Effect of metformin on the reproductive function of women with different phenotypes of polycystic ovary syndrome


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Objective. To evaluate the efficacy of metformin in the androgen and non-androgen phenotypes of polycystic ovary syndrome (PCOS). Subject and methods. The investigation included 143 women (mean age, 26.4±4.6years; mean body mass index, 23.8±4.8 kg/m2) with PCOS. A comprehensive examination, Including a pelvic ultrasound, was made; serum androgens, anti-Müllerian hormone (AMH), luteinizing hormone (LH), and follicle-stimulating hormone levels were determined; and two-hour glucose tolerance test was carried out to estimate the levels of glucose and insulin at baseline and after 6 months of therapy. The patients were divided into two groups: 1) 101 women with the androgen phenotypes of PCOS; 2) 42 women with its non-androgen phenotype. All the patients were treated with metformin 1500 mg/day for 6 months. Results. The mean levels of AMH and LH were higher in the androgen phenotype group (p < 0.05). There were no differences in the frequency of metabolic disorders; the mean level of fasting insulin was higher in women with hyperandrogenism. After 6 months of metformin therapy, there were decreases in the level of LH, androgens, and insulin in Group 1 (p < 0.05) and in that of AMH in both groups. Regardless of the phenotype of PCOS, the menstrual cycle was regulated in every two patients; pregnancy occurred in every three patients. Conclusion. Therapy with metformin at a dose of 1500 mg daily can be considered as an effective approach to correcting ovulatory dysfunction irrespective of the phenotype of the syndrome.

Full Text

Restricted Access

About the authors

A. A Naidukova

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: aleeshka@mail.ru
post-graduate student, Department of Gynecological Endocrinology

E. V Ananyev

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: new_vision@mail.ru
head of the 2nd maternity ward

