Hyperreninemia Characterizing Women with Polycystic Ovary Syndrome Improves after Metformin Therapy

Diamanti-Kandarakis, Evanthia; Economou, Frangiskos; Livadas, Sarantis; Tantalaki, Evangelia; Piperi, Christina; Papavassiliou, Athanasios G.; Panidis, Dimitrios

doi:10.1159/000201791

Cited by 19 publications

(13 citation statements)

References 101 publications

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“…Aldosterone impairs endothelial function through increased NADPH oxidase activity and mitochondrial generation of reactive oxygen species, which decrease bioavailability of nitric oxide (15,32). The RALES study showed that spironolactone (25 mg), added to conventional therapy for chronic heart failure, dramatically reduced mortality (30). Yet, spironolactone in the study did not have a clinically significant hemodynamic effect.…”

Section: Discussionmentioning

confidence: 96%

“…activity of the cytochrome was reported only at very high doses or under in vitro experimental conditions, for example in bovine and human adrenal cortical mitochondria (28,29). Spironolactone-induced improvement of endothelial function could also be in part a consequence of aldosterone antagonism, as shown in studies investigating chronic heart failure (30). PCOS patients were reported to have significantly increased aldosterone levels in comparison with controls, although values were still within the normal range (13).…”

Section: Discussionmentioning

confidence: 99%

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Influence of spironolactone treatment on endothelial function in non-obese women with polycystic ovary syndrome

Studen¹,

Šebeštjen²,

Pfeifer³

et al. 2011

European Journal of Endocrinology

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Objective: Accumulating evidence connects polycystic ovary syndrome (PCOS) with increased risk of cardiovascular disease. Endothelial dysfunction is present in PCOS and represents an early, reversible marker of cardiovascular damage. As androgens and renin-angiotensin-aldosterone system are implicated in the atherogenesis process of PCOS, we tested the hypothesis that treatment with spironolactone, an androgen and mineralocorticoid receptor blocking drug, might reverse endothelial dysfunction in PCOS. Patients: A total of 30 non-obese PCOS patients, compared with 20 body mass index matched control subjects, were evaluated. PCOS patients were given spironolactone 100 mg daily in 21-day long intervals followed by a 7-day pause, for 6 months. Measurements: Flow-mediated dilatation (FMD), glyceryl trinitrate-induced dilatation, free testosterone, androstenedione, DHEA-sulfate, total, low-density lipoprotein (LDL)-, high-density lipoproteincholesterol, and triglycerides were determined at baseline and after 6 months. Results: Results are expressed as median (25-75th percentile). At baseline, FMD was significantly lower in PCOS patients than in controls: 6.0 (0.0-11.7) vs 10.2 (6.8-15.9) %, PZ0.018. This difference disappeared after 6 months of spironolactone treatment, as FMD in PCOS patients significantly increased to 8.3 (5.7-10.3) %, PZ0.034, and was no longer different from controls. In PCOS patients, serum androgen levels did not change during treatment, while total and LDL-cholesterol decreased significantly from 4.8 (4.1-5.1) mmol/l to 4.4 (3.9-4.8) mmol/l and from 2.5 (2.1-3.1) to 2.2. (2.1-2.5) mmol/l, P!0.05 and P!0.05 respectively. Conclusion: Treatment with spironolactone normalized endothelial function and improved cholesterol levels in non-obese PCOS patients.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Influence of spironolactone treatment on endothelial function in non-obese women with polycystic ovary syndrome

Studen¹,

Šebeštjen²,

Pfeifer³

et al. 2011

European Journal of Endocrinology

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“…The RAS is activated in women with PCOS, and telmisartan, an angiotensin AT1 receptor antagonist, reduces their blood pressure 42, 43 . We found that angiotensinogen mRNA expression was increased 10 fold in HAF rats.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular-Renal and Metabolic Characterization of a Rat Model of Polycystic Ovary Syndrome

