Obstetrics, Gynecology and Reproduction

Advanced search

Significance of the pineal gland hormone melatonin in maintaining the health of women of reproductive age (a review)

Full Text:


Introduction. Maintaining women's reproductive health is an important task that requires safe approaches based on the pathogenesis. More and more studies address the role of the pineal gland (epiphysis) hormone melatonin (МТ) in the functioning of the reproductive system, as well as the impact of МТ deficiency on the women’s health.

Aim: to analyze and summarize the available literature about the role of the pineal gland hormone МТ in the pathogenesis of gynecological diseases in women of reproductive age (infertility, endometriosis, polycystic ovary syndrome, premenstrual syndrome), and also about the impact of МТ deficiency on the health of women working night shifts.

Materials and methods. The relevant publications were searched in domestic (eLibrary, and international (Pubmed, Cochrane Library) databases; we looked up the materials published in the recent 7 years. In our search, we prioritized the free access to full text articles. The selection of sources was limited to the period from 2012 to 2019.

Results. МТ is involved in the development of follicles by causing the oocytes maturation, promoting the development of embryos, inhibiting the synthesis of steroids in the ovaries and, therefore, reducing the level of steroids in the blood. MT delays ovarian aging through a variety of mechanisms, including the antioxidant action, the maintenance of the due length of the telomere, the upregulated expression of the aging-related SIRT genes, and also the regulation of the ribosome functioning. As MT protects germ cells from oxidative stress, it is essential for normal ovulation, fertilization and further development of the embryo; this hormone has an impact on the duration of the woman's fertility and the onset of menopause. MT has a potential therapeutic effect on endometriosis. The oncostatic role of MT in hormone-dependent breast tumors has been described. Disruption of normal MT production during night shifts is associated with the risk of developing breast cancer in shift workers. MT deficiency leads to circadian desynchronosis and may cause both somatic disorders (metabolic syndrome, obesity, oncopathology) and neuroendocrine dysregulation of the female reproductive system.

Conclusion. The variety of physiological functions of the pineal gland hormone MT emphasizes the pathogenetic role of its deficiency in many gynecological and somatic diseases. Of particular relevance is the increased risk of cardiovascular disorders, the development of metabolic syndrome and breast cancer in women who work night shifts. Therefore, it is important both to maintain normal endogenous level of MT and also use its therapeutic potential to maintain the health of women of reproductive age.

About the Authors

M. V. Danilova
City Clinical Hospital № 1
Russian Federation

Marina V. Danilova – Obstetrician-gynecologist

16 Vorovskogo St., Chelyabinsk 454048, Russia.

E. N. Usoltseva
South Ural State Medical University, Health Ministry of Russian Federation
Russian Federation

Elena N. Usoltseva – MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Institute of Continuing Professional Education

64 Vorovskogo St., Chelyabinsk 454092, Russia.


1. Chronobiology and chronomedicine: monograph. [Hronobiologiya i hronomedicina: monografiya. Pod red. S.M. Chibisova, S.I. Rapoporta, M.L. Blagonravova]. Moskva: RUDN, 2018. 828 s. (In Russ.).

2. Borjigin J., Zhang L.S., Calinescu A.A. Circadian regulation of pineal gland rhythmicity. Mol Cell Endocrinol. 2012;349(1):13–9. DOI: 10.1016/j.mce.2011.07.009.

3. Amaral F.G.D., Cipolla-Neto J. A brief review about melatonin, a pineal hormone. Arch Endocrinol Metab. 2018;62(4):472–9. DOI: 10.20945/2359-3997000000066.

4. Riaz H., Yousuf M.R., Liang A. et al. Effect of melatonin on regulation of apoptosis and steroidogenesis in cultured buffalo granulosacells. Anim Sci J. 2019;90(4):473–80. DOI: 10.1111/asj.13152.

5. Woo M.M., Tai C.J., Kang S.K. et al. Direct action of melatonin in human granulosa-luteal cells. J Clin Endocrinol Metab. 2001;86(10):4789–97. DOI: 10.1210/jcem.86.10.7912.

