Pathogenesis of ovarian dysfunction in women with diabetes mellitus 1 type

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Abstract

The main ideas about the pathogenesis of ovarian dysfunction in women with diabetes mellitus (DM) type 1 are presented. The role of increased opioid and dopaminergic tone in the pathogenesis of reducing the synthesis of the gonadotropin-releasing hormone by the hypothalamus in women with type 1 diabetes was analyzed. Presented the data of relationship between ovarian hormonal insufficiency in women with type 1 diabetes with possible damage of positive feedback mechanism of the ovaries and the pituitary gland, which intactness is necessary for the maturation of the dominant follicle and ovulation. The results of studies, suggested that the high doses of exogenously administered insulin in type 1 DM lead to stimulation of androgen synthesis in teca cells and ovarian stroma and the development of ovarian  hyperandrogenemia, as well as polycystic ovary syndrome, are reduced. In addition to exogenous hyperinsulinemia, in the pathogenesis of ovarian dysfunction, the value of the deficiency of endogenous insulin, leading to a violation of steroidogenesis in the tissues of the ovary and anovulation, is proved. The role of insulin deficiency and hyperglycemia in the development of metabolic stress lead to ovarian dysfunction in patients with type 1 diabetes was analyzed.

About the authors

Margarita G. Tolpygina

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

Author for correspondence.
Email: chetmar@mail.ru

PhD, student

Russian Federation, Saint Petersburg

Elena I. Abashova

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

Email: abashova@yandex.ru

PhD, senior researcher at the Department of Endocrinology

Russian Federation, Saint Petersburg

Natalia V. Borovik

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

Email: Borovik1970@yandex.ru

PhD, Department of Endocrinology

Russian Federation, Saint Petersburg

Alena V. Tiselko

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

Email: alenadoc@mail.ru

PhD, senior researcher at the Department of Endocrinology

Russian Federation, Saint Petersburg

References

  1. Сахарный диабет и репродуктивная система женщины: руководство для врачей / ред. Э.К. Айламазян. — М.: ГЭОТАР-Медиа, 2017. [Sakharnyy diabet i reproduktiv naya sistema zhenshchiny: rukovodstvo dlya vrachey. Ed by E.K. Aylamazyan. Moscow: GEOTAR-Media; 2017. (In Russ.)]
  2. Толпыгина М.Г., Потин В.В., Тарасова М.А. Функция яичников у женщин с сахарным диабетом 1-го типа // Журнал акушерства и женских болезней. — 2014. — Т. LXIII. — Вып. 3. — С. 53–57. [Tolpygina MG, Potin VV, Tarasova MA. Ovarian function in women with type 1 diabetes mellitus. Journal of Obstetrics and Women’s Diseases. 2014;63(3):53-7. (In Russ.)]
  3. Потин В.В., Боровик Н.В., Тиселько А.В., и др. Сахарный диабет и репродуктивная система женщины: пособие для врачей / ред. Э.К. Айламазян. — СПб.: Изд-во Н-Л, 2008. [Potin VV, Borovik NV, Tiselko AV, et al. Sakharnyy diabet i reproduktivnaya sistema zhenshchiny: posobiye dlya vrachey. Ed by E.K. Aylamazyan. Saint Petersburg: Izd-vo N-L; 2008. (In Russ.)]
  4. Djursing H, Carstensen L, Hagen C, Andersen AN. Possible altered dopaminergic modulation of pituitary function in normalmenstruatig women with insulin-dependent diabetes mellitus [IDDM]. Acta Endocrinol Metab. 1991;72:151-6.
  5. Сибирская Е.В. Механизмы нарушений менструального цикла у больных сахарным диабетом 1-го типа: автореф. дис. … канд. мед. наук. — М., 2007. [Sibirskaja EV. Mehanizmy narushenij menstrual’nogo cikla u bol’nyh saharnym diabetom 1 tipa [dissertation]. Moscow; 2007. (In Russ.)]
