A validated model of serum anti-müllerian hormone from conception to menopause

Abstract

Background: Anti-Müllerian hormone (AMH) is a product of growing ovarian follicles. The concentration of AMH in blood may also reflect the non-growing follicle (NGF) population, i.e. the ovarian reserve, and be of value in predicting reproductive lifespan. A full description of AMH production up to the menopause has not been previously reported.

Methodology/principal findings: By searching the published literature for AMH concentrations in healthy pre-menopausal females, and using our own data (combined n = 3,260) we have generated and robustly validated the first model of AMH concentration from conception to menopause. This model shows that 34% of the variation in AMH is due to age alone. We have shown that AMH peaks at age 24.5 years, followed by a decline to the menopause. We have also shown that there is a neonatal peak and a potential pre-pubertal peak. Our model allows us to generate normative data at all ages.

Conclusions/significance: These data highlight key inflection points in ovarian follicle dynamics. This first validated model of circulating AMH in healthy females describes a transition period in early adulthood, after which AMH reflects the progressive loss of the NGF pool. The existence of a neonatal increase in gonadal activity is confirmed for females. An improved understanding of the relationship between circulating AMH and age will lead to more accurate assessment of ovarian reserve for the individual woman.

Figure 1. Serum AMH data.

The red line is the model that best fits the 3,260 datapoints shown as triangles. The coefficient of determination, , is 0.34, indicating that 34% of variation in serum AMH concentrations is due to age alone. Peak serum AMH is at 24.5 years.

Figure 2. The normal range for serum AMH in girls and women.

The red line is the log-unadjusted validated AMH model using IBC assay values. The blue and green lines are the 68% and 95% prediction limits for the model (plus and minus one and two standard deviations respectively).