Cancer Causes & Control

, Volume 25, Issue 5, pp 583–589

Anti-Mullerian hormone and risk of invasive serous ovarian cancer

  • H. Schock
  • E. Lundin
  • M. Vääräsmäki
  • K. Grankvist
  • A. Fry
  • J. F. Dorgan
  • E. Pukkala
  • M. Lehtinen
  • H. M. Surcel
  • A. Lukanova
Original paper



Epithelial ovarian cancers either arise directly from Mullerian-type epithelium or acquire Mullerian characteristics in the course of neoplastic transformation. The anti-Mullerian hormone (AMH) causes regression of Mullerian structures during fetal development in males and has been shown to inhibit the growth of epithelial ovarian cancer. Therefore, we hypothesized that pre-diagnostic serum concentrations of AMH are inversely associated with risk of invasive serous ovarian cancer.


A case–control study (107 cases, 208 controls) was nested within the population-based Finnish Maternity Cohort (1986–2007). The sample donated during the first trimester of the last pregnancy preceding cancer diagnosis of the case subjects was selected for the study. For each case, two controls, matched on age and date at sampling, as well as parity at sampling and at cancer diagnosis were selected. AMH was measured by a second-generation AMH ELISA. Conditional logistic regression was used to compute odds ratios (OR) and 95 % confidence intervals (CI) for invasive serous ovarian cancer associated with AMH concentrations.


Overall AMH concentrations were not associated with risk of invasive serous ovarian cancer (OR 0.93; 95 % CI 0.49–1.77 for top vs. bottom tertile, Ptrend = 0.83). In women older than the median age at sampling (32.7 years), a doubling of AMH was associated with decreased risk (OR 0.69; 95 % CI 0.49–0.96), whereas an increased risk (OR 1.64; 95 % CI 1.06–2.54) was observed in younger women, Phomogeneity = 0.002.


In this first prospective investigation, risk of invasive serous ovarian cancer was not associated with pre-diagnostic AMH concentrations overall; however, the association may depend on age at AMH measurement.


Anti-Mullerian hormone Ovarian neoplasms Pregnancy Case–control studies Prospective studies 


