Skip to main content

Advertisement

SpringerLink
Log in

Anti-Müllerian hormone levels and breast cancer risk in the study of women’s health across the nation

  • Original Paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Purpose

The relation of premenopausal anti-Müllerian hormone (AMH) levels with breast cancer risk has been evaluated in a few studies, but primarily in non-Hispanic White women.

Methods

We evaluated the association of AMH levels with breast cancer risk in Study of Women’s Health Across the Nation (SWAN), a multi-ethnic cohort of women. At enrollment, participants had an intact uterus and ≥ 1 ovary, and ≥ 1 menstrual period in the last 3 months. AMH at first measurement was assessed in 1,529 pre- or perimenopausal women using a high-sensitivity ELISA assay; values were natural log transformed. Breast cancer diagnoses were assessed at enrollment and subsequent follow-up visits through 2018 (median 6.1 years).

Results

In total, 84 women reported an incident breast cancer diagnosis. In multivariable Cox regression models adjusting for age, race and ethnicity, body mass index, and other factors, higher AMH levels were associated with a non-significant increased breast cancer risk. Compared to women in the 1st quartile, the hazard ratio (95% confidence interval) for women in the 4th quartile was 1.77 (0.87–3.60).

Conclusion

Our results did not suggest a significant association between AMH and breast cancer risk; however, estimates were consistent with prior studies that reported positive associations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

Data will be made available on request.

Code availability

Not applicable.

References

  1. Tehrani FR, Solaymani-Dodaran M, Tohidi M, Gohari MR, Azizi F (2013) Modeling age at menopause using serum concentration of anti-mullerian hormone. J Clin Endocrinol Metab 98:729–735

    Article  CAS  Google Scholar 

  2. Broekmans FJ, Soules MR, Fauser BC (2009) Ovarian aging: mechanisms and clinical consequences. Endocr Rev 30:465–493

    Article  CAS  Google Scholar 

  3. Visser JA, Themmen AP (2005) Anti-Mullerian hormone and folliculogenesis. Mol Cell Endocrinol 234:81–86

    Article  CAS  Google Scholar 

  4. Durlinger AL, Visser JA, Themmen AP (2002) Regulation of ovarian function: the role of anti-Mullerian hormone. Reproduction 124:601–609

    Article  CAS  Google Scholar 

  5. de Vet A, Laven JS, de Jong FH, Themmen AP, Fauser BC (2002) Antimullerian hormone serum levels: a putative marker for ovarian aging. Fertil Steril 77:357–362

    Article  Google Scholar 

  6. 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 97:4650–4655

    Article  CAS  Google Scholar 

  7. Lee MM, Donahoe PK, Hasegawa T et al (1996) Mullerian inhibiting substance in humans: normal levels from infancy to adulthood. J Clin Endocrinol Metab 81:571–576

    CAS  PubMed  Google Scholar 

  8. Freeman EW, Sammel MD, Lin H, Gracia CR (2012) Anti-mullerian hormone as a predictor of time to menopause in late reproductive age women. J Clin Endocrinol Metab 97:1673–1680

    Article  CAS  Google Scholar 

  9. Broer SL, Eijkemans MJ, Scheffer GJ et al (2011) Anti-mullerian hormone predicts menopause: a long-term follow-up study in normoovulatory women. J Clin Endocrinol Metab 96:2532–2539

    Article  CAS  Google Scholar 

  10. Sowers M, McConnell D, Gast K et al (2010) Anti-Mullerian hormone and inhibin B variability during normal menstrual cycles. Fertil Steril 94:1482–1486

    Article  CAS  Google Scholar 

  11. Hehenkamp WJ, Looman CW, Themmen AP, de Jong FH, Te Velde ER, Broekmans FJ (2006) Anti-Mullerian hormone levels in the spontaneous menstrual cycle do not show substantial fluctuation. J Clin Endocrinol Metab 91:4057–4063

    Article  CAS  Google Scholar 

  12. Kevenaar ME, Meerasahib MF, Kramer P et al (2006) Serum anti-mullerian hormone levels reflect the size of the primordial follicle pool in mice. Endocrinology 147:3228–3234

    Article  CAS  Google Scholar 

  13. Dewailly D, Andersen CY, Balen A et al (2014) The physiology and clinical utility of anti-Mullerian hormone in women. Hum Reprod Update 20:370–385

    Article  Google Scholar 

  14. Hoshiya Y, Gupta V, Kawakubo H et al (2003) Mullerian inhibiting substance promotes interferon gamma-induced gene expression and apoptosis in breast cancer cells. J Biol Chem 278:51703–51712