6. Tamura H., Takasaki A., Taketani T. et al. Melatonin as a free radical scavenger in the ovarian follicle. Endocr J. 2013;60(1):1–13. DOI: 10.1507/endocrj.EJ12-0263.

7. Tenorio F., Simões M.J., Teixeira V.W., Teixeira Á.A. Effects of melatonin and prolactin in reproduction: review of literature. Rev Assoc Med Bras (1992). 2015;61(3):269–74. DOI: 10.1590/1806-9282.61.03.269.

8. Sánchez-Barceló E.J., Cos S., Mediavilla D. et al. Melatonin-estrogen interactions in breast cancer. J Pineal Res. 2005;38(4):217–22. DOI: 10.1111/j.1600-079X.2004.00207.x.

9. Menéndez-Menéndez J., Martínez-Campa C. Melatonin: an anti-tumor agent in hormone-dependent cancers. Int J Endocrinol. 2018;2018:3271948. DOI: 10.1155/2018/3271948.

10. Kuznetsova I.V. Melatonin and premenstrual syndrome. [Melatonin i predmenstrual'nyj sindrom]. Rossijskij vestnik akushera-ginekologa. 2018;18(6):100–4. (In Russ.). DOI: 10.17116/rosakush201818061100.

11. Shechter A., Lespérance P., Ng Ying Kin N.M.K., Boivin D.B. Pilot investigation of the circadian plasma melatonin rhythm across the menstrual cycle in a small group of women with premenstrual dysphoric disorder. PloS One. 2012;7(12):e51929. DOI: 10.1371/journal.pone.0051929.

12. Infertile marriage: versions and contra-version. [Besplodnyj brak: versii i kontraversii. Pod red. V.E. Radzinskogo]. Moskva: GEOTAR-Media, 2018. 404 s. (In Russ.).

13. Tamura H., Takasaki A., Taketani T. et al. The role of melatonin as an antioxidant in the follicle. J Ovarian Res. 2012;5:5. DOI: 10.1186/1757-2215-5-5.

14. Andreeva E.N., Absatarova Yu.S., Sheremetyeva E.V. et al. Analysis of the informativeness of melatonin evaluation in polycystic ovary syndrome. [Analiz informativnosti opredeleniya melatonina pri sindrome polikistoznyh yaichnikov]. Ozhirenie i metabolizm. 2016;13(4):15–20. (In Russ.). DOI: 10.14341/OMET2016415-20.

15. Jamilian M., Foroozanfard F., Mirhosseini N. et al. Effects of melatonin supplementation on hormonal, inflammatory, genetic, and oxidative stress parameters in women with polycystic ovary syndrome. Front Endocrinol. 2019;10:273. DOI: 10.3389/fendo.2019.00273.

16. Tagliaferri V., Romualdi D., Scarinci E. Melatonin treatment may be able to restore menstrual cyclicity in women with PCOS: a pilot study. Reprod Sci. 2017;25(2):269–75. DOI: 10.1177/1933719117711262.

17. Gupta S., Agarwal A., Krajcir N., Alvarez J.G. Role of oxidative stress in endometriosis. Reprod Biomed Online. 2006;13(1):126–34. PMID: 16820124.

18. Yarmolinskaya M.I., Zaitsev D.V., Tkhazaplizheva S.Sh. Melatonin and genital endometriosis – new possibilities of therapy. [Melatonin i genital'nyj endometrioz – novye vozmozhnosti terapii]. Zhurnal akusherstva i zhenskih boleznej. 2015;(1):67–75. (In Russ.).

19. Kocadal N.C., Attar R., Yildirim G. et al. Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. J Turk Ger Gynecol Assoc. 2013;14(2):81–6. DOI: 10.5152/jtgga.2013.53179.

20. Yarmolinskaya M.I., Tkhazaplizheva S.Sh., Molotkov A.S. et al. Effectiveness of melatonin in the treatment of surgically induced endometriosis in rats. [Effektivnost' melatonina v lechenii hirurgicheski inducirovannogo endometrioza u krys]. Problemy reprodukcii. 2018;24(5):33–40. (In Russ.).

