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Hum. Reprod. Advance Access published online on March 2, 2007
Human Reproduction, doi:10.1093/humrep/dem036
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Anti-Müllerian hormone and anti-Müllerian hormone type II receptor polymorphisms are associated with follicular phase estradiol levels in normo-ovulatory women

Marlies E. Kevenaar1,7, Axel P.N. Themmen1, Joop S.E. Laven4, Barbara Sonntag5, Sharon Lie Fong4, André G. Uitterlinden1,2,3, Frank H. de Jong1, Huibert A.P. Pols1,2, Manuela Simoni6 and Jenny A. Visser1

1 Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands 2 Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam, The Netherlands 3 Department of Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands 4 Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, Rotterdam, The Netherlands 5 Department of Obstetrics and Gynaecology, Münster University Hospital, Münster, Germany 6 Institute for Reproductive Medicine, Münster University Hospital, Münster, Germany

7 To whom correspondence should be addressed at: Deptartment of Internal Medicine, Room Ee532, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Tel.: +31 10 4087346; Fax: +31 10 4635430; E-mail: m.kevenaar{at}erasmusmc.nl

BACKGROUND: In mice, anti-Müllerian hormone (AMH) inhibits primordial follicle recruitment and decreases FSH sensitivity. Little is known about the role of AMH in human ovarian physiology. We hypothesize that in women AMH has a similar role in ovarian function as in mice and investigated this using a genetic approach.

METHODS: The association of the AMH Ile49Ser and the AMH type II receptor (AMHR2) –482 A>G polymorphisms with menstrual cycle characteristics was studied in a Dutch (n = 32) and a German (n = 21) cohort of normo-ovulatory women.

RESULTS: Carriers of the AMH Ser49 allele had higher serum estradiol (E2) levels on menstrual cycle day 3 when compared with non-carriers in the Dutch cohort (P = 0.012) and in the combined Dutch and German cohort (P = 0.03). Carriers of the AMHR2 –482G allele also had higher follicular phase E2 levels when compared with non-carriers in the Dutch cohort (P = 0.028), the German cohort (P = 0.048) and hence also the combined cohort (P = 0.012). Women carrying both AMH Ser49 and AMHR2 –482G alleles had highest E2 levels (P = 0.001). For both polymorphisms no association with serum AMH or FSH levels was observed.

CONCLUSIONS: Polymorphisms in the AMH and AMHR2 genes are associated with follicular phase E2 levels, suggesting a role for AMH in the regulation of FSH sensitivity in the human ovary.

Key words: anti-Müllerian hormone/estrogen/menstrual cycle/ovarian function/polymorphism

Submitted on November 13, 2006; resubmitted on December 22, 2006; accepted on January 22, 2007.


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