    Article  CAS  Google Scholar 

  15. Segev DL, Hoshiya Y, Stephen AE et al (2001) Mullerian inhibiting substance regulates NFkappaB signaling and growth of mammary epithelial cells in vivo. J Biol Chem 276:26799–26806

    Article  CAS  Google Scholar 

  16. Ge W, Clendenen TV, Afanasyeva Y et al (2018) Circulating anti-Mullerian hormone and breast cancer risk: a study in ten prospective cohorts. Int J Cancer 142:2215–2226

    Article  CAS  Google Scholar 

  17. Eliassen AH, Zeleniuch-Jacquotte A, Rosner B, Hankinson SE (2016) Plasma Anti-mullerian hormone concentrations and risk of breast cancer among premenopausal women in the nurses’ health studies. Cancer Epidemiol Biomark Prev 25:854–860

    Article  CAS  Google Scholar 

  18. Nichols HB, Baird DD, Stanczyk FZ et al (2015) Anti-Mullerian hormone concentrations in premenopausal women and breast cancer risk. Cancer Prev Res (Phila) 8:528–534

    Article  CAS  Google Scholar 

  19. Dorgan JF, Stanczyk FZ, Egleston BL et al (2009) Prospective case-control study of serum mullerian inhibiting substance and breast cancer risk. J Natl Cancer Inst 101:1501–1509

    Article  CAS  Google Scholar 

  20. McCoy AC, Kliethermes B, Zhang K et al (2011) Serum Mullerian inhibiting substance levels are lower in premenopausal women with breast precancer and cancer. BMC Res Notes 4:152

    Article  Google Scholar 

  21. Verdiesen RMG, van Gils CH, Stellato RK et al (2021) Anti-mullerian hormone levels and risk of cancer in women. Maturitas 143:216–222

    Article  CAS  Google Scholar 

  22. Bleil ME, Gregorich SE, Adler NE, Sternfeld B, Rosen MP, Cedars MI (2014) Race/ethnic disparities in reproductive age: an examination of ovarian reserve estimates across four race/ethnic groups of healthy, regularly cycling women. Fertil Steril 101:199–207

    Article  Google Scholar 

  23. Seifer DB, Golub ET, Lambert-Messerlian G et al (2009) Variations in serum mullerian inhibiting substance between white, black, and Hispanic women. Fertil Steril 92:1674–1678

    Article  Google Scholar 

  24. Nelson SM, Aijun S, Ling Q et al (2020) Ethnic discordance in serum anti-Mullerian hormone in healthy women: a population study from China and Europe. Reprod Biomed Online 40:461–467

    Article  CAS  Google Scholar 

  25. Sowers M, Crawford S, Sternfeld B et al (2000) SWAN: a multicenter, multiethnic, community-based cohort study of women and the menopausal transition. In: Lobo R, Kelsey J, R M (eds) Menopause: biology and pathobiology. Academic Press, San Diego, pp 175–188

    Chapter  Google Scholar 

  26. Sternfeld B, Cauley J, Harlow S, Liu G, Lee M (2000) Assessment of physical activity with a single global question in a large, multiethnic sample of midlife women. Am J Epidemiol 152:678–687

    Article  CAS  Google Scholar 

  27. Sowers MR, Finkelstein JS, Ettinger B et al (2003) The association of endogenous hormone concentrations and bone mineral density measures in pre- and perimenopausal women of four ethnic groups: SWAN. Osteoporos Int 14:44–52

    Article  CAS  Google Scholar 

  28. Little RJA, Rubin DB (2002) Statistical analysis with missing data, 2nd edn. Wiley, Hoboken

    Book  Google Scholar 

  29. Peigne M, Decanter C (2014) Serum AMH level as a marker of acute and long-term effects of chemotherapy on the ovarian follicular content: a systematic review. Reprod Biol Endocrinol 12:26

    Article  Google Scholar 

  30. Freour T, Barriere P, Masson D (2017) Anti-mullerian hormone levels and evolution in women of reproductive age with breast cancer treated with chemotherapy. Eur J Cancer 74:1–8

    Article  CAS  Google Scholar 

  31. Curb JD, McTiernan A, Heckbert SR et al (2003) Outcomes ascertainment and adjudication methods in the women’s health initiative. Ann Epidemiol 13:S122–S128

