Effect of resveratrol on menstrual cyclicity, hyperandrogenism and metabolic profile in women with PCOS

  • Asieh Mansour
    Affiliations
    Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute Shahid Beheshti University of Medical Science, Tehran, Iran
    Search for articles by this author
  • Majid Samadi
    Affiliations
    Radiology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
    Search for articles by this author
  • Milad Sanginabadi
    Affiliations
    Radiology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
    Search for articles by this author
  • Hadis Gerami
    Affiliations
    Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
    Search for articles by this author
  • Sara Karimi
    Affiliations
    Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute Shahid Beheshti University of Medical Science, Tehran, Iran
    Search for articles by this author
  • Saeed Hosseini
    Affiliations
    Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, International Campus, Tehran University of Medical Sciences, Tehran, Iran
    Search for articles by this author
  • Nooshin Shirzad
    Affiliations
    Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Depateman of Endocrinology, Vali-Asr Hospital, Endocrinology and Metabolism Research Center, Imam Khomeini Complex Hospital, Tehran University of Medical Sciences, Tehran, Iran
    Search for articles by this author
  • Azita Hekmatdoost
    Affiliations
    Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute Shahid Beheshti University of Medical Science, Tehran, Iran
    Search for articles by this author
  • Armita Mahdavi-Gorabi
    Affiliations
    Social Determinants of Health Research Center, Alborz University of Medical Sciences, Karaj, Iran
    Search for articles by this author
  • Author Footnotes
    1 Equally contributed as corresponding authors.
    Mohammad Reza Mohajeri-Tehrani
    Footnotes
    1 Equally contributed as corresponding authors.
    Affiliations
    Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
    Search for articles by this author
  • Author Footnotes
    1 Equally contributed as corresponding authors.
    Mostafa Qorbani
    Correspondence
    Corresponding author.
    Footnotes
    1 Equally contributed as corresponding authors.
    Affiliations
    Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran

    Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
    Search for articles by this author
  • Author Footnotes
    1 Equally contributed as corresponding authors.
Published:February 06, 2021DOI:https://doi.org/10.1016/j.clnu.2021.02.004

      Summary

      Aim

      The aim of this randomized trial was to find whether resveratrol could improve menstrual dysfunction, clinical signs (i.e., acne and hair loss), and the biochemical evidence of hyperandrogenism in the women with PCOS.

      Methods

      Women, in the age range of 18–40 years, diagnosed with PCOS, as defined by the Rotterdam criteria, and no other known cause of abnormal menstruation, were recruited. Participants were randomized based on a 1:1 ratio, to either 1000 mg resveratrol or 1000 mg placebo daily groups, for a period of 3 months.

      Results

      Seventy-eight patients were randomized: 39 to the resveratrol group and 39 to placebo. Results were analyzed according to the intention-to-treat principle. At the end of study, it was found that women who received resveratrol had a statistically higher regular menstruation rate, as compared to those who got placebo (76.47% vs. 51.61%; p = 0.03), and lower hair loss (32.10% vs. 68.00%; p = 0.009). We also found no significant differences between the two groups in terms of ovarian and adrenal androgens, sex hormone binding globulin (SHBG) levels, free androgen index (FAI), glycoinsulinemic metabolism and lipid profile. Moreover, the resveratrol treatment did not interfere with the thyroid, liver and kidney functions. The negative effect of resveratrol on the body composition was also observed, though not influencing changes in the weight, relative to the placebo group.