  6. Pal L, Chu HP, Shu J, et al. In vitro evidence of glucose-induced toxicity in GnRH secreting neurons: high glucose concentrations influence GnRH secretion, impair cell viability , and induce apoptosis in the GT1-1 neuronal cell line. Fertil Steril. 2007;88(suppl.4):1143-9. doi: 10.1016/j.fertnstert.2007.01.007.
  7. Salvi R, Castillo E, Voirol MJ, et al. Gonadotropin-releasing hormone-expressing neurons immortalized conditionally are activated by insulin: implication of the mitogen-activated protein kinase pathway. Endocrinology. 2006;147:816-26. doi: 10.1210/en.2005-0728.
  8. Gaete X, Vivanco M, Eyzaguirre FC, et al. Menstrual cycle irregularities and their relationship with HbA1c and insulin dose in adolescents with type 1 diabetes mellitus. Fertil Steril. 2010;94(5):1822-6. doi: 10.1016/j.fertnstert.2009.08.039.
  9. Castellano JM, Bentsen AH, Mikkelsen JD, Tena-Sempere M. Kisspeptins: bridging energy homeostasis and reproduction. Brain Res. 2010;1364:129-38. doi: 10.1016/j.brainres.2010.08.057.
  10. Мешкова И.П., Григорян О.Р., Зилов А.В., и др. Роль аутоантител к ткани яичников и надпочечников в патогенезе нарушений менструального цикла у девушек, больных сахарным диабетом 1-го типа // Проблемы репродукции. — 2000. — № 5. — С. 11–15. [Meshkova IP, Grigoryan OR, Zilov AV, et al. Rol’ autoantitel k tkani yaichnikov i nadpochechnikov v patogeneze narusheniy men strual’nogo tsikla u devushek, bol’nykh sakharnym diabetom 1 tipa. Problemy reproduktsii. 2000;(5):11-5. (In Russ.)]
  11. Айламазян Э.К., Потин В.В., Тарасова М.А., и др. Гинекология от пубертата до постменопаузы: практическое руководство для врачей. — М.: МЕДпресс-информ, 2004. [Aylamazyan EK, Potin VV, Tarasova MA, et al. Ginekolo giya ot pubertata do postmenopauzy: prakticheskoye rukovodstvo dlya vrachey. Moscow: MEDpress-inform; 2004. (In Russ.)]
  12. Godrum E, Hangaard J, Christensen L, et al. Dopaminergic inhibition of pulsatile luteinizing hormone secretion is abnormal in regularly menstruating women with insulin-dependent diabetes mellitus. Fertil Steril. 1995;64:279-84.
  13. Giustina A, Desenzani P, Perini P, et al. Glutamate decarboxylase autoimmunityand growth hormone secretion in type I diabetes mellitus. Metabolism. 1997;46(4):382-7. doi: 10.1016/S0026-0495(97)90052-4.
  14. Coiro V, Volpi R, Capretti L, et al. Luteinizing hormone responses to gonadotropin-releasing hormone and naloxone in menstruating women with type 1 diabetes of different duration. Fertil Steril. 1991;55:712-6. doi: 10.1016/S0015-0282(16)54235-6.
  15. O’Hare J, Eichold BH, Vignati L. Hypogonadotropic secondary amenorrhea in diabetes: effects of central opiate blockade and improved metabolic control. Am J Med. 1987;83:1080-4. doi: 10.1016/0002-9343(87)90945-4.
  16. la Marca A, Morgante G, De Leo V. Evaluation of hypotalamic-pituitary-adrenal axis in amenorrheic women with insulin-dependent diabetes. Hum Reprod. 1999;14:298-302. doi: 10.1093/humrep/14.2.298.
  17. Djursing H, Andersen AN, Hagen C, Petersen LM. Gonadotropin secretion before and during acute and chronic dopamine-receptor blockade in insulin-dependent diabetic patients with amenorrhea. Fertil Steril. 1985;44:49-55. doi: 10.1016/S0015-0282(16)48676-0.
  18. Grossman A, Moult PJA, McIntyre H. Opiate mediation of amenorrhea in hyperprolactinemia and in weight loss mediated amenorrhea. Clin Endocrinol. 1982;17:379-85. doi: 10.1111/j.1365-2265.1982.tb01603.x.
