Background: Glycosylation of immunoglobulin G (IgG) is an important regulator of the immune system and its changes are believed to be a significant contributor to inflammaging. Gonadal hormones affect IgG glycome composition, suggesting that alterations in IgG glycosylation might be one of the molecular mechanisms behind increased disease risk in perimenopause. Methods: IgG was isolated from 5,354 plasma samples collected from 1,940 females and 113 males at multiple time points. IgG glycans were released, labelled with a fluorescent dye and analysed by ultra-high-performance liquid chromatography. Mixed modelling was used to determine average levels of individual IgG glycans in pre-menopausal women, menopausal women, and men. Findings: Large and statistically significant differences in IgG glycome composition were observed, mainly reflecting decreased galactosylation and sialylation of glycans in menopausal women. During perimenopause women had a significant higher rate of increase in agalactosylated structures (0.051/yr; 95%CI = 0.043 - 0.059, p