A cross-sectional and 10-year prospective study of postmenopausal estrogen therapy and blood pressure, renal function, and albuminuria

Fung, Maple M.; Poddar, Sameer; Bettencourt, Ricki; Jassal, Simerjot K; Barrett‐Connor, Elizabeth

doi:10.1097/gme.0b013e3181fca9c4

Cited by 43 publications

(40 citation statements)

References 51 publications

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“…These results confirm differential pathogenesis of hypertension and its end-organ diseases in premenopausal and post menopausal states, as well as corroborate the role of ovarian hormones in postmenopausal hypertension–protective role(s) for blood pressure and for hypertensive renal disease. These observations are concordant with the studies reporting that estrogen/progestin replacement therapy improved renal function [8]–[10].…”

Section: Discussionsupporting

confidence: 91%

“…In studies using ovariectomized Dahl-S rats as an animal model of surgically-induced postmenopausal salt-sensitive hypertension, 17β-estradiol attenuated age-related renal dysfunction [19], [20]. However, studies of hormone replacement therapy in aging women are controversial, with some studies showing improvement [8]–[10] and others showing loss of kidney function [12].…”

Section: Discussionmentioning

confidence: 99%

“…However, cumulative data report polar results regarding the benefits from hormone replacement therapy for hypertension [7] as well as for its end-organ complications with some studies reporting improvement in kidney function [8]–[10] while other studies detecting either no change [11] or worsening of postmenopausal kidney function in postmenopausal women [12]. These discordant results have been attributed to several factors such as the use of distinct study populations [8], [9], [11], the type of hormone replacement therapy (estrogen or progestin), and/or differences in dosing or route of delivery [9], [11].…”

Section: Introductionmentioning

confidence: 99%

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Worse Renal Disease in Postmenopausal F2[Dahl S x R]-Intercross Rats: Detection of Novel QTLs Affecting Hypertensive Kidney Disease

et al. 2013

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The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs) affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS) as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01) and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37) and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28), all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a protective role of ovarian hormones. Furthermore, the detection of distinct GIS-QTLs in postmenopausal intercross female rats suggests that distinct genetic mechanisms underlie hypertensive glomerulosclerosis in premenopausal and postmenopausal states.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Worse Renal Disease in Postmenopausal F2[Dahl S x R]-Intercross Rats: Detection of Novel QTLs Affecting Hypertensive Kidney Disease

et al. 2013

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“…Estrogen supplementation also downregulated the AT 1 -receptor expression, linking augmented oxidative stress and the renin-angiotensin system to prolonged estrogen deprivation, but not necessarily to aging per se. In the recently published Rancho Bernardo Study, a 10-yr follow-up showed that, in postmenopausal women, estrogen use improved blood pressure and decreased urine albumin-to-creatinine ratio, without affecting in glomerular filtration rate (13). These observations suggest that continuous estrogen use attenuates albuminuria, which may be mediated by improved blood pressure control or possibly by decreased renal fibrosis, as observed in the present study.…”

Section: E984supporting

confidence: 67%

Age-dependent renal cortical microvascular loss in female mice

Urbieta-Caceres

Syed²,

Lin

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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LO. Age-dependent renal cortical microvascular loss in female mice. Am J Physiol Endocrinol Metab 302: E979 -E986, 2012. First published February 7, 2012 doi:10.1152/ajpendo.00411.2011.-Renal function and blood flow decline during aging in association with a decrease in the number of intrarenal vessels, but if loss of estrogen contributes to this microvascular, rarefaction remains unclear. We tested the hypothesis that the decreased renal microvascular density with age is aggravated by loss of estrogen. Six-month-old female C57/BL6 mice underwent ovariectomy (Ovx) or sham operation and then were allowed to age to 18 -22 mo. Another comparable group was replenished with estrogen after Ovx (OvxϩE), while a 6-mo-old group served as young controls. Kidneys were then dissected for evaluation of microvascular density (by micro-computed tomography) and angiogenic and fibrogenic factors. Cortical density of small microvessels (20 -200 m) was decreased in all aged groups compared with young controls (30.3 Ϯ 5.8 vessels/mm 2 , P Ͻ 0.05), but tended to be lower in sham compared with Ovx and OvxϩE (9.9 Ϯ 1.7 vs. 17.2 Ϯ 4.2 and 18 Ϯ 3.0 vessels/mm 2 , P ϭ 0.08 and P ϭ 0.02, respectively). Cortical density of larger microvessels (200 -500 m) decreased only in aged sham (P ϭ 0.04 vs. young control), and proangiogenic signaling was attenuated. On the other hand, renal fibrogenic mechanisms were aggravated in aged Ovx compared with aged sham, but blunted in OvxϩE, in association with downregulated transforming growth factor-␤ signaling and decreased oxidative stress in the kidney. Therefore, aging induced in female mice renal cortical microvascular loss, which was likely not mediated by loss of endogenous estrogen.

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“…Results include the finding of the Women's Health Initiative (WHI) trial that hormone replacement with conjugated equine oestrogens (CEEs) results in a small increase in BP [33]. However, other studies have shown that CEEs result in a lower BP after 10 years of treatment [34]. It has been suggested that the method of HRT delivery influences CEEs' effects on BP.…”

Section: Sex Ovarian Hormones and Sympathetic Outflowmentioning

confidence: 96%

Sex, the brain and hypertension: brain oestrogen receptors and high blood pressure risk factors

Hay

2015

Clinical Science

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Hypertension is a major contributor to worldwide morbidity and mortality rates related to cardiovascular disease. There are important sex differences in the onset and rate of hypertension in humans. Compared with age-matched men, premenopausal women are less likely to develop hypertension. However, after age 60, the incidence of hypertension increases in women and even surpasses that seen in older men. It is thought that changes in levels of circulating ovarian hormones as women age may be involved in the increase in hypertension in older women. One of the key mechanisms involved in the development of hypertension in both men and women is an increase in sympathetic nerve activity (SNA). Brain regions important for the regulation of SNA, such as the subfornical organ, the paraventricular nucleus and the rostral ventral lateral medulla, also express specific subtypes of oestrogen receptors. Each of these brain regions has also been implicated in mechanisms underlying risk factors for hypertension such as obesity, stress and inflammation. The present review brings together evidence that links actions of oestrogen at these receptors to modulate some of the common brain mechanisms involved in the ability of hypertensive risk factors to increase SNA and blood pressure. Understanding the mechanisms by which oestrogen acts at key sites in the brain for the regulation of SNA is important for the development of novel, sex-specific therapies for treating hypertension.

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A cross-sectional and 10-year prospective study of postmenopausal estrogen therapy and blood pressure, renal function, and albuminuria

Cited by 43 publications

References 51 publications

Worse Renal Disease in Postmenopausal F2[Dahl S x R]-Intercross Rats: Detection of Novel QTLs Affecting Hypertensive Kidney Disease

Worse Renal Disease in Postmenopausal F2[Dahl S x R]-Intercross Rats: Detection of Novel QTLs Affecting Hypertensive Kidney Disease

Age-dependent renal cortical microvascular loss in female mice

Sex, the brain and hypertension: brain oestrogen receptors and high blood pressure risk factors

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