Background: Current recommendations limit the use of menopausal hormone therapy (MHT) principally to the management of menopausal symptoms, largely because of concerns regarding increased breast cancer (BC) risk. The impact of MHT use on systemic biological aging and blood methylome and its overlap with that of menopause timing remains incompletely understood. Methods: In females (N=78,209) of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, we used Cox models to assess the associations of menopause timing (ordinal age at menopause; binary early-M [