Menstrual disorders, infertility and premature menopause are common but often underrecognized phenomena among women with chronic kidney disease. Hypothalamic, rather than ovarian dysfunction, may be the cause of the abnormal reproductive milieu, which can be at least partially reversed by kidney transplantation and increased intensity of hemodialysis. Endogenous sex hormones, and specifically estradiol, appear to be renoprotective in women, although the effects of exogenous estradiol (as an oral contraceptive and postmenopausal hormone therapy) on kidney function are more controversial. Treatment with postmenopausal hormone therapy in women with end-stage kidney disease (ESKD) has been associated with improved quality of life, bone health and markers of cardiovascular risk, as well as an increased risk of arteriovenous access thrombosis. The selective estrogen receptor modulator raloxifene has been associated with both a decreased fracture risk as well as renoprotection in women with kidney disease. Young women with ESKD are more likely to die from infection or develop malignancy, suggesting an immunomodulatory role of estrogen. Whether the premature menopause commonly observed in female patients with kidney disease results in increased cardiovascular morbidity and mortality is unknown, although preliminary studies have suggested a possible therapeutic role for manipulation of the sex hormone milieu to mitigate risk in this population. Large, prospective, randomized studies examining the role of sex hormones in women with kidney disease are required to address the question.

Background:Chronic kidney disease (CKD) in reproductive-age women is accompanied by menstrual and fertility disorders and premature menopause.Objective:We sought to determine nephrologists’ and allied health care providers’ perceptions on management of sex hormone status in women with CKD.Methods:An anonymous, Internet-based survey was sent to nephrology society members from Canada, Australia, New Zealand, and the United Kingdom, and the Canadian Association of Nephrology Nurses and Technologists (February-November 2015). We assessed reported perceptions and management of sex hormone status in women with CKD.Results:One hundred seventy-five nephrologists (21% response rate) and 121 allied health care providers (30%; 116 nurses, 5 pharmacists) responded. Sixty-eight percent of nephrologists and 46% of allied providers were between the ages of 30 and 50 years, and 38% of nephrologists and 89% of allied workers were female. Ninety-five percent of nephrologists agreed that kidney function impacts sex hormone status, although only a minority of nephrologists reported often discussing fertility (35%, female vs male nephrologists, P = .06) and menstrual irregularities with their patients (15%, female vs male nephrologists,P = .02). Transplant nephrologists reported discussing fertility more often than did nontransplant nephrologists (53% vs 30%, P = .03). Physicians were more likely to report discussing fertility (33% vs 7.5%, P < .001) and menstrual irregularities (15% vs 9%, P = .04) with patients than allied health care providers. Forty-three percent of physicians reported uncertainty about the role for postmenopausal hormone therapy in women with CKD.Conclusion:Nephrologists and allied health care providers recognize an impact of CKD on sex hormones in women but report not frequently discussing sex hormone–related issues with patients. Our international survey highlights an important knowledge gap in nephrology.

Diabetes confers greater cardiovascular risk to women than to men. Whether insulin-resistance-mediated risk extends to the healthy population is unknown. Measures of insulin resistance (fasting insulin, homeostatic model assessment, hemoglobin A1c, quantitative insulin sensitivity check index, glucose) were determined in 48 (56% female) healthy subjects. Heart rate variability (HRV) was calculated by spectral power analysis and arterial stiffness was determined using noninvasive applanation tonometry. Both were measured at baseline and in response to angiotensin II infusion. In women, there was a non-statistically significant trend towards increasing insulin resistance being associated with an overall unfavourable HRV response and increased arterial stiffness to the stressor, while men demonstrated the opposite response. Significant differences in the associations between insulin resistance and cardiovascular physiological profile exist between healthy women and men. Further studies investigating the sex differences in the pathophysiology of insulin resistance in cardiovascular disease are warranted.

Background Young women with end-stage kidney disease (ESKD) have early menopause compared with women in the general population and the highest mortality among the dialysis population. We hypothesized that low estrogen status was associated with death in women with ESKD. Methods We measured estradiol and sex hormone levels in female ESKD patients initiating hemodialysis from 2005 to 2012 in four Canadian centers. We divided women into quintiles based on estradiol levels and tested for associations between the estradiol level and cardiovascular (CV), non-CV and all-cause mortality. Participants were further dichotomized by age. Results A total of 482 women (60 ± 15 years of age, 53% diabetic, estradiol 116 ± 161 pmol/L) were followed for a mean of 2.9 years, with 237 deaths (31% CV). Estradiol levels were as follows (mean ± standard deviation): Quintile 1: 19.3 ± 0.92 pmol/L; Quintile 2: 34.6 ± 6.6 pmol/L; Quintile 3: 63.8 ± 10.6 pmol/L; Quintile 4: 108.9 ± 19.3; Quintile 5: 355 ± 233 pmol/L. Compared with Quintile 1, women in Quintiles 4 and 5 had significantly higher adjusted all-cause mortality {hazard ratio [HR] 2.12 [95% confidence interval (CI) 1.38–3.25] and 1.92 [1.19–3.10], respectively}. Similarly, compared with Quintile 1, women in Quintile 5 had higher non-CV mortality [HR 2.16 (95% CI 1.18–3.96)]. No associations were observed between estradiol levels and CV mortality. When stratified by age, higher quintiles were associated with greater all-cause mortality (P for trend &lt;0.001) and non-CV mortality (P for trend = 0.02), but not CV mortality in older women. Conclusions In women with ESKD treated with hemodialysis, higher estradiol levels were associated with greater all-cause and non-CV mortality. Further studies are required to determine the mechanism for the observed increased risk.