title: Phase II study of gonadotropin-releasing hormone analog for ovarian function preservation in hematopoietic stem cell transplantation patients.
abstract: OBJECTIVE
  Premature ovarian failure occurs in 40%-70% of patients who receive conventional chemotherapy alone. However, the incidence is higher, 70%-100%, in patients who undergo myeloablative chemotherapy with hematopoietic stem cell transplantation (HSCT). Gonadotropin-releasing hormone (GnRH) analogs, such as leuprolide, in a continuous-release formulation, may protect the ovaries from the gonadotoxic effects of chemotherapy. In non-HSCT settings, GnRH analogs have reduced the risk for premature ovarian failure to <10%. We conducted a phase II clinical trial based on the hypothesis that giving leuprolide before conditioning chemotherapy in HSCT patients reduces premature ovarian failure incidence.
  
  
  METHODS
  Eligible patients were women aged ≤40 years who were HSCT candidates, were premenopausal, and had both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels ≤20 IU/L. Two 22.5-mg leuprolide doses were delivered in 3-month depot i.m. injections, the first within 2 months before HSCT. Patients were monitored for menstruation return, and ovarian function tests (FSH, LH, and estradiol) were done every 2 months starting 90 days after the last leuprolide dose.
  
  
  RESULTS
  Sixty eligible patients were enrolled, 59 underwent HSCT, and 44 were evaluable (median age, 25 years; median follow-up, 355 days). Only seven of 44 patients (16%) regained ovarian function. Of the 33 who received myeloablative regimens, six (18%) regained ovarian function. However, among the 11 who received nonmyeloablative regimens, only one (9%) regained ovarian function (p = .66).
  
  
  CONCLUSIONS
  Leuprolide did not preserve ovarian function in patients who underwent HSCT using either myeloablative or nonmyeloablative regimens. Other measures that protect ovarian function need to be investigated.
authors.affiliation: Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Yee Chung
authors.initials: YC
authors.lastname: Cheng
authors.forename: Mariko
authors.initials: M
authors.lastname: Takagi
authors.forename: Andrea
authors.initials: A
authors.lastname: Milbourne
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016729:Leuprolide / Q000009:adverse effects / Q000627:therapeutic use*; D010053:Ovary / Q000187:drug effects* / Q000503:physiopathology; D016649:Primary Ovarian Insufficiency / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D016729:Leuprolide