title: No Evidence for the Benefit of Gonadotropin-Releasing Hormone Agonist in Preserving Ovarian Function and Fertility in Lymphoma Survivors Treated With Chemotherapy: Final Long-Term Report of a Prospective Randomized Trial.
abstract: We have reported previously that after 1-year follow up, gonadotropin-releasing hormone agonist (GnRHa) did not prevent chemotherapy-induced premature ovarian failure (POF) in patients with lymphoma, but may provide protection of the ovarian reserve. Here, we report the final analysis of the cohort after 5 years of follow up.
  
  
  
  A total of 129 patients with lymphoma were randomly assigned to receive either triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) during chemotherapy. Ovarian function and fertility were reported after 2, 3, 4, and 5 to 7 years of follow up. The primary end point was POF, defined as at least one follicle-stimulating hormone value of > 40 IU/L after 2 years of follow up.
  
  
  
  Sixty-seven patients 26.21 ± 0.64 years of age had available data after a median follow-up time of 5.33 years in the GnRHa group and 5.58 years in the control group (P = .452). Multivariate logistic regression analysis showed a significantly increased risk of POF in patients according to age (P = .047), the conditioning regimen for hematopoietic stem cell transplant (P = .002), and the cumulative dose of cyclophosphamide > 5 g/m(2) (P = .019), but not to the coadministration of GnRHa during chemotherapy (odds ratio, 0.702; P = .651). The ovarian reserve, evaluated using anti-Müllerian hormone and follicle-stimulating hormone levels, was similar in both groups. Fifty-three percent and 43% achieved pregnancy in the GnRHa and control groups, respectively (P = .467).
  
  
  
