How are COMT and Wechseljahre related?

COMT (catechol-O-methyltransferase) is an enzyme that degrades catecholamines and estrogens. During menopause (Wechseljahre), endogenous estrogen production declines, making the COMT pathway more relevant for clearing remaining estrogens. The well-studied Val158Met variant (rs4680) alters enzyme activity: the Met variant degrades estrogens more slowly, which could theoretically increase the risk of hot flashes or mood disturbances. However, evidence is mixed – some studies find associations, others do not. Effect sizes are small and confounded by lifestyle, diet, and other genetic factors. Currently, no DNA test for menopausal symptoms is clinically validated. The evidence grade is unclear; any recommendations should be discussed with a healthcare provider.