Use Of Gonadotropin-releasing Hormone Agonists Research Articles

Final analysis of the PROMISE-GIM6 phase III trial assessing GnRH agonist use during chemotherapy as a strategy to preserve ovarian function in premenopausal patients with early breast cancer.

516 Background: Current guidelines recommend GnRH agonist (GnRHa) use during chemotherapy (CT) as a strategy to reduce the risk of premature ovarian insufficiency (POI) in premenopausal patients with early breast cancer (EBC). However, no long-term safety data are available raising some concerns on concurrent use of GnRHa during CT in patients with hormone receptor-positive disease. In addition, there is no evidence on the protective role of this strategy in patients with germline BRCA mutations ( mBRCA). Here, we report the final analysis of the PROMISE-GIM6 phase III randomized study, the largest trial addressing the role of GnRHa use during CT in premenopausal EBC patients (Del Mastro et al, JAMA 2011 & Lambertini et al, JAMA 2015). Methods: From October 2003 to January 2008, 281 premenopausal patients aged 18 to 45 years with stage I-III EBC candidates for (neo)adjuvant CT were randomized to receive CT alone or combined with the GnRHa triptorelin. Primary endpoint was incidence of CT-induced POI (defined as amenorrhea and post-menopausal FSH/estradiol levels 1 year following CT). This final analysis reports on post-treatment pregnancies, disease-free survival (DFS) and overall survival (OS). An exploratory descriptive analysis in mBRCA patients is also reported. (ClinicalTrial.gov: NCT00311636) Results: Of the 281 randomized patients (CT+GnRHa arm = 148; CT alone arm = 133), 80% had hormone receptor-positive disease. At the time of this final analysis, 38 (13.5%) patients were lost to follow-up. Median follow-up was 12.4 years (IQR: 11.3-13.2 years). In the CT+GnRHa and CT alone arms, respectively, 9 (10-year cumulative incidence of pregnancy 6.5%, 95% CI 3.5%-12.3%) and 4 (10-year cumulative incidence of pregnancy 3.2%, 95% CI 1.2%-8.3%) patients had a post-treatment pregnancy (HR 2.14, 95% CI 0.66-6.92). No differences in 10-year DFS (72.4% in CT+GnRHa arm vs. 71.2% in CT alone arm: HR 1.16, 95% CI 0.76-1.77) nor in 10-year OS (82.0% in CT+GnRHa arm vs. 85.9% in CT alone arm: HR 1.17, 95% CI 0.67-2.03) were observed. There was no interaction between treatment effect and hormone receptor status. In patients with hormone receptor-positive disease, HR was 1.02 (95% CI 0.63-1.63) for DFS and 1.12 (95% CI 0.59-2.11) for OS. Out of 43 patients tested for BRCA, overall incidence of POI, irrespective of treatment arm, was 20% in mBRCA patients (n = 10) and 12% in patients without mBRCA (n = 33). In mBRCA patients, incidence of POI was 0% and 33% in the CT+GnRHa and CT alone arms, respectively. One post-treatment pregnancy was described in a patient with mBRCA1 in the CT alone arm. Conclusions: The final analysis of the PROMISE-GIM6 trial at a median follow-up of 12.4 years provides reassuring evidence on the safety of GnRHa use during CT as a strategy to preserve ovarian function in premenopausal patients with hormone receptor-positive EBC. Clinical trial information: NCT00311636.

Triggering change in stimulation protocols: a matter of oocyte maturation and beyond.

Since the birth of Louise Brown, in vitro fertilization (IVF) stimulation protocols have evolved significantly. One particular area of focus has been the process of final oocyte maturation, during which the oocyte gains competence to support fertilization and early embryonic development up to implantation. The field of human assisted reproductive technology (ART) is witnessing increased utilization of GnRH agonists (GnRHa) as trigger agents, in addition to or instead of the traditionally used human chorionic gonadotropin (hCG). Future translational studies will reveal whether oocyte developmental competence, as reflected in live birth outcomes, are not only non-inferior, but also superior with the use of GnRHa as a trigger for both nuclear and cytoplasmic oocyte maturation.

Gonadotropin-Releasing Hormone Agonist Induced Pituitary Apoplexy

Background: Gonadotropin-releasing hormone agonists (GnRHa), used in the treatment of prostate cancer (PC) and for reproductive purposes in women, have been implicated as the cause of pituitary apoplexy (PA), a potentially life-threatening condition. The pathophysiology of PA after GnRHa has not been completely elucidated. Proposed mechanisms include a stimulatory effect of GnRHa on pituitary adenoma cell metabolism, causing mismatched blood supply prompting hemorrhage or infarction. Prior documentation of PA associated with GnRHa has been scarce and limited to case reports. Methods: This is a detailed clinical case series of GnRH-induced PA from a single institution, obtained by a Research Patient Data Repository query. Clinical characteristics of the patients including demographics, detailed history, time interval between GnRHa and PA, physical exam, biochemical data, pituitary imaging and pathology were reviewed. Results: Seven cases were identified between 1990-2020; six men (aged 55 – 83 years) receiving treatment for PC and one woman (aged 22 years) receiving GnRHa for oocyte donation. All patients presented with headache; four within 48 hours of, one >1 month after, and one 5 months after, receiving GnRHa. One patient had insufficient data on time between GnRHa and PA. Most patients (86%) presented with nausea and vomiting. Other symptoms included ophthalmoplegia (43%), visual field defects (17%), and altered consciousness (29%). All patients had sellar masses and/or evidence of hemorrhage on MRI. Five patients underwent pituitary surgery while the others were managed medically. Of those who underwent surgical resection, 80% had positive histopathological staining for gonadotropins. Five patients with reliable hypothalamic-pituitary-adrenal (HPA) axis testing had impairment of this axis after PA; 40% recovered adrenal function. Central hypothyroidism occurred in 60% of whom 66% recovered. Hyponatremia occurred in 43%. Conclusions: Patients with gonadotrope-secreting adenomas may develop PA in response to GnRHa, more frequently in elderly men who are receiving GnRHa treatment for PC. This may be due to older age and higher prevalence of GnRHa use in this group. However, as demonstrated here and in prior case reports, women are not exonerated from this complication. Headache and adrenal insufficiency are typically present. HPA axis recovers in a subset. While most patients present <48 hours after GnRHa treatment, delayed presentations may occur. Therefore, a history of prior GnRHa exposure should be ascertained in patients presenting with PA. While the incidence of PA after GnRHa is low, this case series and prior case reports suggest that this serious potential complication should be recognized prior to treatment, especially in patients with known pituitary macroadenomas.

Prospective Study of Fertility Preservation in Young Women With Breast Cancer in Mexico.

Despite the risk of treatment-related infertility, implementation of fertility-preservation (FP) strategies among young patients with breast cancer is often suboptimal in resource-constrained settings such as Mexico. The "Joven & Fuerte: Program for Young Women With Breast Cancer" strives to enhance patient access to supportive care services, including FP measures through alliances with assisted-reproduction units and procurement of coverage of some of these strategies. This study describes patients from Joven & Fuerte who have preserved fertility, and assesses which characteristics were associated with the likelihood of undergoing FP. Women aged ≤40 years with recently diagnosed breast cancer were prospectively accrued. Sociodemographic and clinicopathologic data were collected from patient-reported and provider-recorded information at diagnosis and 1-year follow-up. Descriptive statistics, chi-square test, and simple logistic regression were used to compare patients who preserved fertility with those who did not. In total, 447 patients were included, among which 53 (12%) preserved fertility, representing 38% of the 140 women who desired future biologic children. Oocyte/embryo cryopreservation was the most frequently used method for FP (59%), followed by temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy (26%), and use of both GnRHa and oocyte/embryo cryopreservation (15%). Younger age, higher educational level, being employed, having private healthcare insurance, and having one or no children were associated with a significantly higher likelihood of preserving fertility. By facilitating referral and seeking funds and special discounts for underserved patients, supportive care programs for young women with breast cancer can play a crucial role on enhancing access to oncofertility services that would otherwise be prohibitive because of their high costs, particularly in resource-constrained settings. For these efforts to be successful and widely applied in the long term, sustained and extended governmental coverage of FP options for this young group is warranted.

The role of gonadotropin-releasing hormone agonists in female fertility preservation.

Advances in anticancer treatments have resulted in increasing survival rates among cancer patients. Accordingly, the quality of life after treatment, particularly the preservation of fertility, has gradually emerged as an essential consideration. Cryopreservation of embryos or unfertilized oocytes has been considered as the standard method of fertility preservation among young women facing gonadotoxic chemotherapy. Other methods, including ovarian suppression and ovarian tissue cryopreservation, have been considered experimental. Recent large-scale randomized controlled trials have demonstrated that temporary ovarian suppression using gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy is beneficial for preventing chemotherapy-induced premature ovarian insufficiency in breast cancer patients. It should also be emphasized that GnRHa use during chemotherapy does not replace established fertility preservation methods. All young women facing gonadotoxic chemotherapy should be counseled about and offered various options for fertility preservation, including both GnRHa use and cryopreservation of embryos, oocytes, and/or ovarian tissue.

Use of GnRH Agonist in Dogs Affected with Leishmaniosis.

Simple SummaryMost parasitic diseases, including Leishmania infection, often show more severe clinical signs in males than females. This is related to a different immune response, presumably related to testosterone activity. The present study aimed to evaluate the efficacy of a gonadotropin-releasing hormone GnRH agonist implant (deslorelin acetate) in association with meglumine antimoniate plus allopurinol in the treatment of dogs affected by Leishmania. Deslorelin acetate is a GnRH agonist, widely used for chemical reversible sterilization in male dogs, inducing testosterone suppression. Dogs treated with deslorelin show a significant decrease of clinical scores and serological test, suggesting a possible employ of GnRH agonist in the treatment of canine leishmaniosis.Sex-associated hormones such as testosterone have been demonstrated to modulate immune responses, which can result in different disease outcomes. The present study was aimed at evaluating the efficacy of a gonadotropin-releasing hormone GnRH agonist implant as deslorelin acetate in association with meglumine antimoniate plus allopurinol in dogs with canine leishmaniosis (CanL). Twenty-two dogs with CanL confirmed by clinical findings and laboratory tests were included in the study. Dogs were randomized into two groups. A control group (CTR, n = 12) was treated with meglumine antimoniate 50 mg/kg SC q 12 h for 28 days plus allopurinol at 10 mg/kg PO q 12 h for the whole study period (six months). An experimental group was treated with allopurinol and meglumine antimoniate, plus an implant of 4.7 mg deslorelin acetate (DES, n = 10). The animals were observed for three months, during which clinical evaluation, indirect fluorescent antibody test (IFAT) titre and testosterone assay were performed on time at day (D)0, 90 and 180. A significantly lower clinical score was recorded in DES than in CTR (p < 0.01) at D90 and D180 (p < 0.01). After 180 days of treatment (D180), a significant reduction of mean levels of IFAT was observed in the DES group (p = 0.03). A highly significant reduction of testosterone (p = 0.01) was observed in the DES group during the study. No statistical correlation between clinical scores, IFAT titres and testosterone within two groups was observed. Data suggested that the agonist of GnRH may be useful in the treatment of CanL.

Risk of dementia and Parkinson's disease in patients treated with androgen deprivation therapy using gonadotropin-releasing hormone agonist for prostate cancer: A nationwide population-based cohort study.

Recent studies reported conflicting results on the association of androgen deprivation therapy (ADT) with dementia and Parkinson's disease in patients with prostate cancer (Pca). Therefore, this study aimed to investigate whether use of gonadotropin-releasing hormone agonist (GnRHa) increases the risk of both diseases. A nationwide population cohort study was conducted involving newly diagnosed patients with Pca %who started ADT with GnRHa (GnRHa users, n = 3,201) and control (nonusers, n = 4,123) between January 1, 2012, and December 31, 2016, using data from the National Health Insurance Service. To validate the result, a hospital cohort of patients with Pca consisting of GnRHa users (n = 205) and nonusers (n = 479) in a tertiary referral center from January 1, 2006 to December 31, 2016, were also analyzed. Traditional and propensity score-matched Cox proportional hazards models were used to estimate the effects of ADT on the risk of dementia and Parkinson's disease. In univariable analysis, risk of dementia was associated with GnRHa use in both nationwide and hospital validation cohort (hazard ratio [HR], 1.696; 95% CI, 1.425-2.019, and HR, 1.352; 95% CI, 1.089-1.987, respectively). In a nationwide cohort, ADT was not associated with dementia in both traditional and propensity score-matched multivariable analysis, whereas in a hospital validation cohort, ADT was associated with dementia only in unmatched analysis (HR, 1.203; 95% CI, 1.021-1.859) but not in propensity score-matched analysis. ADT was not associated with Parkinson's disease in either nationwide and validation cohorts. This population-based study suggests that the association between GnRHa use as ADT and increased risk of dementia or Parkinson's disease is not clear, which was also verified in a hospital validation cohort.

Outcome of GnRH antagonist ICSI cycles triggered by GnRH agonist plus Recombinant hCG versus triggered with Recombinant hCG alone in fresh autologous ICSI cycle

To explore whether dual triggering for final oocyte maturation using a low dose of recombinant human chorionic gonadotropin (hCG) plus gonadotropin-releasing hormone agonist (GnRH-a) is as effective as the standard dose of recombinant hCG triggering alone in term of a total number of retrieved oocytes, fertilization and pregnancy rate in fresh autologous antagonist intracytoplasmic sperm injection (ICSI) cycles. 80 infertile women undergoing ICSI, aged ˂ 40 years, 18˂ Body mass index ˂30 Kg/m2 included in fresh autologous antagonist ICSI cycles. 40 women received a Standard dose of recombinant hCG (500 µg) alone and 40 women received GnRH-a (0.2 mg triptorelin plus 250 µg recombinant hCG) were used for final oocytes maturation. This study was conducted at the High Institute for Infertility Diagnosis and Assisted Reproductive Techniques, Al Nahrain University. The mean total number of retrieved oocytes, fertilization, and pregnancy rate were measured. The mean total oocyte number being statistically higher in the dual trigger group. The mean number of fertilized oocytes and clinical pregnancy rates was higher in the dual trigger group than in the control group, but the difference showed borderline statistical significance. Furthermore, fertilization rates show no statistical difference between the control group and the dual trigger group. Results of the study confirm that dual triggers show favorable improvement in fresh autologous antagonist ICSI cycles with the use of GnRH agonists plus hCG compared with hCG alone for triggering of final oocyte maturation.

Systematic Review: Puberty suppression with GnRH analogues in adolescents with gender incongruity.

Gender incongruence is defined as disharmony between assigned gender and gender identity. Several interventions are liable in this case including genital affirming surgery among other surgical interventions such as harmonization, and also the use of gonadotropin-releasing hormone agonists (GnRHa) for gonadal shielding. This aids in preventing the development of secondary sexual characteristics related to the genetic sex. Systematically review the treatment of gender incongruity with GnRHa analogues. The data source of this research is from Pubmed-Medline and Embase. Articles published between 2009 and 2019 which studied transgender adolescents treated with GnRHa were carefully selected. Were extracted: design, sample size, study context, targeted subjects of intervention, outcome measures, and results. Eleven studies were included. The use of GnRHa seems to be well tolerated by the studied population. When started in pubertal transition, it was associated with a more distinct resemblance to body shape than to the affirmed sex. In addition to preventing the irreversible phenotypic changes that occur in cross-hormonal therapy, the use of GnRHa can equally contribute to the mental health of these adolescents. There are few consistent studies on the use of GnRHa for gender incongruence. As the population of transgender children and adolescents grows, they acquire knowledge and greater access to the various forms and stages of treatment for sex reassignment. The medical community needs to be adequately prepared to better serve this population and offer the safest resources available.

