The role of oxytocin in the pathogenesis of endometriosis: various aspects of the problem

Cover Page


Cite item

Full Text

Abstract

Hypothesis/aims of study. Endometriosis is a chronic recurrent disease that leads to a significant decrease in the quality of life. Despite the existing therapeutic methods, the prevalence of the disease is steadily increasing. The pathogenesis of endometriosis has not been studied enough, resulting in failure to achieve high efficiency in its treatment. Due to chronic pelvic pain, infertility, and dissatisfaction with the quality of life, women suffering from endometriosis present with various mental disorders of different degrees of severity. This study aims to summarize the literature discussing the possible role of oxytocin in the pathogenesis of both endometriosis and affective disorders.

Study design, materials, and methods. Literature data for the period from 1986 to 2019.

Conclusion. The role of oxytocin in the pathogenesis of endometriosis needs further study. Oxytocin receptor antagonists can be considered promising in the treatment of this medical condition, as well as in prevention and management of affective disorders in patients with endometriosis.

About the authors

Maria I. Yarmolinskaya

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott; North-Western State Medical University named after I.I. Mechnikov

Author for correspondence.
Email: m.yarmolinskaya@gmail.com
ORCID iD: 0000-0002-6551-4147
SPIN-code: 3686-3605

MD, PhD, DSci (Medicine), Professor of the Russian Academy of Sciences, the Head of the Department of Endocrinology of Reproduction, the Head of the Diagnostics and Treatment of Endometriosis Center; Professor. The Department of Obstetrics and Gynecology

