Increased pro‐inflammatory gene expression in aged ovariectomized female Norway‐Brown rat with late estrogen replacement

Loss of estrogen (E2) with aging is associated with an acceleration of cardiovascular disease; however clinical trials have found no CV benefit from E2 replacement in post‐menopausal women. Recent work suggests that the timing of hormone treatment plays a critical role in the benefits of E2 replacement. We hypothesized that late E2 replacement is associated with an increase in inflammatory gene expression. In this study, we investigated the effect of ovx on inflammatory gene expression and how this was modulated by immediate E2 replacement vs late replacement in aged Norway‐Brown rats. E2 was delivered through a sustained release pellet implanted immediately after ovx (Early) or 9 weeks after ovx (Late). Gene expression level changes in the hearts of these rats were detected using a PCR array. We found that the mRNA levels of pro‐inflammatory proteins Scye1 and Abcf1 increased substantially in the Late group as compared to all other groups. Conclusions: This is the first report of a distinct gene change associated with late E2 replacement. Changes in these 2 pro‐inflammatory genes could contribute to the harmful effects of late post‐menopausal E2 replacement in humans.