trelstar and Hodgkin-Disease

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.

Topics: Adolescent; Adult; Animals; Antineoplastic Agents; Autoimmune Diseases; Azoospermia; Clinical Trials as Topic; Cohort Studies; Combined Modality Therapy; Cyclophosphamide; Embryo Transfer; Female; Fertilization in Vitro; Germ Cells; Gonadotropin-Releasing Hormone; Hematologic Neoplasms; Hodgkin Disease; Humans; Infertility, Female; Infertility, Male; Lymphoma, Non-Hodgkin; Macaca mulatta; Male; Mice; Ovary; Pregnancy; Pregnancy Outcome; Primary Ovarian Insufficiency; Radiotherapy; Sex Characteristics; Triptorelin Pamoate

The investigational endeavors of ovarian cryopreservation await the clinical experience of auto- or xenotransplantation, in vitro maturation of thawed primordial follicles, their in vitro fertilization and embryo transfer. Although promising, this experience is not yet available. Moreover, the risk of possible reimplantation of malignant stem cells with the thawed cryoperserved ovary has been raised following experimental animal observations. Therefore, until these innovative endeavors prove successful, we have attempted to minimize the gonadotoxic effect of chemotherapy by the co-treatment with a gonadotropin-releasing hormone agonistic analog (GnRH-a) to induce a temporary prepubertal milieu. The immunoreactive inhibin-A and -B in these patients was measured before, during and following the gonadotoxic chemotherapy.. A prospective clinical protocol was undertaken in 60 women aged 15-40 years with lymphoma, 10 with leukemia and 10 undergoing chemotherapeutic treatments for non-malignant diseases such as systemic lupus erythematosus or other autoimmune diseases. A monthly injection of depot D-TRP(6)-GnRH-a was administered from before starting the chemotherapy until its conclusion, up to a maximum of 6 months. Hormonal profile [follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, T, P4, insulin-like growth factor (IGF)-1, IGF-BP3 and prolactin) was taken before starting the GnRH-a/chemotherapy co-treatment, and monthly thereafter until resumtion of spontaneous ovulation. This group was compared with a control group of 60 women who have been treated with similar chemotherapy.. Whereas all but three (40, 36 and 34 year old) of the surviving patients within the GnRH-a/ chemotherapy co-treatment group resumed spontaneous ovulation and menses within 12 months, less than half of the patients in the 'control' group (chemotherapy without GnRH-a co-treatment) resumed ovarian function and regular cyclic activity (P <0.05). The remaining 55% experienced premature ovarian failure (POF). Temporarily increased FSH concentrations were experienced by about one-third of the patients resuming cyclic ovarian function, suggesting reversible ovarian damage in a larger proportion of women than those experiencing POF. Inhibin-A and -B decreased during the GnRH-a/ chemotherapy co-treatment but increased to normal levels in patients who resumed regular ovarian cyclicity, and/or spontaneously conceived, as compared with low levels in those who developed POF.. If these preliminary data are consisent in a larger group of patients, GnRH-a co-treatment should be considered in every woman of reproductive age receiving chemotherapy, in addition to assisted reproductive technologies and the investigation into ovarian cryopreservation for future in vitro maturation, autotransplantation or xenotransplantation.

Topics: Adolescent; Adult; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cryopreservation; Female; Fertility; Hodgkin Disease; Humans; Inhibins; Organ Preservation; Ovary; Ovum; Primary Ovarian Insufficiency; Triptorelin Pamoate

