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Anti-Müllerian Hormone Is a Sensitive Serum Marker for Gonadal Function in Women Treated for Hodgkin’s Lymphoma during Childhood

Department of Pediatric Hematology/Oncology (R.D.v.B., M.M.v.d.H.-E., F.G.H.-C., R.P.), and Department of Pediatric Endocrinology (R.D.v.B., S.M.P.F.d.M.K.-S.), and Erasmus MC–Sophia Children’s Hospital Rotterdam, and Department of Gynecology and Obstetrics (J.S.E.L.), Division of Reproductive Medicine, and Department of Internal Medicine (F.H.d.J., A.P.N.T.), Erasmus MC Rotterdam, 3000 CB Rotterdam, The Netherlands; and Department of Pediatric Oncology (C.v.d.B., H.v.d.B.), Emma Children’s Hospital-Academic Medical Center Amsterdam, 1100 DE Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: Sabine M. P. F. de Muinck Keizer-Schrama, Erasmus MC/Sophia Children’s Hospital, Room Sp3435, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands. E-mail: s.demuinckkeizer-schrama{at}erasmusmc.nl.

Purpose: The aim of this study was 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: LH, FSH, inhibin B, and AMH were measured in 32 women treated from 1974 to 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 doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) or EBVD with or without mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). Because of incomplete remission or relapse, involved field radiotherapy was needed in seven of 32 women. Results were compared with a healthy control group.

Results: Patients treated with six 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 vs. 6.0 U/liter (P < 0.05); inhibin B, 23.0 vs. 112.5 ng/liter (P < 0.01); AMH, 0.39 vs. 2.10 µg/liter (P < 0.01)]. AMH was also significantly lower, compared with women treated without MOPP (median 0.39 vs. 1.40 µg/liter; 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 with healthy women. Moreover, AMH seems to be the only predictor that is sufficiently sensitive to detect this decrease in ovarian reserve.