Preventing Chemotherapy-associated Amenorrhea (CRA) With Leuprolide In Young Women With Early-stage Breast Cancer

Heather Jones, MD

University of Pennsylvania Cancer
Last Modified: May 15, 2001

Presenter: Kevin R. Fox
Affiliation: University of Pennsylvania Cancer Center, Philadelphia, PA


    Premature amenorrhea is often associated with adjuvant chemotherapy treatment for breast cancer. The rate of amenorrhea varies to 10 to 100% in studies depending on the age of patients and the type of chemotherapy used. Whether or not the induction of premature menopause by adjuvant chemotherapy might be advantageous with respect to disease-free and overall survival in patients with early-stage breast cancer remains a subject of dispute. In this study, patients who had a strong desire of maintaining menstrual function for purposes of maintaining fertility, were given leuprolide therapy during the course of adjuvant therapy as a means of inducing temporary amenorrhea and thus protecting the ovary from the cytotoxic effects of chemotherapy.

Materials and Methods:

  • Thirteen patients (pts) diagnosed between 1994 and 1999 were placed on this study. A
  • Age from 26-39 years (median age 35), with node-negative breast cancer in five pts, and node positive breast cancer in eight. Three pts had T1 lesions and eight had T2 lesions.
  • Six pts received standard doxorubicin and cyclophosphamide (AC) for four cycles, five pts received AC followed by paclitaxel for four cycles, one received CAF for six months, and one received doxorubicin/docetaxel followed by CMF.
  • In 11 pts, leuprolide was given in a dose of 3.75mg IM one week before chemotherapy, and repeated every three to four weeks until completion of chemotherapy. Two pts received leuprolide 7.5mg on a similar schedule.
  • No leuprolide was given after chemotherapy.


  • All pts became amenorrheic by the second cycle of chemotherapy.
  • Menstrual periods resumed in all pts within 12 months of the completion of chemotherapy, with a mean time to recovery of 4.9 months.
  • Twelve of 13 pts report regular cycles, one reports irregular menses at 16 months from completion of treatment.
  • Four patients also taking tamoxifen continue regular menses.
  • Two pts have developed metastatic disease at 19 and 36 months after diagnosis.
  • One patient became pregnant 10 months after the resumption on menses and had a normal delivery and healthy birth outcome. Four other patients are actively attempting to conceive. One patient had a spontaneous natural abortion 14 months after completion of therapy.

Authors' Conclusions

    Although the probability of chemotherapy- associated amenorrhea in this cohort of patients is low without leuprolide, the maintenance of regular posttreatment menses in most of our pts is encouraging.

Clinical/Scientific Implications:

    This is a provocative small pilot study, which generates a number of questions. First of which, is leuprolide therapy even needed in a young population of patients if AC chemotherapy is given in the adjuvant setting. Studies indicate that AC in young women tends to cause less chemotherapy-induced amenorrhea, but more data is needed. Second question would be, if leuprolide were an effective protective ovarian agent then what is the correct sequence/timing between leuprolide administration and a standard chemotherapy regimen. SWOG is considering using the information obtained in this trial to formulate an ovarian sparing/ follicular rest protocol.

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