Download PDF
Semin Reprod Med 2020; 38(04/05): 263-269
DOI: 10.1055/s-0040-1722319
Review Article

Anti-Müllerian Hormone in the Diagnosis and Prediction of Premature Ovarian Insufficiency

Richard A. Anderson 
1   MRC Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
,
Scott M. Nelson
2   School of Medicine, University of Glasgow, Glasgow, United Kingdom
3   NIHR Bristol Biomedical Research Centre, Bristol, United Kingdom
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

The menopause and its pathological version, premature ovarian insufficiency (POI), are characterized by the cessation of follicle growth in the ovary, with consequent lack of estrogen production and amenorrhea. The measurement of a specific product of ovarian follicles would therefore be expected to be a valuable biomarker in women with POI, and to be of likely clinical value in the diagnosis and perhaps prediction of POI. Anti-Müllerian hormone (AMH) is produced by the granulosa cells of growing follicles and is therefore likely to be of value in this context. Current data indicate that measurement of AMH is an accurate indicator of POI in many situations and has diagnostic validity and may facilitate more timely diagnosis. AMH seems to be of limited value in predicting age at natural menopause, even with multiple measurements, and there are scarce data regarding prediction of POI, other than when it is imminent, and in some contexts where there is an immediate iatrogenic threat to ovarian function. AMH therefore appears to have considerable value as a diagnostic test for POI, but apart from highlighting broadly those at increased risk, it has inadequate precision to be able to predict accurately the timing of onset of impending POI.

Keywords

AMH - ovarian reserve - POI - menopause - biomarker

Competing Interests

No funding bodies have any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. R.A.A. has participated in advisory boards and received speakers or consultancy fees from Roche Diagnostics, Ferring, IBSA, Merck, KaNDy Therapeutics, and Sojournix Inc. S.M.N. has participated in advisory boards and received speakers or consultancy fees from Access Fertility, Beckman Coulter, Ferring, Finox, Merck, MSD, Roche Diagnostics, and The Fertility Partnership.




