Figure 1. Schematic representation of the proposed divergent effects of HRT treatment in postmenopause.

If hormone replacement therapy (HRT) is prescribed in the early stages of postmenopause (first 10 years), the estrogen from HRT will slow the progression of atherosclerosis (left; dark blue). Experiments in mice suggest it does this by reducing the levels of Mdm2, an enzyme that signals for the degradation of certain proteins. This results in higher levels of the receptor for estrogen, ERα, which also helps to maintain healthy blood vessels. HRT has the opposite effect when prescribed during the later stages of postmenopause (10 years or more), where it will increase the progression of atherosclerosis (right; light blue). Xu et al. propose that this is due to older individuals having higher levels of iron accumulating in their tissues, which causes estrogen to boost the amount of Mdm2 instead, resulting in lower levels of ERα and increased progression of atherosclerosis.