Russian Federation, Saint Petersburg

Vladislav V. Khobets

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: 9562635@gmail.com

MD, Post-Graduate Student. The Department of Endocrinology of Reproduction

Russian Federation, Saint Petersburg

References

  1. Mechsner S, Grum B, Gericke C, et al. Possible roles of oxytocin receptor and vasopressin-1alpha receptor in the pathomechanism of dysperistalsis and dysmenorrhea in patients with adenomyosis uteri. Fertil Steril. 2010;94(7):2541-2546. https://doi.org/10.1016/j.fertnstert.2010.03.015.
  2. He Y, Wu H, He X, et al. Administration of atosiban in patients with endometriosis undergoing frozen-thawed embryo transfer: a prospective, randomized study. Fertil Steril. 2016;106(2):416-422. https://doi.org/10.1016/j.fertnstert.2016.04.019.
  3. Lien YJ, Chang HH, Tsai HC, et al. Plasma oxytocin levels in major depressive and bipolar II disorders. Psychiatry Res. 2017;258:402-406. https://doi.org/10.1016/j.psychres.2017.08.080.
  4. Novais F, Araujo A, Godinho P. Historical roots of histrionic personality disorder. Front Psychol. 2015;6:1463. https://doi.org/10.3389/fpsyg.2015.01463.
  5. Decker HS. The psychiatric works of Emil Kraepelin: a many-faceted story of modern medicine. J Hist Neurosci. 2004;13(3):248-276. https://doi.org/10.1080/09647040490510470.
  6. Blanco C, Compton WM, Saha TD, et al. Epidemiology of DSM-5 bipolar I disorder: Results from the National Epidemiologic Survey on Alcohol and Related Conditions III. J Psychiatr Res. 2017;84:310-317. https://doi.org/10.1016/j.jpsychires.2016.10.003.
  7. Dessotte CA, Silva FS, Furuya RK, et al. Somatic and cognitive-affective depressive symptoms among patients with heart disease: differences by sex and age. Rev Lat Am Enfermagem. 2015;23(2):208-215. https://doi.org/10.1590/0104-1169.0287.2544.
  8. Delisle VC, Beck AT, Dobson KS, et al. Revisiting gender differences in somatic symptoms of depression: much ado about nothing? PLoS One. 2012;7(2):e32490. https://doi.org/10.1371/journal.pone.0032490.
  9. O’Donnell S, Vanderloo S, McRae L, et al. Comparison of the estimated prevalence of mood and/or anxiety disorders in Canada between self-report and administrative data. Epidemiol Psychiatr Sci. 2016;25(4):360-369. https://doi.org/10.1017/S2045796015000463.
  10. Galea LAM, Frick KM, Hampson E, et al. Why estrogens matter for behavior and brain health. Neurosci Biobehav Rev. 2017;76(Pt B):363-379. https://doi.org/10.1016/j.neubiorev.2016.03.024.
  11. Van Oudenhove L, Cuypers SE. The philosophical “mind-body problemˮ and its relevance for the relationship between psychiatry and the neurosciences. Perspect Biol Med. 2010;53(4):545-557. https://doi.org/10.1353/pbm.2010.0012.
  12. Seng JS. Posttraumatic oxytocin dysregulation: is it a link among posttraumatic self disorders, posttraumatic stress disorder, and pelvic visceral dysregulation conditions in women? J Trauma Dissociation. 2010;11(4):387-406. https://doi.org/10.1080/15299732.2010.496075.
  13. Paaby AB, Rockman MV. The many faces of pleiotropy. Trends Genet. 2013;29(2):66-73. https://doi.org/10.1016/j.tig.2012.10.010.
  14. Sharma D, Handa RJ, Uht RM. The ERbeta ligand 5alpha-androstane, 3beta,17beta-diol (3beta-diol) regulates hypothalamic oxytocin (Oxt) gene expression. Endocrinology. 2012;153(5):2353-2361. https://doi.org/10.1210/en.2011-1002.
  15. Breton C, Zingg HH. Expression and region-specific regulation of the oxytocin receptor gene in rat brain. Endocrinology. 1997;138(5):1857-1862. https://doi.org/10.1210/endo.138.5.5127.
  16. Levin ER, Hammes SR. Nuclear receptors outside the nucleus: extranuclear signalling by steroid receptors. Nat Rev Mol Cell Biol. 2016;17(12):783-797. https://doi.org/10.1038/nrm.2016.122.
  17. Carter CS. Sex differences in oxytocin and vasopressin: implications for autism spectrum disorders? Behav Brain Res. 2007;176(1):170-186. https://doi.org/10.1016/j.bbr.2006.08.025.
  18. Mechsner S, Bartley J, Loddenkemper C, et al. Oxytocin receptor expression in smooth muscle cells of peritoneal endometriotic lesions and ovarian endometriotic cysts. Fertil Steril. 2005;83 Suppl 1:1220-1231. https://doi.org/10.1016/j.fertnstert.2004.11.038.
  19. Barcena de Arellano ML, Gericke J, Reichelt U, et al. Immunohistochemical characterization of endometriosis-associated smooth muscle cells in human peritoneal endometriotic lesions. Hum Reprod. 2011;26(10):2721-2730. https://doi.org/10.1093/humrep/der253.
  20. Zeitoun KM, Bulun SE. Aromatase: a key molecule in the pathophysiology of endometriosis and a therapeutic target. Fertil Steril. 1999;72(6):961-969. https://doi.org/10.1016/s0015-0282(99)00393-3.
  21. Kim S, Choi Y, Spencer TE, Bazer FW. Effects of the estrous cycle, pregnancy and interferon tau on expression of cyclooxygenase two (COX-2) in ovine endometrium. Reprod Biol Endocrinol. 2003;1:58. https://doi.org/10.1186/1477-7827-1-58.
