Loss of Ovarian Hormones Increases Salt Sensitivity in Normotensive Women

Salt sensitivity is associated with an elevated risk of developing hypertension and is an independent risk factor for cardiovascular morbidity and mortality. Cross-sectional studies have suggested that postmenopausal women are more salt sensitive than premenopausal women. The purpose of the present study was to investigate prospectively the prevalence of salt sensitivity among healthy premenopausal women and determine whether the loss of ovarian hormones increases salt sensitivity. We enrolled 40 normotensive (systolic blood pressure 127 ± 2, diastolic blood pressure 78 ± 1; Mean ± SEM), non-diabetic women (age 47 ± 0.6) undergoing hysterectomy and ovariectomy for non-neoplastic processes to determine the effect of changes in sodium intake on blood pressure the day before and 4 months after surgical menopause. After a 1-week diet containing 120 mmol/day NaCl, salt loading was achieved with a 2-liter infusion of normal saline, followed by salt depletion produced by 40 mg of intravenous furosemide. A decrease of 10 mm Hg in systolic blood pressure between salt loading and salt depletion was used to define salt sensitivity. Premenopausal salt sensitive women exhibited higher waist/hip ratio (0.85 ± 0.017 vs. 0.82 ± 0.007; P = 0.001), fasting glucose (105.9 ± 2.9 vs. 98.5 ± 3.1 mg/dL; P = 0.03), triglycerides (155 ± 35 vs. 90 ± 6 mg/dL; P < 0.0001), uric acid (4.5 ± 0.22 vs. 3.7 ± 0.16 mg/dL; P < 0.0001), apoB (145.6 ± 5.4 vs. 112.5 ± 3.3 mg/dL; P < 0.0001) and microalbuminuria (20.2 ± 7.3 vs. 4.5 ± 1.4 mg/24hr; P < 0.0001) than salt resistant women. Four months after surgical menopause, none of the women were on hormone replacement and all remained normotensive (systolic blood pressure 127 ± 3, diastolic blood pressure 77 ± 2). However, the prevalence of salt sensitivity was significantly higher after menopause (21 women, 52.5%) than before (9 women, 22.5%, P = 0.01), because 12 (38.7%) salt resistant women developed salt sensitivity after menopause. Thus, we found that the prevalence of salt sensitivity doubled as early as 4 months after surgical menopause, due to the development of salt sensitivity in previously salt resistant women. The women who developed salt sensitivity did not manifest an increase in blood pressure or in the above markers of cardiovascular risk. However, epidemiological studies indicate that, in most women, development of hypertension does not occur until 5-10 years after menopause. We surmise that the loss of ovarian hormones unmasks a population of women prone to salt sensitivity that with aging would be at higher risk for the development of hypertension and its associated cardiovascular morbidity and mortality.