Contents lists available at ScienceDirect Complementary Therapies in Medicine journal homepage: www.elsevier.com/locate/ctim Efficacy of Salvia officinalis extract on the prevention of insulin resistance in euglycemic patients with polycystic ovary syndrome: A double-blinded placebo-controlled clinical trial Leila Amini (PhD) a,1 , Faraz Mojab (PhD) b,2 , Shayesteh Jahanfar (PhD) c,3 , Mahdi Sepidarkish (PhD) d,4 , Zahra Raoofi (MD) e,5 , Arezoo Maleki-Hajiagha (MSc) a,f, * a Department of Midwifery, School of Nursing and Midwifery, Iran University of Medical Sciences, Tehran, Iran b Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran c Department of Public Health, the Herbert H. & Grace A. Dow College of Health Professions, Central Michigan University, United States d Department of Biostatistics and Epidemiology, Babol University of Medical Sciences, Babol, Iran e Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran f Research Development Center, Arash Women’s Hospital, Tehran University of Medical Sciences, Tehran, Iran ARTICLE INFO Keywords: Polycystic ovary syndrome Metabolism disorders Insulin resistance Obesity Salvia officinalis Common sage ABSTRACT Objectives: At the present study, we aimed at evaluating the effect of Salvia officinalis (S. officinalis) extract on "anthropometric indices" and "insulin resistance markers" in Polycystic Ovary Syndrome (PCOS) patients. Design and setting: This was a randomized, triple-blinded, controlled trial performed in gynecology hospitals affiliated to Iran University of Medical Sciences. Participants: Sixty PCOS patients diagnosed according to Rotterdam criteria. Interventions: Consumption of the 330 mg oral S. officinalis extract or placebo capsules daily for eight weeks. Main outcome measures: Body mass index (BMI), waist to hip ratio (WHR), blood pressure, homoeostatic model assessment-insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI). Results: Results showed a statistically significant decrease in the BMI (P = 0.001) in S. officinalis group, but, there were no significant differences between the two groups for WHR (P = 0.164). Although we failed to find a significant effect of S. officinalis extract on systolic blood pressure (P = 0.283) but using a multivariate model showed a significant difference between two groups regarding diastolic blood pressure (P = 0.025). Also, the consumption of S. officinalis extract, compared to the placebo, resulted in a significant decrease in Insulin levels (P < 0.001), and HOMA-IR (P < 0.001). As well as, S. officinalis extract supplementation resulted in a greater increase in QUICKI (P < 0.001) compared with placebo groups. Conclusion: S. officinalis extract at a dose of 330 mg/day could decrease BMI and systolic blood pressure, and it could enhance insulin resistance markers in euglycemic PCOS patients. Trial Registration: Iranian Registry of Clinical Trials (IRCT201504146917N2, 2015-10-03). 1. Background Polycystic ovary syndrome (PCOS) is the most common en- docrinopathy in women of reproductive age. 1 Irregular menstrual cy- cles, clinical or biochemical hyperandrogenemia, anovulatory infertility, and metabolic risk factors are common complications of this syndrome. 2,3 Women with PCOS are found to have an increased pre- valence of impaired glucose tolerance, type 2 diabetes mellitus (T2DM), 4 and insulin resistance. 5 Management of underlying metabolic abnormalities and reduction https://doi.org/10.1016/j.ctim.2019.102245 Received 23 July 2019; Received in revised form 19 October 2019; Accepted 12 November 2019 ⁎ Corresponding author at: Arash Women’s Hospital, Eastern 162th St., Baghdarnia st., Resalat Highway, Tehranpars, Tehran, Iran. E-mail addresses: amini.l@iums.ac.ir (L. Amini), sfmojab@sbmu.ac.ir (F. Mojab), jahan2s@cmich.edu (S. Jahanfar), mahdisepidarkish@gmail.com (M. Sepidarkish), raoofi.z@iums.ac.ir (Z. Raoofi), a-maleki@farabi.tums.ac.ir (A. Maleki-Hajiagha). 1 Iran School of Nursing & Midwifery, Rashid Yasemi St., Valiasr St., Tehran, Iran. 2 Shahid Beheshti School of Pharmacy, Niayesh Highway, Valiasr Ave, Tehran, Iran. 3 Dow College of Health Professions,Central Michigan University,1280 E Campus, Dr Mount Pleasant, MI 48859. 4 Babol University of Medical Sciences, Ganjafrooz Street, Babol, Mazandaran, Iran. 5 Firoozgar Hospital, Beh Afarin St.,Karim Khan Zand Ave. Tehran, Iran. Complementary Therapies in Medicine 48 (2020) 102245 Available online 13 November 2019 0965-2299/ © 2019 Elsevier Ltd. All rights reserved. T