G. E Chernukha

Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia

Email: c-galina1@yandex.ru
head of the Department of Gynecological Endocrinology

References

  1. National Institutes of Health. Evidence-based Methodology Workshop on Polycystic Ovary Syndrome. December 3-5, 2012.
  2. Lizneva D., Kirubakaran R., Mykhalchenko K., Suturina L., Chernukha G., Diamond M.P., Azziz R. Phenotypes and body mass in women with polycystic ovary syndrome identified in referral versus unselected populations: systematic review and meta-analysis. Fertil. Steril. 2016; 106(6): 1510-20. e2. doi: 10.1016/j. fertnstert.2016.07.1121.
  3. Mehrabian F., Khani B., Kelishadi R., Kermani N. The prevalence of metabolic syndrome and insulin resistance according to the phenotypic subgroups of polycystic ovary syndrome in a representative sample of Iranian females. J. Res. Med. Sci. 2011; 16(6): 763-9.
  4. Sujata K. Anthropometric, clinical, and metabolic comperisons of the four Rotterdam PCOS phenotypes: a prospective study of PCOS women. J. Hum. Reprod. Sci. 2013; 6(3): 194-200.
  5. Romualdi D., Di Florio C., Tagliaferri V., De Cicco S., Gagliano D., Immediata V. et al. The role of Anti-Müllerian hormone in the characterization of the different polycystic ovary syndrome phenotypes. Reprod. Sci. 2016; 23(5): 655-61. doi: 10.1177/1933719115611751.
  6. Panidis D., Tziomalos K., Macut D., Delkos D., Betsas G., Misichronis G., Katsikis I. Cross-sectional analysis of the effects of age on the hormonal, metabolic, and ultrasonographic features and the prevalence of the different phenotypes of polycystic ovary syndrome. Fertil. Steril. 2012; 97(2): 494-500. doi: 10.1016/j. fertnstert.2011.11.041.
  7. Yildiz B.O., Bozdag G., Yapici Z., Esinler I., Yarali H. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum. Reprod. 2012; 27(10): 3067-73.
  8. Moran L.J., Misso M.L., Wild R.A., Norman R.J. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum. Reprod. Update. 2010; 16(4): 347-63. doi: 10.1093/humupd/dmq001. Epub 2010 Feb 16.
  9. Nestler J.E., Jakubowicz D.J., deVargas A.F., Brik C., Quintero N., Medina F. Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositol glycan mediators as the signal transduction system. J. Clin. Endocrinol. Metab. 1998; 83(6): 2001-5.
  10. Will M.A., Palaniappan M., Peegel H., Kayampily P., Menon K.M. Metformin: Direct inhibition of rat ovarian theca-interstitial cell proliferation. Fertil. Steril. 2012; 98(1): 207-14.
  11. Attia G.R., Rainey W.E., Carr B.R. Metformin directly inhibits androgen production in human thecal cells. Fertil. Steril. 2001; 76(3): 517-24.
  12. Skinner M.K. Regulation of primordial follicle assembly and development. Hum. Reprod. Update. 2005; 11(5): 461-71.
  13. Balen A.H., Conway G.S., Homburg R., Legro R.S. Polycystic ovary syndrome: a guide to clinical management. London, New York: Taylor & Francis; 2005.
  14. Romualdi D., Di Florio C., Tagliaferri V., De Cicco S., Gagliano D., Immediata V. et al. The role of Anti-Müllerian hormone in the characterization of the different polycystic ovary syndrome phenotypes. Reprod. Sci. 2016; 23(5): 655-61. doi: 10.1177/1933719115611751.
  15. Çelik E., Türkçüoglu I., Ata B., Karaer A., Kirici P., Eraslan S. et al. Metabolic and carbohydrate characteristics of different phenotypes of polycystic ovary syndrome. J. Turk. Ger. Gynecol. Assoc. 2016; 17(4): 201-8. eCollection 2016.
  16. Блинова И.В. Функциональное состояние эндотелия и особенности эндокринно-метаболического профиля больных с различными фенотипаси сидрома поликистозных яичников: автореф. дисс.. канд. мед. наук. М.; 2009. 28с. [Blinova I.V. Functional state of the endothelium and features of the endocrine-metabolic profile of patients with various phenotypesis of the polycystic ovary syndrome: author’s abstract. diss.. cand. med. sciences. Moscow; 2009. 28p. (in Russian)]
  17. Moran L., Teede H. Metabolic features of the reproductive phenotypes of polycystic ovary syndrome. Hum. Reprod. Update. 2009; 15(4): 477-88.
  18. Moran L.J., Misso M.L., Wild R.A., Norman R.J. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum. Reprod. Update. 2010; 16(4): 347-63.
  19. Genazzani A.D., Battaglia C., Malavasi B., Strucchi C., Tortolani F., Gamba O. Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with PCOS. Fertil. Steril. 2004; 81(1): 114-9.
  20. Kurzthaler D., Hadziomerovic-Pekic D., Wildt L., Seeber B.E. Metformin induces a prompt decrease in LH-stimulated testosterone response in women with PCOS independent of its insulin-sensitizing effects. Reprod. Biol. Endocrinol. 2014; 12: 98. doi: 10.1186/1477-7827-12-98.
  21. Carlsen S.M., Vanky E., Fleming R. Anti-Müllerian hormone concentrations in androgen-suppressed women with polycystic ovary syndrome. Hum. Reprod. 2009; 24(7): 1732-8. doi: 10.1093/humrep/dep074.
  22. Grigoryan O., Absatarova J., Andreeva E., Melnichenko G., Dedov I. Effect of metformin on the level of anti-Mullerian hormone in therapy of polycystic ovary syndrome in obese women. Minerva Ginecol. 2014; 66(1): 85-9.
  23. Romualdi D., DeCicco S., Tagliaferri V., Proto C., Lanzone A., Guido M. The metabolic status modulates the effect of metformin on the antimullerian hormone-androgens-insulin interplay in obese women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 2011; 96(5): E821-4. doi: 10.1210/jc.2010-1725.
  24. Kai Y., Kawano Y., Yamamoto H., Narahara H. A possible role for AMP-activated protein kinase activated by metformin and AICAR in human granulosa cells. Reprod. Biol. Endocrinol. 2015; 13: 27. doi: 10.1186/s12958-015-0023-2.
  25. Diamond M.P., Legro R.S., Coutifaris C., Alvero R., Robinson R.D., Casson P. et al.; NICHD Reproductive Medicine Network. Letrozole, gonadotropin, or clomiphene for unexplained infertility. N. Engl. J. Med. 2015; 373(13): 1230-40. doi: 10.1056/NEJMoa1414827.
  26. Российский Национальный Консенсус: Гестационный сахарный диабет: диагностика, лечение, послеродовой наблюдение. Российская ассоциация эндокринологов. Российская ассоциация акушеров-гинекологов. ФГБУ « Эндокринологический Научный центр» МЗ РФ (2012). Приняты в 2012 г. на VI Всероссийском конгрессе эндокринологов. Утверждены на VI Всероссийском диабетологическом конгрессе и на 14 Всероссийском научном форуме «Мать и дитя». М.; 2012. 18с.
  27. Ghazeeri G.S., Nassar A.H., Younes Z., Awwad J.T. Pregnancy outcomes and the effect of metformintreatment in women with polycystic ovary syndrome: an overview. Acta Obstet. Gynecol. Scand. 2012; 91(6): 658-78. doi: 10.1111/j.1600-0412.2012.01385.x.
  28. Palomba S., Chiossi G., Falbo A., Orio F., Tolino A., Colao A. et al. Low-grade chronic inflammation in pregnant women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 2014; 99(8): 2942-51.
  29. Palomba S., Falbo A., Chiossi G., Tolino A., Tucci L., La Sala G.B., Zullo F. Early trophoblast invasion and placentation in women with different polycystic ovary syndrome phenotypes. Reprod. Biomed. Online. 2014; 29(3): 370-81.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2017 Bionika Media