Publication History

Article published online:
11 January 2021

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Schultz AH. The Life of Primates. New York: Universe books; 1969
    Google Scholar
  • 2 te Velde ER, Pearson PL. The variability of female reproductive ageing. Hum Reprod Update 2002; 8 (02) 141-154
    CrossrefPubMedGoogle Scholar
  • 3 Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol 1986; 67 (04) 604-606
    PubMedGoogle Scholar
  • 4 Webber L, Davies M, Anderson R. et al; European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI. ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod 2016; 31 (05) 926-937
    CrossrefPubMedGoogle Scholar
  • 5 Panay N, Anderson RA, Nappi RE. et al. Premature ovarian insufficiency: an International Menopause Society White Paper. Climacteric 2020; 23 (05) 426-446
    CrossrefPubMedGoogle Scholar
  • 6 van Dorp W, Haupt R, Anderson RA. et al. reproductive function and outcomes in female survivors of childhood, adolescent, and young adult cancer: a review. J Clin Oncol 2018; 36 (21) 2169-2180
    CrossrefPubMedGoogle Scholar
  • 7 Mittal M, Kreatsa M, Narvekar N, Savvas M, Hamoda H. Fertility desires, choice of hormone replacement and the effect of length of time since menopause on bone density in women with premature ovarian insufficiency: a review of 223 consecutive new referrals to a tertiary centre. Post Reprod Health 2014; 20 (03) 104-111
    CrossrefPubMedGoogle Scholar
  • 8 Panay N, Anderson RA, Nappi RE. et al. Premature ovarian insufficiency: an International Menopause Society White Paper. Climacteric 2020; 23 (05) 426-446
    CrossrefPubMedGoogle Scholar
  • 9 McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. Endocr Rev 2000; 21 (02) 200-214
    PubMedGoogle Scholar
  • 10 Dunlop CE, Anderson RA. The regulation and assessment of follicular growth. Scand J Clin Lab Invest Suppl 2014; 244 (244) 13-17 , discussion 17
    CrossrefPubMedGoogle Scholar
  • 11 Weenen C, Laven JS, Von Bergh AR. et al. Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 2004; 10 (02) 77-83
    CrossrefPubMedGoogle Scholar
  • 12 Jeppesen JV, Anderson RA, Kelsey TW. et al. Which follicles make the most anti-Mullerian hormone in humans? Evidence for an abrupt decline in AMH production at the time of follicle selection. Mol Hum Reprod 2013; 19 (08) 519-527
    CrossrefPubMedGoogle Scholar
  • 13 Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev 1996; 17 (02) 121-155
    CrossrefPubMedGoogle Scholar
  • 14 Hansen KR, Hodnett GM, Knowlton N, Craig LB. Correlation of ovarian reserve tests with histologically determined primordial follicle number. Fertil Steril 2011; 95 (01) 170-175
    CrossrefPubMedGoogle Scholar
  • 15 Kevenaar ME, Meerasahib MF, Kramer P. et al. Serum anti-mullerian hormone levels reflect the size of the primordial follicle pool in mice. Endocrinology 2006; 147 (07) 3228-3234
    CrossrefPubMedGoogle Scholar
  • 16 von Wolff M, Roumet M, Stute P, Liebenthron J. Serum anti-Mullerian hormone (AMH) concentration has limited prognostic value for density of primordial and primary follicles, questioning it as an accurate parameter for the ovarian reserve. Maturitas 2020; 134: 34-40
    CrossrefPubMedGoogle Scholar
  • 17 Kelsey TW, Wright P, Nelson SM, Anderson RA, Wallace WH. A validated model of serum anti-müllerian hormone from conception to menopause. PLoS One 2011; 6 (07) e22024
    CrossrefPubMedGoogle Scholar
  • 18 Fleming R, Kelsey TW, Anderson RA, Wallace WH, Nelson SM. Interpreting human follicular recruitment and antimüllerian hormone concentrations throughout life. Fertil Steril 2012; 98 (05) 1097-1102
    CrossrefPubMedGoogle Scholar
  • 19 van Rooij IAJ, Broekmans FJM, te Velde ER. et al. Serum anti-Müllerian hormone levels: a novel measure of ovarian reserve. Hum Reprod 2002; 17 (12) 3065-3071