  22. Stormshak F. Biochemical and endocrine aspects of oxytocin production by the mammalian corpus luteum. Reprod Biol Endocrinol. 2003;1:92. https://doi.org/10.1186/1477-7827-1-92.
  23. Sales KJ, Jabbour HN. Cyclooxygenase enzymes and prostaglandins in pathology of the endometrium. Reproduction. 2003:559-567. https://doi.org/10.1530/rep.0.1260559.
  24. Brosens JJ, de Souza NM, Barker FG. Uterine junctional zone: function and disease. Lancet. 1995;346(8974):558-560. https://doi.org/10.1016/s0140-6736(95)91387-4.
  25. De Ziegler D, Bulletti C, Fanchin R, et al. Contractility of the nonpregnant uterus. Ann N Y Acad Sci. 2001;943(1):172-184. https://doi.org/10.1111/j.1749-6632.2001.tb03801.x.
  26. Lesny P, Killick SR. REVIEW: The junctional zone of the uterus and its contractions. BJOG. 2004;111(11):1182-1189. https://doi.org/10.1111/j.1471-0528.2004.00350.x.
  27. Guo SW, Mao X, Ma Q, Liu X. Dysmenorrhea and its severity are associated with increased uterine contractility and overexpression of oxytocin receptor (OTR) in women with symptomatic adenomyosis. Fertil Steril. 2013;99(1):231-240. https://doi.org/10.1016/j.fertnstert.2012.08.038.
  28. Zhang Y, Yu P, Sun F, et al. Expression of oxytocin receptors in the uterine junctional zone in women with adenomyosis. Acta Obstet Gynecol Scand. 2015;94(4):412-418. https://doi.org/10.1111/aogs.12595.
  29. Bulletti C, de Ziegler D, Polli V, et al. Uterine contractility during the menstrual cycle. Hum Reprod. 2000;15 Suppl 1:81-89. https://doi.org/10.1093/humrep/15.suppl_1.81.
  30. Aguilar HN, Mitchell BF. Physiological pathways and molecular mechanisms regulating uterine contractility. Hum Reprod Update. 2010;16(6):725-744. https://doi.org/10.1093/humupd/dmq016.
  31. Richter ON, Bartz C, Dowaji J, et al. Contractile reactivity of human myometrium in isolated non-pregnant uteri. Hum Reprod. 2006;21(1):36-45. https://doi.org/10.1093/humrep/dei295.
  32. Leyendecker G, Kunz G, Noe M, et al. Endometriosis: a dysfunction and disease of the archimetra. Hum Reprod Update. 1998;4(5):752-762. https://doi.org/10.1093/humupd/4.5.752.
  33. Bulletti C. Characteristics of uterine contractility during menses in women with mild to moderate endometriosis. Fertil Steril. 2002;77(6):1156-1161. https://doi.org/10.1016/s0015-0282(02)03087-x.
  34. Huang M, Li X, Guo P, et al. The abnormal expression of oxytocin receptors in the uterine junctional zone in women with endometriosis. Reprod Biol Endocrinol. 2017;15(1):1. https://doi.org/10.1186/s12958-016-0220-7.
  35. Leyendecker G, Kunz G, Herbertz M, et al. Uterine peristaltic activity and the development of endometriosis. Ann N Y Acad Sci. 2004;1034:338-355. https://doi.org/10.1196/annals.1335.036.
  36. Exacoustos C, Luciano D, Corbett B, et al. The uterine junctional zone: a 3-dimensional ultrasound study of patients with endometriosis. Am J Obstet Gynecol. 2013;209(3):248 e241-247. https://doi.org/10.1016/j.ajog.2013.06.006.
  37. Tosti C, Zupi E, Exacoustos C. Could the uterine junctional zone be used to identify early-stage endometriosis in women? Womens Health (Lond). 2014;10(3):225-227. https://doi.org/10.2217/whe.14.20.
  38. Simsek Y, Celik O, Karaer A, et al. Therapeutic efficiency of Atosiban, an oxytocin receptor blocking agent in the treatment of experimental endometriosis. Arch Gynecol Obstet. 2012;286(3):777-783. https://doi.org/10.1007/s00404-012-2390-7.
  39. Merikangas KR, Jin R, He JP, et al. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011;68(3):241-251. https://doi.org/10.1001/archgenpsychiatry.2011.12.
  40. Dell’Aglio Jr JC, Basso LA, Argimon IIdL, Arteche A. Systematic review of the prevalence of bipolar disorder and bipolar spectrum disorders in population-based studies. Trends Psychiatry Psychother. 2013;35(2):99-105. https://doi.org/10.1590/s2237-60892013000200002.
  41. Scott J, Murray G, Henry C, et al. Activation in bipolar disorders: A Systematic Review. JAMA Psychiatry. 2017;74(2):189-196. https://doi.org/10.1001/jamapsychiatry.2016.3459.
  42. Teatero ML, Mazmanian D, Sharma V. Effects of the menstrual cycle on bipolar disorder. Bipolar Disord. 2014;16(1):22-36. https://doi.org/10.1111/bdi.12138.
  43. Frey BN, Dias RS. Sex hormones and biomarkers of neuroprotection and neurodegeneration: implications for female reproductive events in bipolar disorder. Bipolar Disord. 2014;16(1):48-57. https://doi.org/10.1111/bdi.12151.
  44. Osorio FL, Carvalho AC, Donadon MF, et al. Chronic pelvic pain, psychiatric disorders and early emotional traumas: Results of a cross sectional case-control study. World J Psychiatry. 2016;6(3):339-344. https://doi.org/10.5498/wjp.v6.i3.339.
  45. Kumar V, Khan M, Vilos GA, Sharma V. Revisiting the association between endometriosis and bipolar disorder. J Obstet Gynaecol Can. 2011;33(11):1141-1145. https://doi.org/10.1016/s1701-2163(16)35082-4.