  19. South SA, Asplin CM, Carlsen EC, et al. Alterations in luteinizing hormone secretory activity in women with insulin-dependent diabetes mellitus and secondary amenorrhea. J Clin Endocrinol Metab. 1993;76(4):1048-53.
  20. Wiesław Zarzycki, Magdalena Zieniewicz. Reproductive disturbances in type 1 diabetic women. Neuroendocrinology. 2005;26(6):733-8.
  21. Потин В.В., Боровик Н.В., Тиселько А.В. Сахарный диабет и репродуктивная система женщины // Журнал акушерства и женских болезней. — 2006. — Т. LV. — № 1. — С. 85–90. [Potin VV, Borovik NV, Tiselko AV. Diabetes mellitus and female reproductive system. Journal of Obstetrics and Women’s Diseases. 2006;55(1):85-90. (In Russ.)]
  22. Snajderová M, Martínek J, Horejsí J, et al. Premenarchal and postmenarchal girls with insulin-dependent diabetes mellitus: ovarian and other organ-specific autoantibodies, menstrual cycle. J Pediatr Adolesc Gynecol. 1999;12(4):209-14. doi: 10.1016/S1083-3188(99)00023-6.
  23. Овсянникова Т.В., Демидова И.Ю., Глазкова О.И. Гонадо тропная функция инсулина. Гиперандрогения и гипер инсулинемия // Проблемы репродукции. — 1998. — № 6. — С. 5–8. [Ovsyannikova TV, Demidova IYu, Glazkova OI. Gonadotropnaya funktsiya insulina. Giperandroge niya i giperinsulinemiya. Problemy reproduktsii. 1998;(6):5-8. (In Russ.)]
  24. Григорян О.Р., Макарова И.И., Гродницкая Е.Э., Андре ева Е.Н. Особенности синдрома поликистозных яичников у женщин с сахарным диабетом 1-го типа // Проблемы репродукции. — 2009. — № 1. — С. 57–62. [Grigoryan OR, Makarova II, Grodnitskaya EE, Andreeva EN. Features of polycystic ovarian syndrome in women with type 1 diabetes mellitus. Problemy reproduktsii. 2009;(1):57-62. (In Russ).]
  25. Codner Е, Escobar-Morreale НF. Hyperandrogenism and Polycystic Ovary Syndrome in Women with Type 1 Diabetes Mellitus. J Clin Endocrinol Metab. 2007;92(4):1209-16. doi: 10.1210/jc.2006-2641.
  26. Codner E, Soto N, Lopez P, et al. Diagnostic criteria for polycystic ovary syndrome and ovarian morphology in women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2006;91:2250-6. doi: 10.1210/jc.2006-0108.
  27. Bucholts DC, Chiesa A, Pappano WN, et al. Regulation of Pulsatile Luteinizing Hormone Secretion by Insulin in the Diabetic Male Lamb. Biology of Reproduction. 2000;62(5):1248-55. doi: 10.1095/biolreprod62.5.1248.
  28. Подзолкова Н.М., Глазкова О.Л., Пинегин Б.В., и др. Особенности менструальной функции больных сахарным диабетом 1-го типа // Гинекология. — 2005. — Т. 7. — № 3. — С. 23–30. [Podzolkova NM, Glazkova OL, Pinegin BV, et al. Features of menstrual function in patients with type 1 diabetes mellitus. Gynecology. 2005;7(3):23-30. (In Russ.)]
  29. Roldán В, Héctor F, Escobar-Morreale, Raquel Barrio, et al. Identification of the Source of Androgen Excess in Hyperandrogenic Type 1 Diabetic Patients. Diabetes Care. 2001;24(7):1297-9. doi: 10.2337/diacare.24.7.1297.
  30. Codner E, Iñíguez G, Villarroel C, et al. Hormonal profile in women with polycystic ovarian syndrome with or without type 1 diabetes mellitus. J Clin Endocrinol Metab. 2007;92(12):4742-6. doi: 10.1210/jc.2007-1252.
  31. Codner E, Iñiguez G, Hernández IM, et al. Elevated anti-Müllerian hormone (AMH) and inhibin B levels in prepubertal girls with type 1 diabetes mellitus. Clin Endocrinol. 2011;74(1):73-8. doi: 10.1111/j.1365-2265.2010.03887.x.
  32. Боровик Н.В., Потин В.В., Рутенбург Е.Л. Диабетические микрососудистые осложнения (ретинопатия и нефропатия) и беременность // Журнал акушерства и женских болезней. — 2013. — Т. LXII. — Вып. 2. — С. 75–82. [Borovik NV, Potin VV, Rutenburg YeL. Diabetic microvascular complications (retinopathy and nephropathy) and pregnancy. Journal of Obstetrics and Women’s Diseases. 2013;62(2):75-82. (In Russ.)]