    CrossrefPubMedGoogle Scholar
  • 20 de Vet A, Laven JSE, de Jong FH, Themmen APN, Fauser BCJM. Antimüllerian hormone serum levels: a putative marker for ovarian aging. Fertil Steril 2002; 77 (02) 357-362
    CrossrefPubMedGoogle Scholar
  • 21 van Rooij IA, Tonkelaar Id, Broekmans FJ. et al. Anti-müllerian hormone is a promising predictor for the occurrence of the menopausal transition. Menopause 2004; 11 (6, Pt 1): 601-606
    CrossrefPubMedGoogle Scholar
  • 22 Knauff EA, Eijkemans MJ, Lambalk CB. et al; Dutch Premature Ovarian Failure Consortium. Anti-Mullerian hormone, inhibin B, and antral follicle count in young women with ovarian failure. J Clin Endocrinol Metab 2009; 94 (03) 786-792
    CrossrefPubMedGoogle Scholar
  • 23 Li HW, Anderson RA, Yeung WS, Ho PC, Ng EH. Evaluation of serum antimullerian hormone and inhibin B concentrations in the differential diagnosis of secondary oligoamenorrhea. Fertil Steril 2011; 96 (03) 774-779
    CrossrefPubMedGoogle Scholar
  • 24 Pigny P, Merlen E, Robert Y. et al. 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 (12) 5957-5962
    CrossrefPubMedGoogle Scholar
  • 25 Iliodromiti S, Kelsey TW, Anderson RA, Nelson SM. Can anti-Mullerian hormone predict the diagnosis of polycystic ovary syndrome? A systematic review and meta-analysis of extracted data. J Clin Endocrinol Metab 2013; 98 (08) 3332-3340
    CrossrefPubMedGoogle Scholar
  • 26 La Marca A, Brozzetti A, Sighinolfi G, Marzotti S, Volpe A, Falorni A. Primary ovarian insufficiency: autoimmune causes. Curr Opin Obstet Gynecol 2010; 22 (04) 277-282
    CrossrefPubMedGoogle Scholar
  • 27 De Bellis A, Bellastella G, Falorni A. et al; On the behalf of the Italian Addison Network. Natural history of autoimmune primary ovarian insufficiency in patients with Addison's disease: from normal ovarian function to overt ovarian dysfunction. Eur J Endocrinol 2017; 177 (04) 329-337
    CrossrefPubMedGoogle Scholar
  • 28 Grynberg M, Jacquesson L, Sifer C. In vitro maturation of oocytes for preserving fertility in autoimmune premature ovarian insufficiency. Fertil Steril 2020; 114 (04) 848-853
    CrossrefPubMedGoogle Scholar
  • 29 Jayasinghe YL, Wallace WHB, Anderson RA. Ovarian function, fertility and reproductive lifespan in cancer patients. Expert Rev Endocrinol Metab 2018; 13 (03) 125-136
    CrossrefPubMedGoogle Scholar
  • 30 Anderson RA, Themmen APN, Al-Qahtani A, Groome NP, Cameron DA. The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer. Hum Reprod 2006; 21 (10) 2583-2592
    CrossrefPubMedGoogle Scholar
  • 31 Su HI, Sammel MD, Green J. et al. Antimullerian hormone and inhibin B are hormone measures of ovarian function in late reproductive-aged breast cancer survivors. Cancer 2010; 116 (03) 592-599
    CrossrefPubMedGoogle Scholar
  • 32 Anderson RA, Cameron DA. Pretreatment serum anti-müllerian hormone predicts long-term ovarian function and bone mass after chemotherapy for early breast cancer. J Clin Endocrinol Metab 2011; 96 (05) 1336-1343
    CrossrefPubMedGoogle Scholar
  • 33 Fréour T, Barrière P, Masson D. Anti-müllerian hormone levels and evolution in women of reproductive age with breast cancer treated with chemotherapy. Eur J Cancer 2017; 74: 1-8
    CrossrefPubMedGoogle Scholar
  • 34 Dezellus A, Barriere P, Campone M. et al. Prospective evaluation of serum anti-Müllerian hormone dynamics in 250 women of reproductive age treated with chemotherapy for breast cancer. Eur J Cancer 2017; 79: 72-80
    CrossrefPubMedGoogle Scholar
  • 35 Lie Fong S, Lugtenburg PJ, Schipper I. et al. Anti-müllerian hormone as a marker of ovarian function in women after chemotherapy and radiotherapy for haematological malignancies. Hum Reprod 2008; 23 (03) 674-678
    CrossrefPubMedGoogle Scholar