  1. 1.
    Dubeau L (2008) The cell of origin of ovarian epithelial tumours. Lancet Oncol 9(12):1191–1197PubMedCrossRefGoogle Scholar
  2. 2.
    Scully RE (1977) Ovarian tumors. A review. Am J Pathol 87(3):686–720PubMedCentralPubMedGoogle Scholar
  3. 3.
    Auersperg N, Wong AS, Choi KC, Kang SK, Leung PC (2001) Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev 22(2):255–288PubMedGoogle Scholar
  4. 4.
    MacLaughlin DT, Donahoe PK (2010) Mullerian inhibiting substance/anti-mullerian hormone: a potential therapeutic agent for human ovarian and other cancers. Future Oncol 6(3):391–405PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Weenen C, Laven JS, Von Bergh AR et al (2004) Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 10(2):77–83PubMedCrossRefGoogle Scholar
  6. 6.
    Kelsey TW, Wright P, Nelson SM, Anderson RA, Wallace WH (2011) A validated model of serum anti-mullerian hormone from conception to menopause. PLoS ONE 6(7):e22024PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    La Marca A, Sighinolfi G, Giulini S et al (2010) Normal serum concentrations of anti-Mullerian hormone in women with regular menstrual cycles. Reprod Biomed Online 21(4):463–469PubMedCrossRefGoogle Scholar
  8. 8.
    Nelson SM, Stewart F, Fleming R, Freeman DJ (2010) Longitudinal assessment of antimullerian hormone during pregnancy-relationship with maternal adiposity, insulin, and adiponectin. Fertil Steril 93(4):1356–1358PubMedCrossRefGoogle Scholar
  9. 9.
    Lutterodt M, Byskov AG, Skouby SO, Tabor A, Yding AC (2009) Anti-Mullerian hormone in pregnant women in relation to other hormones, fetal sex and in circulation of second trimester fetuses. Reprod Biomed Online 18(5):694–699PubMedCrossRefGoogle Scholar
  10. 10.
    Meirelles K, Benedict LA, Dombkowski D et al (2012) Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance. Proc Natl Acad Sci USA 109(7):2358–2363PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Bakkum-Gamez JN, Aletti G, Lewis KA et al (2008) Mullerian inhibiting substance type II receptor (MISIIR): a novel, tissue-specific target expressed by gynecologic cancers. Gynecol Oncol 108(1):141–148PubMedCrossRefGoogle Scholar
  12. 12.
    Song JY, Chen KY, Kim SY et al (2009) The expression of Mullerian inhibiting substance/anti-Mullerian hormone type II receptor protein and mRNA in benign, borderline and malignant ovarian neoplasia. Int J Oncol 34(6):1583–1591PubMedGoogle Scholar
  13. 13.
    Chang HL, Pieretti-Vanmarcke R, Nicolaou F et al (2011) Mullerian inhibiting substance inhibits invasion and migration of epithelial cancer cell lines. Gynecol Oncol 120(1):128–134PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Koskela P, Anttila T, Bjorge T et al (2000) Chlamydia trachomatis infection as a risk factor for invasive cervical cancer. Int J Cancer 85(1):35–39PubMedCrossRefGoogle Scholar
  15. 15.
    Teppo L, Pukkala E, Lehtonen M (1994) Data quality and quality control of a population-based cancer registry. Experience in Finland. Acta Oncol 33(4):365–369PubMedCrossRefGoogle Scholar
  16. 16.
    Cleveland WS, Loader C (1996) Smoothing by Local Regression: Principles and Methods. In: Härdle W, Schimek MG (eds) Statistical theory and computational aspects of smoothing, 1st edn. Physica-Verlag, Heidelberg, pp 10–49CrossRefGoogle Scholar
  17. 17.
    Cohen J, Cohen P, West SG, Aiken LS (2003) Multiple Regression/Correlation with two or more independent variables. Applied Multiple Regression/Correlation Analysis for the Behavioral Sciences, 3rd edn. Lawrence Erlbaum Associates, Mahwah, NJ, pp 64–100Google Scholar
  18. 18.
    Whitehead A, Whitehead J (1991) A general parametric approach to the meta-analysis of randomized clinical trials. Stat Med 10(11):1665–1677PubMedCrossRefGoogle Scholar
  19. 19.
    Josso N (2008) Professor Alfred Jost: the builder of modern sex differentiation. Sex Dev 2(2):55–63PubMedCrossRefGoogle Scholar
  20. 20.
    Picard JY, Josso N (1984) Purification of testicular anti-Mullerian hormone allowing direct visualization of the pure glycoprotein and determination of yield and purification factor. Mol Cell Endocrinol 34(1):23–29PubMedCrossRefGoogle Scholar
  21. 21.
    Grynnerup AG, Lindhard A, Sorensen S (2012) The role of anti-Mullerian hormone in female fertility and infertility—an overview. Acta Obstet Gynecol Scand 91(11):1252–1260PubMedCrossRefGoogle Scholar
  22. 22.
    Teixeira J, Maheswaran S, Donahoe PK (2001) Mullerian inhibiting substance: an instructive developmental hormone with diagnostic and possible therapeutic applications. Endocr Rev 22(5):657–674PubMedGoogle Scholar
  23. 23.
