Skip to main content

Advertisement

SpringerLink
Log in

Anti-Mullerian hormone and puberty development in girls and adolescents who underwent cancer treatment

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Background

High survival rates of children diagnosed with cancer have led to a growing population of women with premature ovarian failure (POF) due to chemotherapy and radiotherapy. The POF process occurs due to the disruption of the hypothalamic–pituitary and gonadal axis followed by the delay of puberty development. Evaluation of reproductive function in children with cancer is essential to determine the fertility preservation plan. This study aimed to describe reproductive functions in children and adolescents with cancer who received chemotherapy based on Tanner stage evaluation, menstrual cycle, and anti-Mullerian hormone (AMH) examination using electro-chemiluminescence immunoassay kit.

Results

Twenty-three girls aged 12–18 years old and had menarche who underwent cancer therapy in January–August 2019 in Dr. Sardjito General Hospital were included in the study. Among them, 61% had low AMH levels and were defined as diminished ovarian reserve (DOR). Two subjects with DOR experienced delayed puberty. Regular menstrual cycle was reported in 65.2% of subjects and irregular menstrual cycle in 34.8%, while 21.7% with irregular menstrual cycle encountered secondary amenorrhea.

Conclusion

Chemotherapy exposure affected DOR occurrence in 60.9% of patients with childhood and adolescence cancer. Moreover, it also altered menstrual regularity in 34.8% and delayed puberty development in 8.7% subjects.

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

Availability of data and material

Data findings are available from corresponding author upon reasonable request.

Abbreviations

POF:

Premature ovarian failure

HRC:

High-risk chemotherapy

LRC:

Low-risk chemotherapy

AMH:

Anti-Mullerian hormone

ECLIA:

Electro-chemiluminescence immunoassay

DOR:

Diminished ovarian reserve

OR:

Odds ratio

CI:

Confidence interval

SPSS:

Statistical package for the social sciences

ALL:

Acute lymphoblastic leukemia

HL:

Hodgkin lymphoma

NHL:

Non-Hodgkin lymphoma

CML:

Chronic myelogenous leukemia

DNA:

Deoxyribonucleic acid

References

  1. Gatta G, Zigon G, Capocaccia R, Coebergh JW, Desandes E, Kaatsch P et al (2009) Survival of European children and young adults with cancer diagnosed 1995–2002. Eur J Cancer 45:992–1005

    Article  Google Scholar 

  2. Larsen EC, Muller J, Rechnitzer C, Schmiegelow K, Andersen AN (2003) Diminished ovarian reserve in female childhood cancer survivors with regular menstrual cycles and basal FSH <10 IU/l. Hum Reprod 18(2):417–422

    Article  CAS  Google Scholar 

  3. Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K et al (2006) American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol 24(18):2917–2931

    Article  Google Scholar 

  4. Issaoui ME, Giorgione V, Mamsen LS, Rechnitzer C, Birkebæk N, Clausen N, Kelsey TW, Andersen CY (2016) Effect of first line cancer treatment on the ovarian reserve and follicular density in girls under the age of 18 years. Fertil Steril 106(7):1757–62.e1

    Article  Google Scholar 

  5. Hagen CP, Aksglaede L, Sørensen K, MainKM BM, Cleemann L et al (2010) Serum levels of anti-Mullerian hormone as a marker of ovarian function in 926 healthy females from birth to adulthood and in 172 Turner syndrome patients. J Clin Endocrinol Metab 95(11):5003–5010

    Article  CAS  Google Scholar 

  6. Patton GC, Hemphill SA, Beyers JM, Bond L, Toumbourou JW, McMorris BJ et al (2007) Pubertal stage and deliberate self-harm in adolescents. J Am Acad Child Adolesc Psychiatry 46(4):508–514

    Article  Google Scholar 

  7. Herbison AE (2016) Control of puberty onset and fertility by gonadotropin-releasing hormone neurons. Nat Rev Endocrinol 12(8):452–466

    Article  CAS  Google Scholar 

  8. Bozzola M, Albanese A, Butler GE, Cherubini V, Cicognani A, Caruso-Nicoletti M et al (2001) Unresolved problems in optimal therapy of pubertal disorders in oncological and bone marrow transplanted patients. J Pediatr Endocrinol Metab 14:997–1002

    Article  Google Scholar 

  9. Emmanuel M, Bokor BR (2021) Tanner stages [Updated 2020 Dec 18]. In: StatPearls [Internet]. StatPearls Publishing, Treasure Island (FL). Available from: https://www.ncbi.nlm.nih.gov/books/NBK470280/

  10. Lie FS, Visser JA, Welt CK, de Rijke YB, Eijkemans MJC, Broekmans FJ et al (2012) Serum anti-Mullerian hormone levels in healthy females: a nomogram ranging from infancy to adulthood. J Clin Endocrinol Metab 97(12):4650–4655

    Article  Google Scholar 

  11. Dunlop CE, Anderson RA (2015) Uses of anti-Müllerian hormone (AMH) measurement before and after cancer treatment in women. Maturitas 80(3):245–250

