Prevention of irreversible chemotherapy-induced ovarian damage in young women with lymphoma by a gonadotrophin-releasing hormone agonist in parallel to chemotherapy.
To examine whether the concomitant administration of a gonadotrophin-releasing hormone agonist (GnRHa) during combination chemotherapy to young women with lymphoma may facilitate preservation of gonadal function, a prospective clinical protocol was undertaken in 18 cycling women with lymphoma, aged 15-40 years. Thirteen patients suffered from Hodgkin disease (HD) and 5 from non-Hodgkin lymphoma. After informed consent a monthly injection of depot D-TRP6-GnRHa was administered for a maximum of 6 months starting prior to chemotherapy. Most of these patients (15/18) were treated with the MOPP/ABV(D) combination chemotherapy followed by mantle field irradiation in 10 patients. Hormonal profile [luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol, testosterone, progesterone, insulin-like growth factor (IGF)-1, prolactin] was taken before the GnRHa/chemotherapy co-treatment, and monthly thereafter until resuming spontaneous ovulation and menses. This group of prospectively treated lymphoma patients was compared to a matched control group of 18 women (aged 17-40 years) who have been treated with chemotherapy, mostly MOPP/ABV (14/18), with (11) or without (7) mantle field radiotherapy. Fourteen had Hodgkin's and four non-Hodgkin's lymphoma. Gonadal function was determined clinically, hormonally (LH, FSH, oestradiol, progesterone), and sonographically. Two of the patients in each group died from refractory disease. Of the remaining 16 patients, 15 (93.7%) resumed spontaneous ovulation and menses within 3-8 months of termination of the combined chemotherapy/GnRHa co-treatment. In contrast, only seven (39%) of the 18 similarly treated patients in the control group (chemotherapy without GnRHa) resumed ovarian cyclic activity (regular menses). The other 11 experienced premature ovarian failure (POF) (61%). Out preliminary data suggest a possible significant protective effect of GnRHa co-treatment with chemotherapy from irreversible ovarian damage (POF).
Blumenfeld
Z
Z
Department of Obsterics and Gynecology, Rambam Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel.
Avivi
I
I
Linn
S
S
Epelbaum
R
R
Ben-Shahar
M
M
Haim
N
N
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000503:physiopathology; D006728:Hormones / Q000097:blood; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000503:physiopathology; D008466:Mechlorethamine / Q000009:adverse effects / Q000627:therapeutic use; D010049:Ovarian Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D010053:Ovary / Q000503:physiopathology; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011344:Procarbazine / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D006728:Hormones; D007987:Gonadotropin-Releasing Hormone; D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D003520:Cyclophosphamide; D011241:Prednisone