    Fanchin R, Taieb J, Lozano DH, Ducot B, Frydman R, Bouyer J (2005) High reproducibility of serum anti-Mullerian hormone measurements suggests a multi-staged follicular secretion and strengthens its role in the assessment of ovarian follicular status. Hum Reprod 20(4):923–927PubMedCrossRefGoogle Scholar
  24. 24.
    Dorgan JF, Spittle CS, Egleston BL, Shaw CM, Kahle LL, Brinton LA (2010) Assay reproducibility and within-person variation of Mullerian inhibiting substance. Fertil Steril 94(1):301–304PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    van Rooij I, Broekmans FJ, Scheffer GJ et al (2005) Serum antimullerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: a longitudinal study. Fertil Steril 83(4):979–987PubMedCrossRefGoogle Scholar
  26. 26.
    Baird DD, Steiner AZ (2012) Anti-Mullerian hormone: a potential new tool in epidemiologic studies of female fecundability. Am J Epidemiol 175(4):245–249PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    La Marca A, Spada E, Grisendi V et al (2012) Normal serum anti-Mullerian hormone levels in the general female population and the relationship with reproductive history. Eur J Obstet Gynecol Reprod Biol 163(2):180–184PubMedCrossRefGoogle Scholar
  28. 28.
    Dolleman M, Verschuren WM, Eijkemans MJ et al (2013) Reproductive and lifestyle determinants of anti-Mullerian hormone in a large population-based study. J Clin Endocrinol Metab 98(5):2106–2115PubMedCrossRefGoogle Scholar
  29. 29.
    Plante BJ, Cooper GS, Baird DD, Steiner AZ (2010) The impact of smoking on antimullerian hormone levels in women aged 38 to 50 years. Menopause 17(3):571–576PubMedCentralPubMedGoogle Scholar
  30. 30.
    Smith ER, Xu XX (2008) Ovarian ageing, follicle depletion, and cancer: a hypothesis for the aetiology of epithelial ovarian cancer involving follicle depletion. Lancet Oncol 9(11):1108–1111PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Durlinger AL, Visser JA, Themmen AP (2002) Regulation of ovarian function: the role of anti-Mullerian hormone. Reproduction 124(5):601–609PubMedCrossRefGoogle Scholar
  32. 32.
    Visser JA, Durlinger AL, Peters IJ et al (2007) Increased oocyte degeneration and follicular atresia during the estrous cycle in anti-Mullerian hormone null mice. Endocrinology 148(5):2301–2308PubMedCrossRefGoogle Scholar
  33. 33.
    Masse V, Ferrari P, Boucoiran I, Delotte J, Isnard V, Bongain A (2011) Normal serum concentrations of anti-Mullerian hormone in a population of fertile women in their first trimester of pregnancy. Hum Reprod 26(12):3431–3436PubMedCrossRefGoogle Scholar
  34. 34.
    Lie Fong S, Visser JA, Welt CK et al (2012) Serum anti-mullerian hormone levels in healthy females: a nomogram ranging from infancy to adulthood. J Clin Endocrinol Metab 97(12):4650–4655PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Kristensen SL, Ramlau-Hansen CH, Andersen CY et al (2012) The association between circulating levels of antimullerian hormone and follicle number, androgens, and menstrual cycle characteristics in young women. Fertil Steril 97(3):779–785PubMedCrossRefGoogle Scholar
  36. 36.
    Piltonen T, Morin-Papunen L, Koivunen R, Perheentupa A, Ruokonen A, Tapanainen JS (2005) Serum anti-Mullerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome. Hum Reprod 20(7):1820–1826PubMedCrossRefGoogle Scholar
  37. 37.
    Moorman PG, Calingaert B, Palmieri RT et al (2008) Hormonal risk factors for ovarian cancer in premenopausal and postmenopausal women. Am J Epidemiol 167(9):1059–1069PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • H. Schock
    • 1
    • 2
  • E. Lundin
    • 2
    • 3
  • M. Vääräsmäki
    • 4
    • 5
  • K. Grankvist
    • 2
  • A. Fry
    • 6
  • J. F. Dorgan
    • 7
  • E. Pukkala
    • 8
    • 9
  • M. Lehtinen
    • 9
  • H. M. Surcel
    • 5
  • A. Lukanova
    • 1
    • 2
  1. 1.Division of Cancer EpidemiologyGerman Cancer Research CenterHeidelbergGermany
  2. 2.Department of Medical BiosciencesUniversity of UmeåUmeåSweden
  3. 3.Public Health and Clinical Medicine: Nutritional ResearchUniversity of UmeåUmeåSweden
  4. 4.Department of Obstetrics and GynecologyUniversity of OuluOuluFinland
  5. 5.Department of Children, Young People and FamiliesNational Institute for Health and WelfareOuluFinland
  6. 6.Imperial College LondonLondonUK
  7. 7.Department of Epidemiology and Public HealthUniversity of Maryland School of MedicineBaltimoreUSA
  8. 8.Finnish Cancer RegistryInstitute for Statistical and Epidemiological Cancer ResearchHelsinkiFinland
  9. 9.School of Public HealthUniversity of TampereTampereFinland

Personalised recommendations