  33. Дедов И.И., Шестакова М.В. Сахарный диабет: острые и хронические осложнения. — М.: МИА, 2011. [Dedov II, Shestakova MV. Sakharnyy diabet: ostryye i khronicheskiye oslozhneniya. Moscow: MIA; 2011. (In Russ.)]
  34. Wendt T, Tanji N, Guo J, et al. Glucose, glycation, and RACE: implications for amplification of cellular dysfunction in diabetic nephropathy. J Am Soc Nephrol. 2003;14(5):1383-95. doi: 10.1097/01.ASN.0000065100.17349.CA.
  35. Yan SF, D′Agati V, Schmidt AM, Ramasamy R. Receptor for Advanced Glycation Endproducts (RAGE): a formidable force in the pathogenesis of the cardiovascular complications of diabetes & aging. Curr Mol Med. 2007;7:699-710. doi: 10.2174/156652407783220732.
  36. Brownlee M. Glycosylation products as toxic mediators of diabetic complications. Annu Rev Med. 2005;42:159-166. doi: 10.1146/annurev.me.42.020191.001111.
  37. Carvalho VF, Florim LT, de O Barreto E, et al. Inhibition of advanced glycation end products by aminoguanidine restores mast cell numbers and reactivity in alloxan-diabetic rats. Eur J Pharmacol. 2011;669(1-3):143-8. doi: 10.1016/j.ejphar.2011.08.004.
  38. Chabrolle C, Jeanpierre E, Tosca L, et al. Effects of high levels of glucose on the steroidogenesis and the expression of adiponectin receptors in rat ovarian cells. Reprod Biol Endo crinol. 2008;19:6-11. doi: 10.1186/1477-7827-6-11.
  39. Roa J, Tena-Sempere M. Energy balance and puberty onset: emerging role of central mTOR signaling. Trends Endocrinol Metab. 2010;21(9):519-28. doi: 10.1016/j.tem.2010.05.003.
  40. Chang AS, Dale AN, Moley KH. Maternal diabetes adversely affects preovulatory oocyte maturation, development, and granulosa cell apoptosis. Endocrinology. 2005;146(5):2445-53. doi: 10.1210/en.2004-1472.
  41. Fernandez-Fernandez R, Martini AC, Navarro VM, et al. Novel signals for the integration of energy balance and reproduction. Mol Cell Endocrinol. 2006;25;254-5:127-32. doi: 10.1016/j.mce.2006.04.026.
  42. Hill JW, Elmquist JK, Elias CF. Hypothalamic pathways linking energy balance and reproduction. Am J Physiol Endocrinol Metab. 2008;294(5):827-32. doi: 10.1152/ajpendo.00670.2007.
  43. García-Galiano D, Pinilla L, Tena-Sempere M. Sex steroids and the control of the Kiss1 system: developmental roles and major regulatory actions. J Neuroendocrinol. 2012;24(1):22-33. doi: 10.1111/j.1365-2826.2011.02230.x.
  44. Luque RM, Kineman RD, Tena-Sempere M. Regulation of hypothalamic expression of KiSS-1 and GPR54 genes by metabolic factors: analyses using mouse models and a cell line. Endocrinology. 2007;148(10):4601-11. doi: 10.1210/en.2007-0500.
  45. Fu LY, van den Pol AN. Kisspeptin directly excites anorexigenic proopiomelanocortin neurons but inhibits orexigenic neuropeptide Y cells by an indirect synaptic mechanism. J Neurosci. 2010;28(30):10205-19. doi: 10.1523/JNEUROSCI.2098-10.2010.
  46. Backholer K, Smith JT, Rao A, et al. Kisspeptin cells in the ewe brain respond to leptin and communicate with neuro peptide Y and proopiomelanocortin cells. Endocrinology. 2010;151(5):2233-43. doi: 10.1210/en.2009-1190.
  47. Roa J, Navarro VM, Tena-Sempere M. Kisspeptins in reproductive biology: consensus knowledge and recent developments. Biol Reprod. 2011;85(4):650-60. doi: 10.1095/biolreprod.111.091538.
  48. Barbieri RL, Smith S, Ryan KJ. The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism. Fertil Steril. 1988;50(2):197-212. doi: 10.1016/S0015-0282(16)60060-2.

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