Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials

J Clin Oncol. 2013 Jan 10;31(2):231-9. doi: 10.1200/JCO.2012.44.3721. Epub 2012 Nov 13.

Abstract

Purpose: To optimize fertility advice in patients with Hodgkin lymphoma (HL) before therapy and during survivorship, information on the impact of chemotherapy is needed. Therefore, we analyzed gonadal functions in survivors of HL.

Patients and methods: Women younger than age 40 and men younger than 50 years at diagnosis in ongoing remission at least 1 year after therapy within the German Hodgkin Study Group HD13 to HD15 trials for early- and advanced-stage HL were included. Hormone parameters, menstrual cycle, symptoms of hypogonadism, and offspring were evaluated.

Results: A total of 1,323 (55%) of 2,412 contacted female and male survivors were evaluable for the current analysis (mean follow-up, 46 and 48 months, respectively). Follicle-stimulating hormone, anti-Müllerian hormone, and inhibin B levels correlated significantly with therapy intensity (P < .001). Low birth rates were observed in survivors after advanced-stage treatment within the observation time (women, 6.5%; men, 3.3%). Regular menstrual cycle was reported by more than 90% of female survivors of early-stage HL (recovery time mostly ≤ 12 months). After six to eight cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, menstrual activity was strongly related to age (< v ≥ 30 years: 82% v 45%, respectively; P < .001; prolonged recovery time). Thirty-four percent of women age ≥ 30 years suffered severe menopausal symptoms (three- to four-fold more frequently than expected). In contrast, male survivors had mean levels of testosterone within the normal range and reported no increased symptoms of hypogonadism.

Conclusion: The present analysis in a large group of survivors of HL provides well-grounded information on gonadal toxicity of currently used treatment regimens and allows risk-adapted fertility preservation and comprehensive support during therapy and follow-up.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / administration & dosage
  • Bleomycin / adverse effects
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dacarbazine / administration & dosage
  • Dacarbazine / adverse effects
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Fertility / physiology*
  • Fertility Preservation
  • Follicle Stimulating Hormone / blood
  • Germany / epidemiology
  • Gonadotropin-Releasing Hormone / analogs & derivatives
  • Gonadotropin-Releasing Hormone / therapeutic use
  • Hodgkin Disease / blood
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / epidemiology
  • Hodgkin Disease / physiopathology*
  • Humans
  • Inhibins / blood
  • Male
  • Menstrual Cycle / drug effects
  • Menstrual Cycle / physiology
  • Middle Aged
  • Oligospermia / epidemiology
  • Ovary / physiology*
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Pregnancy
  • Procarbazine / administration & dosage
  • Procarbazine / adverse effects
  • Randomized Controlled Trials as Topic
  • Survivors
  • Testis / physiology*
  • Testosterone / blood
  • Vinblastine / administration & dosage
  • Vinblastine / adverse effects
  • Vincristine / administration & dosage
  • Vincristine / adverse effects
  • Young Adult

Substances

  • inhibin B
  • Bleomycin
  • Gonadotropin-Releasing Hormone
  • Procarbazine
  • Testosterone
  • Inhibins
  • Vincristine
  • Vinblastine
  • Etoposide
  • Dacarbazine
  • Doxorubicin
  • Cyclophosphamide
  • Follicle Stimulating Hormone
  • Prednisone

Supplementary concepts

  • ABVD protocol
  • BEACOPP protocol