Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer.
OBJECTIVE
Chemotherapy-induced amenorrhea is a serious concern for women undergoing cancer therapy. This prospective randomized trial evaluated the use of gonadotropin-releasing hormone (GnRH) analog triptorelin to preserve ovarian function in women treated with chemotherapy for early-stage breast cancer.


METHODS
Premenopausal women age 44 years or younger were randomly assigned to receive either triptorelin or no triptorelin during (neo)adjuvant chemotherapy and were further stratified by age (< 35, 35 to 39, > 39 years), estrogen receptor status, and chemotherapy regimen. Objectives included the resumption of menses and serial monitoring of follicle-stimulating hormone (FSH) and inhibin A and B levels.


RESULTS
Targeted for 124 patients with a planned 5-year follow-up, the trial was stopped for futility after 49 patients were enrolled (median age, 39 years; range, 21 to 43 years); 47 patients were treated according to assigned groups with four cycles of adriamycin plus cyclophosphamide alone or followed by four cycles of paclitaxel or six cycles of fluorouracil, epirubicin, and cyclophosphamide. Menstruation resumed in 19 (90%) of 21 patients in the control group and in 23 (88%) of 26 in the triptorelin group (P= .36). Menses returned after a median of 5.8 months (range, 1 to 19 months) after completion of chemotherapy in the triptorelin versus 5.0 months (range, 0 to 28 months) in the control arm (P= .58). Two patients (age 26 and 35 years at random assignment) in the control group had spontaneous pregnancies with term deliveries. FSH and inhibin B levels correlated with menstrual status.


CONCLUSIONS
When stratified for age, estrogen receptor status, and treatment regimen, amenorrhea rates on triptorelin were comparable to those seen in the control group.
University of California, San Francisco, CA, USA. pmunster@medicine.ucsf.edu
Pamela N
PN
Munster
Amy P
AP
Moore
Roohi
R
Ismail-Khan
Charles E
CE
Cox
Mensura
M
Lacevic
Margaret
M
Gross-King
Ping
P
Xu
W Bradford
WB
Carter
Susan E
SE
Minton
D000328:Adult; D000568:Amenorrhea / Q000139:chemically induced / Q000517:prevention & control*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000009:adverse effects; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000009:adverse effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D005472:Fluorouracil / Q000009:adverse effects; D005640:Follicle Stimulating Hormone / Q000097:blood; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000031:analogs & derivatives; D006801:Humans; D007265:Inhibins / Q000097:blood; D008598:Menstruation; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D010053:Ovary / Q000187:drug effects*; D017239:Paclitaxel / Q000009:adverse effects; D013629:Tamoxifen / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D017329:Triptorelin Pamoate / Q000008:administration & dosage / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; C422362:inhibin A; C422364:inhibin B; D017329:Triptorelin Pamoate; D013629:Tamoxifen; D007987:Gonadotropin-Releasing Hormone; D015251:Epirubicin; D007265:Inhibins; D004317:Doxorubicin; D003520:Cyclophosphamide; D005640:Follicle Stimulating Hormone; D017239:Paclitaxel; D005472:Fluorouracil