Gender difference: fertility preservation in young women but not in men exposed to gonadotoxic chemotherapy.
Decreased secretion of pituitary gonadotropins, by decreasing gonadal function, may possibly protect against the sterilizing effects of chemotherapy. Although previous claims that primordial germ cells fare better than germ cells that are part of an active cell cycle have been made, this hypothesis has not been seriously tested clinically until recently. The only prospective randomized study performed to date found that gonadotropin releasing hormone agonistic analogue (GnRH-a) protected the ovary against cyclophosphamide-induced damage in Rhesus monkeys by significantly decreasing the number of follicles lost during the chemotherapeutic insult. We have administered a monthly depot i.m. injection of GnRH-a to more than 125 young patients exposed to gonadotoxic chemotherapy for malignant or nonmalignant diseases, after informed consent, starting before chemotherapy for up to 6 months, in parallel and until the end of chemotherapeutic treatment. Less than 7% developed irreversible hypergonadotropic amenorrhea. The remainder (>93%) resumed cyclic ovarian function, of which 32 patients spontaneously conceived 46 times. These patients were compared to a control group of over 125 patients of comparable age (15-40 years), who were similarly treated with chemotherapy but without the GnRH-a adjuvant. The 2 groups were similar in age, diagnosis, and the ratio of HD to non-Hodgkin lymphoma patients. The 2 groups also received similar doses of radiotherapy exposure and the proportion of radio-plus chemotherapy-treated patients was similar. The cumulative doses of each chemotherapeutic agent and the mean or median radiotherapy exposure did not differ between the groups. Our and others' results support the effectiveness of GnRH-a administration also to patients receiving cyclophosphamide pulses for systemic lupus erythematosus and other autoimmune diseases. Possible explanations for the beneficial effect of the GnRH-a on minimizing the gonadotoxic effect of chemotherapy are discussed. Multi-center prospective, randomized studies are awaited to substantiate the in vivo effect of GnRH-a as an unequivocal means of minimizing follicular apoptosis.
Blumenfeld
Z
Z
Reproductive Endocrinology, Department of Obstetrics and Gynecology, Rambam Medical Centre, Technion, Faculty of Medicine, Haifa, Israel. z_blumenfeld@rambam.health.gov.it
D000293:Adolescent; D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy; D053713:Azoospermia / Q000139:chemically induced / Q000209:etiology; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro; D005854:Germ Cells / Q000187:drug effects / Q000528:radiation effects; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000031:analogs & derivatives; D019337:Hematologic Neoplasms / Q000150:complications / Q000188:drug therapy / Q000532:radiotherapy; D006689:Hodgkin Disease / Q000150:complications / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D007247:Infertility, Female / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D007248:Infertility, Male / Q000139:chemically induced*; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000188:drug therapy / Q000532:radiotherapy; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D010053:Ovary / Q000503:physiopathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced / Q000517:prevention & control / Q000532:radiotherapy; D011878:Radiotherapy / Q000009:adverse effects; D012727:Sex Characteristics; D017329:Triptorelin Pamoate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D003520:Cyclophosphamide