The Effects of Menopause Hormone Therapy on Lipid Profile in Postmenopausal Women: A Systematic Review and Meta-Analysis

Abstract

Importance: The incidence of dyslipidemia increases after menopause. Menopause hormone therapy (MHT) is recommended for menopause related disease. However, it is benefit for lipid profiles is inconclusive. Objective: To conduct a systematic review and meta-analysis of randomized controlled trials to evaluate the effects of MHT on lipid profile in postmenopausal women. Evidence Review: Related articles were searched on PubMed/Medline, EMBASE, Web of Science, and Cochrane Library databases from inception to December 2020. Data extraction and quality evaluation were performed independently by two reviewers. The methodological quality was assessed using the "Cochrane Risk of Bias checklist". Results: Seventy-three eligible studies were selected. The results showed that MHT significantly decreased the levels of TC (WMD: -0.43, 95% CI: -0.53 to -0.33), LDL-C (WMD: -0.47, 95% CI: -0.55 to -0.40) and LP (a) (WMD: -49.46, 95% CI: -64.27 to -34.64) compared with placebo or no treatment. Oral MHT led to a significantly higher TG compared with transdermal MHT (WMD: 0.12, 95% CI: 0.04-0.21). The benefits of low dose MHT on TG was also concluded when comparing with conventional-dose estrogen (WMD: -0.18, 95% CI: -0.32 to -0.03). The results also showed that conventional MHT significantly decreased LDL-C (WMD: -0.35, 95% CI: -0.50 to -0.19), but increase TG (WMD: 0.42, 95%CI: 0.18-0.65) compared with tibolone. When comparing with the different MHT regimens, estrogen (E) + progesterone (P) regimen significantly increased TC (WMD: 0.15, 95% CI: 0.09 to 0.20), LDL-C (WMD: 0.12, 95% CI: 0.07-0.17) and Lp(a) (WMD: 44.58, 95% CI:28.09-61.06) compared with estrogen alone. Conclusion and Relevance: MHT plays a positive role in lipid profile in postmenopausal women, meanwhile for women with hypertriglyceridemia, low doses or transdermal MHT or tibolone would be a safer choice. Moreover, E + P regimen might blunt the benefit of estrogen on the lipid profile. Clinical Trial Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018092924], identifier [No. CRD42018092924].

Keywords: lipid profile; menopause hormone therapy; meta-analysis; postmenopausal women; system review.

FIGURE 1

Flow Diagram. A total of 6,784 articles were retrieved, and 73 articles were included in the current meta-analysis.

FIGURE 2

Summary of risk in bias.

FIGURE 3

Risk of bias graph.

FIGURE 4

Comparing MHT wih placebo or no treatment. The treatment duration was classified into the following periods in each lipid index: < 3 months, 3–5 months, 6–12 months, 13–24 months, and >24 months. MHT led to a significant reduction in TC concentration, LDL-C concentration and Lp(a) concentration compared with placebo or no treatment. (A) TC concentration; (B) LDL-C concentration; (C) TG concentration; (D) HDL-C concentration; (E) Lp(a) concentration.

FIGURE 5

Comparing oral estrogen with transdermal estrogen Oral MHT significantly decreased LDL-C concentration and increased TG concentration compared with that in transdermal MHT group. (A) TC concentration; (B) LDL-C concentration; (C) TG concentration; (D) HDL-C concentration; (E) Lp(a) concentration.

FIGURE 6

Studies comparing low-dose estrogen with conventional-dose estrogen. A low-dose estrogen led to a significant reduction in TG concentration compared with a conventional-dose estrogen. (A) TC concentration; (B) LDL-C concentration; (C) TG concentration; (D) HDL-C concentration; (E) Lp(a) concentration.

FIGURE 7

Studies comparing conventional MHT with Tibolone. The conventional MHT could decrease LDL-C concentration, increase TG concentration and HDL-C concentration compared with Tibolone. (A) TC concentration; (B) LDL-C concentration; (C) TG concentration; (D) HDL-C concentration; (E) Lp(a) concentration.

FIGURE 8

Studies comparing estrogen alone with estrogen plus progestogen regimen. The estrogen plus progestogen regimen could significantly increased TC, LDL-C, HDL-C, and Lp(a) concentration compared with estrogen alone. (A) TC concentration; (B) LDL-C concentration; (C) TG concentration; (D) HDL-C concentration; (E) Lp(a) concentration.

FIGURE 9

Sensitivity analysis for TC in the subgroup of low-dose estrogen. Sensitivity analysis suggested that while omitting the study Kraker 2004, low-dose estrogen could decrease TC significantly (MD: −0.17 mmol/L, 95% CI: −0.31 to −0.02 mmol/L). (A) Sensitivity analysis; (B) forrest plot after omitted study Kraker 2004.

FIGURE 10

Sensitivity analysis for TG in the subgroup of estrogen alone vs. E + P regimen. Sensitivity analysis suggested that while omitting one group of the study Writing−group 1995b, E + P group cause a significantly higher TG (WMD: 0.08 mmol/L, 95% CI: 0.01–0.15 mmol/L) than Estrogen alone. (A) Sensitivity analysis; (B) forest plot after omitted study Writing−group 1995b.

FIGURE 11

Funnel plots examining publication bias. The Egger test suggested that there was no evidence of publication bias in studies with more than 10 articles. (A) MHT vs. Placebo or no treatment; (B) oral MHT vs. transdermal MHT; (C) Conventional MHT vs. Tibolone; (D) Estrogen vs. Estrogen-Progestogen; (E) Low-dose MHT vs. Conventional MHT.