21. DOI: 10.17116/repro20182405133.

22. Cetinkaya N., Attar R., Yildirim G. et al. The effects of different doses of melatonin treatment on endometrial implants in an oophorectomized rat endometriosis model. Arch Gynecol Obstet. 2015;291(3):591–8. DOI: 10.1007/s00404-014-3466-3.

23. Paul S., Sharma A.V., Mahapatra P.D. et al. Role of melatonin in regulating matrix metalloproteinase-9 via tissue inhibitors of metalloproteinase-1 during protection against endometriosis. J Pineal Res. 2008;44(4):439–49. DOI:

24. Schwertner A., Conceição Dos Santos C.C., Costa G.D. et al. Efficacy of melatonin in the treatment of endometriosis: a phase II, randomized, double-blind, placebo-controlled trial. Pain. 2013;154(6):874–81. DOI: 10.1016/j.pain.2013.02.025.

25. Pattanittum P., Kunyanone N., Brown J. et al. Dietary supplements for dysmenorrhoea. Cochrane Database Syst Rev. 201622;3:CD002124. DOI: 10.1002/14651858.CD002124.pub2.

26. Burchakov D.I., Kuznetsova I.V. Melatonin in reproductive medicine for the improvement of oocytes quality. [Melatonin v reproduktivnoj medicine: mozhno li uluchshit' kachestvo oocitov?] Effektivnaya farmakoterapiya. 2017;(35):96–101. (In Russ.).

27. Song C., Peng W., Yin al. Melatonin improves age-induced fertility decline and attenuates ovarian mitochondrial oxidative stress in mice. Sci Rep. 2016;6:35165. DOI: 10.1038/srep35165

28. Tamura H., Kawamoto M., Sato S. et al. Long-term melatonin treatment delays ovarian aging. J Pineal Res. 2017;62(2):e12381. DOI: 10.1111/jpi.12381.

29. Tong J., Sheng S., Sun Y. et al. Melatonin levels in follicular fluid as markers for IVF outcomes and predicting ovarian reserve. Reproduction. 2017;153(4):443–51. DOI: 10.1530/REP-16-0641.

30. Bryukhina E.V., Usoltseva E.N. Melatonin is the key to the adaptation of the female body to climacteric syndrome. [Melatonin – klyuch k adaptacii zhenskogo organizma pri klimaktericheskom syndrome]. Vrach. 2016;(4):68–71. (In Russ.).

31. Showell M.G., Mackenzie-Proctor R., Jordan V., Hart R.J. Antioxidants for female subfertility. Cochrane Database Syst Rev. 2017;7:CD007807. DOI: 10.1002/14651858.CD007807.pub3.

32. Gubin D.G. Melatonin: the amazing diversity of physiological effects. [Mnogoobrazie fiziologicheskih effektov melatonina]. Mezhdunarodnyj zhurnal prikladnyh i fundamental'nyh issledovanij. 2016;(11–6):1048–53. (In Russ.). Available at:

33. Moreno C.R.C., Marqueze E.C., Sargent C. et al. Working Time Society consensus statements: Evidence-based effects of shift work on physical and mental health. Ind Health. 2019;57(2):139–57. DOI: 10.2486/indhealth.SW-1.

34. Spinedi E., Cardinali D.P. The polycystic ovary syndrome and the metabolic syndrome: a possible chronobiotic-cytoprotective adjuvant therapy. Int J Endocrinol. 2018;2018:1349868. DOI: 10.1155/2018/1349868.

35. Lawson C.C., Johnson C.Y., Chavarro J.E. et al. Work schedule and physically demanding work in relation to menstrual function: the Nurses' Health Study 3. Scand J Work Environ Health. 2015;41(2):194–203. DOI: 10.5271/sjweh.3482.

