Endocrine Abstracts (2017) 49 GP141 | DOI: 10.1530/endoabs.49.GP141

Effects of central sympathoinhibition with moxonidine on the elevated sympathetic nervous activity and downstream metabolic abnormalities observed in polycystic ovary syndrome

Soulmaz Shorakae1,2, Elisabeth Lambert3,4, Eveline Jona1, Carolina Ika Sari3, Barbora de Courten1,2, Gavin Lambert3,4 & Helena Teede1,2

1Monash Centre for Health Research and Implementation, Monash University, Melbourne, Australia; 2Diabetes and Vascular Medicine Unit, Monash Health, Melbourne, Australia; 3Human Neurotransmitters Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Australia; 4Department of Physiology, Monash University, Melbourne, Australia.

The role of the sympathetic nervous system (SNS) in the pathophysiology of PCOS and associated cardiometabolic risks is emerging. Previous studies support increased SNS activity in PCOS, potentially contributing to metabolic features via multiple mechanisms including insulin resistance. Moxonidine is a second-generation imidazoline I1 agonist, acting centrally, inhibiting sympathetic outflow at the level of rostral ventrolateral medulla with known beneficial effects on hypertension, insulin sensitivity, dyslipidemia and inflammation. This study aimed to explore pharmacological modification of SNS activity, for the first time, in women with PCOS, using moxonidine. 51 premenopausal women (mean age: 29.8±5.9 years, mean BMI: 29.0±5.4 kg/m2) with PCOS were recruited, from a community setting, in a double blind placebo controlled clinical trial. 48 women were weaned off any interacting medication for 3 months then randomized to moxonidine (0.2mg daily initially, up titrated to 0.4mg daily in 2 weeks) (n=23) or placebo (n=25) for 3 months. Multiunit muscle SNS activity (MSNA by microneurography), heart rate variability (HRV) and endothelial function (ischaemic reactive hyperaemia index (RHI)) were examined. Fasting lipids, serum androgens, markers of insulin resistance and inflammatory markers were measured prior to and following intervention. 45 women completed the trial (19 moxonidine and 23 placebo). Change in MSNA (−3.23±6.71 vs −2.81±8.2 bursts per minute, P=NS), HRV (5.26±13.56 vs 2.95±15.37 nu in low frequency component, P=NS) and endothelial function (0.10±0.70 vs 0.06±0.67 in RHI, P=NS) did not differ significantly with moxonidine compared to the placebo. Mean changes in BP, fasting lipids, HOMA-IR, hs-CRP and androgens were similar in both groups. In women on moxonidine, change in BMI correlated positively with change in MSNA (r2=0.593, P=0.03). Central sympathoinhibition with moxonidine does not modify higher SNS activity and downstream metabolic abnormalities in PCOS. Sympathoexcitation in PCOS may be driven peripherally or from other brain regions with further research needed.

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