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This version published online on July 1, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2008-0567
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Submitted on March 11, 2008
Accepted on June 19, 2008

Anti-Mullerian Hormone and Inhibin B in the Definition of Ovarian Aging and the Menopause Transition

MaryFran R. Sowers*, Aimee D. Eyvazzadeh, Daniel McConnell, Matheos Yosef, Mary L. Jannausch, Daowen Zhang, Sioban Harlow, and John F. Randolph Jr.

Department of Epidemiology; School of Public Health; University of Michigan; Ann Arbor, MI; Department of Obstetrics and Gynecology; University of Michigan Health Sciences System; Ann Arbor, MI; Department of Statistics, North Carolina State University, Raleigh, NC

* To whom correspondence should be addressed. E-mail: mfsowers{at}umich.edu.

Context/Objective: To determine if Anti-Mullerian Hormone (AMH) and inhibin B are viable endocrine biomarkers for framing the menopause transition from initiation to the final menstrual period (FMP).

Design: We assayed AMH, inhibin B and follicle stimulating hormone (FSH) in 300 archival follicular phase specimens from 50 women with 6 consecutive annual visits commencing in 1993 when all women were in the pre- and perimenopausal menopause stages. Subsequently, each woman had a documented FMP. The assay results were fitted as individual-woman profiles and then related to time to FMP and age at FMP as outcomes.

Results: Based on annual values from six time points prior to the FMP, logAMH longitudinal profiles declined and were highly associated with a time point 5 years prior to FMP [including both observed and values below detection (P<0.0001 and P=0.0001, respectively)]. Baseline AMH profiles were also associated with age at FMP (P=0.035). Models of declining loginhibin B profiles (including both observed and values below detection) were associated with time to FMP (P<0.0001 and P=0.0003, respectively). There was no significant association of loginhibin B profiles with age at FMP.

Conclusions: AMH, an endocrine marker that reflects the transition of resting primordial follicles to growing follicles, declined to a time point 5 years prior to the FMP; this may represent a critical biological juncture in the menopause transition. Low and non-detectable levels inhibin B levels also were observed 4–5 years prior to the FMP, but were less predictive of time to FMP or age at FMP.


Key words: menopause • ovarian reserve • ovarian aging • follicle depletion







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