  • 36 Decanter C, Morschhauser F, Pigny P, Lefebvre C, Gallo C, Dewailly D. Anti-Müllerian hormone follow-up in young women treated by chemotherapy for lymphoma: preliminary results. Reprod Biomed Online 2010; 20 (02) 280-285
    CrossrefPubMedGoogle Scholar
  • 37 Anderson RA, Remedios R, Kirkwood AA. et al. Determinants of ovarian function after response-adapted therapy in patients with advanced Hodgkin's lymphoma (RATHL): a secondary analysis of a randomised phase 3 trial. Lancet Oncol 2018; 19 (10) 1328-1337
    CrossrefPubMedGoogle Scholar
  • 38 Brougham MF, Crofton PM, Johnson EJ, Evans N, Anderson RA, Wallace WH. Anti-Müllerian hormone is a marker of gonadotoxicity in pre- and postpubertal girls treated for cancer: a prospective study. J Clin Endocrinol Metab 2012; 97 (06) 2059-2067
    CrossrefPubMedGoogle Scholar
  • 39 Bath LE, Wallace WH, Shaw MP, Fitzpatrick C, Anderson RA. Depletion of ovarian reserve in young women after treatment for cancer in childhood: detection by anti-Müllerian hormone, inhibin B and ovarian ultrasound. Hum Reprod 2003; 18 (11) 2368-2374
    CrossrefPubMedGoogle Scholar
  • 40 Lie Fong S, Laven JS, Hakvoort-Cammel FG. et al. Assessment of ovarian reserve in adult childhood cancer survivors using anti-Müllerian hormone. Hum Reprod 2009; 24 (04) 982-990
    CrossrefPubMedGoogle Scholar
  • 41 Anderson RA, Mansi J, Coleman RE, Adamson DJA, Leonard RCF. The utility of anti-Müllerian hormone in the diagnosis and prediction of loss of ovarian function following chemotherapy for early breast cancer. Eur J Cancer 2017; 87: 58-64
    CrossrefPubMedGoogle Scholar
  • 42 Chai J, Howie AF, Cameron DA, Anderson RA. A highly-sensitive anti-Müllerian hormone assay improves analysis of ovarian function following chemotherapy for early breast cancer. Eur J Cancer 2014; 50 (14) 2367-2374
    CrossrefPubMedGoogle Scholar
  • 43 Decanter C, Peigne M, Mailliez A. et al. Toward a better follow-up of ovarian recovery in young women after chemotherapy with a hypersensitive antimüllerian hormone assay. Fertil Steril 2014; 102 (02) 483-487
    CrossrefPubMedGoogle Scholar
  • 44 Su HI, Kwan B, Whitcomb BW. et al. Modeling variation in the reproductive lifespan of female adolescent and young adult cancer survivors using AMH. J Clin Endocrinol Metab 2020; 105 (08) 2740-2751
    CrossrefPubMedGoogle Scholar
  • 45 Sowers MR, Eyvazzadeh AD, McConnell D. et al. Anti-mullerian hormone and inhibin B in the definition of ovarian aging and the menopause transition. J Clin Endocrinol Metab 2008; 93 (09) 3478-3483
    CrossrefPubMedGoogle Scholar
  • 46 van Disseldorp J, Faddy MJ, Themmen AP. et al. Relationship of serum antimüllerian hormone concentration to age at menopause. J Clin Endocrinol Metab 2008; 93 (06) 2129-2134
    CrossrefPubMedGoogle Scholar
  • 47 Tehrani FR, Solaymani-Dodaran M, Azizi F. A single test of antimullerian hormone in late reproductive-aged women is a good predictor of menopause. Menopause 2009; 16 (04) 797-802
    CrossrefPubMedGoogle Scholar
  • 48 Tehrani FR, Solaymani-Dodaran M, Tohidi M, Gohari MR, Azizi F. Modeling age at menopause using serum concentration of anti-mullerian hormone. J Clin Endocrinol Metab 2013; 98 (02) 729-735
    CrossrefPubMedGoogle Scholar
  • 49 Depmann M, Eijkemans MJC, Broer SL. et al. Does AMH relate to timing of menopause? Results of an individual patient data meta- analysis. J Clin Endocrinol Metab 2018; 103 (10) 3593-3600
    CrossrefPubMedGoogle Scholar
  • 50 Finkelstein JS, Lee H, Karlamangla A. et al. Antimullerian hormone and impending menopause in late reproductive age: the Study of Women's Health Across the Nation. J Clin Endocrinol Metab 2020; 105 (04) e1862-e1871
    CrossrefPubMedGoogle Scholar
  • 51 Bertone-Johnson ER, Manson JE, Purdue-Smithe AC. et al. Anti-Müllerian hormone levels and incidence of early natural menopause in a prospective study. Hum Reprod 2018; 33 (06) 1175-1182
