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Elevated Serum Level of Anti-Mullerian Hormone in Patients with Polycystic Ovary Syndrome: Relationship to the Ovarian Follicle Excess and to the Follicular Arrest

Laboratory of Endocrinology (P.P.), Clinique Marc Linquette; Departments of Endocrine Gynaecology and Reproductive Medicine (E.M., C.D., S.J., D.D.) and Radiology (Y.R.), Hôpital Jeanne de Flandre; and Department of Diabetology and Endocrinology (C.C.-R.), Centre Hospitalier Régional Universitaire de Lille, 59037 Lille, France

Address all correspondence and requests for reprints to: Didier Dewailly, M.D., Department of Endocrine Gynaecology and Reproductive Medicine, Hôpital Jeanne de Flandre, Avenue Eugne Avinée, CHRU, 59037 Lille, France. E-mail: ddewailly{at}chru-lille.fr.

The serum level of anti-Mullerian hormone (AMH), a product from granulosa cells involved in follicle growth, has been shown to correlate tightly with the small antral follicle number (FN) at ultrasonography (U/S) in women who do not have polycystic ovary syndrome (PCOS). Because PCOS is associated with a 2- to 3-fold increase in growing FN, we investigated whether an increased AMH serum level correlates to other hormonal and/or U/S features of PCOS. Serum AMH has been assayed in 104 women (59 symptomatic PCOS, 45 controls) between d 2 and 7 after the last either spontaneous or progestin-induced (in PCOS) menstrual period. Mean serum AMH level was markedly increased in the PCOS group (47.1 ± 22.9 vs. 20.8 ± 11.6 pmol/liter in controls; P < 0.0001), an increase in the same order of magnitude as the one of the FN in the 2- to 5-mm range at U/S (12.8 ± 8.3 vs. 4.8 ± 1.9; P < 0.0001, respectively). The ratio AMH/FN was similar between the two groups (4.8 ± 3.4 vs. 4.8 ± 2.9; P = 0.55). By simple regression, both in PCOS and controls, the AMH level was positively related to the 2- to 5-mm FN at U/S (P < 0.0001 and P < 0.03, respectively), but not to the 6- to 9-mm FN, and was negatively correlated to the serum FSH level (P < 0.02 and P < 0.04, respectively). AMH was also positively related to the serum testosterone and androstenedione levels, in PCOS exclusively (P < 0.0005 and <0.002, respectively). No relationship was found between AMH and age, serum estradiol, inhibin B, and LH levels in both groups. After multiple regression only the 2- to 5-mm FN remained significantly related to AMH in PCOS whereas testosterone, androstenedione, and FSH were no longer. In conclusion, the assay of the serum AMH may represent an important breakthrough in the diagnosis and in the understanding of PCOS. Our data suggest that the increase of AMH serum level in PCOS is the consequence of the androgen-induced excess in small antral FN and that each follicle produces a normal amount of AMH. We hypothesize that an increased AMH tone within the cohort could be involved in the follicular arrest of PCOS, by interacting negatively with FSH at the time of selection.

This work was supported by grants from the Délégation à la Recherche du Centre Hospitalier Universitaire de Lille and the Direction Régionale des Etudes Doctorales, Université de Lille II.

Abbreviations: AMH, Anti-Mullerian hormone; BMI, body mass index; E2, estradiol; FN, follicle number; GC, granulosa cell; PCO, polycystic ovary; PCOS, PCO syndrome; U/S, ultrasonography.

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