Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial

被引:80
作者
Behringer, K. [1 ]
Thielen, I. [1 ]
Mueller, H. [1 ]
Goergen, H. [1 ]
Eibl, A. D. [1 ]
Rosenbrock, J. [1 ]
Halbsguth, T. [1 ]
Eichenauer, D. A. [1 ]
Fuchs, M. [1 ]
Reiners, K. S. [1 ]
Renno, J. H. [2 ]
van der Ven, K. [3 ]
Kuehr, M. [3 ]
von Wolff, M. [4 ]
Diehl, V. [1 ]
Engert, A. [1 ]
Borchmann, P. [1 ]
机构
[1] Univ Hosp Cologne, Dept Internal Med 1, German Hodgkin Study Grp, D-50924 Cologne, Germany
[2] Univ Cologne, Inst Clin Chem, D-50931 Cologne, Germany
[3] Univ Bonn, Dept Gynecol Endocrinol & Reprod Med, Bonn, Germany
[4] Univ Womens Hosp, Dept Gynecol Endocrinol & Reprod Med, Bern, Switzerland
关键词
chemotherapy; fertility; GnRH analogues; Hodgkin lymphoma; ovarian reserve; ANTI-MULLERIAN HORMONE; ORAL-CONTRACEPTIVES; OVARIAN-FUNCTION; CLINICAL-TRIALS; CHEMOTHERAPY; DISEASE; CANCER; PRESERVATION; THERAPY; WOMEN;
D O I
10.1093/annonc/mdr575
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In the HD14 trial, 2x BEACOPP(escalated) + 2x ABVD (2 + 2) has improved the primary outcome. Compared with 4x ABVD, this benefit might be compromised by more infertility in women. Therefore, we analyzed gonadal function and fertility. Women < 45 years in ongoing remission at least 1 year after therapy were included. Hormone parameters, menopausal symptoms, measures to preserve fertility, menstrual cycle, pregnancies, and offspring were evaluated. Three hundred and thirty one of 579 women addressed participated (57.2%) and 263 per-protocol treated patients qualified (A = ABVD: 137, B = 2 + 2: 126, mean time after therapy 42 and 43 months, respectively). Regular menstrual cycle after treatment (A: 87%, B: 83%) and time to recovery (< 12 months) were not different. Follicle-stimulating hormone and anti-Muellerian hormone were significantly better in arm A. However, pregnancies after therapy favored arm B (A: 15%, B: 26%, P = 0.043) and motherhood rates were equivalent to the German normal population. Multivariate analysis revealed prophylactic use of gonadotropin-releasing hormone (GnRH) analogues as highly significant prognostic factor for preservation of fertility (odds ratio = 12.87, P = 0.001). Severe menopausal symptoms were frequent in women >= 30 years (A: 21%, B: 25%). Hormonal levels after 2 + 2 indicate a reduced ovarian reserve. However, 2 + 2 in combination with GnRH analogues does not compromise fertility within the evaluated observation time.
引用
收藏
页码:1818 / 1825
页数:8
相关论文
共 32 条
[1]   THE EUROPEAN-ORGANIZATION-FOR-RESEARCH-AND-TREATMENT-OF-CANCER QLQ-C30 - A QUALITY-OF-LIFE INSTRUMENT FOR USE IN INTERNATIONAL CLINICAL-TRIALS IN ONCOLOGY [J].
AARONSON, NK ;
AHMEDZAI, S ;
BERGMAN, B ;
BULLINGER, M ;
CULL, A ;
DUEZ, NJ ;
FILIBERTI, A ;
FLECHTNER, H ;
FLEISHMAN, SB ;
DEHAES, JCJM ;
KAASA, S ;
KLEE, M ;
OSOBA, D ;
RAZAVI, D ;
ROFE, PB ;
SCHRAUB, S ;
SNEEUW, K ;
SULLIVAN, M ;
TAKEDA, F .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (05) :365-376
[2]   PREGNANCY OUTCOME IN PATIENTS TREATED FOR HODGKINS-DISEASE [J].
AISNER, J ;
WIERNIK, PH ;
PEARL, P .
JOURNAL OF CLINICAL ONCOLOGY, 1993, 11 (03) :507-512
[3]   Reliability of follicle-stimulating hormone measurements in serum [J].
Alan A Arslan ;
Anne Zeleniuch-Jacquotte ;
Annekatrin Lukanova ;
Sabina Rinaldi ;
Rudolf Kaaks ;
Paolo Toniolo .
Reproductive Biology and Endocrinology, 1 (1)
[4]   RETRACTED: Gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage: prospective randomized study (Retracted article. See vol. 120, pg. 395, 2023) [J].
Badawy, Ahmed ;
Elnashar, Aboubakr ;
El-Ashry, Mohamed ;
Shahat, May .
FERTILITY AND STERILITY, 2009, 91 (03) :694-697
[5]   Secondary amenorrhea after Hodgkin's lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: A report from the German Hodgkin's lymphoma study group [J].
Behringer, K ;
Breuer, K ;
Reineke, T ;
May, M ;
Nogova, L ;
Klimm, B ;
Schmitz, T ;
Wildt, L ;
Diehl, V ;
Engert, A .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (30) :7555-7564
[6]   No protection of the ovarian follicle pool with the use of GnRH-analogues or oral contraceptives in young women treated with escalated BEACOPP for advanced-stage Hodgkin lymphoma. Final results of a phase II trial from the German Hodgkin Study Group [J].
Behringer, K. ;
Wildt, L. ;
Mueller, H. ;
Mattle, V. ;
Ganitis, P. ;
van den Hoonaard, B. ;
Ott, H. W. ;
Hofer, S. ;
Pluetschow, A. ;
Diehl, V. ;
Engert, A. ;
Borchmann, P. .
ANNALS OF ONCOLOGY, 2010, 21 (10) :2052-2060
[7]   Serum mullerian-inhibiting substance levels during normal menstrual cycles [J].
Cook, CL ;
Siow, Y ;
Taylor, S ;
Fallat, ME .
FERTILITY AND STERILITY, 2000, 73 (04) :859-861
[8]   Treatment-related risk factors for premature menopause following Hodgkin lymphoma [J].
De Bruin, Marie L. ;
Huisbrink, Jeannine ;
Hauptmann, Michael ;
Kuenen, Marianne A. ;
Ouwens, Gabey M. ;
van't Veer, Mars B. ;
Aleman, Berthe M. P. ;
van Leeuwen, Flora E. .
BLOOD, 2008, 111 (01) :101-108
[9]   Regulation of ovarian function: the role of anti-Mullerian hormone [J].
Durlinger, ALL ;
Visser, JA ;
Themmen, APN .
REPRODUCTION, 2002, 124 (05) :601-609
[10]   Intensified Chemotherapy and Dose-Reduced Involved-Field Radiotherapy in Patients With Early Unfavorable Hodgkin's Lymphoma: Final Analysis of the German Hodgkin Study Group HD11 Trial [J].
Eich, Hans Theodor ;
Diehl, Volker ;
Goergen, Helen ;
Pabst, Thomas ;
Markova, Jana ;
Debus, Juergen ;
Ho, Anthony ;
Doerken, Bernd ;
Rank, Andreas ;
Grosu, Anca-Ligia ;
Wiegel, Thomas ;
Karstens, Johann Hinrich ;
Greil, Richard ;
Willich, Normann ;
Schmidberger, Heinz ;
Doehner, Hartmut ;
Borchmann, Peter ;
Mueller-Hermelink, Hans-Konrad ;
Mueller, Rolf-Peter ;
Engert, Andreas .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (27) :4199-4206