    CrossrefPubMedGoogle Scholar
  • 52 de Kat AC, van der Schouw YT, Eijkemans MJC, Broer SL, Verschuren WMM, Broekmans FJM. Can menopause prediction be improved with multiple AMH measurements? Results from the prospective Doetinchem Cohort Study. J Clin Endocrinol Metab 2019; 104 (11) 5024-5031
    CrossrefPubMedGoogle Scholar
  • 53 Lunding SA, Aksglaede L, Anderson RA. et al. AMH as predictor of premature ovarian insufficiency: a longitudinal study of 120 Turner syndrome patients. J Clin Endocrinol Metab 2015; 100 (07) E1030-E1038
    CrossrefPubMedGoogle Scholar
  • 54 Freeman EW, Sammel MD, Lin H, Boorman DW, Gracia CR. Contribution of the rate of change of antimullerian hormone in estimating time to menopause for late reproductive-age women. Fertil Steril 2012; 98 (05) 1254-1259 , e1251–1252
    CrossrefPubMedGoogle Scholar
  • 55 Ramezani Tehrani F, Bidhendi Yarandi R, Solaymani-Dodaran M, Tohidi M, Firouzi F, Azizi F. Improving prediction of age at menopause using multiple anti-Müllerian hormone measurements: the Tehran Lipid-Glucose Study. J Clin Endocrinol Metab 2020; 105 (05) dgaa083
    CrossrefPubMedGoogle Scholar
  • 56 Fauser BCJM, Nelson SM. Next steps toward AMH as a robust biomarker for assessing ovarian aging in individual women. J Clin Endocrinol Metab 2020; 105 (07) dgaa220
    PubMedGoogle Scholar
  • 57 Lawrenz B, Fehm T, von Wolff M. et al; Centers of FertiPROTEKT Network. Reduced pretreatment ovarian reserve in premenopausal female patients with Hodgkin lymphoma or non-Hodgkin-lymphoma---evaluation by using antimüllerian hormone and retrieved oocytes. Fertil Steril 2012; 98 (01) 141-144
    CrossrefPubMedGoogle Scholar
  • 58 Lekovich J, Lobel ALS, Stewart JD, Pereira N, Kligman I, Rosenwaks Z. Female patients with lymphoma demonstrate diminished ovarian reserve even before initiation of chemotherapy when compared with healthy controls and patients with other malignancies. J Assist Reprod Genet 2016; 33 (05) 657-662
    CrossrefPubMedGoogle Scholar
  • 59 Su HI, Flatt SW, Natarajan L, DeMichele A, Steiner AZ. Impact of breast cancer on anti-mullerian hormone levels in young women. Breast Cancer Res Treat 2013; 137 (02) 571-577
    CrossrefPubMedGoogle Scholar
  • 60 Yu B, Douglas N, Ferin MJ. et al. Changes in markers of ovarian reserve and endocrine function in young women with breast cancer undergoing adjuvant chemotherapy. Cancer 2010; 116 (09) 2099-2105
    PubMedGoogle Scholar
  • 61 Barnabei A, Strigari L, Marchetti P. et al. Predicting ovarian activity in women affected by early breast cancer: a meta-analysis-based nomogram. Oncologist 2015; 20 (10) 1111-1118
    CrossrefPubMedGoogle Scholar
  • 62 Anderson RA, Rosendahl M, Kelsey TW, Cameron DA. Pretreatment anti-Müllerian hormone predicts for loss of ovarian function after chemotherapy for early breast cancer. Eur J Cancer 2013; 49 (16) 3404-3411
    CrossrefPubMedGoogle Scholar
  • 63 Xue C, Wei W, Sun P. et al. Pretreatment anti-Mullerian hormone-based nomogram predicts menstruation status after chemotherapy for premenopausal women with hormone receptor-positive early breast cancer. Breast Cancer Res Treat 2019; 173 (03) 619-628
    CrossrefPubMedGoogle Scholar
  • 64 Younis JS, Shapso N, Fleming R, Ben-Shlomo I, Izhaki I. Impact of unilateral versus bilateral ovarian endometriotic cystectomy on ovarian reserve: a systematic review and meta-analysis. Hum Reprod Update 2019; 25 (03) 375-391
    CrossrefPubMedGoogle Scholar
  • 65 Wallace WH, Kelsey TW. Human ovarian reserve from conception to the menopause. PLoS One 2010; 5 (01) e8772
    Google Scholar
  • 66 Kelsey TW, Anderson RA, Wright P, Nelson SM, Wallace WH. Data-driven assessment of the human ovarian reserve. Mol Hum Reprod 2012; 18 (02) 79-87
    CrossrefPubMedGoogle Scholar