Vascular Actions of Estrogens: Functional Implications

Miller, Virginia M.; Duckles, Sue Piper

doi:10.1124/pr.107.08002

Cited by 444 publications

(396 citation statements)

References 440 publications

Supporting

Mentioning

367

Contrasting

Unclassified

Order By: Relevance

“…12,35 Estrogens in both human studies and experimental models cause a significant alteration in vascular tone. 23 The antiinflammatory and vascular relaxation effect of estrogen is not seen after a prolonged period of estrogen deprivation, 27,29 which may have a common occurrence in WHI participants who were 50-79 years of age and had a large interval between menopause and initiation of HRT. However, the mechanism underlying the increased risk associated with HRT is probably related to the complex relationship between the ratio of different types of estrogen receptors present in vascular smooth muscles and context specificity of the estrogen hormones.…”

Section: Discussionmentioning

confidence: 99%

Hormone replacement therapy and the risk of subarachnoid hemorrhage in postmenopausal women

Qureshi¹,

Malik²,

Saeed³

et al. 2016

JNS

View full text Add to dashboard Cite

T he risk of intracranial aneurysm formation and subarachnoid hemorrhage (SAH) is higher in postmenopausal women compared with premenopausal women. 8,13,18,19,28 Reduced levels of estrogen in postmenopausal women may increase the risk of aneurysm formation and rupture by reduction in collagen and elastin content and reduced elasticity of arterial walls. 3 In an experimental intracranial aneurysm mouse model, estrogen prevented aneurysmal rupture in ovariectomized mice. 30The protective effect of estrogen seemed to occur through activation of estrogen receptor-b, a predominant subtype of estrogen receptor in human intracranial aneurysms and cerebral arteries. Hormone replacement therapy (HRT) was associated with reduced risk of spontaneous SAH in postmenopausal women in most 19,22 but not all case control studies. 25 The Women's Health Initiative (WHI) randomized trial 33 assessed the effect of estrogen plus progestin on ischemic and hemorrhagic stroke in 608 women 50-79 years of age with an average follow-up of 5.6 years. There was a nonsignificant protective effect on hemorrhagic stroke (HR 0.82, 95% CI 0.43-1.56). However, the study was underpowered because there were only 10 SAH events among the randomized patients. A meta-analysis 24 found a small nonsignificant protective effect of HRT on risk of SAH (HR 0.8, 95% CI 0.57-1.04).We performed this study to determine the effect of abbreviatioNs HRT = hormone replacement therapy; RR = relative risk; SAH = subarachnoid hemorrhage; SE = standard error; WHI = Women's Health Initiative. obJective The incidence of subarachnoid hemorrhage (SAH) increases after menopause. Anecdotal data suggest that hormone replacement therapy (HRT) may reduce the rate of SAH and aneurysm formation in women. The goal of this study was to determine the effect of HRT on occurrence of SAH in a large prospective cohort of postmenopausal women. methods The data were analyzed for 93,676 women 50-79 years of age who were enrolled in the observational arm of the Women's Health Initiative Study. The effect of HRT on risk of SAH was determined over a period of 12 ± 1 years (mean ± SD) using Cox proportional hazards analysis after adjusting for potential confounders. Additional analysis was performed to identify the risk associated with "estrogen only" and "estrogen and progesterone" HRT among women. results Of the 93,676 participants, 114 (0.1%) developed SAH during the follow-up period. The rate of SAH was higher among women on active HRT compared with those without HRT used (0.14% vs 0.11%, absolute difference 0.03%, p < 0.0001). In unadjusted analysis, participants who reported active use of HRT were 60% more likely to suffer an SAH (RR 1.6, 95% CI 1.1-2.3). Compared with women without HRT use, the risk of SAH continued to be higher among women reporting active use of HRT (RR 1.5, 95% CI 1.0-2.2) after adjusting for age, systolic blood pressure, cigarette smoking, alcohol consumption, body mass index, race/ethnicity, diabetes, and cardiovascular disease. The risk of SAH was nonsignificantly h...

show abstract

Section: Discussionmentioning

confidence: 99%

Hormone replacement therapy and the risk of subarachnoid hemorrhage in postmenopausal women

Qureshi¹,

Malik²,

Saeed³

et al. 2016

JNS

View full text Add to dashboard Cite

show abstract

“…These observations are strikingly similar to those identified previously in older postmenopausal women, suggesting estrogen deficiency may influence interactions between sympathoneural activation and end-organ responsiveness. Studies reporting estrogenmediated modulation of adrenergic receptor expression and sensitivity, norepinephrine synthesis and degradation, and postreceptor signaling cascades involved in signal transduction 38,39 support this concept. The long-term consequences of neuro-humoral perturbations in youth are presently unknown, but it is now recognized that sympathetic activation contributes importantly to the development and progression of hypertension and cardiovascular disease, 16 and it is of concern that studies in humans and nonhuman primates have identified estrogen deficiency as a result of FHA as a key contributing factor to premenopausal coronary artery disease.…”

