Abstract
Chronic kidney disease (CKD) is associated with a poor quality of life and high risk of cardiovascular (CV) mortality, specifically sudden cardiac death (SCD), and an upregulated renin angiotensin system. Women with end stage kidney disease (ESKD) experience premature menopause, and in healthy women menopause is correlated with a poor quality of life and higher CV mortality. A series of studies was conducted in healthy women and women with CKD to determine the associations between menopause status, serum estradiol and 1) cardiac autonomic tone (CAT), a surrogate marker for SCD, in a high Angiotensin II (AngII) state 2) mortality in women with ESKD and 3) quality of life(QoL) in women with CKD. We also summarized the impressions of healthcare workers and patients on the discussion of symptoms of low sex hormones in a clinical setting. In healthy men and women, sex hormones did not correlate with baseline CAT; however, men with lower testosterone levels were unable to maintain CAT in response to AngII. At baseline, postmenopausal women had a lower CAT in comparison to premenopausal women. In response to AngII postmenopausal women and premenopausal women in the luteal phase were unable to maintain their CAT. Through a survey of nephrologists we found that nephrologists recognize the impact of CKD on sex hormones in women but report infrequently discussing sex hormone related issues with patients. In a systematic review of studies examining the effect of postmenopausal hormone therapy on CV outcomes in women with ESKD, hormone therapy was associated with a favourable lipid profile. However, we found that peri- and premenopausal women with ESKD on hemodialysis had a higher risk of all-cause, cardiovascular and non-cardiovascular mortality compared to postmenopausal women. Furthermore menopause specific QoL scores did not correlate with kidney function in CKD women. We found that associations between menopause status and CV risk and QoL in the CKD population are complex. This body of work can be used for hypothesis generation for future studies and trials aimed to determine the mediators of cardiovascular risk and poor quality of life in this population.