      Conclusion

      Resveratrol improved menstrual cyclicity and hair loss, even though levels of androgens, insulin and lipids remained unchanged.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Nutrition
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Rencber S.F.
        • Ozbek S.K.
        • Eraldemır C.
        • Sezer Z.
        • Kum T.
        • Ceylan S.
        • et al.
        Effect of resveratrol and metformin on ovarian reserve and ultrastructure in PCOS: an experimental study.
        J Ovarian Res. 2018; 11: 55
        • Arentz S.
        • Abbott J.A.
        • Smith C.A.
        • Bensoussan A.
        Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings.
        BMC Compl Alternative Med. 2014; 14: 511
        • Patel S.
        Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy.
        J Steroid Biochem Mol Biol. 2018; 182: 27-36
        • Mansour A.
        • Hosseini S.
        • Larijani B.
        • Mohajeri-Tehrani M.R.
        Nutrients as novel therapeutic approaches for metabolic disturbances in polycystic ovary syndrome.
        EXCLI journal. 2016; 15: 551
        • Ortega I.
        • Duleba A.J.
        Ovarian actions of resveratrol.
        Ann N Y Acad Sci. 2015; 1348: 86-96
        • Wong D.H.
        • Villanueva J.A.
        • Cress A.B.
        • Duleba A.J.
        Effects of resveratrol on proliferation and apoptosis in rat ovarian theca-interstitial cells.
        Mol Hum Reprod. 2010; 16: 251-259
        • Ortega I.
        • Villanueva J.A.
        • Wong D.H.
        • Cress A.B.
        • Sokalska A.
        • Stanley S.D.
        • et al.
        Resveratrol potentiates effects of simvastatin on inhibition of rat ovarian theca-interstitial cells steroidogenesis.
        J Ovarian Res. 2014; 7: 21
        • Banaszewska B.
        • Wrotyńska-Barczyńska J.
        • Spaczynski R.Z.
        • Pawelczyk L.
        • Duleba A.J.
        Effects of resveratrol on polycystic ovary syndrome: a double-blind, randomized, placebo-controlled trial.
        J Clin Endocrinol Metab. 2016; 101: 4322-4328
        • Bahramrezaie M.
        • Amidi F.
        • Aleyasin A.
        • Saremi A.
        • Aghahoseini M.
        • Brenjian S.
        • et al.
        Effects of resveratrol on VEGF & HIF1 genes expression in granulosa cells in the angiogenesis pathway and laboratory parameters of polycystic ovary syndrome: a triple-blind randomized clinical trial.
        J Assist Reprod Genet. 2019; : 1-12
        • Group Reaspcw
        Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS).
        Hum Reprod. 2004; 19: 41-47
        • Al Kindi M.K.
        • Al Essry F.S.
        • Al Essry F.S.
        • Mula-Abed W.-A.S.
        Validity of serum testosterone, free androgen index, and calculated free testosterone in women with suspected hyperandrogenism.
        Oman Med J. 2012; 27: 471
        • Franks S.
        • Hardy K.
        Androgen action in the ovary.
        Front Endocrinol. 2018; 9: 452
        • Ma H.
        • Qiao Z.
        Analysis of the efficacy of resveratrol treatment in patients with scarred uterus.
        Experimental and therapeutic medicine. 2018; 15: 5410-5414
        • Benrick A.
        • Maliqueo M.
        • Miao S.
        • Villanueva J.A.
        • Feng Y.
        • Ohlsson C.
        • et al.
        Resveratrol is not as effective as physical exercise for improving reproductive and metabolic functions in rats with dihydrotestosterone-induced polycystic ovary syndrome.
        Evid base Compl Alternative Med. 2013; 2013
        • Farzana F.
        • Sulaiman A.
        • Ruckmani A.
        • Vijayalakshmi K.
        • Karunya Lakshmi G.
        • Shri Ranjini S.
        Effects of flaxseeds supplementation in polycystic ovarian syndrome.
        Int J Pharmaceut Sci Rev Res. 2015; 31: 113-119
        • Okpashi V.
        • Obi B.
        • Okagu I.
        • Okoroafor P.
        Epidemiological assessment of testosterone levels in women population: a factorial analysis of cell proliferation.
        Biol Med. 2018; 10: 2
        • Daka B.
        • Rosen T.
        • Jansson P.A.
        • Råstam L.
        • Larsson C.A.
        • Lindblad U.
        Inverse association between serum insulin and sex hormone-binding globulin in a population survey in Sweden.
