Menopause modifies women's lipid profiles. However, the fact that it is still unclear whether high-density lipoprotein-cholesterol (HDL-C) levels decrease in postmenopausal women necessitated a systematic review and meta-analysis. The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched and 498 articles published between 1987 and 2020 were retrieved. Studies reporting HDL-C, low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) levels in both postmenopausal and premenopausal populations were included. The quality of the included studies was assessed using the Cross-Sectional/Prevalence Study Quality tool. The standard mean difference (SMD) and 95% confidence interval (CI) were estimated using random effects models. A meta-regression analysis and subgroup analysis were performed to identify potential modifiers. Egger's test and funnel plots were constructed to evaluate publication biases. Lipid profiles from 18 cross-sectional studies and two cohort studies including 5652 postmenopausal women and 7825 premenopausal women were meta-analyzed. HDL-C levels were not significantly different between the postmenopausal and premenopausal women (SMD = - 0.053, 95% CI - 0.171 to 0.066, p = 0.383) and were not affected by country, publication year, study quality in the meta-regression analysis, or significant publication bias. Higher LDL-C, TC, and TG levels were detected in postmenopausal women than in premenopausal controls. Unlike increased LDL-C, TC, and TG levels, HDL-C levels in pre- and postmenopausal women were not different in this first meta-analysis of lipid profiles in premenopausal and postmenopausal women. Prospective studies with large populations examining HDL-C levels and functions in women with different menopausal statuses are essential in the future. None.