Vascular reactivity is impaired in genetic females taking high-dose androgens

McCredie, Robyn J.; McCrohon, Jane; Turner, Leo; Griffiths, Kalinda; Handelsman, David J.; Celermajer, David S.

doi:10.1016/s0735-1097(98)00416-1

Cited by 149 publications

(96 citation statements)

References 27 publications

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“…27,28 Genetic females taking androgens have larger arteries than control females. 29 Androgen-deprivation therapy in genetic males is associated with smaller brachial artery size compared with control males. 30 These findings support the notion that sex hormone balance has different, and under certain circumstances opposite, effects on conduit artery remodeling with an androgen state causing positive remodeling compared with an estrogen state.…”

Section: Estrogen and Sex/gender-related Differences In Blood Vesselsmentioning

confidence: 99%

Estrogen and Different Aspects of Vascular Disease in Women and Men

Pepine

Nichols

Pauly

2006

Circulation Research

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C onsiderable evidence indicates that sex hormones have an important influence on cardiovascular physiology and pathology. 1,2 Recent work suggests that a mechanism based on estrogen receptor-alpha (ESR1) contributes to a range of structural and functional responses that relate to vascular disease. Most of this work focuses on ESR1 activity within the endothelium and yields variable findings due, at least in part, to differences in the vascular bed or species studied, as well as other experimental conditions such as age, estrogen status, degree of preconstriction, etc. But many findings in conduit arteries (eg, more frequent plaque erosion, increased wall stiffness, spasm, etc) and microvessels (eg, reduced coronary flow reserve, hot flashes, etc) implicate smooth muscle cells (SMCs) in gender differences in vascular disease. These cells are directly responsible for extracellular matrix production and assure the integrity of the artery wall. They may be decreased, apoptotic, or dysfunctional in terms of synthesis and repair of extracellular matrix, which is destroyed in vulnerable plaque by macrophages.In this issue of Circulation Research Montague and colleagues 3 report that activation of ESR1 decreases human aorta SMC differentiation (Figure). Importantly, they found that SMCs of men, compared with women, had reduced ESR1 expression associated with increased differentiation markers. Their work suggests that ESR1 activation switches SMC to a form that may promote plaque vulnerability. Could different activational states of ESR1 be responsible for shifting the functional characteristics of SMCs toward a phenotype that explains some complexities of gender-related differences in vascular disease? Differences in Vascular Disease Between Women and MenRisk conditions and clinical findings indicate that the pathophysiology underlying ischemic vascular disease differs between women and men. 4 A number of conditions are unique to women (eg, early age at menopause, hypertensive disorders of pregnancy, gestational diabetes, peripartum aortic or coronary dissection, polycystic ovarian syndrome, hypothalamic hypoestrogenemia, etc). Other factors linked with vascular disease or dysfunction are much more frequent in women than men (eg, migraine, coronary spasm, vasculitis, Raynaud phenomenon, etc). On this background, postmenopausal women more frequently have many traditional vascular disease risk conditions (eg, diabetes, obesity, hypertension, inactivity, etc) which occur and cluster more frequently in women than men. In addition to this greater burden of risk factors, the woman with vascular disease often is older and has more functional disability than her male counterpart. 5,6 Women have poor clinical outcomes compared with men with acute coronary syndromes, 7 chronic coronary syndromes, 8 coronary revascularization, 9 and heart failure 10 that cannot be explained by simply adjusting for age. So other factors must contribute to the increased severity of vascular disease in women compared with men.

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Section: Estrogen and Sex/gender-related Differences In Blood Vesselsmentioning

confidence: 99%

Estrogen and Different Aspects of Vascular Disease in Women and Men

Pepine

Nichols

Pauly

2006

Circulation Research

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“…In fact, in a preliminary study, we observed that the plasma testosterone level was not related to FMD in postmenopausal women (unpublished observation). It has been reported that testosterone may impair endothelial function in women, and especially in young women with polycystic ovary syndrome (34) and women taking high-dose androgens (35). Aortic rings obtained from female rats treated with testosterone showed a significant decrease in prostacyclin synthesis (36), supporting the idea that testosterone influences vasoconstriction in women.…”

Section: Discussionmentioning

confidence: 75%

Low Testosterone Level Is an Independent Determinant of Endothelial Dysfunction in Men

et al. 2007

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“…Testosterone may act as a direct vasorelaxant through influence on the vascular wall endocrine/ paracrine factors. 32,[36][37][38] It is also reported that the vasorelaxing effect of testosterone is endothelium independent, with the possible involvement of potassium channel modulation. 39,40 There is a pressing need for epidemiological studies in Africa, to determine the risk factors for the development of hypertension in specific living circumstances.…”

Section: Introductionmentioning

confidence: 99%

Prolactin, testosterone and cortisol as possible markers of changes in cardiovascular function associated with urbanization

et al. 2002

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People living in large informal settlements in South Africa showed a significant increase in cardio/cerebrovascular disease. This study was undertaken to compare the cardiovascular and endocrine parameters of urbanized and rural black female and males. The hormone levels such as prolactin, cortisol and testosterone may also change with urbanization and could make a contribution to the high rate of hypertension. For this study, 1202 black subjects were selected from 37 randomly selected rural and urbanized settlements. Resting blood pressure was recorded with a Finapres apparatus. Cardiac output, stroke volume, heart rate, total peripheral vascular resistance and compliance had been obtained with the Fast Modelflow software program. An acute laboratory stressor (hand dynamometer exercise) was applied to challenge the cardiovascular system and the measurements were repeated. Blood sampling was done and hormone levels were determined by biochemical analyses. For females, significant lower levels of cortisol were found in the urban strata in comparison with the rural strata. The testosterone levels were significantly lower and the prolactin levels significantly higher for females in the informal settlements compared with the rural strata. It is noticeable that most cardiovascular parameters showed the highest changes with the application of the stressor in the informal settlement strata and the lowest in people living on farms for both male and female. The prolactin levels in males are significantly higher in the informal settlement stratum. Subjects living in informal settlements showed a noticeable endocrine pattern of ongoing stress that can be associated with changes in the cardiovascular parameters with urbanization. This can partly explain the reported high rate of cardio/cerbrovascular disease in black South Africans living in informal settlements.

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Vascular reactivity is impaired in genetic females taking high-dose androgens

Abstract: Long-term treatment with high-dose androgens is associated with impaired vascular reactivity in genetic females, consistent with a deleterious effect of androgen excess on arterial physiology.

Cited by 149 publications

References 27 publications

Estrogen and Different Aspects of Vascular Disease in Women and Men

Estrogen and Different Aspects of Vascular Disease in Women and Men

Low Testosterone Level Is an Independent Determinant of Endothelial Dysfunction in Men

Prolactin, testosterone and cortisol as possible markers of changes in cardiovascular function associated with urbanization

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