To assess the efficacy of gonadotropin-releasing hormone agonist (GnRHa) in preventing chemotherapy-induced ovarian failure in patients treated for Hodgkin or non-Hodgkin lymphoma within the setting of a multicenter, randomized, prospective trial.. Patients age 18 to 45 years were randomly assigned to receive either the GnRHa triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) concomitantly with alkylating agents containing chemotherapy. The primary end point was the premature ovarian failure (POF) rate (follicle-stimulating hormone [FSH] ≥ 40 IU/L) after 1 year of follow-up.. Eighty-four of 129 randomly assigned patients completed the 1-year follow-up. The mean FSH values were higher in the control group than in the GnRHa group during chemotherapy; however, this difference was no longer observed after 6 months of follow-up. After 1 year, 20% and 19% of patients in the GnRHa and control groups, respectively, exhibited POF (P = 1.00). More than half of patients in each group completely restored their ovarian function (FSH < 10 IU/L), but the anti-Müllerian hormone values were higher in the GnRHa group than in the control group (1.4 ± 0.35 v 0.5 ± 0.15 ng/mL, respectively; P = .040). The occurrence of adverse events was similar in both groups with the exception of metrorrhagia, which was more frequently observed in the control group than the GnRHa group (38.4% v 15.6%, respectively; P = .024).. Approximately 20% of patients in both groups exhibited POF after 1 year of follow-up. Triptorelin was not associated with a significant decreased risk of POF in young patients treated for lymphoma but may provide protection of the ovarian reserve.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Drug Therapy, Combination; Estradiol; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadotropin-Releasing Hormone; Hodgkin Disease; Humans; Luteolytic Agents; Lymphoma; Lymphoma, Non-Hodgkin; Middle Aged; Norethindrone; Premenopause; Primary Ovarian Insufficiency; Prospective Studies; Time Factors; Treatment Failure; Triptorelin Pamoate

To minimize the gonadotoxic effect of chemotherapy by the cotreatment with a GnRH agonistic analogue (GnRH-a).. Prospective nonrandomized study with concurrent and historical controls.. University medical center.. One hundred fifteen female patients with Hodgkin lymphoma (HL).. Sixty-five patients received a monthly injection of GnRH-a, administered before starting chemotherapy until its conclusion, up to a maximum of 6 months. Thirty-five patients were treated with ABVD and 76 with a procarbazine-containing regimen. This group was compared with a control group of 46 women who were treated concurrently with similar chemotherapy (n = 26) without GnRH-a or were historical controls (n = 20).. Cyclic ovarian function (COF) versus premature ovarian failure (POF).. The ovarian function could be determined in 111 patients. In the GnRH-a/chemotherapy group, 63 out of 65 patients resumed ovulation and regular menses (96.9 %), compared with 63% of the 46 control subjects. Twenty of the 22 patients in the BEACOPP/escalated BEACOPP/GnRH-a cotreatment resumed cyclic ovarian function versus 9 of the 14 in the chemotherapy-only group. All 17 MOPP/ABV/GnRH-a cotreated patients resumed COF versus 11 of the 22 in the chemotherapy-only group. There was no significant effect of the GnRH-a cotreatment regarding COF in the ABVD group. There were no significant differences in the cumulative doses of the various alkylating agents between the two groups.. Cotreatment with GnRH-a may reduce ovarian damage significantly in female patients treated for HL and should be considered in addition to assisted reproduction for women in reproductive age receiving gonadotoxic chemotherapy.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hodgkin Disease; Humans; Injections; Menstrual Cycle; Ovary; Pregnancy; Pregnancy Rate; Primary Ovarian Insufficiency; Time Factors; Treatment Outcome; Triptorelin Pamoate

In young women receiving chemotherapy for Hodgkin's disease, the combined use of triptorelin and tibolone cotreatment may be a useful tool for preserving ovarian function because all but three (10%) of the women in this treatment group returned to spontaneous ovulation and menses, in contrast to 23% of subjects in the control group (P<.05). No significant differences were observed in bone mineral density between groups.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Density; Cyclophosphamide; Dacarbazine; Doxorubicin; Female; Gonadotropin-Releasing Hormone; Hodgkin Disease; Humans; Norpregnenes; Ovary; Prednisone; Primary Ovarian Insufficiency; Procarbazine; Triptorelin Pamoate; Vinblastine; Vincristine

We have evaluated the best method to assess the ovarian reserve and the ovarian protective effect of GnRH-analog (GnRH-a), in 29 women with Hodgkin's disease (HD) treated with chemotherapy (CHT). The ovarian reserve was studied by measuring the serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, antimullerian hormone (AMH) and the ultrasound antral follicular count (AFC). The patients were randomly treated with or without GnRH-a. At the time of study menstrual function was normal in 21 cases (72.4%), but absent in 8 (27.5%). Mean basal values of FSH, LH, AMH, inhibin B and AFC were normal in patients less than 30 years old and in the group treated four years or less before observation. AFC appeared to be the best marker of reduced ovarian reserve and a combination of AFC-AMH or inhibin B appeared the best predictor. In the GnRH-a group, no women had amenorrhoea, although ovarian reserve assessment was not significantly different from those who were not treated. The time-interval from CHT was the only significant predictor of ovarian function in GnRH-a treated patients. In conclusion, ovarian reserve evaluation, in young patients treated by CHT, can be performed by AFC. GnRH-a treatment does not have a protective effect, but could delay the development of ovarian failure.