Type of Androgen Deprivation Therapy and Risk of Dementia Among Patients With Prostate Cancer in Taiwan

It remains unclear whether androgen deprivation therapy (ADT) is associated with subsequent dementia risk in patients with prostate cancer. There are limited data regarding dementia risk across ADT types. To examine the association between all-cause dementia, including Alzheimer disease (AD), and different ADT types in patients with prostate cancer. This cohort study used linked data from the Taiwan National Cancer Registry, the National Health Insurance Research Database, and the Taiwan National Death Registry. A cohort of 23 651 patients with newly diagnosed prostate cancer between January 1, 2008, and December 31, 2015, was identified and followed up from 1 year after diagnosis until December 31, 2017. Data analysis was performed between January 2019 and May 2020. Patients who received and did not receive ADT, including gonadotropin-releasing hormone (GnRH) agonists, orchiectomy, or antiandrogen monotherapy. The primary outcomes were all-cause dementia or AD. Stabilized inverse probability of treatment weighting was used to balance baseline covariates. The association between dementia and various ADT types was examined using the Cox proportional hazards model. Furthermore, a multivariate Cox proportional model with age as the time scale was conducted for complementary comparison. In the cohort of 23 651 male patients (median [interquartile range] age, 73 [66-79] years), 6904 (29.2%) did not receive ADT, 11 817 (50.0%) received GnRH agonists, 876 (3.7%) received orchiectomy, and 4054 (17.1%) received antiandrogen monotherapy. Overall, 1525 patients were diagnosed with incident dementia (1.72 per 100 person-years) during a median (interquartile range) follow-up of 3.46 (1.92-5.51) years. Compared with those who did not receive ADT, those using antiandrogen monotherapy showed an increased risk of dementia (weighted hazard ratio [HR], 1.34; 95% CI, 1.16-1.55) and AD (weighted HR, 1.52; 95% CI, 1.13-2.04). The risk of dementia was similar between GnRH agonist use or orchiectomy and no ADT use (GnRH agonist: weighted HR, 1.13; 95% CI, 1.00-1.28; orchiectomy: 1.00; 95% CI, 0.74-1.37). Several sensitivity analyses revealed consistent findings for both outcomes. In this study, the use of antiandrogen monotherapy was associated with increased risk of dementia or AD, while GnRH agonist use and orchiectomy had no significant difference compared with patients who did not receive ADT. Further prospective studies are warranted to confirm these findings.

Feasibility and efficacy of gonadotropin-releasing hormone agonists for the prevention of chemotherapy-induced ovarian insufficiency in patients with malignant ovarian germ cell tumours (KGOG 3048R)

BackgroundThis study assessed the effects of gonadotropin-releasing hormone agonists (GnRHa) on the prevention of chemotherapy-induced ovarian insufficiency among young patients with malignant ovarian germ cell tumour (MOGCT) receiving chemotherapy. MethodsThis multicentre, retrospective study was conducted at 15 sites affiliated with the Korean Gynecologic Oncology Group and enrolled 354 patients between January 1995 and September 2018. Among them, 227 patients were included in this study and divided into two groups according to the use of GnRHa during chemotherapy (GnRHa versus no GnRHa groups). The primary objective was to compare the rates of menstrual resumption between the two groups. We also assessed the clinical determinants affecting menstrual resumption among the study groups. ResultsThere were no significant differences between the GnRHa (n = 63) and no GnRHa (n = 164) groups regarding age at diagnosis, parity, ethnicity, age at menarche, body mass index, International Federation of Gynecology and Obstetrics stage, mode of surgery and surgery type. The rate of menstrual resumption after chemotherapy was 100% (63 of 63) in the GnRHa group and 90.9% (149 of 164) in the no GnRHa group (p = 0.013). The mean periods from last chemotherapy to menstrual resumption were 7.4 and 7.3 months in the GnRHa and no GnRHa groups, respectively. GnRHa co-administration during chemotherapy reduced the likelihood of amenorrhoea after chemotherapy, although statistical significance was not confirmed in the univariate analysis (odds ratio: 0.276; 95% confidence interval, 0.004–1.317; p = 0.077). ConclusionTemporary ovarian suppression with GnRHa during chemotherapy does not significantly increase the chances of menstrual resumption in young patients with MOGCT.

The Risk of Cardiovascular Disease in Prostate Cancer Patients Receiving Androgen Deprivation Therapies.

Androgen deprivation therapy (ADT), with a proven role in prostate cancer management, has been associated with various cardiovascular diseases. However, few studies have investigated these associations by type of ADT, particularly for newer ADTs such as the gonadotropin-releasing hormone (GnRH) antagonist degarelix. We investigated the risk of cardiovascular disease by type of ADT in a real-world setting. We identified men newly diagnosed with prostate cancer, from 2009 to 2015, from the Scottish Cancer Registry and ADTs from the nationwide Prescribing Information System. Cardiovascular events were based upon hospitalization (from hospital records) or death from cardiovascular disease (from death records). We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular events with time-varying ADT exposure, comparing ADT users with untreated patients, after adjusting for potential confounders, including prior cardiovascular disease. The cohort contained 20,216 prostate cancer patients, followed for 73,570 person-years, during which there were 3,853 cardiovascular events. ADT was associated with a 30% increase in cardiovascular events (adjusted HR = 1.3; 95% CI = 1.2, 1.4). This reflected increases in cardiovascular events associated with GnRH agonists (adjusted HR = 1.3; 95% CI = 1.2, 1.4), degarelix (adjusted HR = 1.5; 95% CI = 1.2, 1.9), but not bicalutamide monotherapy (adjusted HR = 1.0; 95% CI = 0.82, 1.3). There were increased risks of cardiovascular disease with the use of GnRH agonists and degarelix, but not with bicalutamide monotherapy. This is the first study to observe increased cardiovascular risks with degarelix, but the cause of this association is unclear and merits further investigation.

Abstract #804543: lymphocytic hypophysitis presenting following GNRH agonist use

Abstract #804543: lymphocytic hypophysitis presenting following GNRH agonist use

The effect of GnRH Agonist use in Frozen Cycles on pregnancy results

Aim: The aim of this study was to investigate the effect of GnRH agonist use on pregnancy and abortion in the preparation of the endometrium in autologous frozen embryo transfers performed with hormone replacement therapy.Material and Methods: All autologous artificial Frozen – thawed embryo transfer (FET) between 1/2016 and 1/2018 were evaluated retrospectively in order to investigate the effect of GnRH agonist use on pregnancy and abortion rates in frozen embryo FET cycles.Results: 226 patients were included in the study. The mean age of the patients included in the study was 30.76 ± 4.72 years. Of the patients, 144 (63.7%) were diagnosed with unexplained infertility, 20 (8.8) with low ovarian reserve, and 62 (27.4) with male factor. No significant difference was found in terms of pregnancy result and abortion in patients using (N: 22) and not using GnRH agonist (p = 0.212, 1,000).Conclusion: No significant effect of GnRH agonist use on pregnancy rate or abortion was detected in autologous frozen embryo transfers performed with HRT. The prospective studies involving larger patient populations are needed to clarify this subject..

Gonadotropin-releasing hormone agonists, anti-androgens and the risk of cardio-cerebrovascular disease in prostate cancer patients: an asian population-based observational study

Purpose: To conduct a population-based study to determine whether the use of GnRH agonist and antiandrogens are associated with an increased risk of cardio-cerebrovascular disease (CCVD) in Asian patients with prostate cancer using the National Health Insurance Service-Elderly Cohort Database (NHIS-ECD).Materials and Methods: We included a total of 2,413 men aged 60 years or older with prostate cancer between January 2003 and December 2008. Outcomes of interest included the first occurrence of cardiovascular events [acute myocardial infarction (AMI), ischemic heart disease (IHD)] and cerebrovascular events [ischemic stroke (IS), and cerebrovascular disease (CVD)].Results: The 5-year AMI-free rates of patients diagnosed with prostate cancer and treated with GnRH agonists, antiandrogens alone, or androgen deprivation therapy (ADT)-naïve interventions were 97.0%, 96.5%, and 98.3%, respectively, while the 5-year IHD-free rates were 93.2%, 92.3%, and 94.5%, respectively. Exposure to GnRH agonists or antiandrogen regimens did not significantly increase the risk of AMI or IHD compared to ADT-naïve treatment in multivariate Cox proportional-hazards models after adjusting for other covariates. Five-year IS-free rates of patients exposed to GnRH agonists, antiandrogens alone, and those with ADT-naïve prostate cancer were 94.8%, 94.7%, and 95.5%, respectively, while the five-year CVD-free rates were 92.9%, 93.3%, and 94.6%, respectively. Cox proportional-hazards models also failed to show that men who received GnRH agonist or antiandrogen treatment alone carried a significantly increased risk for IS or CVD compared to ADT-naïve patients.Conclusions: The current study based on Asian population suggests that treatment with neither GnRH agonist nor antiandrogens increases the risk of cardio-cerebrovascular disease compared to patients with ADT-naïve prostate cancer.

The Use of Gonadotropin-Releasing Hormone Agonist Does Not Affect the Development of Cardiovascular Disease in Prostate Cancer Patients: a Nationwide Population-Based Cohort Study.

BackgroundThe objective of this study was to investigate whether androgen deprivation therapy (ADT) with gonadotropin-releasing hormone agonist (GnRHa) in prostate cancer (Pca) patients is associated with cardiovascular disease in the cohort based from the entire Korean population.MethodsUsing the Korean National Health Insurance database, we conducted an observational study of 579,377 men who sought treatment for Pca between January 1, 2012 and December 31, 2016. After excluding patients with previously diagnosed cardiovascular disease or who had undergone chemotherapy, we extracted the data from 2,053 patients who started GnRHa (GnRHa users) and 2,654 men who were newly diagnosed with Pca (GnRHa nonusers) between July 1, 2012, and December 31, 2012, with follow-up through December 31, 2016. The primary outcomes were cerebrovascular attack (CVA) and ischemic heart disease (IHD).ResultsGnRHa users were older, were more likely to reside in rural areas, had lower socioeconomic status, and had more comorbidities than nonusers (all P < 0.050). Although GnRHa users had an increased incidence of CVA and IHD (P = 0.013 and 0.048, respectively) in univariate analysis, GnRHa use was not associated with the outcomes in multivariate analysis. Furthermore, the cumulative duration of ADT was not associated with the outcomes whereas the associations between age at diagnosis with all diseases were significant.ConclusionOur complete enumeration of the Korean Pca population shows that ADT is not associated with increased risks of cardiovascular disease.

Oncofertilité et cancer du sein

Over the past decades, progresses in oncology have improved the recovery rates after numerous malignant diseases, including breast cancer, that strike young adults in childbearing age. Quality of life of young cancer survivors has become a major issue. However, anticancer therapies can have a detrimental impact on fertility. It is now well-established that all patients should receive information about the fertility risks associated with their cancer treatment and the fertility preservation options available. These techniques aim to limit the negative impact of chemotherapy on the ovaries or to preserve gametes before treatment. Currently, oocyte or embryo freezing after controlled ovarian hyperstimulation represents the most effective method for preserving female fertility. Over the past years innovative protocols of ovarian stimulation have been developed to enable breast cancer patients to undergo oocyte or embryo cryopreservation irrespective of the phase of the cycle or without exogenous follicle-stimulating hormone related increase in serum estradiol levels. When controlled ovarian hyperstimualtion cannot be implemented, other techniques such as cryopreservation of ovarian cortex, in vitro maturation or the use of GnRH agonists may be proposed. However, it is important to inform patients that all these fertility preservation techniques do not represent a guarantee of pregnancy.

Retrospective SHI (Statutory Health Insurances) real-world study on initial GnRH antagonist and agonist therapy for advanced prostate cancer: prescription patterns and hospital costs in Germany

Androgen deprivation therapy (ADT) plays a pivotal role in the treatment of advanced or metastasised prostate cancer (PCa). The aim of this health services research was to compare real-world data on the initial use of different GnRH agonists and antagonists (GnRHa) with regard to prescription patterns, hospitalisation rates and costs. Anonymised claims data from > 70 German health insurance funds between 2010 and 2015 (n = 4 205 227) were analysed (1 year pre-observation period, 1 index quarter with initial GnRHa prescription, ≥ 2 years of follow-up (FU)). The study population included 2382 PCa patients (mean age 75 years). Leuprolide (Leu) was prescribed most frequently (56.6 %). At initial GnRHa administration, 70 % of patients neither had lymph node nor distant metastases. Around 11.2 % of all patients stopped GnRHa treatment after the first prescription, 17.6 % switched their initial therapy to another substance after a mean of 457 days (median: 399 days); in the hybrid (hyb) group 100 days earlier on average than in the agonist group (p = 0.016). The prevalence ranking of the most common comorbidities was consistent over time: hypertension, hyperlipidaemia, cardiovascular disease (CVD) and diabetes. The prevalence of hypertension increased significantly in the agonist group (16.4 %) compared with the antagonist (6.9 %, p = 0.022) and hyb group (11.6 %, p = 0.006). With regard to CVD, there were no significant differences in the relative growth rate between the 3 combined therapy classes. In total, 23.9 % of all patients died within the 3-year FU. The mortality rate was lowest for triptorelin (Trp, 22.1 %) and highest for goserelin (Gos, 29.4 %, n.s.). In the index quarter, 26.4 % of patients had at least one inpatient hospitalisation [min-max: Trp 22.4 %; Gos 30.3 %], with an average length of hospital stay/patient of 3 days [Trp 2.4; Gos 4.5]. The annual hospitalisation rate was between 36.2 and 40.7 %, the average length of hospital stay in the entire FU was between 17.6 (Trp) and 20.8 days (hyb). The average hospital costs in the index quarter were approx. EUR 1200 [Trp 988; Gos 1803] and per FU year approx. EUR 3000. In the Trp cohort, total costs (index quarter + 3 years) were more than EUR 1000 below the average costs of EUR 9476 [Trp 8116; Leu 9779; n.s.]. This comparative retrospective analysis provides real-world information on initial GnRHa treatment for advanced prostate cancer, revealing differences in treatment patterns, hospitalisation rates and hospital costs in Germany.

1038P - The feasibility and efficacy of gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian insufficiency in patient with malignant ovarian germ cell tumours

BackgroundTo assess the effects of a gonadotropin-releasing hormone agonists (GnRHa) administration in young patients with malignant ovarian germ cell tumour (MOGCT) during chemotherapy on the prevention of chemotherapy-induced ovarian insufficiency. MethodsThis multicenter, retrospective study was conducted at fifteen sites in Korea and enrolled 354 patients between January 1995 and January 2018. Among them 227 patients were included in this study according the inclusion criteria: 1) patients diagnosed as pathologically malignant germ cell tumours of the ovaries, 2) who have preserved the uterus and at least one ovary, 3) who received postoperative chemotherapy at least 3 cycles, 4) age at diagnosis, after menarche ∼ < 40 years old, 5) available clinical information on menstrual resumption. Patients were divided into two groups according to the use of GnRHa during chemotherapy (GnRHa group and non-GnRHa group) and compared the incidence of early menopause. ResultsThere was no difference in age, parity, menarche, stage, and type of operation (unilateral or bi-lateral adnexal surgery) among the two groups. The distribution of histology and types of chemotherapy drugs were different. After the end of chemotherapy, the resumption of menstruation was 100% in GnRHa group and 91% in non-GnRHa group (p=0.0132). The univariate analysis of the factors affecting menstrual resumption showed that the use of GnRHa during chemotherapy was statistically significant difference (OR, 0.00 (0∼0.69;95% CI, p=0.013). ConclusionsThe present findings provide evidence for the efficacy of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced ovarian insufficiency and potentially improve fertility in young patients with MOGCT. Legal entity responsible for the studyThe author. FundingCHA Bundang Medical Centre. DisclosureThe author has declared no conflicts of interest.

GnRH agonist use for fertility preservation despite gonadotoxic chemotherapy

GnRH agonist use for fertility preservation despite gonadotoxic chemotherapy