Vascular Reactivity in Congenital Hypogonadal Men before and after Testosterone Replacement Therapy

Bernini, Giampaolo; Versari, Daniele; Moretti, A; Virdis, Agostino; Ghiadoni, Lorenzo; Bardini, Michele; Taurino, Chiara; Canale, Domenico; Taddei, Stefano; Salvetti, Antonio

doi:10.1210/jc.2005-1398

Cited by 52 publications

(25 citation statements)

References 37 publications

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“…With regard to conduit vessels, it was found that males with end-stage kidney disease and who were androgen deficient had decreased flow-mediated and nitrate-mediated dilation of the brachial artery (5). In contrast to those studies, 6 mo of testosterone treatment was shown to decrease microvascular endothelium-dependent vasodilation in hypogonadal men (1). In our present study, testosterone did not appear to have a consistent effect.…”

Section: Discussioncontrasting

confidence: 99%

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Effects of testosterone and estradiol on cutaneous vasodilation during local warming in older men

Sokolnicki

Khosla

Charkoudian

2007

American Journal of Physiology-Endocrinology and Metabolism

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Sokolnicki LA, Khosla S, Charkoudian N. Effects of testosterone and estradiol on cutaneous vasodilation during local warming in older men. Am J Physiol Endocrinol Metab 293: E1426-E1429, 2007. First published September 25, 2007; doi:10.1152/ajpendo.00535.2007.-Microvascular vasodilation in humans can become impaired with age, leading to cardiovascular diseases ranging from mild to life-threatening. Reproductive hormones may confer some protection on the vascular system in women; however, it is unclear whether the same is true in men. Our goal was to evaluate the impact of four hormonal conditions (testosterone only, estradiol only, testosterone and estradiol, no testosterone and no estradiol) on microvascular vasodilator responsiveness in the skin of older men. We hypothesized that in older healthy men estradiol promotes cutaneous microvascular dilation during local warming of the skin and that testosterone inhibits this dilation. We measured skin blood flow using laser Doppler flowmetry during 35 min of cutaneous local warming to 42°C in 52 healthy men (average age 67 Ϯ 1 yr). Subjects were randomized to one of the four hormonal conditions and were studied before and after hormone treatments. The endothelium-dependent vasodilator response to local warming was not different among groups either before or after hormone treatment. For example, with testosterone-only treatment this vasodilator response was 220 Ϯ 13 AU, and with estrogen only the response averaged 246 Ϯ 12 AU (P Ͼ 0.05). We conclude that, within the doses employed in the present study, testosterone and estradiol did not consistently alter cutaneous vasodilator responsiveness in healthy older men. reproductive hormones; skin blood flow; aging; microvasculature A MAJOR HEALTH CONCERN associated with the growing elderly population in the United States is the increased risk for cardiovascular diseases with advancing age. The ability of the microvasculature to dilate has significant implications for protection against these diseases, including hypertension, stroke, and myocardial infarction. Microvascular endothelial function in health and disease has been evaluated by measurement of the cutaneous vasodilator response to local warming (6, 9, 11, 12). During local warming, cutaneous vasodilation occurs via two independent pathways: an initial rapid peak caused by local sensory nerves, followed by a slow rise in skin blood flow (SkBF) that plateaus after ϳ30 min of heating. The plateau phase of vasodilation is mediated in large part by local nitric oxide (NO) release (6, 9).Previously, Charkoudian et al. (3) demonstrated that cutaneous vasodilation to local warming was augmented by exogenous reproductive hormones (oral contraceptives) in young women. The authors hypothesized that this was primarily an effect of estrogen to augment the NO-dependent vasodilator response. In men, testosterone may inhibit NO-dependent vasodilation (5). The effects of estrogen on vascular control in women have been well documented; however, vascular influences of reproductive h...

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Section: Discussioncontrasting

confidence: 99%

“…In contrast, previous studies in women have suggested that estrogen augments cutaneous vasodilator responsiveness (2,3). Potential influences of testosterone on endothelium-dependent vasodilation are less clear (1,5). This is the first study that has looked at the microvascular effects of estrogen and testosterone in healthy older men.…”

Section: Discussionmentioning

confidence: 76%

Effects of testosterone and estradiol on cutaneous vasodilation during local warming in older men

Sokolnicki

Khosla

Charkoudian

2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Testosterone confers symptomatic benefits in patients with coronary heart disease and heart failure (13,14) apparently through its action as a vasodilator. Testosterone can also increase nitric oxide availability and improve flow-mediated dilation in hypogonadal men (15).…”