et al. 2011

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Background Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is also associated with increased risk of cardiovascular disease at the time of PCOS and later in life. Hypertension, a common finding in women with PCOS, is a leading risk factor for cardiovascular disease. The mechanisms responsible for hypertension in women with PCOS has not been elucidated. Objectives To characterize the cardiovascular-renal consequences of hyperandrogenemia in a female rat model. Methods Female Sprague Dawley rats, aged 4–6 weeks, were implanted with DHT or placebo pellets lasting 90 days. Following 10–12 weeks, blood pressure (by radiotelemetry), renal function (glomerular filtration rate, morphology, protein and albumin excretion), metabolic parameters (plasma insulin, glucose, leptin, cholesterol, oral glucose tolerance test), inflammation (plasma TNF-α), oxidative stress (mRNA expression of NADPH oxidase subunits, p22phox, p47phox, gp91phox, and NOX4, nitrate/nitrite excretion), and mRNA expression of components of the renin-angiotensin system (RAS) (angiotensinogen, angiotensin-I-converting enzyme (ACE), AT1 receptor) were determined. Results Plasma DHT was increased 3-fold in hyperandrogenemic female 1 rats, whereas plasma estradiol levels were not different compared to control females. HAF rats exhibited estrus cycle dysfunction. They also had increased food intake and body weight, increased visceral fat, glomerular filtration rate, renal injury, insulin resistance and metabolic dysfunction, oxidative stress, and increased expression of angiotensinogen and ACE and reduced AT1 receptor expression. Conclusions The HAF rat is a unique model that exhibits many of the characteristics of PCOS in women and is a useful model in order to study the mechanisms responsible for hypertension.

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“…The ovarian RAS can induce hyperandrogenism and contribute to the manifestation of PCOS. It is also known that baseline levels of renin are elevated in women with PCOS and correlate with serum androgen levels (32,33). Prorenin production has been detected in the theca cells (34), while the cystic follicles in PCOS have demonstrated increased production of renin and angiotensin II from theca and granulosa cells, as occurs in normal atretic ovarian follicles (35).…”

Section: Discussionmentioning

confidence: 99%

Increased frequency of the DI genotype of the angiotensin-I converting enzyme and association of the II genotype with insulin resistance in polycystic ovary syndrome

Koika

Georgopoulos

Piouka

et al. 2012

European Journal of Endocrinology

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Objective: The polycystic ovary syndrome (PCOS) is a common and complex disease with unclear pattern of inheritance, characterized by an androgen excess, while hyperinsulinemia and insulin resistance (IR) are common features of the syndrome. The angiotensin I converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism was proved to be involved in many pathophysiological conditions, including hypertension and IR. Design: The purpose of this study was to evaluate the involvement of the ACE gene polymorphism in the pathogenesis of PCOS. Methods: In a case-control association study involving 801 PCOS women and 266 healthy controls, hormonal determinations and ACE polymorphism genotyping were performed. The PCOS women were classified into three groups: Group A presented biochemical hyperandrogenism, combined with anovulation and polycystic ovarian morphology; Group B, clinical hyperandrogenism combined with anovulation and polycystic ovarian morphology; and Group C, chronic anovulation and polycystic ovarian morphology. Results: A significant increase in the frequency of the DI genotype of the ACE polymorphism was detected in PCOS women as a whole (PZ0.035), in PCOS Group A (PZ0.039) and Group B (PZ0.010), while there was no difference in Group C (PZ0.939). Significant difference was also observed in hyperandrogenic PCOS women as a whole (Group ACB) (PZ0.017). The II genotype was positively correlated with HOMA-IR and QUICKI and with fasting insulin and glucose/insulin ratio in these groups. Conclusions: The association study of the ACE I/D polymorphism in PCOS women demonstrates an increase in the DI genotype incidence and an association of the II genotype with IR.

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Hyperreninemia Characterizing Women with Polycystic Ovary Syndrome Improves after Metformin Therapy

Cited by 19 publications

References 101 publications

Influence of spironolactone treatment on endothelial function in non-obese women with polycystic ovary syndrome

Influence of spironolactone treatment on endothelial function in non-obese women with polycystic ovary syndrome

Cardiovascular-Renal and Metabolic Characterization of a Rat Model of Polycystic Ovary Syndrome

Increased frequency of the DI genotype of the angiotensin-I converting enzyme and association of the II genotype with insulin resistance in polycystic ovary syndrome

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