Effect of Central Sympathoinhibition With Moxonidine on Sympathetic Nervous Activity in Polycystic Ovary Syndrome—A Randomized Controlled Trial

Sympathetic nervous system (SNS) activity is increased in polycystic ovary syndrome (PCOS). Moxonidine is a centrally acting sympatholytic drug with known beneficial effects on hypertension, insulin sensitivity, dyslipidemia and inflammation. In this double-blind placebo controlled randomized clinic...

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Main Authors: Soulmaz Shorakae, Elisabeth A. Lambert, Eveline Jona, Carolina Ika Sari, Barbora de Courten, John B. Dixon, Gavin W. Lambert, Helena J. Teede
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-10-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphys.2018.01486/full
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author Soulmaz Shorakae
Soulmaz Shorakae
Elisabeth A. Lambert
Eveline Jona
Carolina Ika Sari
Barbora de Courten
Barbora de Courten
John B. Dixon
John B. Dixon
Gavin W. Lambert
Gavin W. Lambert
Helena J. Teede
Helena J. Teede
author_facet Soulmaz Shorakae
Soulmaz Shorakae
Elisabeth A. Lambert
Eveline Jona
Carolina Ika Sari
Barbora de Courten
Barbora de Courten
John B. Dixon
John B. Dixon
Gavin W. Lambert
Gavin W. Lambert
Helena J. Teede
Helena J. Teede
author_sort Soulmaz Shorakae
collection DOAJ
description Sympathetic nervous system (SNS) activity is increased in polycystic ovary syndrome (PCOS). Moxonidine is a centrally acting sympatholytic drug with known beneficial effects on hypertension, insulin sensitivity, dyslipidemia and inflammation. In this double-blind placebo controlled randomized clinical trial we examined the effect of moxonidine on modulating sympathetic activity and downstream metabolic abnormalities in 48 pre-menopausal women with PCOS (Rotterdam diagnostic criteria), recruited from the community (January 2013–August 2015). Participants received moxonidine (0.2 mg daily initially, up titrated to 0.4 mg daily in 2 weeks) (n = 23) or placebo (n = 25) for 12 weeks. Multiunit muscle sympathetic activity (by microneurography) and plasma noradrenaline levels were measured (primary outcomes). Fasting lipids, insulin resistance, serum androgens, and inflammatory markers were measured as secondary outcomes. Forty three women completed the trial (19 moxonidine, 24 placebo). Mean change in burst frequency (−3 ± 7 vs. −3 ± 8 per minute) and burst incidence (−3 ± 10 vs. −4 ± 12 per 100 heartbeat) did not differ significantly between moxonidine and placebo groups. Women on moxonidine had a significant reduction in hs-CRP compared to placebo group (−0.92 ± 2.3 vs. −0.04 ± 1.5) which did not persist post Bonferroni correction. There was a significant association between markers of insulin resistance at baseline and reduction in sympathetic activity with moxonidine. Moxonidine was not effective in modulating sympathetic activity in PCOS. Anti-inflammatory effects of moxonidine and a relationship between insulin resistance and sympathetic response to moxonidine are suggested which need to be further explored.Clinical Trial Registration Number: (NCT01504321)
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spelling doaj.art-b9a0f5e66d2f492495bd01bdb978803f2022-12-21T19:03:38ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-10-01910.3389/fphys.2018.01486378755Effect of Central Sympathoinhibition With Moxonidine on Sympathetic Nervous Activity in Polycystic Ovary Syndrome—A Randomized Controlled TrialSoulmaz Shorakae0Soulmaz Shorakae1Elisabeth A. Lambert2Eveline Jona3Carolina Ika Sari4Barbora de Courten5Barbora de Courten6John B. Dixon7John B. Dixon8Gavin W. Lambert9Gavin W. Lambert10Helena J. Teede11Helena J. Teede12Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, AustraliaDiabetes and Vascular Medicine Unit, Monash Health, Melbourne, VIC, AustraliaFaculty of Health, Arts and Design, Iverson Health Innovation Research Institute, Swinburne University of Technology, Melbourne, VIC, AustraliaMonash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, AustraliaHuman Neurotransmitters Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, AustraliaMonash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, AustraliaDiabetes and Vascular Medicine