Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Renal denervation: a potential new treatment modality for polycystic ovary syndrome? Markus P. Schlaich a , Nora Straznicky a , Mariee Grima a , Carolina Ika-Sari a , Tye Dawood a , Felix Mahfoud b , Elisabeth Lambert a , Reena Chopra a , Flora Socratous a , Sarah Hennebry a , Nina Eikelis a , Michael Bo ¨ hm b , Henry Krum d , Gavin Lambert a , Murray D. Esler a and Paul A. Sobotka c Objective Polycystic ovary syndrome (PCOS) is associated with sympathetic nervous system activation, insulin resistance, and blood pressure elevation. Renal nerve ablation has been demonstrated to reduce sympathetic outflow and improve blood pressure control. Here we report on the effects of renal denervation on hemodynamic, metabolic, and renal parameters in two obese PCOS patients with hypertension. Methods Sympathetic nerve activity was assessed at baseline using microneurography and norepinephrine spillover measurements. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp. Measurements of cystatin-C, creatinine clearance, and urinary albumin- creatinine ratio were also obtained. All measurements were repeated 3 months after bilateral renal denervation achieved via percutaneous endovascular radiofrequency ablation. Results Muscle sympathetic nerve activity and whole body norepinephrine spillover were substantially elevated at baseline in both patients by approximately 2.5–3-fold. Bilateral renal nerve ablation reduced both indices of sympathetic nerve activity. This was associated with moderate reductions in blood pressure and a substantial improvement in insulin sensitivity by approximately 17.5% in the absence of weight changes at 3-month follow-up. Glomerular hyperfiltration and urinary albumin excretion were also reduced. Conclusion These findings corroborate the relevance of sympathetic activation in PCOS and suggest that renal denervation exerts beneficial effects not only on blood pressure control but also on insulin sensitivity, renal, and endocrine abnormalities characteristic of PCOS. J Hypertens 29:991–996 Q 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Journal of Hypertension 2011, 29:991–996 Keywords: insulin sensitivity, norepinephrine, renal denervation, sympathetic Abbreviations: MSNA, muscle sympathetic nerve activity; PCOS, polycystic ovary syndrome a Neurovascular Hypertension and Kidney Disease Laboratory/Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute and Heart Centre, Alfred Hospital, Melbourne, Australia, b Department of Medicine III/Cardiology, University of Homburg/Saar, Homburg/Saar, Germany, c ARDIAN Inc., Palo Alto, California, USA and d Department of Epidemiology and Preventive Medicine, Monash Centre of Cardiovascular Research & Education in Therapeutics, Monash University, Melbourne, Australia Correspondence to Professor Markus Schlaich, Neurovascular Hypertension and Kidney Disease Laboratory, Baker IDI Heart and Diabetes Institute, PO Box 6492, St Kilda Road Central, Melbourne, VIC 8008, Australia Tel: +61 3 8532 1502; fax: +61 3 8532 1100; e-mail: markus.schlaich@bakeridi.edu.au Received 4 December 2010 Revised 10 January 2011 Accepted 20 January 2011 See editorial comment on page 836 Introduction Obesity and hypertension frequently coexist and represent two major cardiovascular risk factors with increasing burden to clinical and public health worldwide [1]. In 2005, around 23% of the world’s adult population was overweight and 10% was obese with a further pro- jected increase over the next two decades [1]. In women, polycystic ovary syndrome (PCOS) represents another major unrecognized cardiovascular risk factor [2] with an estimated prevalence of 10–18% among women in the reproductive age [2,3]. PCOS, in fact, may represent the largest underappreciated segment of the female popu- lation at risk of cardiovascular disease [2]. PCOS is the most common endocrine abnormality in women of repro- ductive age characterized by androgen excess and hyper- insulinemia with additional genetic and environmental factors such as obesity, ovarian dysfunction and hypo- thalamic pituitary abnormalities further contributing to its pathophysiology. Clinical presentation includes repro- ductive (oligo-/amenorrhea, infertility, hirsutism), meta- bolic (obesity, metabolic syndrome, insulin resistance, increased cardiovascular risk profile) and psychological features. Treatment of associated cardiovascular risk factors, including insulin resistance, hypertension, and dyslipidemia, has been recommended to be incorporated into the routine care of patients with PCOS [4]. Recent studies revealed that PCOS is a state of sympath- etic overactivity and that the degree of sympathoexcita- tion is related to the degree of PCOS severity [5]. It was suggested that the augmented sympathetic activity in PCOS contributes to the vascular risk factors associated with the condition and that therapies aimed at reducing sympathetic activity in this condition need to be studied. Original article 991 0263-6352 ß 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/HJH.0b013e328344db3a