  46. Lewis DO, Comite F, Mallouh C, et al. Bipolar mood disorder and endometriosis: preliminary findings. Am J Psychiatry. 1987;144(12):1588-1591. https://doi.org/10.1176/ajp.144.12.1588.
  47. Walker E, Katon W, Jones LM, Russo J. Relationship between endometriosis and affective disorder. Am J Psychiatry. 1989;146(3):380-381. https://doi.org/10.1176/ajp.146.3.380.
  48. Wei M, Cheng Y, Bu H, et al. Length of menstrual cycle and risk of endometriosis: a meta-analysis of 11 case-control studies. Medicine (Baltimore). 2016;95(9):e2922. https://doi.org/10.1097/MD.0000000000002922.
  49. Barron ML, Flick LH, Cook CA, et al. Associations between psychiatric disorders and menstrual cycle characteristics. Arch Psychiatr Nurs. 2008;22(5):254-265. https://doi.org/10.1016/j.apnu.2007.11.001.
  50. Kesebir S, Yaşan Şair B, Unübol B, Tatlıdil Yaylacı E. Is there a relationship between age at menarche and clinical and temperamental characteristics in bipolar disorder? Ann Clin Psychiatry. 2013;25(2):121-124.
  51. Kadaba R, Simpson CW. Disparate effect of tamoxifen in rats with experimentally induced endometriosis. Endocrinology. 1990;126(6):3263-3267. https://doi.org/10.1210/endo-126-6-3263.
  52. Gimpl G, Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiol Rev. 2001;81(2):629-683. https://doi.org/10.1152/physrev.2001.81.2.629.
  53. Wu Y, Guo SW. Histone deacetylase inhibitors trichostatin A and valproic acid induce cell cycle arrest and p21 expression in immortalized human endometrial stromal cells. Eur J Obstet Gynecol Reprod Biol. 2008;137(2):198-203. https://doi.org/10.1016/j.ejogrb.2007.02.014.
  54. Liu X, Guo SW. A pilot study on the off-label use of valproic acid to treat adenomyosis. Fertil Steril. 2008;89(1):246-250. https://doi.org/10.1016/j.fertnstert.2006.11.009.
  55. Goldstein JA. Danazol and the rapid-cycling patient. J Clin Psychiatry. 1986;47(3):153-154.
  56. Godin R, Marcoux V. Vaginally administered danazol: an overlooked option in the treatment of rectovaginal endometriosis? J Obstet Gynaecol Can. 2015;37(12):1098-1103. https://doi.org/10.1016/s1701-2163(16)30075-5.
  57. Pontis A, D’Alterio MN, Pirarba S, et al. Adenomyosis: a systematic review of medical treatment. Gynecol Endocrinol. 2016;32(9):696-700. https://doi.org/10.1080/09513590. 2016.1197200.
  58. Heijnen WT, De Fruyt J, Wierdsma AI, et al. Efficacy of tranylcypromine in bipolar depression: a systematic review. J Clin Psychopharmacol. 2015;35(6):700-705. https://doi.org/10.1097/JCP.0000000000000409.
  59. Sun Q, Ding D, Liu X, Guo SW. Tranylcypromine, a lysine-specific demethylase 1 (LSD1) inhibitor, suppresses lesion growth and improves generalized hyperalgesia in mouse with induced endometriosis. Reprod Biol Endocrinol. 2016;14:17. https://doi.org/10.1186/s12958-016-0154-0.
  60. Watson S, Gallagher P, Porter RJ, et al. A randomized trial to examine the effect of mifepristone on neuropsychological performance and mood in patients with bipolar depression. Biol Psychiatry. 2012;72(11):943-949. https://doi.org/10.1016/j.biopsych.2012.05.029.
  61. Zhang YX. Effect of mifepristone in the different treatments of endometriosis. Clin Exp Obstet Gynecol. 2016;43(3):350-353. https://doi.org/10.12891/ceog3527.2016.
  62. Wang Y, Jiang X, Wang S. The influence of mifepristone to caspase 3 expression in adenomyosis. Clin Exp Obstet Gynecol. 2014;41(2):154-157. https://doi.org/10.12891/ceog16152014.
  63. Kulkarni J, Berk M, Wang W, et al. A four week randomised control trial of adjunctive medroxyprogesterone and tamoxifen in women with mania. Psychoneuroendocrinology. 2014;43:52-61. https://doi.org/10.1016/j.psyneuen.2014.02.004.
  64. Rodgers AK, Falcone T. Treatment strategies for endometriosis. Expert Opin Pharmacother. 2008;9(2):243-255. https://doi.org/10.1517/14656566.9.2.243.
  65. Meinhard N, Kessing LV, Vinberg M. The role of estrogen in bipolar disorder, a review. Nord J Psychiatry. 2014;68(2):81-87. https://doi.org/10.3109/08039488.2013.775341.
  66. Haber GM, Behelak YF. Preliminary report on the use of tamoxifen in the treatment of endometriosis. Am J Obstet Gynecol. 1987;156(3):582-586. https://doi.org/10.1016/0002-9378(87)90057-3.
  67. Rose PG, Alvarez B, Maclennan GT. Exacerbation of endometriosis as a result of premenopausal tamoxifen exposure. Am J Obstet Gynecol. 2000;183(2):507-508. https://doi.org/10.1067/mob.2000.105966.
  68. Parrott E, Butterworth M, Green A, et al. Adenomyosis — a result of disordered stromal differentiation. Am J Pathol. 2001;159(2):623-630. https://doi.org/10.1016/s0002-9440(10)61733-6.
  69. Wardenaar KJ, de Jonge P. Diagnostic heterogeneity in psychiatry: towards an empirical solution. BMC Med. 2013;11:201. https://doi.org/10.1186/1741-7015-11-201.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2019 Yarmolinskaya M.I., Khobets V.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies