goserelin and Primary-Ovarian-Insufficiency

It is still controversial that GnRH agonist (GnRHa) protects ovarian function from chemotherapy-induced gonadotoxicity. Indeed, the results of many studies related to this issue are neither consistent nor convincing because of the weak study design and the inadequate sample size. We identified 11 prospective controlled studies (8 nonrandomized and 3 randomized) for the systemic review and meta-analysis. The meta-analysis showed that GnRHa cotreatment during chemotherapy can protect ovarian function. However, it is worthy to note that the result of this meta-analysis is influenced by nonrandomized studies. The protective effect of GnRHa will remain elusive until the currently ongoing large, prospective, randomized studies are completed. In addition, tamoxifen, a selective estrogen receptor modulator, may have the protective effect against loss of follicles and ovarian function, which was caused by chemotherapy.

Topics: Animals; Antineoplastic Agents; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Menstruation; Neoplasms; Ovary; Primary Ovarian Insufficiency; Randomized Controlled Trials as Topic; Tamoxifen; Triptorelin Pamoate

Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women's health. The OPTION trial tested whether administration of a gonadotropin-releasing hormone agonist during chemotherapy for early breast cancer reduced the risk of POI.. This was a prospective, randomized, parallel group study of the gonadotropin-releasing hormone agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone concentrations to give an additional analysis as rate of POI.. A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% versus 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% versus 34.8% in the control group (P = 0.048). Follicle stimulating hormone concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001, respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups.. This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer term prevention of estrogen deficiency-related outcomes needs to be determined.

Topics: Adult; Amenorrhea; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Breast Neoplasms; Early Diagnosis; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Primary Ovarian Insufficiency; Prospective Studies

Ovarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes.. We randomly assigned 257 premenopausal women with operable hormone-receptor-negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival.. At baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval [CI], 0.09 to 0.97; two-sided P=0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P=0.03); women in the goserelin group also had improved disease-free survival (P=0.04) and overall survival (P=0.05).. Although missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility. (Funded by the National Cancer Institute and others; POEMS/S0230 ClinicalTrials.gov number, NCT00068601.).

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Middle Aged; Pregnancy; Pregnancy Rate; Premenopause; Primary Ovarian Insufficiency; Regression Analysis

Premenopausal patients with breast cancer are at high risk of premature ovarian failure induced by systemic treatments, but no standard strategies for preventing this adverse effect are yet available.. To determine the effect of the temporary ovarian suppression obtained by administering the gonadotropin-releasing hormone analogue triptorelin during chemotherapy on the incidence of early menopause in young patients with breast cancer undergoing adjuvant or neoadjuvant chemotherapy.. The PROMISE-GIM6 (Prevention of Menopause Induced by Chemotherapy: A Study in Early Breast Cancer Patients-Gruppo Italiano Mammella 6) study, a parallel, randomized, open-label, phase 3 superiority trial, was conducted at 16 sites in Italy and enrolled 281 patients between October 2003 and January 2008. The patients were premenopausal women with stage I through III breast cancer who were candidates for adjuvant or neoadjuvant chemotherapy. Assuming a 60% rate of early menopause in the group treated with chemotherapy alone, it was estimated that 280 patients had to be enrolled to detect a 20% absolute reduction in early menopause in the group treated with chemotherapy plus triptorelin. The intention-to-treat analysis was performed by including all randomized patients and using imputed values for missing data.. Before beginning chemotherapy, patients were randomly allocated to receive chemotherapy alone or combined with triptorelin. Triptorelin was administered intramuscularly at a dose of 3.75 mg at least 1 week before the start of chemotherapy and then every 4 weeks for the duration of chemotherapy.. Incidence of early menopause (defined as no resumption of menstrual activity and postmenopausal levels of follicle-stimulating hormone and estradiol 1 year after the last cycle of chemotherapy).. The clinical and tumor characteristics of the 133 patients randomized to chemotherapy alone and the 148 patients randomized to chemotherapy plus triptorelin were similar. Twelve months after the last cycle of chemotherapy (last follow-up, August 18, 2009), the rate of early menopause was 25.9% in the chemotherapy-alone group and 8.9% in the chemotherapy plus triptorelin group, an absolute difference of -17% (95% confidence interval, -26% to -7.9%; P < .001). The odds ratio for treatment-related early menopause was 0.28 (95% confidence interval, 0.14 to 0.59; P < .001).. The use of triptorelin-induced temporary ovarian suppression during chemotherapy in premenopausal patients with early-stage breast cancer reduced the occurrence of chemotherapy-induced early menopause.. clinicaltrials.gov Identifier: NCT00311636.

Topics: Adult; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Goserelin; Humans; Infertility, Female; Injections, Intramuscular; Luteolytic Agents; Menopause; Methotrexate; Middle Aged; Neoadjuvant Therapy; Premenopause; Primary Ovarian Insufficiency; Tamoxifen; Triptorelin Pamoate

To determine whether GnRHa administration before and during combination chemotherapy for breast cancer could preserve posttreatment ovarian function in young women or not.. Prospective randomized controlled study.. Department of Obstetrics and Gynecology, Mansura University Hospital, Mansura, Egypt.. Eighty patients with unilateral adenocarcinoma of the breast and with no metastasis who had undergone modified radical mastectomy or breast-conserving surgery plus full axillary lymph node dissection were included in the study. Patients were assigned randomly to receive combined GnRHa and chemotherapy or chemotherapy alone. One woman in each group dropped out.. Return of spontaneous menstruation and ovulation. Hormonal changes (FSH, LH, E(2), P) during and after the course of treatment.. In the study group, 89.6% resumed menses and 69.2% resumed spontaneous ovulation within 3-8 months of termination of the GnRHa/chemotherapy cotreatment; 11.4% experienced hypergonadotrophic amenorrhoea and ovarian failure 8 months after treatment. In the control group (chemotherapy without GnRHa), 33.3% resumed menses and 25.6% resumed normal ovarian activity. The median FSH and LH concentrations, 6 months after completion of the GnRHa/chemotherapy cotreatment group, were significantly less than the control group. During the GnRHa/chemotherapy cotreatment the concentrations of FSH, LH, and P decreased to almost prepubertal levels. However, within 1-3 months after the last GnRHa injection, an increase in LH and FSH concentrations was detected, followed several weeks later in by an increase in P concentrations to within normal levels.. GnRHa administration before and during combination chemotherapy for breast cancer may preserve posttreatment ovarian function in women <40 years. Long-term studies are required.

Topics: Adenocarcinoma; Adult; Amenorrhea; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Drug Administration Schedule; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Luteinizing Hormone; Lymph Node Excision; Mastectomy; Menstruation; Ovary; Ovulation; Primary Ovarian Insufficiency; Progesterone; Prospective Studies; Time Factors; Treatment Outcome

The purpose of this randomized study was to examine if goserelin concomitant to CMF-chemotherapy as adjuvant treatment for premenopausal breast cancer, protects the ovaries from premature failure. A total of 285 premenopausal breast cancer patients, in a randomized adjuvant trial (Zoladex in premenopausal patients (ZIPP)), were assigned to a study on ovarian function. Node positive patients were assigned to CMF-(cyclophosphamide, methotrexate and 5-fluorouracil) chemotherapy in addition to endocrine therapy. All patients were randomly assigned to receive 2 years of goserelin, goserelin plus tamoxifen, tamoxifen alone or no endocrine treatment. We studied, if menses were affected in the treatment groups, up to 36 months after randomization. One year after completed CMF- and endocrine therapy, 36% of the women in the goserelin group reported menses, compared to 7% in the goserelin plus tamoxifen group, 13% in the tamoxifen group and 10% of the controls. Among women treated with goserelin, there was a statistically significant increase in the proportion of menstruating women, 1 year after completed treatment compared to at 24 months of treatment (P = 0.006), in contrast to all other treatment groups, who were unchanged or more often amenorrheic. In our study, there is some evidence of protective effect of goserelin on ovarian function in CMF treated women. This effect was not observed in the combined tamoxifen and goserelin treatment.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Female; Fluorouracil; Goserelin; Humans; Methotrexate; Middle Aged; Ovarian Function Tests; Ovary; Premenopause; Primary Ovarian Insufficiency; Tamoxifen

Ovarian failure and infertility following adjuvant chemotherapy for early breast cancer are major concerns for some young women. Techniques for oocyte harvesting are associated with delay in starting treatment, potentially undesirable estrogen stimulation and a relatively low success rate. We report an audit of our experience with the luteinising hormone-releasing hormone agonist, goserelin, to achieve transient ovarian suppression during chemotherapy as a means of preserving ovarian function.. Pre-menopausal women were offered goserelin 3.6 mg by subcutaneous injection every 28 days during chemotherapy, starting 0-14 days prior to treatment. The primary end-point was recovery of menstruation. Serum luteinising hormone, follicle stimulating hormone and oestradiol were measured at recovery of menstruation or at first year follow-up if amenorrhoea persisted. Subsequent pregnancies were recorded.. Fifty-one evaluable women were audited. Amenorrhoea occurred in all but one. All received combination anthracycline-containing chemotherapy regimens with a mean cumulative cyclophosphamide dose of 3.9 g/m(2). Forty-five (90%) recovered menstruation during the first year of follow-up; mean time to recovery 5 months. Eight pregnancies in 10 women attempting this so far.. Using goserelin concurrently with chemotherapy is associated with a high rate of ovarian function preservation.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Fertility; Goserelin; Humans; Ovary; Premenopause; Primary Ovarian Insufficiency

To explore the effects of a gonadotropin-releasing hormone (GnRH) agonist depot (goserelin acetate) in women with Hodgkin's disease receiving chemotherapy while taking a continuous combined estrogen-progestin preparation as add-back on the prevention of premature ovarian failure (POF).. In a prospective pilot study, five premenopausal women with Hodgkin's disease received a GnRH agonist depot plus add-back until polychemotherapy was completed. Every 4 weeks during treatment and thereafter, a hormonal profile (follicle-stimulating hormone (FSH), luteinizing hormone, 17beta-estradiol, progesterone and inhibin B) was measured until resumption of menstruation or the development of a hypergonadotropic state (2 x FSH > 30 U/l).. All patients reached prepubertal status during treatment. After discontinuation of goserelin acetate, one patient developed a hypergonadotropic state and four patients resumed menstruation. One of those patients became pregnant and delivered a healthy son.. The effectiveness of GnRH agonist plus add-back on the prevention of POF during polychemotherapy in women with Hodgkin's disease needs further elucidation in randomized controlled trials. The results of our pilot study are promising.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Delayed-Action Preparations; Drug Therapy, Combination; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Hodgkin Disease; Humans; Inhibins; Norethindrone; Norethindrone Acetate; Pilot Projects; Primary Ovarian Insufficiency; Prospective Studies; Treatment Outcome

Premature menopause is a serious long-term side effect of chemotherapy. We evaluated long-term pregnancy and disease-related outcomes for patients in S0230/POEMS, a study in premenopausal women with stage I-IIIA estrogen receptor-negative, progesterone receptor-negative breast cancer to be treated with cyclophosphamide-containing chemotherapy. Women were randomly assigned to standard chemotherapy with or without goserelin, a gonadotropin-releasing hormone agonist, and were stratified by age and chemotherapy regimen. All statistical tests were two-sided. Of 257 patients, 218 were eligible and evaluable (105 in the chemotherapy + goserelin arm and 113 in the chemotherapy arm). More patients in the chemotherapy + goserelin arm reported at least one pregnancy vs the chemotherapy arm (5-year cumulative incidence = 23.1%, 95% confidence interval [CI] = 15.3% to 31.9%; and 12.2%, 95% CI = 6.8% to 19.2%, respectively; odds ratio = 2.34; 95% CI = 1.07 to 5.11; P = .03). Randomization to goserelin + chemotherapy was associated with a nonstatistically significant improvement in disease-free survival (hazard ratio [HR] = 0.55; 95% CI = 0.27 to 1.10; P = .09) and overall survival (HR = 0.45; 95% CI = 0.19 to 1.04; P = .06). In this long-term analysis of POEMS/S0230, we found continued evidence that patients randomly assigned to receive goserelin + chemotherapy were not only more likely to avoid premature menopause, but were also more likely to become pregnant without adverse effect on disease-related outcomes.

Topics: Adult; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Female; Follow-Up Studies; Goserelin; Humans; Menopause, Premature; Middle Aged; Pregnancy; Pregnancy Outcome; Primary Ovarian Insufficiency; Receptors, Estrogen; Survival Rate

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Pregnancy; Primary Ovarian Insufficiency

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Pregnancy; Primary Ovarian Insufficiency

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Pregnancy; Primary Ovarian Insufficiency

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Pregnancy; Primary Ovarian Insufficiency

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Pregnancy; Primary Ovarian Insufficiency

To evaluate whether administration of goserelin, a gonadotropin-releasing hormone (GnRH) agonist, could prevent acute or chronic ovarian insufficiency from cyclophosphamide (CTX) administration to prepubertal mice.. Animal study.. University center.. C57BL/6J mouse strain.. Goserelin administered on day 13 of life, CTX on day 18 of life, euthanasia on day 20 (prepubertal), 56 (pubertal), or 92 of life (mature), measurements of body weight, length, uterine weight, serum antimüllerian hormone and follicle-stimulating hormone, and histologic assessment of ovarian follicles and femur growth, and apoptotic rates by TUNEL.. Assessment of prevention of ovarian insufficiency and defective bone elongation from CTX administration.. Prepubertal mice were randomly assigned to three groups: control (G1), CTX (G2), and goserelin + CTX (GG). A total of 63 mice were euthanized in the three groups. Body weight and length, and uterine weight did not differ among groups at any age. Ovarian size was not different in the three groups. There were fewer primordial and primary follicles/mm(2) in groups GG and G2 than in group G1 at all ages, but there was no difference between groups GG and G2. Corpora lutea/mm(2) were decreased in group GG versus G2. Femur length was statistically significantly greater in groups G1 and GG than group G2.. Goserelin administered to prepubertal mice during CTX treatment fosters maintenance of bone elongation but does not protect the ovaries from follicular depletion.

Topics: Animals; Antineoplastic Agents, Alkylating; Bone Development; Cyclophosphamide; Drug Interactions; Female; Goserelin; Mice; Mice, Inbred C57BL; Ovary; Primary Ovarian Insufficiency; Puberty; Treatment Outcome

Concurrent endocrine therapy with chemotherapy had a concern of potential antagonism. However, gonadotropin-releasing hormone (GnRH) agonist has been used concurrently with chemotherapy to prevent premature ovarian failure for young breast cancer patients. The aim of this study was to determine the impact of concurrent use of GnRH agonists on relapse-free and overall survival, and to establish the oncologic safety of ovarian protection with GnRH agonists.. Premenopausal women aged between 20 and 40 years who received adjuvant chemotherapy for breast cancer from January 2002 to April 2012 were classified into two groups; One treated with GnRH agonists for ovarian protection during chemotherapy, and the other without ovarian protection. A propensity score matching strategy was used to create matched sets of two groups with age, pathologic stage, hormone receptor, and Her2 status.. A total of 101 patients treated with concurrent GnRH agonist during chemotherapy were compared with 335 propensity score matched patients. Among them, 81.2% were younger than 35 years and 58.4% were hormone responsive. Survival analysis using stratified Cox regression showed that women treated with concurrent GnRH agonists had better recurrence-free survival (adjusted Hazard ratio 0.21, p = 0.009; unadjusted Hazard ratio 0.33, p = 0.034).. Ovarian protection using GnRH agonists can be safely considered for young women with breast cancer in terms of oncologic outcomes. Further studies are needed to assess the long-term outcomes of concurrent GnRH agonist use with chemotherapy.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Fertility Agents, Female; Goserelin; Humans; Leuprolide; Logistic Models; Mastectomy; Neoplasm Recurrence, Local; Primary Ovarian Insufficiency; Propensity Score; Retrospective Studies; Survival Analysis

Topics: Adenocarcinoma; Adult; Amenorrhea; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Drug Administration Schedule; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Luteinizing Hormone; Lymph Node Excision; Mastectomy; Menstruation; Ovary; Ovulation; Primary Ovarian Insufficiency; Progesterone; Prospective Studies; Time Factors; Treatment Outcome

Topics: Adenocarcinoma; Adult; Amenorrhea; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infertility, Female; Luteinizing Hormone; Lymph Node Excision; Mastectomy; Menstruation; Ovary; Ovulation; Primary Ovarian Insufficiency

Premenopausal women who develop ovarian failure after receiving chemotherapy are at a higher risk of rapid bone loss. Pharmacists have successfully implemented osteoporosis screening programmes in the general population and thus, assessment of breast cancer survivors for ovarian failure and osteopenia could represent a novel focus for oncology pharmacists. Therefore, we conducted a retrospective chart review to determine the adequacy of ovarian failure and osteoporosis assessment and management in premenopausal breast cancer survivors.. The charts of 20 women diagnosed with early stage breast cancer treated with cyclophosphamide over a 4.5-year timespan were included. Their median age was 36.7 years (range 29.8-41). The median cyclophosphamide cumulative dose was 9 g/m(2) (range 2.4-14.45), with a median duration of follow-up being 4.62 years. The assessment of ovarian failure mainly occurred by documenting menstrual periods, which has been questioned as a reliable method for assessing ovarian failure. Menses stopped while or shortly after receiving chemotherapy in 11 women. Prior to and during cyclophosphamide administration, osteoporosis screening or counselling was not documented for any patient. After completion of chemotherapy administration, eight patients were counselled regarding osteoporosis and seven women were screened for osteoporosis with a dual X-ray absorptimetry (DXA) scan. Five women had DXA scans indicative of osteopenia according to World Health Organization guidelines.. Improvements are needed in the documentation and potentially also the management of ovarian failure and osteoporosis in premenopausal breast cancer survivors receiving cyclophosphamide-based regimens. This represents a potential opportunity for pharmacists to manage long-term chemotherapy toxicity.

Topics: Absorptiometry, Photon; Administration, Oral; Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Breast Neoplasms; Calcium; Contraceptives, Oral; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Drug Utilization Review; Estradiol; Female; Fluorouracil; Follicle Stimulating Hormone; Follow-Up Studies; Goserelin; Humans; Medical Records; Menstruation Disturbances; Methotrexate; Osteoporosis, Postmenopausal; Premenopause; Primary Ovarian Insufficiency; Process Assessment, Health Care; Retrospective Studies; Survivors; Tamoxifen; Time Factors

Topics: Buserelin; Contraceptives, Oral; Dexamethasone; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Goserelin; Growth Hormone; Growth Substances; Humans; Infertility, Female; Leuprolide; Oocyte Donation; Pregnancy; Primary Ovarian Insufficiency