BackgroundChronic kidney disease affects approximately one in ten North Americans and is associated with a high risk of cardiovascular disease. Chronic kidney disease in women is characterized by an abnormal sex hormone profile and low estradiol levels. Since low estradiol levels are associated with an increased cardiovascular risk in healthy women, our objective is to determine the effect of hormone therapy on all-cause mortality, cardiovascular mortality, and cardiovascular morbidity in women with chronic kidney disease.Methods/designStudies examining hormone therapy for adult women with chronic kidney disease will be included. The primary outcome is all-cause or cardiovascular mortality and morbidity. We will search electronic bibliographic databases (MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL)) along with relevant conference proceedings, table of contents of journals, and review articles. Two investigators will independently screen identified abstracts and select observational cohort studies, case–control studies, and randomized controlled trials examining hormone therapy in women with chronic kidney disease. These investigators will also independently abstract data from relevant full-text journal articles and assess risk of bias. Where possible, these data will be summarized using pooled or combined estimates for the risk ratio or hazard ratio of all-cause mortality, cardiovascular mortality, and cardiovascular morbidity in women with chronic kidney disease with and without hormone therapy. A random effects model will be used, and meta-regression and subgroup analyses will be used to explore potential source of heterogeneity.DiscussionGiven the high burden of cardiovascular disease in women with chronic kidney disease, this study will help guide clinical practice by summarizing current evidence on the use of hormone therapy for prevention of all-cause mortality, cardiovascular mortality, and cardiovascular morbidity in this population.Systematic review registrationThe final protocol was registered with PROSPERO (CRD42014014566).