Cortisol-to-cortisone ratio postpartum is associated with anti-Müllerian hormone a decade later: evidence from a prospective study

Objective To assess the associations between serum stress-related hormones (cortisol and cortisone) at one month postpartum and AMH levels at 4- and 10-year follow-ups. Methods In a subset of 107 postpartum mothers enrolled in the PROGRESS cohort (at a mean age of 29.5 years), we measured serum cortisol and cortisone at one month postpartum via untargeted metabolomics. At 4- and 10-year follow-ups, we measured serum AMH levels. Serum cortisol, cortisone, and the cortisol-to-cortisone (F/E) ratio were analyzed both as continuous variables and as tertiles. The association between serum stress hormones and log 2 -transformed AMH levels was assessed using multivariable linear regression. Results The serum cortisol and F/E ratio showed a weak and inverse association with AMH concentration at the 4-year follow-up. However, at the 10-year follow-up, each unit increase in the F/E ratio was associated with a 45% reduction in AMH levels ( β = −0.60, 95% CI: −1.13; −0.07). In addition, when repeated time points were considered in the model, each unit increase in the F/E ratio was associated with a 32% reduction in AMH levels ( β = −0.38, 95% CI: −0.75; −0.01). The analysis by tertiles of serum cortisone showed a dose–response relationship with AMH levels at the 10-year follow-up, while the F/E ratio was only associated in the highest tertile at the 4- and 10-year follow-ups, including when considering the model with repeated time points. Conclusion Our findings suggest that a higher F/E ratio is associated with a lower AMH level, especially in mothers in the highest tertile of serum stress hormone levels. Our results support the role of stress hormone imbalance in ovarian aging.