title: Premature ovarian failure and fertility in long-term survivors of Hodgkin's lymphoma: a European Organisation for Research and Treatment of Cancer Lymphoma Group and Groupe d'Etude des Lymphomes de l'Adulte Cohort Study.
abstract: OBJECTIVE
  In this large cohort of Hodgkin's lymphoma survivors with long follow-up, we estimated the impact of treatment regimens on premature ovarian failure (POF) occurrence and motherhood, including safety of nonalkylating chemotherapy and dose-response relationships for alkylating chemotherapy and age at treatment.
  
  
  METHODS
  The Life Situation Questionnaire was sent to 1,700 women treated in European Organisation for Research and Treatment of Cancer and Groupe d'Étude des Lymphomes de l'Adulte trials between 1964 and 2004. Women treated between ages 15 and 40 years and currently not using hormonal contraceptives (n = 460) were selected to assess occurrence of POF. Cumulative POF risk was estimated using the life-table method. Predictive factors were assessed by Cox regression analysis.
  
  
  RESULTS
  Median follow-up was 16 years (range, 5 to 45 years). Cumulative risk of POF after alkylating chemotherapy was 60% (95% CI, 41% to 79%) and only 3% (95% CI, 1% to 7%) after nonalkylating chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine; epirubicin, bleomycin, vinblastine, and prednisone). Dose relationship between alkylating chemotherapy and POF occurrence was linear. POF risk increased by 23% per year of age at treatment. In women treated without alkylating chemotherapy at age younger than 32 years and age 32 years or older, cumulative POF risks were 3% (95% CI, 1% to 16%) and 9% (95% CI, 4% to 18%), respectively. If menstruation returned after treatment, cumulative POF risk was independent of age at treatment. Among women who ultimately developed POF, 22% had one or more children after treatment, compared with 41% of women without POF.
  
  
  CONCLUSIONS
  Nonalkylating chemotherapy carries little to no excess risk of POF. Dose-response relationships for alkylating chemotherapy and age at treatment are both linear. Timely family planning is important for women at risk of POF.
authors.affiliation: University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Marleen A E
authors.initials: MA
authors.lastname: van der Kaaij
authors.forename: Natacha
authors.initials: N
authors.lastname: Heutte
authors.forename: Paul
authors.initials: P
authors.lastname: Meijnders
authors.forename: Edwige
authors.initials: E
authors.lastname: Abeilard-Lemoisson
authors.forename: Michele
authors.initials: M
authors.lastname: Spina
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Moser
authors.forename: Anouk
authors.initials: A
authors.lastname: Allgeier
authors.forename: Bart
authors.initials: B
authors.lastname: Meulemans
authors.forename: Arnold H M
authors.initials: AH
authors.lastname: Simons
authors.forename: Pieternella J
authors.initials: PJ
authors.lastname: Lugtenburg
authors.forename: Berthe M P
authors.initials: BM
authors.lastname: Aleman
authors.forename: Evert M
authors.initials: EM
authors.lastname: Noordijk
authors.forename: Christophe
authors.initials: C
authors.lastname: Fermé
authors.forename: José
authors.initials: J
authors.lastname: Thomas
authors.forename: Aspasia
authors.initials: A
authors.lastname: Stamatoullas
authors.forename: Christophe
authors.initials: C
authors.lastname: Fruchart
authors.forename: Pauline
authors.initials: P
authors.lastname: Brice
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gaillard
authors.forename: Serge
authors.initials: S
authors.lastname: Bologna
authors.forename: Francisca
authors.initials: F
authors.lastname: Ong
authors.forename: Houchingue
authors.initials: H
authors.lastname: Eghbali
authors.forename: Jeanette K
authors.initials: JK
authors.lastname: Doorduijn
authors.forename: Franck
authors.initials: F
authors.lastname: Morschhauser
authors.forename: Catherine
authors.initials: C
authors.lastname: Sebban
authors.forename: Judith M
authors.initials: JM
authors.lastname: Roesink
authors.forename: Marie
authors.initials: M
authors.lastname: Bouteloup
authors.forename: Achiel
authors.initials: A
authors.lastname: Van Hoof
authors.forename: John M M
authors.initials: JM
authors.lastname: Raemaekers
authors.forename: Michel
authors.initials: M
authors.lastname: Henry-Amar
authors.forename: Hanneke C
authors.initials: HC
authors.lastname: Kluin-Nelemans
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005060:Europe; D005260:Female; D005298:Fertility; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000150:complications* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D015337:Multicenter Studies as Topic; D016649:Primary Ovarian Insufficiency / Q000209:etiology*; D016032:Randomized Controlled Trials as Topic; D011795:Surveys and Questionnaires; D017741:Survivors; D055815:Young Adult