Effect of short-term estrogen therapy on endothelial function: a double-blinded, randomized, controlled trial

Hurtado, Rodrigo; Celani, Marco F.; Geber, Selmo

doi:10.1080/13697137.2016.1201809

Cited by 18 publications

(13 citation statements)

References 27 publications

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“…Estrogen is well known to have vasodilatory effects on peripheral vasculature (23,26,32). This vasodilation could contribute to the lower TPRi in the HH phase of the menstrual cycle, in turn, leading to the increase in Q i and SVi due to reduced cardiac afterload.…”

Section: Standingmentioning

confidence: 99%

Influence of sex, menstrual cycle, and oral contraceptives on cerebrovascular resistance and cardiorespiratory function during Valsalva or standing

Abidi

Nili

Serna

et al. 2017

Journal of Applied Physiology

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Women experience orthostatic intolerance more than men, and they experience faintness more in the early follicular [i.e., low-hormone (LH)] than luteal [i.e., high-hormone (HH)] phase of the menstrual cycle. Men ( = 13, 25.8 ± 1.8 yr old) and women in the LH (; placebo) and HH (; high dose) phases of the menstrual cycle with (OC; = 14, 22.0 ± 0.8 yr old) or without (NOC; = 12, 21.8 ± 0.5 yr old) oral contraceptive (OC) use underwent the Valsalva maneuver and a supine-sit-stand protocol. Blood pressure, normalized stroke volume [stroke volume index (SVi)], cardiac output index, heart rate, end-tidal CO, and middle cerebral artery (MCA) blood flow velocity were measured. When subjected to the Valsalva maneuver, all women had a greater increase in diastolic and mean MCA blood flow velocity than men ( ≤ 0.065), with no significant effect of menstrual cycle phase or OC use. When subjected to the supine-sit-stand protocol, men had lower MCA blood flow velocity ( < 0.038) than all women, and SVi was higher in men than in the NOC group in all postures ( < 0.011) and in the OC group in the LH phase of the menstrual cycle during standing ( = 0.010). Only men experienced higher resistance index ( < 0.001) and pulsatility index ( < 0.001) with standing. The OC group had lower end-tidal CO ( = 0.002) than the NOC group ( = 0.030) and men ( ≤ 0.067). SVi ( = 0.004) and cardiac output index ( = 0.008) were higher in the OC than NOC group. A tendency toward a lower mean MCA blood flow velocity ( = 0.058) and higher SVi ( = 0.059) and pulsatility index ( = 0.058) was noted in the HH than LH phase. Mean arterial pressure was higher in the OC than NOC group in the LH phase ( = 0.049) and lower in the HH than LH phase ( = 0.014). Our results indicate that cycling estrogens/progestins can influence ventilatory, cardiovascular, and/or cerebrovascular physiology. We have found sex differences in the cerebrovascular response to the Valsalva maneuver and standing. Men have greater cerebral vasoconstriction (or women have greater cerebral vasodilation) during late phase II of the Valsalva maneuver, and the cerebrovascular resistance index increases in men, but not in women, during standing. Furthermore, our findings indicate that both the menstrual cycle phase and oral contraceptive use can influence cardiovascular function both at rest and during active standing.

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Section: Standingmentioning

confidence: 99%

Influence of sex, menstrual cycle, and oral contraceptives on cerebrovascular resistance and cardiorespiratory function during Valsalva or standing

Abidi

Nili

Serna

et al. 2017

Journal of Applied Physiology

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“…It is also important to consider the effects of hormonal therapy on vascular function. In a double-blinded randomized controlled trial conducted by Hurtado et al, 100 the effect of conjugated equine estrogens versus placebo was studied in 64 women. Authors found that administration of estrogen for 28 days had a significant effect in improving flowmediated dilation of the brachial artery, a marker of vascular nitric oxideedependent dilatation.…”

Section: Hormonal Therapy and Vascular Functionmentioning

confidence: 99%

“…Authors found that administration of estrogen for 28 days had a significant effect in improving flowmediated dilation of the brachial artery, a marker of vascular nitric oxideedependent dilatation. 100 A separate study by Moreau et al 101 exploring the effect of endurance training on endothelial function in women treated with estrogen therapy and found that estrogen status could have a role in modulating improvements in endothelial function with endurance training in postmenopausal women. There are limited data to suggest an improvement in endothelial vascular function with the use of estrogen replacement.…”

