Use of the GnRH Agonist Leuprolide Acetate (Lupron(Registered Trademark)) to Preserve Ovarian Function in Women Undergoing Chemotherapy
As a result of the inability of female germ cells to regenerate after injury, a number of
chemotherapeutic agents induce premature ovarian failure in the majority of reproductive age
women who receive them. The long-term survival for these women has increased with more
effective chemotherapies, making iatrogenic ovarian failure and infertility an increasingly
significant issue. Currently the choices for maintaining fertility include in vitro
fertilization (IVF) and embryo cryopreservation, oocyte cryopreservation and the use of GnRH
agonist and antagonist to preserve ovarian function.
Much of the evidence for the use of GnRH agonist to prevent premature ovarian failure is
found in the systemic lupus erythematosus literature. Blumenfeld and colleagues have
published a report that demonstrates preservation of ovarian function in 100% of patients
treated with leuprolide acetate prior to cyclophosphamide therapy, compared to a 50% ovarian
failure rate in patients not receiving leuprolide acetate. Although the results of animal
studies and human studies are encouraging, adequately controlled trials are needed. Future
trials will need to have sufficient numbers of patients, receiving multiple types of
chemotherapeutic agents to adequately document the utility of medical prophylaxis. The
experience with ovulation induction suggests GnRH antagonists may have similar efficacy to
GnRH agonists. GnRH antagonists compete directly with GnRH in receptor binding, and as a
result antagonists rapidly inhibit secretion of gonadotropin and sex steroids. Unlike GnRH
agonists, GnRH antagonists have an immediate effect and antagonists can be given independent
of menstrual cycle day. These differences represent several practical benefits offered by
an antagonist. In a recent case series by Sauer et al, cetrorelix acetate, a GnRH
antagonist, was given in doses of 3mg at four day intervals to four patients ages 21-30.
Menses was preserved in all four patients and there was one spontaneous conception. Because
of the potential advantages of the use of a GnRH antagonist when compared to an agonist,
cetrorelix acetate will be studied against placebo in this investigation.
Our specific aim is to compare the rates of ovarian preservation in reproductive age women
receiving chemotherapeutic agents known to affect ovarian function who receive Cetrorelix
acetate co treatment with women who receive these agents and do not receive Cetrorelix
acetate. A second aim is to evaluate the ability of the Cetrorelix acetate co treatment to
induce therapeutic amenorrhea in a study population at risk for thrombocytopenia and
associated heavy vaginal bleeding.
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Prevention
Antimullerian hormone, ovarian follicle count
2-years
No
United States: Federal Government
070193
NCT00507780
July 2007
July 2010
Name | Location |
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National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |