Hormone Replacement Therapy, Breast Cancer & Renovascular Disease

Abstract

This thesis investigates the risks and benefits of hormone replacement therapy (HRT) in high-risk populations, particularly in women who have undergone prophylactic risk-reducing surgeries (PRRS) to prevent familial ovarian cancer and women with chronic kidney disease. It comprises two manuscripts that address the effects of HRT on breast cancer and chronic kidney disease (CKD) progression. Manuscript 1 focuses on the association between breast cancer risk and HRT use after PRRS in women at increased risk of familial ovarian cancer. A systematic review and meta-analysis were conducted, synthesizing data from 8 studies involving 2,689 participants. The analysis revealed no significant increase in breast cancer risk for women using HRT post-PRRS, suggesting that HRT may be a safe option for managing menopause symptoms in this high-risk population. Despite previous concerns over estrogen’s potential to elevate breast cancer risk, the results indicated that estrogen-only HRT did not increase the risk compared to non-users. Manuscript 2 explores the association of exogenous estrogen use with CKD progression and adverse cardiovascular outcomes in women with CKD, using data from the Chronic Renal Insufficiency Cohort (CRIC). The study demonstrated that estrogen use was associated with a 47% lower risk of CKD progression, although it did not show a reduction in adverse cardiovascular events or all-cause mortality. This finding provides some reassurance for the use of estrogen in women with CKD, particularly for those at risk of kidney decline. In both manuscripts, the results emphasize the need for personalized treatment strategies and further prospective studies to validate these findings. This research contributes to understanding the role of HRT in managing risks related to ovarian cancer, breast cancer, and CKD in high-risk women.