Section: Hormonal Therapy and Vascular Functionmentioning

confidence: 99%

Endothelial Vascular Function as a Surrogate of Vascular Risk and Aging in Women

Collins

Maas

Prasad

et al. 2020

Mayo Clinic Proceedings

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Cardiovascular disease is the leading cause of morbidity and mortality in women. We suggest the need to develop a paradigm that connects sex-and age-specific nontraditional risk factors that serve as a common mechanism ultimately leading to an increased risk of cardiovascular events. Vascular injury with abnormal repair leading to functional, rather than structural, abnormalities can be regarded as accelerated vascular aging. It emerges as a common feature that can trigger the early diagnosis and risk stratification for cardiovascular disease in women. We discuss sex-specific risk factors that can contribute to vascular injury with age, and these might not always be considered by cardiovascular physicians. It is important for the primary physician to be aware of these risk factors to enable more intensified management of this at-risk population. Novel technologies that allow the assessment of vascular function noninvasively can serve as key diagnostic and therapeutic tools with which we can identify such individuals and target therapy to manage this important patient population appropriately and effectively. We hope that this article will stimulate interest in this field and encourage further research in these important areas.

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“…flow-mediated dilatation (FMD), a measure of conduit artery endothelial function mediated primarily by NO (Adler et al 2018). When oestrogen levels declines in postmenopausal women, oestradiol administration improves also endothelial function (Hurtado et al 2016) but the magnitude of improvement depends on the timing of when this treatment is initiated. The interactions of oestrogens on multiple pathways regulating vascular function, which also are involved in the ageing process, are complex, multifactorial and not completely understood.…”

Section: Figure 1 Role Of Erα On Endothelium-derived Mediators and Vmentioning

confidence: 99%

Mechanisms underlying the influence of oestrogen on cardiovascular physiology in women

Novella

Pérez‐Cremades

Mompeón

et al. 2019

The Journal of Physiology

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Women show a lower incidence of cardiovascular diseases than age‐matched men, but this benefit disappears after menopause. Oestrogen‐mediated vascular actions are mainly attributed to oestradiol and exerted by oestrogen receptors (ERα, ERβ and G protein‐coupled oestrogen receptor), through rapid and/or genomic mechanisms, but these effects depend on ageing and inflammation. A cardiovascular approach in women's health has arisen due to controversy regarding oestrogen's beneficial impact as reported in experimental and observational studies and large randomized trials. These can be explained, in part, by two mutually non‐exclusive hypotheses. On the one hand, the timing hypothesis, which states that oestrogen‐mediated benefits occur before the detrimental effects of ageing are established in the vasculature; on the other hand, ageing and/or hormonal‐associated changes in ER expression that could lead to a deleterious imbalance in favour of ERβ over ERα, generally associated with higher inflammation and endothelial dysfunction. In experimental studies, oestradiol acting on ERα promotes the release of vasoactive compounds such as nitric oxide (NO) and prostacyclin, and shifts the angiotensin axis towards angiotensin 1–7 production. Mechanisms underlying oestradiol vascular function also include anti‐inflammatory and epigenetic modifications. 17β‐Oestradiol changes the transcriptomic profile of endothelial cells, and the involvement of miRNA in the regulatory pathways of vascular function reinforces assumptions regarding the vascular actions of oestrogen. Thus, the present Symposium Review aims to postulate the role of ERα in oestrogen modulation of endothelium‐derived mediators and vascular physiology, as well as its relationship with miRNA and inflammation, and elucidate how physiological changes in postmenopausal women counteract the observed effects.

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Effect of short-term estrogen therapy on endothelial function: a double-blinded, randomized, controlled trial

Abstract: NCT01482416.

Cited by 18 publications

References 27 publications

Influence of sex, menstrual cycle, and oral contraceptives on cerebrovascular resistance and cardiorespiratory function during Valsalva or standing

Influence of sex, menstrual cycle, and oral contraceptives on cerebrovascular resistance and cardiorespiratory function during Valsalva or standing

Endothelial Vascular Function as a Surrogate of Vascular Risk and Aging in Women

Mechanisms underlying the influence of oestrogen on cardiovascular physiology in women

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