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This version published online on August 28, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-2374
A more recent version of this article appeared on October 1, 2007
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Submitted on October 30, 2006
Accepted on July 20, 2007

Anti-Müllerian Hormone is a Sensitive Serum Marker for Gonadal Function in Women Treated for Hodgkin's Lymphoma During Childhood

Robert D van Beek, Marry M van den Heuvel-Eibrink, Joop SE Laven, Frank H de Jong, Axel PN Themmen, Friederike G Hakvoort-Cammel, Cor van den Bos, Henk van den Berg, Rob Pieters, and Sabine MPF de Muinck Keizer-Schrama*

Erasmus MC-Sophia Children's Hospital Rotterdam, The Netherlands, department of pediatric hematology/oncology, department of pediatric endocrinology, Erasmus MC Rotterdam, The Netherlands, division of reproductive medicine, department of gynecology and obstetrics, department of internal medicine, Emma Children's Hospital - Academic Medical Center Amsterdam, The Netherlands, department of pediatric oncology

* To whom correspondence should be addressed. E-mail: s.demuinckkeizer-schrama{at}erasmusmc.nl.

PURPOSE Aim of this study is to evaluate the long-term effects of combination chemotherapy treatment for girls with Hodgkin's lymphoma (HL) on gonadal function using anti-Müllerian hormone (AMH) and inhibin B as ovarian reserve parameters.

PATIENTS AND METHODS Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), inhibin B and AMH were measured in 32 women treated from 1974–1998 for pediatric HL with chemotherapy, with the intention to avoid radiotherapy. All patients (median age 25.0 yr (range 19.2–40.4 yr.)) were in complete remission with a median follow-up time of 14.0 yr. (range 5,7–24.5 yr.) after therapy. All patients were treated with combination chemotherapy ABVD or EBVD with or without MOPP. Because of incomplete remission or relapse, involved field radiotherapy was needed in 7/32 women. Results were compared with a healthy control group.

RESULTS Patients treated with 6 or more cycles of MOPP combination chemotherapy had significantly higher levels of FSH and lower serum levels of inhibin B and AMH compared with healthy women (FSH 17.0 U/l vs. 6.0 U/l (p<0.05); inhibin B 23.0 ng/l vs. 112.5 ng/l (p<0.01); AMH 0.39 µg/l vs. 2.10 µg/l (p<0.01)). AMH was also significantly lower compared with women treated without MOPP (median 0.39 µg/l vs. 1.40 µg/l; p=0.01).

CONCLUSIONS Women treated during childhood for HL with MOPP seem to have a distinctly lower ovarian reserve as measured by lower AMH values at early adulthood, compared to healthy women. Moreover, AMH seems to be the only predictor that is sufficiently sensitive to detect this decrease in ovarian reserve.


Key words: AMH • gonadal function • Hodgkin's lymphoma • long-term follow-up







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