Endogenous Androgens and Carotid Intimal-Medial Thickness in Women

Bernini, Giampaolo; Sgrò, M; Moretti, A; Argenio, G. F.; Barlascini, Cornelius; Cristofani, Renza; Salvetti, Antonio

doi:10.1210/jcem.84.6.5824

Cited by 120 publications

(58 citation statements)

References 28 publications

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“…This speculation could explain why their role arises only in lean women, when the effect of adiposity is blunted. Consistently, previous studies reported that serum androstenedione and testosterone were inversely associated with intima-media thickness in pre-and postmenopausal women (48,49). We could also speculate that the protective effect of androgens on inflammation might contain the increase in the risk of cardiovascular events that is expected in PCOS women, considering the many metabolic abnormalities they have.…”

Section: Discussionsupporting

confidence: 88%

Body fat and insulin resistance independently predict increased serum C-reactive protein in hyperandrogenic women with polycystic ovary syndrome

Tosi

Dorizzi

Castello

et al. 2009

European Journal of Endocrinology

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Objective: Increased serum C-reactive protein (CRP), an independent predictor of coronary heart disease, was reported in women with polycystic ovary syndrome (PCOS). It remains unclear whether this finding is due to the association between PCOS and either insulin resistance, obesity, or androgen excess, which are all common features of this condition. The aims of this study were to assess whether increased serum CRP is a specific feature of PCOS and to investigate the mechanisms underlying this association. Design and methods: Serum high-sensitivity CRP (hs-CRP) was measured in 86 hyperandrogenic women (age 21.6G4.2 years, body mass index (BMI) 23.6G3.5 kg/m 2 ), 50 with PCOS and 36 with idiopathic hyperandrogenism (HA). Thirty-five BMI-matched healthy women were also studied as controls. In these subjects, endocrine and metabolic profiles were assessed. In all hyperandrogenic subjects and 14 controls, insulin sensitivity was measured by the glucose clamp technique. Body fat was measured by bioelectrical impedance. Results: Hs-CRP concentrations were higher in PCOS women (3.43G2.01 mg/l) than in HA subjects and healthy women (2.43G1.04, P!0.005; and 2.75G0.86 mg/l, P!0.05 respectively versus PCOS). In multiple regression analyses, increased serum hs-CRP was independently predicted by higher body fat and lower insulin sensitivity. However, in lean women, serum-free testosterone was an additional, negative, predictive variable. Conclusions: PCOS is accompanied by a low-grade chronic inflammation. Body fat appears the main determining factor of this finding, which is only partly explained by insulin resistance. At least in lean women, androgen excess per se seems to play an additional, possibly protective, role in this association.

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Section: Discussionsupporting

confidence: 88%

Body fat and insulin resistance independently predict increased serum C-reactive protein in hyperandrogenic women with polycystic ovary syndrome

Tosi

Dorizzi

Castello

et al. 2009

European Journal of Endocrinology

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“…The negative association of these atherogenic molecules with androgens advocates a probable role of androgens in cardiovascular protection in PCOS subjects. The role of androgens in cardiovascular risk factors in women with PCOS has been controversial; however, there are studies suggesting a protective role of androgens (28,29). Interestingly, no association of NGAL and MMP-9/NGAL complex with insulin resistance or hsCRP was demonstrated in this study, a finding that implies alternative pathways of NGAL and MMP-9 regulation.…”

Section: Discussioncontrasting

confidence: 68%

Serum concentrations of atherogenic proteins neutrophil gelatinase-associated lipocalin and its complex with matrix metalloproteinase-9 are significantly lower in women with polycystic ovary syndrome: hint of a protective mechanism?

Diamanti-Kandarakis¹,

Livadas²,

Kandarakis³

et al. 2008

European Journal of Endocrinology

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Background: Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) have been considered as important mediators of vascular remodeling and plaque instability. The formation of a complex with NGAL and MMP-9 is crucial for atherotic plaque erosion and thrombus formation. In women with polycystic ovary syndrome (PCOS), the incidence of cardiovascular clinical events is not increased, despite the fact that they display a wide spectrum of risk factors. Since the instability of atherosclerotic plaque is a key factor in the clinical manifestations of cardiovascular disease, molecules challenging the plaque stability should be investigated. Aim: To determine serum levels of NGAL and MMP-9/NGAL complex in women with PCOS. Subjects and methods: PCOS subjects (40) were compared with those (40) matched for age and body mass index (BMI) controls. In each subject, fasting levels of glucose, insulin, gonadotropins, estradiol, androgens, C-reactive protein, NGAL, and MMP-9/NGAL were determined. Results: NGAL and MMP-9/NGAL complex levels were significantly lower in the PCOS group compared with controls (30.4G24.3 vs 70.7G37.9 mg/l, P!0.0001) and (31.5G26.6 vs 115.1G66.9 mg/l, P!0.0001) respectively. When patients and controls were stratified according to BMI, it was shown that NGAL and MMP-9/NGAL levels were significantly lower in lean (P!0.0002 and P!0.0001 respectively) and overweight (P!0.0004 and P!0.002 respectively) PCOS subjects compared with controls. Conclusions: These findings indicate that NGAL and MMP-9/NGAL complex, two molecules that activate atherotic plaque erosion, is in lower concentrations in PCOS subjects. The role of NGAL and MMP-9/NGAL complex needs to be further investigated, since suppression of these atheromatous molecules might have a protective role in women with PCOS.

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“…122 However, it is unclear whether this decline adversely affects vascular health in women. Higher serum testosterone concentrations, within the physiological range, have been associated with lower carotid intima-media thickness, 123 suggesting potential protective effects of endogenous testosterone on cardiovascular health in pre-and postmenopausal women. Conversely, it is well known that women with polycystic ovary syndrome, who exhibit high androgen levels, are at a higher risk for CVD.…”

Section: Testosterone Deficiency and Cvd In Womenmentioning

confidence: 99%

Hormonal effects on blood vessels

Akishita

2012

Hypertens Res

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The incidence of cardiovascular disease (CVD) is lower in younger women than in men of the same age, but it increases after menopause, implicating the atheroprotective action of endogenous estrogen. Although observational studies have suggested the efficacy of estrogen therapy in postmenopausal women, placebo-controlled, randomized trials, such as the Women's Health Initiative, have not confirmed effects of estrogen therapy on CVD. Conversely, basic, experimental research has progressed and provided mechanistic insight into estrogen's action on blood vessels. By contrast, the vascular effects of androgens remain poorly understood and have been controversial for a long time. In recent years, an increasing body of evidence has suggested that androgens may exert protective effects against the development of atherosclerosis, at least in elderly men. Epidemiological studies have shown that the incidence of and mortality due to CVD were increased in elderly men with low testosterone levels, although the efficacy of androgen therapy remains unknown. Furthermore, recent experimental studies have demonstrated the direct action of androgens on the vasculature. In this review, we illustrate the effects of sex steroids on the cardiovascular system, focusing on the action of testosterone on the blood vessels.

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Endogenous Androgens and Carotid Intimal-Medial Thickness in Women

Cited by 120 publications

References 28 publications

Body fat and insulin resistance independently predict increased serum C-reactive protein in hyperandrogenic women with polycystic ovary syndrome

Body fat and insulin resistance independently predict increased serum C-reactive protein in hyperandrogenic women with polycystic ovary syndrome

Serum concentrations of atherogenic proteins neutrophil gelatinase-associated lipocalin and its complex with matrix metalloproteinase-9 are significantly lower in women with polycystic ovary syndrome: hint of a protective mechanism?

Hormonal effects on blood vessels

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