Menopause is the cessation of menstrual cycling and fertility. Clinically it is recognized by a cessation of menstrual bleeding; menopause is a woman’s status after her final menstrual period (FMP). Menstrual cycling and bleeding are driven by the dynamics of ovarian follicle maturation. Because a woman is born with a limited number of follicles (non-growing “primodial” follicles) that cannot be replaced and are slowly consumed by the monthly maturation of smaller groups of follicles (primary, secondary and antral growing follicles), the natural cause of menopause is the absence of follicles. However, many natural (e.g., certain diseases, starvation, etc.) or interventional processes (chemotherapy, surgical removal of the uterus, ovaries, or pituitary gland, etc.) can cause a cessation of menses that can be either irreversible (e.g., functionally the same as menopause) or reversible. Diagnosing menopause (e.g. the FMP) currently is only done unequivocally after cessation of menses for 12 months in a previously cycling woman.

Naturally occurring (i.e., as a result of aging) menopause is referred to as “spontaneous” and, on average, occurs at the age of 51 years, but there is a very large variance of approximately +/- 10 years with respect to the occurrence of menopause in healthy women. Ovarian function deteriorates gradually leading up to menopause and contributes to the variance observed among women with respect to menopausal status. Ovarian function affects, primarily via the steroid hormones produced by growing follicles, virtually every organ in a woman’s body. Physiological responses to the gradual or abrupt loss of ovarian function include a multitude of menopausal “symptoms” and consequences that affect a woman’s health and quality of life. 1,2

During several years leading up to the FMP and several years immediately following the FMP is a time called the climacteric or menopausal transition, when a woman transitions from the reproductive to a non-reproductive state. The transition is highly variable among women with respect to duration and intensity of associated physiological changes, which affect her well being and level of disease risk. Thus, determining where a woman is in this process must be individualized and is clinically important, particularly during the menopausal transition and the 12 months following the FMP. Quantitative measurement of blood levels of Anti-Müllerian Hormone using the picoAMH assay can aid in determining a woman’s menopausal status during the menopausal transition.

Blood levels of AMH represent one of the markers available to clinicians to determine where a woman is in her menopausal transition. Other clinical tests relevant in this context are estradiol which is produced only by follicles in their final stages of maturation, and thus only indirectly reflects the total number of follicles in the ovary, and FSH which reflects the negative feedback by estradiol on pituitary gland secretion (i.e., also an indirect marker of ovarian follicular pool based on large follicle function). In contrast AMH is produced by the majority of ovarian follicles (primary, secondary and antral).

Blood levels of AMH have been shown to be highly correlated with the number of primordial follicles in an ovary (i.e., true ovarian reserve).3 The picoAMH assay was developed to allow more sensitive measurements. AMH measured using the picoAMH assay provides a significant new parameter to aid physicians in determining the status of women during the menopausal transition.

REFERENCES

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2. Su HI, Freeman EW 2009 Hormone changes associated with the menopausal transition. Minerva Ginecol 61:483-489

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Finkelstein JS, Lee H, Burnett-Bowie SAM, Santoro N, Yu EW, Joffe H, Morrison A, Kumar A, Greendale GA, Gold E, Harlow S, Lasley BL, Derby C, Randolph JF, Matthews KA, Kravitz HM, McConnell DS, Brooks MM, Martin D, Darakananda K, Hirsch SC, Sluss PM. Utility of Anti-Mullerian Hormone (AMH) for Predicting the Time to the Final Menstrual Period: The Study of Women’s Health Across the Nation (SWAN). Presented at 98th Annual Endocrine Society Meeting; 2016 Apr 1-3; Boston, MA

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Jung S, Allen N, Arslan AA, Baglietto L, Brinton LA, Egleston BL, Falk R, Fortner RT, Helzlsouer KJ, Idahl A, Kaaks R, Lundin E, Merritt M, Onland-Moret C, Rinaldi S, Sánchez MJ, Sieri S, Schock H, Shu XO, Sluss PM, Staats PN, Travis RC, Tjønneland A, Trichopoulou A, Tworoger S, Visvanathan K, Krogh V, Weiderpass E, Zeleniuch-Jacquotte A, Zheng W, Dorgan JF. Demographic, lifestyle, and other factors in relation to antimüllerian hormone levels in mostly late premenopausal women. Fertil Steril. 2017 Apr;107(4):1012-1022.e2. PMC542622

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Kristensen SG, Kumar A, Kalra B, Pors SE, Bøtkjær JA, Mamsen LS, Colmorn LB, Fedder J, Ernst E, Owens LA, Hardy K, Franks S, Andersen CY. Quantitative Differences in TGF-β Family Members Measured in Small Antral Follicle Fluids From Women With or Without PCO. J Clin Endocrinol Metab. 2019 Dec 1;104(12):6371-6384. doi: 10.1210/jc.2019-01094. PMID: 31287539.