    Article  CAS  Google Scholar 

  12. Hansen KR, Hodnett GM, Knowlton N, Craig LB (2011) Correlation of ovarian reserve tests with histologically determined primordial follicle number. Fertil Steril 95:170–175

    Article  Google Scholar 

  13. Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA et al (2004) Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 10:77–83

    Article  CAS  Google Scholar 

  14. Sonigo C, Beau I, Grynberg M, Binart N (2019) Anti-Müllerian hormone in fertility preservation: clinical and therapeutic applications. Clin Med Insights Reprod Health 13:1–7

    Article  Google Scholar 

  15. Angarita AM, Johnson CA, Fader AN, Christianson MS (2016) Fertility preservation: a key survivorship issue for young women with cancer. Front Oncol 6:1–10

    Article  Google Scholar 

  16. Fraser IA, Critchley HOD, Broder M, Munro MG (2011) The FIGO Recommendations on terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med 29(5):383–390

    Article  Google Scholar 

  17. Cui L, Qin Y, Gao X, Lu J, Geng L, Ding L et al (2016) Anti-Müllerian hormone: correlation with age and androgenic and metabolic factors in women from birth to postmenopause. Fertil Steril 105(2):481-485.e1

    Article  CAS  Google Scholar 

  18. Brougham MFH, Crofton PM, Johnson EJ, Evans N, Anderson RA, Wallace WHB (2012) Anti-Müllerian hormone is a marker of gonadotoxicity in pre- and postpubertal girls treated for cancer: a prospective study. J Clin Endocrinol Metab 97(6):2059–2067

    Article  CAS  Google Scholar 

  19. Lunsford AJ, Whelan K, Mccormick K, Mclaren JF (2013) Mullerian hormone as a measure of reproductive function in female childhood cancer survivors. Fertil Steril 101(1):227–231

    Article  Google Scholar 

  20. Mitchison TJ (2012) The proliferation rate paradox in antimitotic chemotherapy. MBoC 23(1):1–6

    Article  CAS  Google Scholar 

  21. Meirow D, Biederman H, Anderson RA, Wallace WHB (2010) Toxicity of chemotherapy and radiation on female reproduction. Clin Obstet Gynecol 53(4):727–739

    Article  Google Scholar 

  22. Feigin E, Freud E, Fisch B, Orvieto R, Kravarusic D, Avrahami G (2008) Fertility preservation in female adolescents with malignancies. In: Cancer in female adolescents. USA Science Publishers, Hauppauge, pp 38–101

    Google Scholar 

  23. Decanter C, Cloquet M, Dassonneville A, Orazio ED, Mailliez A, Pigny P (2018) Different patterns of ovarian recovery after cancer treatment suggest various individual ovarian susceptibilities to chemotherapy. Reprod Biomed Online 36(6):711–718

    Article  CAS  Google Scholar 

  24. Cosimo SD, Alimonti A, Ferretti G, Sperduti I, Carlini P, Papaldo P et al (2004) Incidence of chemotherapy-induced amenorrhea depending on the timing of treatment by menstrual cycle phase in women with early breast cancer. Breast Cancer 15(7):1065–1071

    Google Scholar 

  25. Muller J (2002) Disturbance of pubertal development after cancer treatment. Best Pract Res Clin Endocrinol Metab 16(1):91–103

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to express their gratitude to the staff of Klinik Bahasa for language assistance.

Funding

This study received funding from a research grant from Dr. Sardjito Hospital, Yogyakarta to cover AMH level examination cost, and did not receive any other funding from public or commercial sectors.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia

    Sarrah Ayuandari & Agung Dewanto

  2. Department of Pediatrics, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia

    Sri Mulatsih

  3. Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia

    Rizki Oktasari, Naafi Rizqi Rahmawati, Nurulita Ainun Alma & Kuky Cahya Hamurajib

Authors
  1. Sarrah Ayuandari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Agung Dewanto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rizki Oktasari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Naafi Rizqi Rahmawati
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nurulita Ainun Alma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kuky Cahya Hamurajib
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sri Mulatsih
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SA was involved in the study design, data interpretation, manuscript writing and review; AD was involved in the study design and manuscript review; KH contributed to data analysis, data interpretation, manuscript writing, and editing; NA contributed to data analysis, data interpretation, manuscript writing, and editing; RO was involved in the data collection; NR was involved in the data collection; SM was involved in the study design and manuscript review. All authors have read and approved the final version of the manuscript.

Corresponding author

Correspondence to Sarrah Ayuandari.

Ethics declarations

Conflict of interest

Authors declare no conflict of interest.

Ethics approval

All procedures in this research had been approved by The Medical and Health Research Ethics Committee (MHREC) Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada—Dr. Sardjito General Hospital, Yogyakarta, Indonesia with reference number: KE/FK/0726/EC/2019.

Consent to participate

Written informed consents were obtained from every parents of the patients who participated in the study.

Consent for publications

Not applicable.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ayuandari, S., Dewanto, A., Oktasari, R. et al. Anti-Mullerian hormone and puberty development in girls and adolescents who underwent cancer treatment. Arch Gynecol Obstet 305, 1581–1586 (2022). https://doi.org/10.1007/s00404-021-06364-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-021-06364-5

Keywords

Search

Navigation