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Anti-müllerian hormone is a promising predictor for the occurrence of the menopausal transition

van Rooij, Ilse A.J. PhD1; Tonkelaar, Isolde den PhD2; Broekmans, Frank J.M. PhD1; Looman, Caspar W.N. MSc3; Scheffer, Gabrielle J. PhD1; de Jong, Frank H. PhD4; Themmen, Axel P.N. PhD4; te Velde, Egbert R. PhD1

doi: 10.1097/01.GME.0000123642.76105.6E

Objective: Age at menopause and age at the start of the preceding period of cycle irregularity (menopausal transition) show considerable individual variation. In this study we explored several markers for their ability to predict the occurrence of the transition to menopause.

Design: A group of 81 normal women between 25 and 46 years of age visited the clinic two times (at T1 and T2) with an average interval of 4 years. All had a regular menstrual cycle pattern at T1. At T1, anti-müllerian hormone (AMH), follicle-stimulating hormone (FSH), inhibin B and estradiol (E2) were measured, and an antral follicle count (AFC) was made during the early follicular phase. At T2, information regarding cycle length and variability was obtained. Menopause transition was defined as a mean cycle length of less than 21 days or more than 35 days or as a mean cycle length of 21 to 35 days, but with the next cycle not predictable within 7 days during the last half year. A logistic regression analysis was performed, with the outcome measure as menopause transition. The area under the receiver operating curve (ROCAUC) was calculated as a measure of predictive accuracy.

Results: In 14 volunteers, the cycle had become irregular at T2. Compared with women with a regular cycle at T2, these women were significantly older (median 44.7 vs 39.8 y, P < 0.001) and differed significantly in AFC, AMH, FSH, and inhibin B levels assessed at T1. All parameters with the exception of E2 were significantly associated with the occurrence of cycle irregularity; AMH, AFC, and age had the highest predictive accuracy (ROCAUC 0.87, 0.80, and 0.82, respectively). After adjusting for age, only AMH and inhibin B were significantly associated with cycle irregularity. Inclusion of inhibin B and age to AMH in a multivariable model improved the predictive accuracy (ROCAUC 0.92).

Conclusions: The novel marker AMH is a promising predictor for the occurrence of menopausal transition within 4 years. Adding inhibin B improved the prediction. Therefore, AMH alone or in combination with inhibin B may well prove a useful indicator for the reproductive status of an individual woman.

Anti-müllerian hormone has, independent of age, a clear predictive value for the transition to menopause within subsequent years. Therefore, this marker may be considered a useful indicator for the reproductive status of an individual woman.

From the 1 Department of Reproductive Medicine, University Medical Center, Utrecht, The Netherlands; 2 International Health Foundation, Utrecht, The Netherlands; and the Departments of 3 Public Health and 4 Internal Medicine, Rotterdam, The Netherlands.

Received September 25, 2003; revised and accepted January 22, 2004.

Address correspondence to: Ilse A.J. van Rooij, Department of Reproductive Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. E-mail:

©2004The North American Menopause Society