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Kumar A, Kalra B, Patel A, Shah S, Savjani G, Themmen A, Visser J, Pruysers, Robertson D. Development of Stable picoAnti-Müllerian Hormone ELISA: Sensitive, Reliable and Reproducible Results. Poster session presented at the 96th Annual Endocrine Society Meeting; 2014 Jun 21-24; Chicago, IL.

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Lu J, Holt C, Choi M, Kalp K, Straseski J. Quantitation of Anti-Müllerian Hormone by the AnshLabs picoAMH ELISA Assay. Poster session presented at American Association for Clinical Chemistry; 2014 Jul 27-31; Chicago, IL.

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Lukaszuk K, Plociennik L,, Lukaszuk A, Dialobrzeska D. The Heterogenity of Anti-Mullerian Hormone Depletion in Models Across Assays in 12917 Women. Poster session at American Society for Reproductive Medicine; 2015 Oct 17-21; Baltimore, Maryland

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Mamsen LS, Munthe-Fog L, Petersen TS, Jeppesen JV, Møllgård K, Grøndahl ML, Larsen A, Ernst E, Oxvig C, Kumar A, Kalra B, Andersen CY. Reply: Methodological considerations in measuring different AMH splice forms using ELISA: validity of proAMH ELISA. Mol Hum Reprod. 2016 May;22(5):374-5. PMID 26965311

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Marsh EE, Bernardi LA, Steinberg ML, de Chavez PJ, Visser JA, Carnethon MR, Baird DD. Novel correlates between antimullerian hormone and menstrual cycle characteristics in African-American women (23–35 years-old). Fertil Steril. 2016 Apr 23. pii: S0015-0282(16)61100-7. Epub ahead of print. PMID 27114331

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Morse, H. Anti-Müllerian hormone as a marker of ovarian reserve in girls before, during and after treatment for childhood cancer. [Dissertation, 2017]. Lund (Sweden): Lund University.

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Nichols H, Baird D, Stanczyk F. Anti-Müllerian Hormone Concentrations in Premenopausal Women and Breast Cancer Risk. Cancer Prevention Research. 2015 April 14 epub ahead of print. PMID 25873369

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Pilsgaard F, Grynnerup AG, Løssl K, Bungum L, Pinborg A. The use of anti‐Müllerian hormone for controlled ovarian stimulation in assisted reproductive technology, fertility assessment and ‐counseling. Acta Obstet Gynecol Scand. 2018 Feb 24.

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Robertson DM, Kumar A, Kalra B, Shah S, Pruysers E, Vanden Brink H, Chizen D, Visser JA, Themmen AP, Baerwald A. Detection of serum antimüllerian hormone in women approaching menopause using sensitive antimüllerian hormone enzyme-linked immunosorbent assays. Menopause. 2014 Dec; 21(12):1277-86. PMID 24781853

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Straseski J, Lu J, Holt C, Choi M, Kalp K. Analytical Evaluation of the Ansh Labs picoAMH ELISA assay for Anti-Mullerian Hormone. Poster session presented at the 96th Annual Endocrine Society Meeting; 2014 Jun 21-24; Chicago, IL.

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Su HI, Sammel MD, Homer MV, Bui K, Haunschild C, Stanczyk FZ. Comparability of antimüllerian hormone levels among commercially available immunoassays. Fertility and Sterility. 2014 Jun; 101(6):1766-72.e1. PMID 24726216

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Toribio M, Neilan TG, Awadalla M, Stone LA, Rokicki A, Rivard C, Mulligan CP, Cagliero D, Fourman LT, Stanley TL, Ho JE, Triant VA, Burdo TH, Nelson MD, Szczepaniak LS, Zanni MV. Intramyocardial Triglycerides Among Women With vs Without HIV: Hormonal Correlates and Functional Consequences. J Clin Endocrinol Metab. 2019 Dec 1;104(12):6090-6100. doi: 10.1210/jc.2019-01096. PMID: 31393564; PMCID: PMC6954489.

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White A, Sandler D, D’Aloisio A, Stanczyk F, Whitworth K, Baird D, Nichols H. Anti-Mullerian hormone (AMH) in relation to tobacco and marijuana use and sources of indoor heating/cooking. Fertility and Sterility. First published online May 27, 2016. PMID 27240193

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