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

The administration of 17β-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 17β-estradiol plus norethisterone acetate treatment on lipoprotein (a) and apolipoproteins' values in females. 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). The administration of 17β-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 17β-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). The present meta-analysis of RCTs demonstrates that 17β-estradiol plus norethisterone acetate treatment reduces lipoprotein (a) and apolipoprotein B levels in postmenopausal women.