Topics: Adolescent; Adult; Amenorrhea; Anti-Mullerian Hormone; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dacarbazine; Dexamethasone; Doxorubicin; Female; Follicle Stimulating Hormone; Glycoproteins; Hodgkin Disease; Humans; Infertility, Female; Inhibins; Luteinizing Hormone; Mechlorethamine; Ovarian Follicle; Ovary; Predictive Value of Tests; Prednisolone; Prednisone; Primary Ovarian Insufficiency; Procarbazine; Sensitivity and Specificity; Survivors; Testicular Hormones; Time Factors; Triptorelin Pamoate; Ultrasonography; Vinblastine; Vincristine

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Female; Fertility Agents, Female; Hodgkin Disease; Humans; Menstrual Cycle; Pregnancy; Pregnancy Rate; Primary Ovarian Insufficiency; Treatment Outcome; Triptorelin Pamoate

Frequent negative consequence of chemotherapy (CHT) is ovarian damage and premature ovarian failure (POF). Aim of this prospective case-control study is evaluation of GnRH analogue (GnRH-a) administration to patients with Hodgkin lymphoma (HL) during CHT and prevention of ovarian damage depending upon CHT regimen.. Study group consists of 72 patients in fertile age (18-35 years) with HL diagnosis treated in 2004-2005 by curative CHT together with GnRH analogue (Triptorelin) administration according to a standardized protocol. Patients were divided into three groups according to the stage of disease and treated by three types of CHT regimens (A,B,C) with increased cytotoxicity. Ovarian function of all patients was assessed by gonadotrophin levels (FSH, LH) analysis from peripheral blood before treatment and also 6 and 12 month after it. The number of women with POF after CHT in study group was compared with control group (n = 45, age 18-35 years) of patients treated in 2002-2003 according to the same protocol but without protective GnRH analogue application.. In study group with GnRH analogue administration during CHT, there was significantly (P < 0.001) fewer cases with POF 6 and 12 month after the end of CHT (37.5% and 20.8%, respectively) than in control group (73.3% and 71.1%, respectively). Comparative analysis depending on cytotoxicity of CHT regimen used showed significant differences in percentage of patient with acquired POF between study and control group only in less aggressive CHT protocols.. Study showed a significant reduction of ovarian failure risk in women with HL treated with less aggressive CHT regimens plus a GnRH analogue.

Topics: Adolescent; Adult; Case-Control Studies; Drug Therapy; Female; Follicle Stimulating Hormone; Hodgkin Disease; Humans; Luteinizing Hormone; Luteolytic Agents; Ovary; Primary Ovarian Insufficiency; Treatment Outcome; Triptorelin Pamoate

We conducted a retrospective study on treatment-related ovarian failure in 61 women with Hodgkin lymphoma who were under treatment from 1994 to 2006. To minimize the risk of treatment-related gonadotoxicity, triptorelin (Decapeptyl), a gonadotropin-releasing hormone analog (GnRHa), was administered monthly. All patients were treated with frontline polychemotherapy with or without radiotherapy. Seven refractory or relapsed patients received salvage treatment, and six of these patients further received peripheral blood stem cell transplantation. Fifty patients (82%) recovered regular menses, four patients (6%) reported menstrual abnormalities, and seven patients (12%) who were under salvage treatment became amenorrheic. We found a clear correlation between age at the time of treatment, advanced disease, cumulative therapeutic load and ovarian failure. After the completion of treatment, 13 patients who attempted conception conceived. GnRHa may preclude ovarian damage and infertility in young women receiving frontline polychemotherapy alone or in combination with supradiaphragmatic radiotherapy. In refractory or relapsed patients, GnRHa does not seem to be very effective, and further experimental approaches are required for fertility preservation.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Hodgkin Disease; Humans; Infertility, Female; Luteolytic Agents; Neoplasm Recurrence, Local; Peripheral Blood Stem Cell Transplantation; Primary Ovarian Insufficiency; Reproduction; Retrospective Studies; Salvage Therapy; Triptorelin Pamoate