    Article  Google Scholar 

Download references

Funding

The Study of Women’s Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), the NIH Office of Research on Women’s Health (ORWH), and the SWAN Repository (Grants U01NR004061; U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, U19AG063720, and U01AG017719). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH or the NIH. Clinical Centers: University of Michigan, Ann Arbor – Siobán Harlow, PI 2011 – present, MaryFran Sowers, PI 1994-2011; Massachusetts General Hospital, Boston, MA – Sherri‐Ann Burnett‐Bowie, PI 2020 – Present; Joel Finkelstein, PI 1999 – 2020; Robert Neer, PI 1994 – 1999; Rush University, Rush University Medical Center, Chicago, IL – Imke Janssen, PI 2020 – Present; Howard Kravitz, PI 2009 – 2020; Lynda Powell, PI 1994 – 2009; University of California, Davis/Kaiser – Elaine Waetjen and Monique Hedderson, PIs 2020 – Present; Ellen Gold, PI 1994 - 2020; University of California, Los Angeles – Arun Karlamangla, PI 2020 – Present; Gail Greendale, PI 1994 - 2020; Albert Einstein College of Medicine, Bronx, NY – Carol Derby, PI 2011 – present, Rachel Wildman, PI 2010 – 2011; Nanette Santoro, PI 2004 – 2010; University of Medicine and Dentistry – New Jersey Medical School, Newark – Gerson Weiss, PI 1994 – 2004; and the University of Pittsburgh, Pittsburgh, PA – Rebecca Thurston, PI 2020 – Present; Karen Matthews, PI 1994 - 2020. NIH Program Office: National Institute on Aging, Bethesda, MD – Rosaly Correa-de-Araujo 2020 - present; Chhanda Dutta 2016- present; Winifred Rossi 2012–2016; Sherry Sherman 1994 – 2012; Marcia Ory 1994 – 2001; National Institute of Nursing Research, Bethesda, MD – Program Officers. Central Laboratory: University of Michigan, Ann Arbor – Daniel McConnell (Central Ligand Assay Satellite Services). NIA Biorepository - Rosaly Correa-de-Araujo 2019 - Present; SWAN Repository: University of Michigan, Ann Arbor – Siobán Harlow 2013 - 2018; Dan McConnell 2011 - 2013; MaryFran Sowers 2000 – 2011. Coordinating Center: University of Pittsburgh, Pittsburgh, PA – Maria Mori Brooks, PI 2012 - present; Kim Sutton-Tyrrell, PI 2001 – 2012; New England Research Institutes, Watertown, MA - Sonja McKinlay, PI 1995 – 2001. Steering Committee: Susan Johnson, Current Chair; Chris Gallagher, Former Chair. We thank the study staff at each site and all the women who participated in SWAN.

Author information

Authors and Affiliations

  1. Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, 715 North Pleasant Street, Amherst, MA, 01003, USA

    Nydjie P. Grimes, Elizabeth R. Bertone-Johnson, Brian W. Whitcomb & Katherine W. Reeves

  2. Department of Health Promotion and Policy, University of Massachusetts Amherst, Amherst, MA, USA

    Elizabeth R. Bertone-Johnson

  3. Department of Anthropology, University of Massachusetts Amherst, Amherst, MA, USA

    Lynnette L. Sievert

  4. Graduate School of Nursing, University of Massachusetts Medical School, Worcester, MA, USA

    Sybil L. Crawford

  5. Department of Public Health Sciences, University of California Davis, Davis, CA, USA

    Ellen B. Gold

  6. Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Nancy E. Avis

  7. David Geffen School of Medicine, University of California, Los Angeles, USA

    Gail A. Greendale

  8. Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO, USA

    Nanette Santoro

  9. Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA

    Laurel A. Habel

Authors
  1. Nydjie P. Grimes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth R. Bertone-Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian W. Whitcomb
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lynnette L. Sievert
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sybil L. Crawford
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ellen B. Gold
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nancy E. Avis
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gail A. Greendale
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nanette Santoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Laurel A. Habel
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Katherine W. Reeves
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nydjie P. Grimes.

Ethics declarations

Conflict of interest

The authors have not disclosed any competing interests.

Ethical approval

Compliance with ethical standards.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 119 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grimes, N.P., Bertone-Johnson, E.R., Whitcomb, B.W. et al. Anti-Müllerian hormone levels and breast cancer risk in the study of women’s health across the nation. Cancer Causes Control 33, 1039–1046 (2022). https://doi.org/10.1007/s10552-022-01596-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-022-01596-5

Keywords

Search

Navigation