Unit, Monash Health, Melbourne, VIC, AustraliaHuman Neurotransmitters Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, AustraliaClinical Obesity Research Laboratories, Baker Heart & Diabetes Institute, Melbourne, VIC, AustraliaFaculty of Health, Arts and Design, Iverson Health Innovation Research Institute, Swinburne University of Technology, Melbourne, VIC, AustraliaHuman Neurotransmitters Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, AustraliaMonash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, AustraliaDiabetes and Vascular Medicine Unit, Monash Health, Melbourne, VIC, AustraliaSympathetic nervous system (SNS) activity is increased in polycystic ovary syndrome (PCOS). Moxonidine is a centrally acting sympatholytic drug with known beneficial effects on hypertension, insulin sensitivity, dyslipidemia and inflammation. In this double-blind placebo controlled randomized clinical trial we examined the effect of moxonidine on modulating sympathetic activity and downstream metabolic abnormalities in 48 pre-menopausal women with PCOS (Rotterdam diagnostic criteria), recruited from the community (January 2013–August 2015). Participants received moxonidine (0.2 mg daily initially, up titrated to 0.4 mg daily in 2 weeks) (n = 23) or placebo (n = 25) for 12 weeks. Multiunit muscle sympathetic activity (by microneurography) and plasma noradrenaline levels were measured (primary outcomes). Fasting lipids, insulin resistance, serum androgens, and inflammatory markers were measured as secondary outcomes. Forty three women completed the trial (19 moxonidine, 24 placebo). Mean change in burst frequency (−3 ± 7 vs. −3 ± 8 per minute) and burst incidence (−3 ± 10 vs. −4 ± 12 per 100 heartbeat) did not differ significantly between moxonidine and placebo groups. Women on moxonidine had a significant reduction in hs-CRP compared to placebo group (−0.92 ± 2.3 vs. −0.04 ± 1.5) which did not persist post Bonferroni correction. There was a significant association between markers of insulin resistance at baseline and reduction in sympathetic activity with moxonidine. Moxonidine was not effective in modulating sympathetic activity in PCOS. Anti-inflammatory effects of moxonidine and a relationship between insulin resistance and sympathetic response to moxonidine are suggested which need to be further explored.Clinical Trial Registration Number: (NCT01504321)https://www.frontiersin.org/article/10.3389/fphys.2018.01486/fullpolycystic ovary syndromesympathetic nervous systeminsulin resistancemoxonidinerandomized controlled trial
spellingShingle Soulmaz Shorakae
Soulmaz Shorakae
Elisabeth A. Lambert
Eveline Jona
Carolina Ika Sari
Barbora de Courten
Barbora de Courten
John B. Dixon
John B. Dixon
Gavin W. Lambert
Gavin W. Lambert
Helena J. Teede
Helena J. Teede
Effect of Central Sympathoinhibition With Moxonidine on Sympathetic Nervous Activity in Polycystic Ovary Syndrome—A Randomized Controlled Trial
Frontiers in Physiology
polycystic ovary syndrome
sympathetic nervous system
insulin resistance
moxonidine
randomized controlled trial
title Effect of Central Sympathoinhibition With Moxonidine on Sympathetic Nervous Activity in Polycystic Ovary Syndrome—A Randomized Controlled Trial
title_full Effect of Central Sympathoinhibition With Moxonidine on Sympathetic Nervous Activity in Polycystic Ovary Syndrome—A Randomized Controlled Trial
title_fullStr Effect of Central Sympathoinhibition With Moxonidine on Sympathetic Nervous Activity in Polycystic Ovary Syndrome—A Randomized Controlled Trial
title_full_unstemmed Effect of Central Sympathoinhibition With Moxonidine on Sympathetic Nervous Activity in Polycystic Ovary Syndrome—A Randomized Controlled Trial
title_short Effect of Central Sympathoinhibition With Moxonidine on Sympathetic Nervous Activity in Polycystic Ovary Syndrome—A Randomized Controlled Trial
title_sort effect of central sympathoinhibition with moxonidine on sympathetic nervous activity in polycystic ovary syndrome a randomized controlled trial
topic polycystic ovary syndrome
sympathetic nervous system
insulin resistance
moxonidine
randomized controlled trial
url https://www.frontiersin.org/article/10.3389/fphys.2018.01486/full
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