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

Ann Oncol. 2012 Jul;23(7):1818-25. doi: 10.1093/annonc/mdr575. Epub 2012 Jan 6.

Abstract

Background: In the HD14 trial, 2×BEACOPPescalated+2×ABVD (2+2) has improved the primary outcome. Compared with 4×ABVD, this benefit might be compromised by more infertility in women. Therefore, we analyzed gonadal function and fertility.

Patients and methods: 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.

Results: 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%).

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Mullerian Hormone / blood
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / adverse effects
  • Bleomycin / therapeutic use
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Dacarbazine / adverse effects
  • Dacarbazine / therapeutic use
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use
  • Etoposide / adverse effects
  • Etoposide / therapeutic use
  • Female
  • Fertility / drug effects*
  • Follicle Stimulating Hormone / blood
  • Gonadotropin-Releasing Hormone / analogs & derivatives
  • Gonadotropin-Releasing Hormone / therapeutic use
  • Hodgkin Disease / drug therapy*
  • Humans
  • Logistic Models
  • Menopause / drug effects
  • Menstrual Cycle / drug effects
  • Middle Aged
  • Multivariate Analysis
  • Ovary / drug effects
  • Ovary / physiopathology*
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Pregnancy
  • Procarbazine / adverse effects
  • Procarbazine / therapeutic use
  • Randomized Controlled Trials as Topic
  • Survivors*
  • Vinblastine / adverse effects
  • Vinblastine / therapeutic use
  • Vincristine / adverse effects
  • Vincristine / therapeutic use
  • Young Adult

Substances

  • Bleomycin
  • Gonadotropin-Releasing Hormone
  • Procarbazine
  • Vincristine
  • Vinblastine
  • Etoposide
  • Dacarbazine
  • Doxorubicin
  • Anti-Mullerian Hormone
  • Cyclophosphamide
  • Follicle Stimulating Hormone
  • Prednisone

Supplementary concepts

  • ABVD protocol
  • BEACOPP protocol