 178-estradiol plus norethisterone acetate resulted in a significant decrease of lipoprotein (a) (WMD: -67.59 mg/L, 95 % CI: -106.39 to -28.80; P < 0.001) and apolipoprotein B concentrations (WMD: -3.71 mg/dL, 95 % CI: -6.68 to -0.75; P = 0.014), respectively. No effect of 178-estradiol plus norethisterone acetate on apolipoprotein AI (WMD: 0.23 mg/dL, 95 % CI: -3.99 to 4.46; P = 0.91) or AII (WMD: 0.21 mg/dL, 95 % CI: -2.24 to 2.68; P = 0.86) concentrations was detected. In the stratified analysis, there was a notable reduction in lipoprotein (a) levels in the RCTs with a duration of >= 6 months (WMD: -73.34 mg/L), in postmenopausal women with a BMI >= 25 kg/m2 (WMD: -69.85 mg/L) and in postmenopausal women aged <60 years (WMD: -61.93 mg/L). Conclusion: The present meta-analysis of RCTs demonstrates that 178-estradiol plus norethisterone acetate treatment reduces lipoprotein (a) and apolipoprotein B levels in postmenopausal women.