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Cited by 91Ovarian function and disordersCircadian rhythm and melatoninReproductive Biology and Fertility

Effects of Melatonin Supplementation on Hormonal, Inflammatory, Genetic, and Oxidative Stress Parameters in Women With Polycystic Ovary Syndrome

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Jamilian, Mehri, Foroozanfard, Fatemeh, Mirhosseini, Naghmeh, Kavossian, Elham, Aghadavod, Esmat, Bahmani, Fereshteh, Ostadmohammadi, Vahidreza, Kia, Mersedeh +4 more·2019·Frontiers in Endocrinology
DOI 10.3389/fendo.2019.00273PMC PMC6527800
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Abstract

Purpose: The aim of the current study was to evaluate the effect of melatonin administration on clinical, hormonal, inflammatory and genetic parameters in women with PCOS. Methods: The present randomized, double-blinded, placebo-controlled clinical trial was conducted among 56 patients with PCOS, aged 18-40 years old. Subjects were randomly allocated to take either 5 mg melatonin supplements (n=28) or placebo (n=28) twice a day for 12 weeks. Results: Melatonin administration significantly reduced hirsutism (β -0.47; 95% CI, -0.86, -0.09; P=0.01), serum total testosterone (β -0.11 ng/mL; 95% CI, -0.21, -0.02; P=0.01), high-sensitivity C-reactive protein (hs-CRP) (β -0.61 mg/L; 95% CI, -0.95, -0.26; P=0.001) and plasma malondialdehyde (MDA) levels (β -0.25 µmol/L; 95% CI, -0.38, -0.11; P<0.001), and significantly increased plasma total antioxidant capacity (TAC) levels (β 106.07 mmol/L; 95% CI, 62.87, 149.28; P<0.001) and total glutathione (GSH) (β 81.05 µmol/L; 95% CI, 36.08, 126.03; P=0.001) compared with the placebo. Moreover, melatonin supplementation downregulated gene expression of interleukin-1 (IL-1) (P=0.03) and tumor necrosis factor alpha (TNF-α) (P=0.01) compared with the placebo. Conclusions: Overall, melatonin administration for 12 weeks to women with PCOS significantly reduced hirsutism, total testosterone, hs-CRP and MDA, while increased TAC and GSH levels. In addition, melatonin administration reduced gene expression of IL-1 and TNF-α.

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  • Jamilian et al. (2019) RCT found that 5 g melatonin twice daily for 12 weeks decreased hirsutism, total testosterone, hs-CRP, and MDA, and increased TAC and total GSH compared to placebo in women with PCOS.

    “Jamilian et al. (2019) performed a randomized controlled trial involving 56 women with PCOS, revealing a decrease in hirsutism, total testosterone, hs-CRP, and MDA, alongside an increase in TAC and total GSH among participants administered 5 g of melatonin twice daily for 12 weeks, in contrast to the placebo group [186].”

    From Nutritional and herbal interventions for polycystic ovary syndrome (PCOS): a comprehensive review of dietary approaches, macronutrient impact, and herbal medicine in management (2025) · cites this paper as [186]

    The Discussion reports reductions in hirsutism, total testosterone, hs-CRP, and MDA and increases in TAC and GSH after 12 weeks; the Results define GSH as total glutathione. But Materials and Methods (Supplementation) specifies 2 × 5 mg/day in 28 women per group, not 5 g twice daily. The outcome and participant claims are supported, but the dose is wrong by a factor of 1,000. (LLM, conf=0.94)

