The effect of 17β-estradiol plus norethisterone acetate treatment on the lipid profile in women: a dose-response meta-analysis of randomized controlled trials

Abstract

Background and aim: The impact of 17β-estradiol plus norethisterone acetate administration on serum lipids in women is controversial as previously published studies have produced conflicting results. Thus, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the effects of 17β-estradiol plus norethisterone acetate therapy on total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in females. Methods: We searched the PubMed/MEDLINE, Scopus, Embase, and Web of Science databases for relevant trials published in English until 15 July 2021. The weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated using a random-effects model (the DerSimonian and Laird methods). Results: A total of 32 RCTs were included in the final analysis. Treatment with 17β-estradiol plus norethisterone acetate significantly decreased LDL-C (WMD: −13.49 mg/dL, 95% CI: −16.46 to −10.52; P < 0.001), HDL-C (WMD: −3.57 mg/dL, 95% CI: −5.56 to −1.58; P < 0.001), TC (WMD: −19.33 mg/dL, 95% CI: −24.14 to −14.52; P < 0.001), and TG (WMD: −10.86 mg/dL, 95% CI: −16.06 to −5.13; P < 0.001) levels in females. The non-linear dose-response meta-analysis revealed a negative correlation between HDL-C levels and increased treatment periods (P ˂ 0.001). Conclusion: Evidence to date suggests that the administration of 17β-estradiol plus norethisterone acetate in females reduces LDL-C, HDL-C, TC, and TG concentrations. Future investigations should clarify whether the reduction in HDL-C following the administration of 17β-estradiol plus norethisterone acetate is clinically significant and poses any risks to the subjects who receive this treatment.