The effect of transdermal 17β-estradiol combined with norethisterone acetate treatment on the lipid profile in postmenopausal women: A meta-analysis and systematic review of randomized controlled trials

Abstract

Background and aim: The effect of transdermal 17β-estradiol and norethisterone acetate co-administration on the lipid profile in postmenopausal women remains controversial as randomized controlled trials (RCTs) conducted to investigate this research question have produced conflicting results. Consequently, to clarify this issue, we conducted a systematic review and meta-analysis of RCTs that evaluated the impact of transdermal 17β-estradiol combined with norethisterone acetate treatment on the concentrations of serum lipids in postmenopausal women. Methods: Relevant articles published before February 1st, 2022 were identified by searching the PubMed/Medline, Scopus, and Embase, and Web of Science electronic databases. A random-effects model, employing the method of DerSimonian and Laird, was used to evaluate effect sizes, and results were expressed as weighted mean difference (WMD) and 95% confidence intervals (CIs). Results: Pooled results from 7 RCTs with 9 intervention arms demonstrated that transdermal 17β-estradiol combined with norethisterone acetate administration significantly decreased total cholesterol (TC) (WMD: −13.43 mg/dL, 95% CI: −18.11 to −8.75, P < 0.001) and low-density lipoprotein cholesterol (LDL-C) (WMD: −13.90 mg/dL, 95% CI: −20.40 to −7.41, P < 0.001). In the subgroup analyses, a notable reduction in TC was observed in subjects with baseline TC concentrations ≥ 130 mg/dL (WMD −14.49 mg/dL), when treatment duration was ≤ 6 months (WMD: −17.21 mg/dL), and in participants with a body mass index (BMI) ≥ 25 kg/m2 (WMD: −21.71 mg/dL). Moreover, in the subgroup analyses, transdermal 17β-estradiol combined with norethisterone acetate decreased triglycerides (TG) levels when the treatment duration was ≤ 6 months (WMD: −21.37 mg/dL). However, the prescription of transdermal 17β-estradiol combined with norethisterone acetate in postmenopausal women did not change high-density lipoprotein cholesterol (HDL-C) values. Conclusions: Based on our findings, the co-administration of transdermal 17β-estradiol and norethisterone acetate in postmenopausal females can decrease TC and LDL-C levels, as well as TG values, but does not influence HDL-C concentrations.