Effects of estradiol on biological age measured using the glycan age index

Glycan age is a recently developed biomarker based on glycans attached to immunoglobulin G (IgG). In large population cohorts glycan age associates well with lifestyle and disease-risk biomarkers, while some studies suggested that change in glycans precede development of several age-associated diseases. In this study we evaluated effects of estrogen on the glycan age. Gonadal hormones were suppressed in 36 healthy young women by gonadotropin releasing hormone agonist therapy for 6 months. In 15 of them estradiol was supplemented, while 21 received placebo resulting in very low estrogen levels during intervention. IgG was isolated from plasma samples before intervention, after 6 months of intervention and after subsequent 4-month recovery. In the placebo group the removal of gonadal hormones resulted in median increase of glycan age for 9.1 years (IQR 6.8 – 11.5 years, p = 3.73×10 −8 ), which was completely prevented by transdermal estradiol supplementation. After the recovery period glycan age returned to baseline values also in the placebo group. These results suggest that IgG glycans and consequently also the glycan age are under strong influence of gonadal hormones and that hormone replacement therapy can prevent the increase of glycan age that occurs in the perimenopausal period.