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References 55 · Cited by 91

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  1. [1]Baptiste CG Battista MC Trottier A Baillargeon JP. Insulin and hyperandrogenism in women with polycystic ovary syndrome. J Steroid Biochem Mol Biol. (2010) 122: 42– 52. 10.1016/j.jsbmb.2009.12.010 20036327 PMC3846536 · DOI
  2. [2]Nelson VL Legro RS Strauss JF McAllister JM. Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Mol Endocrinol. (1999) 13: 946– 57. 10.1210/mend.13.6.0311 10379893 · DOI · Paper page
  3. [4]Gonzalez F Rote NS Minium J Kirwan JP. Reactive oxygen species–induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. J Clin Endocrinol Metab. (2006) 91: 336– 40. 10.1210/jc.2005-1696 16249279 · DOI
  4. [5]Gonzalez F. Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids. (2012) 77: 300– 5. 10.1016/j.steroids.2011.12.003 22178787 PMC3309040 · DOI · Paper page
  5. [6]Boots CE Jungheim ES. Inflammation and human ovarian follicular dynamics. Semin Reprod Med. (2015) 33: 270– 5. 10.1055/s-0035-1554928 26132931 PMC4772716 · DOI
  6. [8]Reiter RJ Mayo JC Tan DX Sainz RM Alatorre-Jimenez M Qin L. Melatonin as an antioxidant: under promises but over delivers. J Pineal Res. (2016) 61: 253– 78. 10.1111/jpi.12360 27500468 · DOI
  7. [9]Klein DC Moore RY Pineal N-acetyltransferase and hydroxyindole-O-methyl-transferase: control by the retinohypothalamic tract and the suprachiasmatic nucleus. Brain Res. (1979) 174: 245– 62. 10.1016/0006-8993(79)90848-5 487129 · DOI
  8. [11]Maestroni GJ Conti A Pierpaoli W. Role of the pineal gland in immunity: circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immunosuppressive effect of corticosterone. J Neuroimmunol. (1986) 13: 19– 30. 10.1016/0165-5728(86)90047-0 2944914 · DOI
  9. [12]Tan D-X Manchester LC Esteban-Zubero E Zhou Z Reiter RJ. Melatonin as a potent and inducible endogenous antioxidant: synthesis and metabolism. Molecules. (2015) 20: 18886– 906. 10.3390/molecules201018886 26501252 PMC6332205 · DOI · Paper page
  10. [13]Tan D Reiter RJ Manchester LC Yan M El-Sawi M Sainz RM. Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Top Med Chem. (2002) 2: 181– 97. 10.2174/1568026023394443 11899100 · DOI
  11. [14]Esposito E Cuzzocrea S. Antiinflammatory activity of melatonin in central nervous system. Curr Neuropharmacol. (2010) 8: 228– 42. 10.2174/157015910792246155 21358973 PMC3001216 · DOI
  12. [15]Ecklund LC Usadi RS. Endocrine and reproductive effects of polycystic ovarian syndrome. Obstet Gynecol Clin North Am. (2015) 42: 55– 65. 10.1016/j.ogc.2014.09.003 25681840 · DOI
  13. [16]Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. (2008) 23: 462– 77. 10.1093/humrep/dem426 18308833 · DOI
  14. [17]Cagnacci A Volpe A. A role for melatonin in PCOS? Fertil Steril. (2002) 77: 1089. author reply:90. 10.1016/S0015-0282(02)03070-4 12009381 · DOI
  15. [18]Tamura H Nakamura Y Korkmaz A Manchester LC Tan DX Sugino N. Melatonin and the ovary: physiological and pathophysiological implications. Fertil Steril. (2009) 92: 328– 43. 10.1016/j.fertnstert.2008.05.016 18804205 · DOI
  16. [19]Jain P Jain M Haldar C Singh TB Jain S. Melatonin and its correlation with testosterone in polycystic ovarian syndrome. J Hum Reprod Sci. (2013) 6: 253– 8. 10.4103/0974-1208.126295 24672165 PMC3963309 · DOI · Paper page
  17. [20]Yang HL Zhou WJ Gu CJ Meng YH Shao J Li DJ. Pleiotropic roles of melatonin in endometriosis, recurrent spontaneous abortion, and polycystic ovary syndrome. Am J Reprod Immunol. (2018) 80: e12839. 10.1111/aji.12839 29493042 · DOI
  18. [21]Shreeve N Cagampang F Sadek K Tolhurst M Houldey A Hill CM. Poor sleep in PCOS; is melatonin the culprit? Hum Reprod. (2013) 28: 1348– 53. 10.1093/humrep/det013 23438443 · DOI · Paper page
  19. [22]Spinedi E Cardinali DP. The polycystic ovary syndrome and the metabolic syndrome: a possible chronobiotic–cytoprotective adjuvant therapy. Int J Endocrinol. (2018) 2018: 1349868. 10.1155/2018/1349868 30147722 PMC6083563 · DOI