Section: Perspectivesmentioning

confidence: 93%

Discordant Orthostatic Reflex Renin–Angiotensin and Sympathoneural Responses in Premenopausal Exercising-Hypoestrogenic Women

et al. 2015

View full text Add to dashboard Cite

Its prevalence is markedly higher in recreationally and competitively exercising women and women with physically demanding jobs (≈1% to 44%) than in sedentary women (≈2% to 5%).2,3 Hypothalamic-pituitary-ovarian suppression in physically active women with FHA (ExFHA) has been related causally to energy deficiency (ie, caloric deficit) in association with high energy expenditure and insufficient energy intake (ie, low caloric intake). 4Circulating estradiol concentrations in women with ExFHA are chronically low and resemble those observed in postmenopausal women and in men. 5,6 In postmenopausal women, estrogen deficiency is associated with increases in blood pressure (BP) and a marked acceleration in the development and progression of atherosclerosis.7 Cardiovascular consequences of premenopausal hypoestrogenemia in ExFHA women are not yet known, but disruption of the menstrual cycle during the reproductive years is also associated with the premature development and progression of coronary artery disease. 8,9 However, in contrast to postmenopausal women, ExFHA women have lower resting systolic blood pressure (SBP) and heart rate (HR) than age-and fitness-matched estrogen-replete physically active women.10,11 The presence of low arterial BP, despite hypoestrogenemia, suggests that estrogen deficiency may have different consequences for BP regulation in premenopausal and postmenopausal women.The sympathetic nervous system and the renin-angiotensinaldosterone system (RAAS) are cornerstones of BP regulation. Estrogen modulates both. In estrogen-deficient Abstract-Our prior observations in normotensive postmenopausal women stimulated the hypotheses that compared with eumenorrheic women, active hypoestrogenic premenopausal women with functional hypothalamic amenorrhea would demonstrate attenuated reflex renin-angiotensin-aldosterone system responses to an orthostatic challenge, whereas to defend blood pressure reflex increases in muscle, sympathetic nerve activity would be augmented. To test these hypotheses, we assessed, in recreationally active women, 12 with amenorrhea (ExFHA; aged 25±1 years; body mass index 20.7±0.7 kg/m 2 ; mean±SEM) and 17 with eumenorrhea (ExOv; 24±1 years; 20.9±0.5 kg/m 2 ), blood pressure, heart rate, plasma renin, angiotensin II, aldosterone, and muscle sympathetic nerve activity at supine rest and during graded lower body negative pressure (−10, −20, and −40 mm Hg). At baseline, heart rate and systolic blood pressure were lower (P<0.05) in ExFHA (47±2 beats/min and 94±2 mm Hg) compared with ExOv (56±2 beats/min and 105±2 mm Hg), but muscle sympathetic nerve activity and renin-angiotensin-aldosterone system constituents were similar (P>0.05). In response to graded lower body negative pressure, heart rate increased (P<0.05) and systolic blood pressure decreased (P<0.05) in both groups, but these remained consistently lower in ExFHA (P<0.05). Lower body negative pressure elicited increases (P<0.05) in renin, angiotensin II, and aldosterone in ExOv, but not in ExFHA (P>0.05). Muscle sympatheti...

show abstract

“…Concerning the vascular effects of estrogen, a large amount of data support the notion that estrogen may play a beneficial role in vascular aging (Miller and Duckles, 2008). More specifically, it has been shown that estradiol treatment has a marked neuroprotective effect in old female gerbils (Wappler et al, 2010).…”

Section: Introductionmentioning

confidence: 97%

Microvascular changes in estrogen-α sensitive brainstem structures of aging female hamsters

Gerrits

Weerd

Want

et al. 2010

Neuroscience Research

View full text Add to dashboard Cite

Vascular Actions of Estrogens: Functional Implications

Cited by 444 publications

References 440 publications

Hormone replacement therapy and the risk of subarachnoid hemorrhage in postmenopausal women

Hormone replacement therapy and the risk of subarachnoid hemorrhage in postmenopausal women

Discordant Orthostatic Reflex Renin–Angiotensin and Sympathoneural Responses in Premenopausal Exercising-Hypoestrogenic Women

Microvascular changes in estrogen-α sensitive brainstem structures of aging female hamsters

Contact Info

Product

Resources

About