Endocrinology: Prevention of irreversible chemotherapy-induced ovarian damage in young women with lymphoma by a gonadotrophin-releasing hormone agonist in parallel to chemotherapy

Abstract

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).

Ovarian recovery after stem cell transplantation

“…Further trials are needed to validate clinical potential of GnRH in the preservation of fertility. [17][18][19][20] In spite of the fact that almost all women who undergo BMT have developed an ovarian failure, recovery is possible. A large retrospective survey of fertility after SCT involving 37 362 patients revealed that only 0.6% of patients conceived after one autologous or allogeneic SCT.…”

Fertility Preservation in Young Women Undergoing Breast Cancer Therapy

“…In a recent mouse study, ovarian suppression by either a GnRHa or oral contraceptive did not prove effective against cyclophosphamide-induced ovarian damage [60]. There is a limited number of prospective studies in humans, which are flawed because of short-term follow-up and/or because of a lack of control subjects [61][62][63][64].…”

“…There was no control group. Blumenfeld et al [61] administered a GnRHa concurrently with chemotherapy in 18 women with Hodgkin's or non-Hodgkin's lymphomas. The study group was compared with a historical control group of 18 women treated with similar regimens.…”

Preservação de fertilidade

“…Dentre as opções propostas com esta fi nalidade estão os contraceptivos hormonais combinados 2 , aqueles com progesterona exclusiva 48 e os análogos do GnRH 49 . Os contraceptivos não foram efi cazes em diminuir a incidência de falência ovariana 2,48 , provavelmente porque o efeito supressor dos contraceptivos não promove bloqueio completo do eixo hipotálamo-hipofi sário, havendo recrutamento folicular no ová-rio sem dominância folicular e ovulação 50 .…”

“…Já os análogos do GnRH têm seus resultados controversos. Blummenfeld et al 49 encorajam a utilização desta droga após encontrarem redução de 61 (11/18) para 6,7% (15/16) na incidência de falência ovariana no grupo de pacientes que receberam o análogo simultaneamente à quimioterapia comparado com pacientes que não receberam a droga; entretanto, estes dados não foram confi rmados por nenhum outro autor, nem em estudos retrospectivos, nem em trabalhos prospectivos de pequena casuística 3 . Atualmente em nosso serviço o acetato de leuprolide vem sendo utilizado rotineiramente durante a quimioterapia em pacientes com cânceres hematológicos, com fi nalidade de produzir amenorréia e evitar o sangramento menstrual, que costuma ser abundante devido à plaquetopenia secundária à quimioterapia.…”