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Use of the GnRH Agonist Leuprolide Acetate (Lupron(Registered Trademark)) to Preserve Ovarian Function in Women Undergoing Chemotherapy

Phase 4
10 Years
21 Years
Not Enrolling
Ovarian Function, Preservation of Ovarian Function

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Trial Information

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.

Inclusion Criteria


All reproductive age women menarche - age 21, undergoing chemotherapy with agents known to
affect ovarian function that have a follicle stimulating hormone level (FSH) less than 20
mIU/L will be offered enrollment. We define premature ovarian failure as the development
before age 40 years of greater than 4 months of amenorrhea or menstrual irregularity,
associated with two serum FSH levels in the menopausal range (sampled at least 1 mo


FSH greater than 20 mIU/L

Sensitivity or allergy to oral contraceptives (lo ovral) or cetrorelix acetate

Patients who have had surgical removal of their ovaries

Patients who are currently pregnant or attempting conception

Severe renal impairment

Premenarchal patients

Patients greater than 21

Patients who have undergone radiation therapy or who are scheduled to undergo radiation
therapy during the study period.

Patients with a family history of premature ovarian failure

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Outcome Measure:

Antimullerian hormone, ovarian follicle count

Outcome Time Frame:


Safety Issue:



United States: Federal Government

Study ID:




Start Date:

July 2007

Completion Date:

July 2010

Related Keywords:

  • Ovarian Function
  • Preservation of Ovarian Function
  • GnRH Antagonist
  • Premature Ovarian Failure
  • Fertility
  • Chemotherapy
  • POF



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