  To the best of our knowledge, this is the first long-term analysis confirming that GnRHa is not efficient in preventing chemotherapy-induced POF in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drug's benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma.
authors.affiliation: Isabelle Demeestere, Julie Dechene, Yvon Englert, and Viviane De Maertelaer, Université Libre de Bruxelles; Alain Kentos and Yvon Englert, Erasme Hospital; Eric Van Den Neste, Cliniques Universitaires UCL Saint-Luc; Dominique Bron, J. Bordet Institute, Brussels; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerpen, Belgium; Pauline Brice, St Louis Hospital, APHP; Jehan Dupuis, Hôpital Henri Mondor, Paris; Olivier Casasnovas, CHU de Dijon, Dijon, France; and Fedro A. Peccatori, Istituto Europeo di Oncologia, Milano, Italy. idemeest@ulb.ac.be.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Demeestere
authors.affiliation: Isabelle Demeestere, Julie Dechene, Yvon Englert, and Viviane De Maertelaer, Université Libre de Bruxelles; Alain Kentos and Yvon Englert, Erasme Hospital; Eric Van Den Neste, Cliniques Universitaires UCL Saint-Luc; Dominique Bron, J. Bordet Institute, Brussels; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerpen, Belgium; Pauline Brice, St Louis Hospital, APHP; Jehan Dupuis, Hôpital Henri Mondor, Paris; Olivier Casasnovas, CHU de Dijon, Dijon, France; and Fedro A. Peccatori, Istituto Europeo di Oncologia, Milano, Italy.
authors.forename: Pauline
authors.initials: P
authors.lastname: Brice
authors.affiliation: Isabelle Demeestere, Julie Dechene, Yvon Englert, and Viviane De Maertelaer, Université Libre de Bruxelles; Alain Kentos and Yvon Englert, Erasme Hospital; Eric Van Den Neste, Cliniques Universitaires UCL Saint-Luc; Dominique Bron, J. Bordet Institute, Brussels; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerpen, Belgium; Pauline Brice, St Louis Hospital, APHP; Jehan Dupuis, Hôpital Henri Mondor, Paris; Olivier Casasnovas, CHU de Dijon, Dijon, France; and Fedro A. Peccatori, Istituto Europeo di Oncologia, Milano, Italy.
authors.forename: Fedro A
authors.initials: FA
authors.lastname: Peccatori
authors.affiliation: Isabelle Demeestere, Julie Dechene, Yvon Englert, and Viviane De Maertelaer, Université Libre de Bruxelles; Alain Kentos and Yvon Englert, Erasme Hospital; Eric Van Den Neste, Cliniques Universitaires UCL Saint-Luc; Dominique Bron, J. Bordet Institute, Brussels; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerpen, Belgium; Pauline Brice, St Louis Hospital, APHP; Jehan Dupuis, Hôpital Henri Mondor, Paris; Olivier Casasnovas, CHU de Dijon, Dijon, France; and Fedro A. Peccatori, Istituto Europeo di Oncologia, Milano, Italy.
authors.forename: Alain
authors.initials: A
authors.lastname: Kentos
authors.affiliation: Isabelle Demeestere, Julie Dechene, Yvon Englert, and Viviane De Maertelaer, Université Libre de Bruxelles; Alain Kentos and Yvon Englert, Erasme Hospital; Eric Van Den Neste, Cliniques Universitaires UCL Saint-Luc; Dominique Bron, J. Bordet Institute, Brussels; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerpen, Belgium; Pauline Brice, St Louis Hospital, APHP; Jehan Dupuis, Hôpital Henri Mondor, Paris; Olivier Casasnovas, CHU de Dijon, Dijon, France; and Fedro A. Peccatori, Istituto Europeo di Oncologia, Milano, Italy.
authors.forename: Jehan
authors.initials: J
authors.lastname: Dupuis
authors.affiliation: Isabelle Demeestere, Julie Dechene, Yvon Englert, and Viviane De Maertelaer, Université Libre de Bruxelles; Alain Kentos and Yvon Englert, Erasme Hospital; Eric Van Den Neste, Cliniques Universitaires UCL Saint-Luc; Dominique Bron, J. Bordet Institute, Brussels; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerpen, Belgium; Pauline Brice, St Louis Hospital, APHP; Jehan Dupuis, Hôpital Henri Mondor, Paris; Olivier Casasnovas, CHU de Dijon, Dijon, France; and Fedro A. Peccatori, Istituto Europeo di Oncologia, Milano, Italy.
authors.forename: Pierre
authors.initials: P
authors.lastname: Zachee
authors.affiliation: Isabelle Demeestere, Julie Dechene, Yvon Englert, and Viviane De Maertelaer, Université Libre de Bruxelles; Alain Kentos and Yvon Englert, Erasme Hospital; Eric Van Den Neste, Cliniques Universitaires UCL Saint-Luc; Dominique Bron, J. Bordet Institute, Brussels; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerpen, Belgium; Pauline Brice, St Louis Hospital, APHP; Jehan Dupuis, Hôpital Henri Mondor, Paris; Olivier Casasnovas, CHU de Dijon, Dijon, France; and Fedro A. Peccatori, Istituto Europeo di Oncologia, Milano, Italy.
authors.forename: Olivier
authors.initials: O
authors.lastname: Casasnovas
authors.affiliation: Isabelle Demeestere, Julie Dechene, Yvon Englert, and Viviane De Maertelaer, Université Libre de Bruxelles; Alain Kentos and Yvon Englert, Erasme Hospital; Eric Van Den Neste, Cliniques Universitaires UCL Saint-Luc; Dominique Bron, J. Bordet Institute, Brussels; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerpen, Belgium; Pauline Brice, St Louis Hospital, APHP; Jehan Dupuis, Hôpital Henri Mondor, Paris; Olivier Casasnovas, CHU de Dijon, Dijon, France; and Fedro A. Peccatori, Istituto Europeo di Oncologia, Milano, Italy.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Den Neste
authors.affiliation: Isabelle Demeestere, Julie Dechene, Yvon Englert, and Viviane De Maertelaer, Université Libre de Bruxelles; Alain Kentos and Yvon Englert, Erasme Hospital; Eric Van Den Neste, Cliniques Universitaires UCL Saint-Luc; Dominique Bron, J. Bordet Institute, Brussels; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerpen, Belgium; Pauline Brice, St Louis Hospital, APHP; Jehan Dupuis, Hôpital Henri Mondor, Paris; Olivier Casasnovas, CHU de Dijon, Dijon, France; and Fedro A. Peccatori, Istituto Europeo di Oncologia, Milano, Italy.
authors.forename: Julie
authors.initials: J
authors.lastname: Dechene
authors.affiliation: Isabelle Demeestere, Julie Dechene, Yvon Englert, and Viviane De Maertelaer, Université Libre de Bruxelles; Alain Kentos and Yvon Englert, Erasme Hospital; Eric Van Den Neste, Cliniques Universitaires UCL Saint-Luc; Dominique Bron, J. Bordet Institute, Brussels; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerpen, Belgium; Pauline Brice, St Louis Hospital, APHP; Jehan Dupuis, Hôpital Henri Mondor, Paris; Olivier Casasnovas, CHU de Dijon, Dijon, France; and Fedro A. Peccatori, Istituto Europeo di Oncologia, Milano, Italy.
authors.forename: Viviane
authors.initials: V
authors.lastname: De Maertelaer
authors.affiliation: Isabelle Demeestere, Julie Dechene, Yvon Englert, and Viviane De Maertelaer, Université Libre de Bruxelles; Alain Kentos and Yvon Englert, Erasme Hospital; Eric Van Den Neste, Cliniques Universitaires UCL Saint-Luc; Dominique Bron, J. Bordet Institute, Brussels; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerpen, Belgium; Pauline Brice, St Louis Hospital, APHP; Jehan Dupuis, Hôpital Henri Mondor, Paris; Olivier Casasnovas, CHU de Dijon, Dijon, France; and Fedro A. Peccatori, Istituto Europeo di Oncologia, Milano, Italy.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bron
authors.affiliation: Isabelle Demeestere, Julie Dechene, Yvon Englert, and Viviane De Maertelaer, Université Libre de Bruxelles; Alain Kentos and Yvon Englert, Erasme Hospital; Eric Van Den Neste, Cliniques Universitaires UCL Saint-Luc; Dominique Bron, J. Bordet Institute, Brussels; Pierre Zachee, Algemeen Ziekenhuis Stuivenberg, Antwerpen, Belgium; Pauline Brice, St Louis Hospital, APHP; Jehan Dupuis, Hôpital Henri Mondor, Paris; Olivier Casasnovas, CHU de Dijon, Dijon, France; and Fedro A. Peccatori, Istituto Europeo di Oncologia, Milano, Italy.
authors.forename: Yvon
authors.initials: Y
authors.lastname: Englert
mesh_terms: D000328:Adult; D005260:Female; D005298:Fertility / Q000187:drug effects; D059247:Fertility Preservation / Q000379:methods; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy*; D008875:Middle Aged; D009640:Norethindrone / Q000627:therapeutic use; D010053:Ovary / Q000187:drug effects* / Q000502:physiology; D016649:Primary Ovarian Insufficiency / Q000517:prevention & control*; D011446:Prospective Studies; D017329:Triptorelin Pamoate / Q000008:administration & dosage
chemical_list: D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D009640:Norethindrone