36. Wang Y., Gu F., Deng M. et al. Rotating shift work and menstrual characteristics in a cohort of Chinese nurses. BMC Womens Health. 2016;16:24. DOI: 10.1186/s12905-016-0301-y.

37. Moen B.E., Baste V., Morken T. et al. Menstrual characteristics and night work among nurses. Ind Health. 2015;53(4):354–60. DOI: 10.2486/indhealth.2014-0214.

38. Albert-Sabater J.A., Martínez J.M., Baste V. et al. Comparison of menstrual disorders in hospital nursing staff according to shift work pattern. J Clin Nurs. 2016;25(21–22):3291–9. DOI: 10.1111/

39. jocn.13371.

40. Stevens R.G. Electric power use and breast cancer: a hypothesis. Am J Epidemiol. 1987;125 (4):556–61. DOI: 10.1093/oxfordjournals. aje.a114569.

41. International Agency for Research on Cancer. List of classifications (Volumes 1–120). IARC Monographs of the Carcinogenic Risks to Humans. Lyon, France: International Agency for Research on Cancer. 2018. Available at:

42. Fritschi L., Glass D.C., Heyworth J.S. et al. Hypotheses for mechanisms linking shiftwork and cancer. Med Hypotheses. 2011;77(3):430–6. DOI: 10.1016/j.mehy.2011.06.002.

43. Van Dycke K.C., Rodenburg W., van Oostrom C.T. et al. Chronically alternating light cycles increase breast cancer risk in mice. Curr Biol. 2015;25(14):1932–7. DOI: 10.1016/j.cub.2015.06.012.

44. Gómez-Acebo I., Dierssen-Sotos T., Papantoniou K. et al. Association between exposure to rotating night shift versus day shift using levels of 6-sulfatoxymelatonin and cortisol and other sex hormones in women. Chronobiol Int. 2015;32(1):128–35. DOI: 10.3109/07420528.2014.958494.

45. Bracci M., Manzella N., Copertaro al. Rotating-shift nurses after a day off: peripheral clock gene expression, urinary melatonin, and serum17-β-estradiol levels. Scand J Work Environ Health. 2014;40(3):295–304. DOI: 10.5271/sjweh.3414.

46. Papantoniou K., Pozo O.J., Espinosa A. et al. Increased and mistimed sex hormone production in night shift workers. Cancer Epidemiol Biomarkers Prev. 2015;24(5):854–63. DOI: 10.1158/1055-9965.EPI-14-1271.

47. Langley A.R., Graham C.H., Grundy A.L. et al. A crosssectional study of breast cancer biomarkers among shift working nurses. BMJ Open. 2012;2:e000532. DOI: 10.1136/bmjopen-2011-000532.

48. Samulin Erdem J., Skare Ø., Petersen-Øverleir M. et al. Mechanisms of breast cancer in shift workers: DNA methylation in five core circadian genes in nurses working night shifts. J Cancer. 2017;8(15):2876–84. DOI: 10.7150/jca.21064.

49. Wang F., Yeung K.L., Chan W.C. et al. A meta-analysis on dose-response relationship between night shift work and the risk of breast cancer. Ann Oncol. 2013;24(11):2724–32. DOI: 10.1093/annonc/mdt283.

50. Ijaz S., Verbeek J., Seidler A. et al. Night-shift work and breast cancer – a systematic review and meta-analysis. Scand J Work Environ Health. 2013;39(5):431–47. DOI: 10.5271/sjweh.3371.

51. He C., Anand S.T., Ebell M.H. et al. Circadian disrupting exposures and breast cancer risk: a meta-analysis. Int Arch Occup Environ Health. 2015l;88(5):533–47. DOI: 10.1007/s00420-014-0986-x.

For citation:

Danilova M.V., Usoltseva E.N. Significance of the pineal gland hormone melatonin in maintaining the health of women of reproductive age (a review). Obstetrics, Gynecology and Reproduction. 2019;13(4):337-344. (In Russ.)

Views: 38

ISSN 2313-7347 (Print)
ISSN 2500-3194 (Online)