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

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

Department of Epidemiology (M.F.R.S., D.M., M.Y., M.L.J., S.H.), School of Public Health, University of Michigan 48109, and Department of Obstetrics and Gynecology (M.F.R.S., A.D.E., J.F.R.), University of Michigan Health Sciences System, Ann Arbor, Michigan 48109; and Department of Statistics (D.Z.), North Carolina State University, Raleigh, North Carolina 27695

Address all correspondence and requests for reprints to: MaryFran Sowers, Ph.D., Department of Epidemiology, School of Public Health, University of Michigan, 109 Observatory, Room 1846, Ann Arbor, Michigan 48109. E-mail: [email protected].

Received March 11, 2008. Accepted June 19, 2008.

First Published Online July 1, 2008

Abbreviations: AMH, Anti-Mullerian hormone; BMI, body mass index; CV, coefficient of variation; E2, estradiol; FMP, final menstrual period; MBHMS, Michigan Bone Health and Metabolism Study.

Journal of Clinical Endocrinology & Metabolism 93(9):p 3478-3483, September 2008.

Context/Objective:

The objective of the study was to determine whether 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 FSH in 300 archival follicular phase specimens from 50 women with six 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 yr 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 yr prior to the FMP; this may represent a critical biological juncture in the menopause transition. Low and nondetectable levels inhibin B levels also were observed 4-5 yr prior to the FMP but were less predictive of time to FMP or age at FMP.