Association of Chronological Age, Subjective Age, Epigenetic Age and Bio-functional Age With Serum Anti-müllerian Hormone

As life expectancy is increasing and has significant effects on health, economy and other aspects, the need for an Active and Healthy ageing (AHA) strategy becomes more important. Although ageing is often defined by chronological age (CA), it is significantly influenced by other factors such as psychological, social and mental-emotional factors. To evaluate these influences, the bio-functional status (BFS) was created which consists of 45 non-invasive assessments of different categories and reflects a normal middle-European population. By means of BFS the bio-functional age (BFA) can be calculated, revealing individual strengths and resources for healthy ageing as well as potential health risks.

In women ageing leads to a depletion of the ovarian reserves and change of sex hormone levels introducing menopause. Age at menopause is associated with several health issues. Women with premature (age ≤40) or early menopause (age ≤45) are not only considered to have higher risk for osteoporosis but also cardiovascular diseases and cognitive disorders such as dementia. Late menopause (age ≥55) increases the risk of breast and ovarian cancer. Timely preventative measures might limit these risks. For example, hormone replacement therapy has shown to reduce later development of issues associated with premature or early menopause.

The difficulty lies in the variability of age at menopause between 40 and 60 years. In order to take appropriate preventative measures, the age of menopause has to be predicted individually for every woman. This requires a reliable predictive marker for menopause. In studies serum anti-müllerian hormone (AMH) was described as a potential predictor.

AMH is synthetized in granulosa cells of the follicles and reduces the effects of the follicle-stimulating hormone (FSH) on said cells preventing further recruitment of follicles. Hence, AMH is associated with the functional ovarian reserve and declines with age. It is mainly used for detection of reproductive age in women and might be a reliable predictive marker for menopause.

Using the epiAge-test the epigenetic age, also called the biological age, can be calculated. The epiAge-Test was created by Prof. Dr. Moshe Szyf based on the research of Steve Horvath's epigenetic clock. Horvath discovered that DNA methylation can be directly associated with ageing. The methylation occurs on cytosine nucleotides followed by guanine nucleotides creating so called CpG-islands. Taking mathematical and statistical analyses into account, Horvath identified 353 CpG-islands which were consistently altered with age. Szyf further developed Horvath's calculator and created the epiAge-test using 13 CpG-islands that show the highest correlation with ageing to calculate the epigenetic age.