        Endocrine connections. 2013; 2: 18-22
        • Sathyapalan T.
        • Atkin S.L.
        Evidence for statin therapy in polycystic ovary syndrome.
        Therapeutic advances in endocrinology and metabolism. 2010; 1: 15-22
        • Ortega I.
        • Wong D.H.
        • Villanueva J.A.
        • Cress A.B.
        • Sokalska A.
        • Stanley S.D.
        • et al.
        Effects of resveratrol on growth and function of rat ovarian granulosa cells.
        Fertil Steril. 2012; 98: 1563-1573
        • Ortega I.
        • Villanueva J.A.
        • Wong D.H.
        • Cress A.B.
        • Sokalska A.
        • Stanley S.D.
        • et al.
        Resveratrol reduces steroidogenesis in rat ovarian theca-interstitial cells: the role of inhibition of Akt/PKB signaling pathway.
        Endocrinology. 2012; 153: 4019-4029
        • Jonard S.
        • Dewailly D.
        The follicular excess in polycystic ovaries, due to intra-ovarian hyperandrogenism, may be the main culprit for the follicular arrest.
        Hum Reprod Update. 2004; 10: 107-117
        • Alpañés M.
        • Fernández-Durán E.
        • Escobar-Morreale H.F.
        • Carmina
        • Asuncion
        • Azziz
        • et al.
        Androgens and polycystic ovary syndrome.
        Expet Rev Endocrinol Metabol. 2012; 7: 91-102
        • Hirano Y.
        • Kondo R.
        • Sakai K.
        5α-Reductase inhibitory compounds produced by polymerization of resveratrol with horseradish peroxidase.
        J Wood Sci. 2002; 48: 64-68
        • Rahman Siddique H.
        • Nanda S.
        • Parray A.
        • Saleem M.
        Androgen receptor in human health: a potential therapeutic target.
        Curr Drug Targets. 2012; 13: 1907-1916
        • Tagliaferri V.
        • Romualdi D.
        • Scarinci E.
        • Cicco S.D.
        • Florio C.D.
        • Immediata V.
        • et al.
        Melatonin treatment may be able to restore menstrual cyclicity in women with PCOS: a pilot study.
        Reprod Sci. 2018; 25: 269-275
        • Mousavi S.
        • Milajerdi A.
        • Sheikhi A.
        • Kord-Varkaneh H.
        • Feinle-Bisset C.
        • Larijani B.
        • et al.
        Resveratrol supplementation significantly influences obesity measures: a systematic review and dose–response meta-analysis of randomized controlled trials.
        Obes Rev. 2019; 20: 487-498
        • Christenson J.
        • Whitby S.J.
        • Mellor D.
        • Thomas J.
        • McKune A.
        • Roach P.D.
        • et al.
        The effects of resveratrol supplementation in overweight and obese humans: a systematic review of randomized trials.
        Metab Syndr Relat Disord. 2016; 14: 323-333
        • Poulsen M.M.
        • Vestergaard P.F.
        • Clasen B.F.
        • Radko Y.
        • Christensen L.P.
        • Stødkilde-Jørgensen H.
        • et al.
        High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition.
        Diabetes. 2013; 62: 1186-1195
        • Huhn S.
        • Beyer F.
        • Zhang R.
        • Lampe L.
        • Grothe J.
        • Kratzsch J.
        • et al.
        Effects of resveratrol on memory performance, hippocampus connectivity and microstructure in older adults–A randomized controlled trial.
        Neuroimage. 2018; 174: 177-190
        • Zortea K.
        • Franco V.
        • Francesconi L.
        • Cereser K.
        • Lobato M.
        • Belmonte-de-Abreu P.
        Resveratrol supplementation in schizophrenia patients: a randomized clinical trial evaluating serum glucose and cardiovascular risk factors.
        Nutrients. 2016; 8: 73
        • Zhu X.
        • Wu C.
        • Qiu S.
        • Yuan X.
        • Li L.
        Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: systematic review and meta-analysis.
        Nutr Metab. 2017; 14: 60
        • Kolodziejczyk B.
        • Duleba A.J.
        • Spaczynski R.Z.
        • Pawelczyk L.
        Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome.
        Fertil steril. 2000; 73: 1149-1154
        • Bermudez V.
        • Cano R.
        • Cano C.
        • Bermudez F.
        • Leal E.
        • Acosta K.
        • et al.
        Homeostasis model assessment (HOMA) as surrogate insulinization criteria in patients with type 2 diabetes.
        Revista Latinoamericana de Hipertensión. 2007; 2: 128-134