What to watch with COMT and menopause?

COMT (catechol-O-methyltransferase) is a key enzyme for degrading estrogens and catecholamines. During menopause, ovarian estrogen production drops sharply, while peripheral estrogen (e.g., from adipose tissue) continues. The common COMT polymorphism rs4680 (Val158Met) affects enzyme activity: carriers of the Met variant have lower activity, potentially leading to higher estrogen levels and an increased risk for hormone-sensitive conditions like breast cancer. Conversely, reduced COMT activity may slow dopamine and adrenaline breakdown, possibly contributing to mood swings, sleep issues, or heightened stress responses. During menopause, attention to methylation (e.g., via MTHFR) and nutrient status (magnesium, B vitamins) may be beneficial. However, individual SNP effects are small and heavily influenced by lifestyle, diet, and other genetic factors. A DNA test can provide insight but should not replace medical advice. Evidence: moderate human studies, but no RCTs specifically for COMT and menopause.