  20. [23]Pacchiarotti A Carlomagno G Antonini G Pacchiarotti A. Effect of myo-inositol and melatonin versus myo-inositol, in a randomized controlled trial, for improving in vitro fertilization of patients with polycystic ovarian syndrome. Gynecol Endocrinol. (2016) 32: 69– 73. 10.3109/09513590.2015.1101444 26507336 · DOI · Paper page
  21. [24]Unfer V Raffone E Rizzo P Buffo S. Effect of a supplementation with myo-inositol plus melatonin on oocyte quality in women who failed to conceive in previous in vitro fertilization cycles for poor oocyte quality: a prospective, longitudinal, cohort study. Gynecol Endocrinol. (2011) 27: 857– 61. 10.3109/09513590.2011.564687 21463230 · DOI
  22. [25]Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. (2004) 81: 19– 25. 10.1016/j.fertnstert.2003.10.004 14711538 · DOI · Paper page
  23. [27]Jamilian M Foroozanfard F Bahmani F Talaee R Monavari M Asemi Z. Effects of zinc supplementation on endocrine outcomes in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Biol Trace Elem Res. (2016) 170: 271– 8. 10.1007/s12011-015-0480-7 26315303 · DOI
  24. [28]Hatch R Rosenfield RL Kim MH Tredway D. Hirsutism: implications, etiology, and management. Am J Obstet Gynecol. (1981) 140: 815– 30. 10.1016/0002-9378(81)90746-8 7258262 · DOI
  25. [29]Ramezani Tehrani F Minooee S Azizi F Validation of a simplified method to assess hirsutism in the Iranian population. Eur J Obstet Gynecol Reprod Biol. (2014) 174: 91– 5. 10.1016/j.ejogrb.2013.12.008 24393448 · DOI
  26. [30]Tatsch E Bochi GV Pereira Rda S Kober H Agertt VA de Campos MM. A simple and inexpensive automated technique for measurement of serum nitrite/nitrate. Clin Biochem. (2011) 44: 348– 50. 10.1016/j.clinbiochem.2010.12.011 21185277 · DOI
  27. [31]Benzie IF Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of antioxidant power: the FRAP assay. Anal Biochem. (1996) 239: 70– 6. 10.1006/abio.1996.0292 8660627 · DOI
  28. [32]Beutler E Gelbart T. Plasma glutathione in health and in patients with malignant disease. J Lab Clin Med. (1985) 105: 581– 4. 3989350
  29. [33]Dunkley PR Jarvie PE Robinson PJ. A rapid Percoll gradient procedure for preparation of synaptosomes. Nat Protoc. (2008) 3: 1718– 28. 10.1038/nprot.2008.171 18927557 · DOI
  30. [34]Cassone VM Natesan AK. Time and time again: the phylogeny of melatonin as a transducer of biological time. J Biol Rhythms. (1997) 12: 489– 97. 10.1177/074873049701200602 9406022 · DOI
  31. [35]Nakamura Y Tamura H Takayama H Kato H Increased endogenous level of melatonin in preovulatory human follicles does not directly influence progesterone production. Fertil Steril. (2003) 80: 1012– 6. 10.1016/S0015-0282(03)01008-2 14556825 · DOI
  32. [36]Ronnberg L Kauppila A Leppaluoto J Martikainen H Vakkuri O. Circadian and seasonal variation in human preovulatory follicular fluid melatonin concentration. J Clin Endocrinol Metab. (1990) 71: 492– 6. 10.1210/jcem-71-2-493 2380343 · DOI
  33. [37]Wetterberg L Arendt J Paunier L Sizonenko PC Donselaar W Heyden T. Human serum melatonin changes during the menstrual cycle. J Clin Endocrinol Metab. (1976) 42: 185– 8. 10.1210/jcem-42-1-185 1249188 · DOI
  34. [38]Wickenheisser JK Quinn PG Nelson VL Legro RS Strauss JF McAllister JM. Differential activity of the cytochrome P450 17alpha-hydroxylase and steroidogenic acute regulatory protein gene promoters in normal and polycystic ovary syndrome theca cells. J Clin Endocrinol Metab. (2000) 85: 2304– 11. 10.1210/jcem.85.6.6631 10852468 · DOI
  35. [39]Kumar A Woods KS Bartolucci AA Azziz R. Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS). Clin Endocrinol. (2005) 62: 644– 9. 10.1111/j.1365-2265.2005.02256.x 15943823 · DOI
  36. [41]Boztosun A Acmaz G Ozturk A Muderris II. Clinical efficacy of low dose flutamide plus Diane-35 in the treatment of idiopathic hirsutism and polycystic ovary syndrome. Ginekol Pol. (2013) 84: 258– 62. 10.17772/gp/1573 23700857 · DOI
  37. [42]Tagliaferri V Romualdi D Scarinci E Cicco S Florio CD Immediata V. Melatonin treatment may be able to restore menstrual cyclicity in women with PCOS: a pilot study. Reprod Sci. (2018) 25: 269– 75. 10.1177/1933719117711262 28558523 · DOI · Paper page