Section: Introductionmentioning

confidence: 99%

Effect of testosterone replacement therapy on arterial stiffness in older hypogonadal men

Yaron

Greenman

Rosenfeld

et al. 2009

European Journal of Endocrinology

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Objective: To assess arterial stiffness in a cohort of hypogonadal males and to investigate the effect of testosterone replacement therapy on arterial properties in this specific group. Design: Eighteen male patients with untreated acquired hypogonadism due to either adult-onset idiopathic hypogonadotropic hypogonadism (nZ9) or pituitary tumor (nZ9) and 12 age-, sex, and weight-matched eugonadal healthy controls were recruited for the study. Arterial properties, plasma glucose, lipid profile, total, and bioavailable testosterone (BT) levels were measured in fasting state. In the hypogonadal subjects, the effect of transdermal testosterone replacement therapy on arterial properties was studied by repeat noninvasive measurements at baseline, as well as 48 h and 90 days following the initiation of treatment. Methods: Arterial stiffness was evaluated using applanation tonometry and pulse wave analysis by three different standard devices that assess various measures of arterial stiffness: pulse wave velocity (PWV), augmentation index (AIx), and large/small artery compliance (C1 and C2). Results: Age-and blood pressure-adjusted PWV was significantly higher in hypogonadal men (8.90G 2.29 vs 6.78G1.16 m/s in the control group; PZ0.025). Testosterone therapy increased BT level from 2.01G1.04 to 4.68G2.43 and 7.83G6.2 nmol/l after 48 h and 3 months respectively (PZ0.001). PWV decreased from 8.9G2.29 to 8.24G1.39 and 8.25G1.82 m/s after 48 h and 3 months of treatment respectively (PZ0.03). Conclusions: Male hypogonadism is associated with increased PWV, which is rapidly but incompletely ameliorated by normalization of circulating testosterone levels.

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“…Pero, la administración de testosterona no mejora la vasodilatación, y por el contrario empeora la disponibilidad del NO (35) .…”

Section: El Papel De Los Estrógenosunclassified

Endotelio y mujer: similaridad y diferencias con el hombre

2014

An Fac med

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ResumenExisten diferencias intrasexo en lo referente a función y disfunción endotelial. Aunque ambos sexos comparten los mismos receptores hormonales (estrogénicos y de testosterona), varían en su expresión. Los receptores estrogénicos en la mujer ejercen acción protectora vascular por vía genómica y no genómica, mediadas a través del óxido nítrico. La mujer está 'protegida' para la aterotrombosis hasta la menopausia. La pérdida abrupta de la protección vascular conlleva a magnificación del daño vascular posmenopausia, más si ya tiene disfunción endotelial. La mujer hasta la menopausia tiene un ambiente vascular menos oxidativo con relación al hombre. Las mujeres tienen más angina microvascular y menos infarto con elevación del segmento ST, debido a que hacen más disfunción endotelial ante los factores de riesgo. Las mujeres posmenopáusicas hacen más hipertensión sistólica y por consiguiente tienen mayor presión de pulso y rigidez arterial, esto último mediado por el óxido nítrico. Palabras clave: Endotelio, endotelio y mujer, estrógenos y endotelio. Abstract There are intra-sexual differences in both endothelial function and dysfunction. Although both sexes share the same hormonal receptors (estrogen and testosterone receptors) these differ in expression. Female estrogen receptors exert vascular protective action through nitric oxide-mediated genomic and non-genomic pathways. Women are 'protected' from atherothrombosis until menopause. The abrupt loss of vascular protection leads to a magnification of post-menopausal vascular damage, which is higher when endothelial dysfunction is already present. Women have a less oxidative vascular environment until menopause than men. Women experience more microvascular angina and less myocardial infarction with ST segment elevation, because they display more endothelial dysfunction when risk factors are present. Post-menopausal women develop more prominently systolic hypertension and therefore higher pulse pressure and arterial stiffness, the latter mediated by nitric oxide. Keywords: Endothelium, vascular sex differences, estrogens and endothelium. An

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Vascular Reactivity in Congenital Hypogonadal Men before and after Testosterone Replacement Therapy

Abstract: Hypogonadal patients show impaired vascular reactivity, including endothelial-dependent vasodilation due to reduced nitric oxide availability. TS administration further impairs nitric oxide availability in these patients.

Cited by 52 publications

References 37 publications

Effects of testosterone and estradiol on cutaneous vasodilation during local warming in older men

Effects of testosterone and estradiol on cutaneous vasodilation during local warming in older men

Effect of testosterone replacement therapy on arterial stiffness in older hypogonadal men

Endotelio y mujer: similaridad y diferencias con el hombre

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