Abstract
Reproductive fitness and its influence on overall health has been a topic of significant
study and interest. Multiple studies have found that age at last reproduction associates
with overall health. Women who conceive later in life are significantly more likely
to outlive their peers who are unable to conceive. The mechanisms behind these observations
are not well understood. Earlier age at menopause associates with shorter life span,
increased risk for diabetes mellitus, and increased risk of heart disease, and represents
a surrogate marker for the age at last reproduction. Recent applications of genome-wide
association studies as well as whole-exome sequencing to familial primary ovarian
insufficiency (POI) and menopause have identified new genomic regions that link reproductive
aging and adverse health outcomes. The preponderance of DNA damage response genes
in menopause and POI represents a relatively new paradigm in this area, and links
overall aging and reproduction at the molecular level. Identification of the subset
of individuals who are at risk for adverse health outcomes remains a significant and
high priority research challenge. The combination of epidemiologic studies in women
with diminished ovarian reserves, ovarian insufficiency, and early menopause, as well
as appropriate animal studies, will be necessary to dissect genotype–phenotype correlations
not only in the cause of ovarian dysfunction but also in the cause of adverse health
outcomes.
Keywords
ovarian reserve - menopause - primary ovarian insufficiency - DNA damage response
genes