  38. [43]Nikmard F Hosseini E Bakhtiyari M Ashrafi M Amidi F Aflatoonian R. Effects of melatonin on oocyte maturation in PCOS mouse model. Anim Sci J. (2017) 88: 586– 92. 10.1111/asj.12675 27530294 · DOI
  39. [44]Pai SA Majumdar AS. Protective effects of melatonin against metabolic and reproductive disturbances in polycystic ovary syndrome in rats. J Pharm Pharmacol. (2014) 66: 1710– 21. 10.1111/jphp.12297 25176048 · DOI
  40. [45]Mistraletti G Paroni R Umbrello M D'Amato L Sabbatini G Taverna M. Melatonin pharmacological blood levels increase total antioxidant capacity in critically Ill patients. Int J Mol Sci. (2017) 18: 759. 10.3390/ijms18040759 28368352 PMC5412344 · DOI
  41. [46]Kozirog M Poliwczak AR Duchnowicz P Koter-Michalak M Sikora J Broncel M. Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome. J Pineal Res. (2011) 50: 261– 6. 10.1111/j.1600-079X.2010.00835.x 21138476 · DOI · Paper page
  42. [47]Pakravan H Ahmadian M Fani A Aghaee D Brumanad S Pakzad B. The effects of melatonin in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Adv Biomed Res. (2017) 6: 40. 10.4103/2277-9175.204593 28503495 PMC5414412 · DOI
  43. [48]Akbari M Ostadmohammadi V Tabrizi R Lankarani KB Heydari ST Amirani E The effects of melatonin supplementation on inflammatory markers among patients with metabolic syndrome or related disorders: a systematic review and meta-analysis of randomized controlled trials. Inflammopharmacology. (2018) 26: 899– 907. 10.1007/s10787-018-0508-7 29907916 · DOI
  44. [49]Mesri Alamdari N Mahdavi R Roshanravan N Lotfi Yaghin N Ostadrahimi AR Faramarzi E A double-blind, placebo-controlled trial related to the effects of melatonin on oxidative stress and inflammatory parameters of obese women. Horm Metab Res. (2015) 47: 504– 8. 10.1055/s-0034-1384587 25126957 · DOI · Paper page
  45. [50]Alviggi C Conforti A De Rosa P Strina I Palomba S Vallone R. The distribution of stroma and antral follicles differs between insulin-resistance and hyperandrogenism-related polycystic ovarian syndrome. Front Endocrinol. (2017) 8: 117. 10.3389/fendo.2017.00117 28620353 PMC5449504 · DOI
  46. [51]Pawelczak M Rosenthal J Milla S Liu YH Shah B. Evaluation of the pro-inflammatory cytokine tumor necrosis factor-alpha in adolescents with polycystic ovary syndrome. J Pediatr Adolesc Gynecol. (2014) 27: 356– 9. 10.1016/j.jpag.2014.01.104 25256873 PMC4536070 · DOI
  47. [52]Alviggi C Cariati F Conforti A De Rosa P Vallone R Strina I. The effect of FT500 Plus((R)) on ovarian stimulation in PCOS women. Reprod Toxicol. (2016) 59: 40– 4. 10.1016/j.reprotox.2015.10.014 26545973 · DOI
  48. [53]Lin YW Lee LM Lee WJ Chu CY Tan P Yang YC. Melatonin inhibits MMP-9 transactivation and renal cell carcinoma metastasis by suppressing Akt-MAPKs pathway and NF-kappaB DNA-binding activity. J Pineal Res. (2016) 60: 277– 90. 10.1111/jpi.12308 26732239 · DOI
  49. [54]Mohan N Sadeghi K Reiter RJ Meltz ML. The neurohormone melatonin inhibits cytokine, mitogen and ionizing radiation induced NF-kappa B. Biochem Mol Biol Int. (1995) 37: 1063– 70. 8747536

Authors
Jamilian, M., Foroozanfard, F., Mirhosseini, N., Kavossian, E., Aghadavod, E., Bahmani, F., Ostadmohammadi, V., Kia, M., Eftekhar, T., Ayati, E., Mahdavinia, M., & Asemi, Z.
Affiliations
  • Arak University of Medical Sciences (IR)
  • Kashan University of Medical Sciences (IR)
  • University of Saskatchewan (CA)
  • Islamic Azad University of Gorgan (IR)
  • University of Tehran (IR)
  • Razi Hospital (IR)
Corresponding author
  • Eftekhar, Tahereh
  • Asemi, Zatollah
ORCID
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2019-05-14
Volume
10
Pages
273-273
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2019.00273
PMC
PMC6527800
OpenAlex
W2946176610
Cited by
91
References
55
Citations by year
2026: 11 · 2025: 19 · 2024: 14 · 2023: 8 · 2022: 13 · 2021: 17 · 2020: 6 · 2019: 2 · 2018: 1
FWCI
9.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
Keywords
melatonin supplementation, polycystic ovary syndrome, hirsutism, testosterone, C-reactive protein, oxidative stress, malondialdehyde, total antioxidant capacity, glutathione, interleukin-1, TNF-α, inflammation, gene expression

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