Gonadal function in males after chemotherapy for early-stage Hodgkin's lymphoma treated in four subsequent trials by the European Organisation for Research and Treatment of Cancer: EORTC Lymphoma Group and the Groupe d'Etude des Lymphomes de l'Adulte.
OBJECTIVE
To analyze fertility in male patients treated with various combinations of radiotherapy and chemotherapy, with or without alkylating agents, or with radiotherapy alone for Hodgkin's lymphoma.


METHODS
Follicle-stimulating hormone (FSH) levels were measured in patients with early-stage upper-diaphragmatic disease enrolled in four European Organisation for Research and Treatment of Cancer (EORTC) trials (H6-H9). Median follow-up after therapy was 32 months. Patients with FSH measurement at least 12 months after end of treatment (n = 355) were selected to assess post-treatment fertility. Patients with FSH measurement 0 to 9 months after therapy (n = 349) were selected to analyze fertility recovery; of these, patients with elevated FSH (> 10 U/L; n = 101) were followed until recovery. Factors predictive for therapy-related infertility were assessed by logistic regression.


RESULTS
The proportion of elevated FSH was 3% and 8% in patients treated with radiotherapy only or with nonalkylating chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine [ABVD], epirubicin, bleomycin, vinblastine, prednisone [EBVP]); it was 60% (P < .001) after chemotherapy containing alkylating agents (mechlorethamine, vincristine, procarbazine, prednisone [MOPP], MOPP/doxorubicin, bleomycin, vinblastine [ABV], bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone [BEACOPP]). After a median time of 19 months, recovery of fertility occurred in 82% of patients treated without alkylating chemotherapy. This proportion was 30%, statistically (P < .001) lower in those treated with alkylating chemotherapy, and median time to recovery was 27 months. The post-treatment proportion of elevated FSH increased significantly (P < .001) with the dose of alkylating chemotherapy administered, and recovery was less frequent and slower after higher doses. Age more than 50 years and stage II disease also contributed to poor outcome.


CONCLUSIONS
Fertility can be secured after nonalkylating chemotherapy for Hodgkin's lymphoma. In contrast, alkylating chemotherapy has a dismal effect, even after a limited number of cycles.
van der Kaaij
Marleen A E
MA
Department of Hematology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Heutte
Natacha
N
Le Stang
Nolwenn
N
Raemaekers
John M M
JM
Simons
Arnold H M
AH
Carde
Patrice
P
Noordijk
Evert M
EM
Fermé
Christophe
C
Thomas
José
J
Eghbali
Houchingue
H
Kluin-Nelemans
Hanneke C
HC
Henry-Amar
Michel
M
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000494:pharmacology*; D015331:Cohort Studies; D005060:Europe; D005640:Follicle Stimulating Hormone / Q000097:blood; D006689:Hodgkin Disease / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007248:Infertility, Male / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D012044:Regression Analysis; D013091:Spermatogenesis / Q000187:drug effects; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D005640:Follicle Stimulating Hormone