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Horm Metab Res 2011; 43(10): 723-727
DOI: 10.1055/s-0031-1286307
Humans, Clinical
Georg Thieme Verlag KG Stuttgart · New York

Anti-Müllerian Hormone in Women with Polycystic Ovary Syndrome Before and After Therapy with Metformin

А. Tomova
1   Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria
,
F. Deepinder
2   Department of Endocrinology, Diabetes and Metabolism, Cedars Sinai Medical Center – UCLA School of Medicine, Los Angeles, California
,
R. Robeva
1   Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria
,
G. Kirilov
1   Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria
,
Z. Mechandjiev
3   SHАTAG “Majchin dom”, Medical University, Sofia, Bulgaria
,
P. Kumanov
1   Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria
› Author Affiliations
Further Information

Publication History

received 24 February 2011

accepted 11 July 2011

Publication Date:
19 September 2011 (online)

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Abstract

Anti-Müllerian hormone (AMH) is largely expressed throughout folliculogenesis and its levels may represent both the quantity and quality of ovarian follicle pool. We conducted this study to evaluate the levels of AMH in women with polycystic ovarian syndrome (PCOS) before and after metformin therapy. 22 consecutive patients with PCOS and 20 healthy age-matched controls were investigated. The patients received 2 550 mg/day metformin for 6 months. Serum levels of AMH, sex hormones, insulin, blood glucose, and lipids were measured before and after metformin therapy. The basal AMH levels in patients with PCOS (42.34±6.42 pmol/l) were significantly elevated in comparison with the controls (21.58±3.41 pmol/l), p=0.008. 17 patients completed 6 months therapy with metformin. Of them, 13 responded clinically by restoration of regular menstrual cycles. The AMH levels of these 13 women decreased from 45.67±9.30 pmol/l to 38.25±6.89 pmol/l (16.27%). In the other 4 patients who did not show satisfactory clinical response to metformin, AMH levels increased from 31.30±16.52 to 80.77±12.73 (p=0.021). The patients who responded to metformin were significantly overweight, had higher BMI, waist circumference, body fat, and blood pressure as compared to nonresponders. AMH levels are significantly elevated in women with PCOS and they may serve as a marker for evaluation of treatment efficacy with metformin. Furthermore, obese PCOS patients are more likely to respond to metformin therapy with maximal doses as compared to the ones with low body mass index.

Key words

anti-Müllerian hormone - polycystic ovary syndrome - hyperandrogenism - hyperinsulinism - testosterone
 

  • References

  • 1 Cate RL, Mattaliano RJ, Hession C, Tizard R, Farber NM, Cheung A, Ninfa EG, Frey AZ, Gash DJ, Chow EP. Isolation of the bovine and human genes for Müllerian inhibiting substance and expression of the human gene in animal cells. Cell 1986; 45: 685-698
    CrossrefPubMedGoogle Scholar
  • 2 La Marca A, Volpe A. Anti-Müllerian hormone (AMH) in female reproduction: is measurement of circulating AMH a useful tool?. Clin Endocrinol 2006; 64: 603-610
    CrossrefPubMedGoogle Scholar
  • 3 de Vet A, Laven JS, de Jong FH, Themmen AP, Fauser BC. Antimüllerian hormone serum levels: a putative marker for ovarian aging. Fertil Steril 2002; 77: 357-362
    CrossrefPubMedGoogle Scholar
  • 4 Van Rooij IA, Broekmans FJ, Scheffer GJ, Looman CW, Habbema JD, de Jong FH, Fauser BJ, Themmen AP, te Velde ER. Serum antimullerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: a longitudinal study. Fertil Steril 2005; 83: 979-987
    CrossrefPubMedGoogle Scholar
  • 5 Cook CL, Siow Y, Brenner AG, Fallat ME. Relationship between serum müllerian-inhibiting substance and other reproductive hormones in untreated women with polycystic ovary syndrome and normal women. Fertil Steril 2002; 77: 41-46
    PubMedGoogle Scholar
  • 6 Pigny P, Merlen E, Robert Y, Cortet-Rudelli C, Decanter C, Jonard S, Dewailly D. Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab 2003; 88: 57-62
    PubMedGoogle Scholar
  • 7 Laven JS, Mulders AG, Visser JA, Themmen AP, de Jong FH, Fauser BC. Anti-Müllerian hormone serum concentrations in normoovulatory and anovulatory women of reproductive age. J Clin Endocrinol Metab 2004; 89: 318-323
    CrossrefPubMedGoogle Scholar
  • 8 La Marca A, Orvieto R, Giulini S, Jasonni VM, Volpe A, De Leo V. Mullerian-inhibiting substance in women with polycystic ovary syndrome: relationship with hormonal and metabolic characteristics. Fertil Steril 2004; 82: 970-972
    CrossrefPubMedGoogle Scholar
  • 9 Pigny P, Jonard S, Robert Y, Dewailly D. Serum Anti-Müllerian hormone as a surrogate for antral follicle count for definition of the polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91: 941-945
    CrossrefPubMedGoogle Scholar
  • 10 Cheang KI, Sharma ST, Nestler JE. Is metformin a primary ovulatory agent in patients with polycystic ovary syndrome?. Gynecol Endocrinol 2006; 22: 595-604
    CrossrefPubMedGoogle Scholar
  • 11 De Leo V, Musacchio MC, Morgante G, Piomboni P, Petraglia F. Metformin treatment is effective in obese teenage girls with PCOS. Hum Reprod 2006; 21: 2252-2256
    CrossrefPubMedGoogle Scholar
  • 12 Kocak I, Ustun C. Effects of metformin on insulin resistance, androgen concentration, ovulation and pregnancy rates in women with polycystic ovary syndrome following laparoscopic ovarian drilling. J Obstet Gynaecol Res 2006; 32: 292-298
    CrossrefPubMedGoogle Scholar
  • 13 Fleming R, Harborne L, MacLaughlin DT, Ling D, Norman J, Sattar N, Seifer DB. Metformin reduces serum mullerian-inhibiting substance levels in women with polycystic ovary syndrome after protracted treatment. Fertil Steril 2005; 83: 30-36
    CrossrefPubMedGoogle Scholar
  • 14 Piltonen T, Morin-Papunen L, Koivunen R, Perheentupa A, Ruokonen A, Tapanainen JS. Serum anti-Müllerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome. Hum Reprod 2005; 20: 1820-1826
    CrossrefPubMedGoogle Scholar
  • 15 Carlsen SM, Vanky E, Fleming R. Anti-Mulerian hormone concentrations in androgen-supressed women with polycystic ovary syndrome. Hum Reprod 2009; 24: 1732-1738
    CrossrefPubMedGoogle Scholar
  • 16 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
    PubMedGoogle Scholar
  • 17 Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961; 21: 1440-1447
    CrossrefPubMedGoogle Scholar
  • 18 De Simone M, Verrotti A, Iughetti L, Palumbo M, Farello G, Di Cesare E, Bernabei R, Rosato T, Lozzi S, Criscione S. Increased visceral adipose tissue is associated with increased circulating insulin and decreased sex hormone binding globulin levels in massively obese adolescent girls. J Endocrinol Invest 2001; 24: 438-444
    PubMedGoogle Scholar
  • 19 Matthews DR, Hosker JP, Rudenski AS, Navlor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
    Google Scholar
  • 20 Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999; 84: 3666-3672
    CrossrefPubMedGoogle Scholar
  • 21 Azziz R, Marin C, Hoq L, Badamgarav E, Song P. Health care-related economic burden of polycystic ovary syndrome during the reproductive life span. J Clin Endocrinol Metab 2005; 90: 4650-4658
    CrossrefPubMedGoogle Scholar
  • 22 Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997; 18: 774-800
    CrossrefPubMedGoogle Scholar
  • 23 Poretsky L, Cataldo NA, Rosenwaks Z, Giudice LC. The insulin-related ovarian regulatory system in health and disease. Endocr Rev 1999; 20: 535-582
    CrossrefPubMedGoogle Scholar
  • 24 Escobar-Morreale HF, Roldan B, Barrio R, Alonso M, Sancho J, de la Calle H, García-Robles R. High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus. J Clin Endocrinol Metab 2000; 85: 4182-4187
    CrossrefPubMedGoogle Scholar
  • 25 Chen MJ, Yang WS, Chen CL, Wu MY, Yang YS, Ho HN. The relationship between anti-Müllerian hormone, androgen and insulin resistance on the number of antral follicles in women with polycystic ovary syndrome. Hum Reprod 2008; 23: 952-957
    CrossrefPubMedGoogle Scholar
  • 26 Palomba S, Falbo A, Orio Jr F, Tolino A, Zullo F. Efficacy predictors for metformin and clomiphene citrate treatment in anovulatory infertile patients with polycystic ovary syndrome. Fertil Steril 2009; 91: 2557-2567
    CrossrefPubMedGoogle Scholar
  • 27 Maciel GA, Soares Júnior JM, Alves da Motta EL, Abi Haidar M, de Lima GR, Baracat EC. Nonobese women with polycystic ovary syndrome respond better than obese women to treatment with metformin. Fertil Steril 2004; 81: 355-360
    CrossrefPubMedGoogle Scholar
  • 28 Harborne LR, Sattar N, Norman JE, Fleming R. Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses. J Clin Endocrinol Metab 2005; 90: 4593-4598
    CrossrefPubMedGoogle Scholar