gonadotropin-releasing hormone agonist (GnRHa) in prostate cancer (Pca) patients is associated with cardiovascular disease in the cohort based from the entire Korean population.METHODS: Using 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).RESULTS: GnRHa 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.CONCLUSION: Our complete enumeration of the Korean Pca population shows that ADT is not associated with increased risks of cardiovascular disease.]]>
Antineoplastic Agents ; Cardiovascular Diseases ; Cohort Studies ; Comorbidity ; Diagnosis ; Drug Therapy ; Follow-Up Studies ; Gonadotropin-Releasing Hormone ; Humans ; Incidence ; Male ; Morinda ; Multivariate Analysis ; Myocardial Ischemia ; National Health Programs ; Observational Study ; Passive Cutaneous Anaphylaxis ; Prostate ; Prostatic Neoplasms ; Social Class

PURPOSE: Although combining aromatase inhibitors (AI) with gonadotropin-releasing hormone agonists (GnRHa) is becoming more common, it is still not clear if GnRHa is as effective as bilateral salpingo-oophorectomy (BSO). MATERIALS AND METHODS: We retrospectively analyzed data of 66 premenopausal patients with hormone receptor– positive, human epidermal growth factor receptor 2–negative recurrent and metastatic breast cancer who had been treated with AIs in combination with GnRHa or BSO between 2002 and 2015. RESULTS: The median patient age was 44 years. Overall, 24 (36%) received BSO and 42 (64%) received GnRHa. The clinical benefit rate was higher in the BSO group than in the GnRHa group (88% vs. 69%, p=0.092). Median progression-free survival (PFS) was longer in the BSO group, although statistical significance was not reached (17.2 months vs. 13.3 months, p=0.245). When propensity score matching was performed, the median PFS was 17.2 months for the BSO group and 8.2 months for the GnRHa group (p=0.137). Multivariate analyses revealed that the luminal B subtype (hazard ratio, 1.67; 95% confidence interval [CI], 1.08 to 2.60; p=0.022) and later-line treatment (≥ third line vs. first line; hazard ratio, 3.24; 95% CI, 1.59 to 6.59; p=0.001) were independent predictive factors for a shorter PFS. Incomplete ovarian suppression was observed in a subset of GnRHa-treated patients whose disease showed progression, with E2 levels higher than 21 pg/mL. CONCLUSION: Both BSO and GnRHa were found to be effective in our AI-treated premenopausal metastatic breast cancer patient cohort. However, further studies in larger populations are needed to determine if BSO is superior to GnRHa.
Aromatase Inhibitors* ; Aromatase* ; Breast Neoplasms* ; Breast* ; Cohort Studies ; Disease-Free Survival ; Female ; Gonadotropin-Releasing Hormone* ; Humans ; Multivariate Analysis ; Ovariectomy ; Phenobarbital ; Premenopause ; Propensity Score ; Receptor, Epidermal Growth Factor ; Retrospective Studies

The proper development and coordination of the hypothalamic-pituitary-gonadal (HPG) axis are essential for normal reproductive competence. The key factor that regulates the function of the HPG axis is gonadotrophin-releasing hormone (GnRH). Timely release of GnRH is critical for the onset of puberty and subsequent sexual maturation. Misregulation in this system can result in delayed or absent puberty and infertility. Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are genetic disorders that are rooted in a GnRH deficiency but often accompanied by a variety of non-reproductive phenotypes such as the loss of the sense of smell and defects of the skeleton, eye, ear, kidney, and heart. Recent progress in DNA sequencing technology has produced a wealth of information regarding the genetic makeup of CHH and KS patients and revealed the resilient yet complex nature of the human reproductive neuroendocrine system. Further research on the molecular basis of the disease and the diverse signal pathways involved will aid in improving the diagnosis, treatment, and management of CHH and KS patients as well as in developing more precise genetic screening and counseling regime.
Adolescent ; Counseling ; Diagnosis ; Ear ; Genetic Testing ; Gonadotropin-Releasing Hormone ; Gonadotropins ; Heart ; Humans ; Hypogonadism* ; Infertility ; Kallmann Syndrome* ; Kidney ; Mental Competency ; Neurosecretory Systems ; Olfaction Disorders ; Phenotype ; Puberty ; Sequence Analysis, DNA ; Sexual Maturation ; Signal Transduction ; Skeleton ; Smell ; Axis, Cervical Vertebra

OBJECTIVETo explore the effects of obesity on the peak level of luteinizing hormone (LH) in the gonadotropin-releasing hormone (GnRH) agonist test and obesity-related hormones in girls with central precocious puberty (CPP).

METHODSThree hundred and thirty-three girls with CPP who underwent the GnRH agonist test between 2012 and 2014 were classified into three groups: normal weight (n=123), overweight (n=108), and obesity (n=102), according to body mass index (BMI). The sexual development indices were compared between the three groups. Twenty girls were randomly selected from each group for evaluation of the serum levels of leptin, sex hormone binding globulin (SHBG), neurokinin B, and kisspeptin. The correlation of BMI with the levels of various hormones was assessed using Pearson correlation analysis.

RESULTSThere was no significant difference in mean age at diagnosis between the three groups; however, the bone age was significantly higher in the overweight and obesity groups than in the normal weight group (P<0.05). The peak level of LH in the GnRH agonist test and SHBG level in the normal weight group were significantly higher than those in the overweight and the obesity groups, while the serum levels of leptin and neurokinin B were significantly lower in the normal weight group than in the overweight and the obesity groups (P<0.05). BMI was negatively correlated with the peak level of LH in the GnRH agonist test and SHBG level (P<0.05), and positively correlated with the levels of leptin and neurokinin B (P<0.05).

CONCLUSIONSThe effects of BMI on the result of the GnRH agonist test and levels of obesity-related hormones should be taken into account in girls with precocious puberty.

Body Mass Index ; Child ; Female ; Gonadotropin-Releasing Hormone ; agonists ; Humans ; Leptin ; blood ; Luteinizing Hormone ; blood ; Neurokinin B ; blood ; Obesity ; blood ; Puberty, Precocious ; blood ; Sex Hormone-Binding Globulin ; analysis

Sometimes, the clinical findings and the results of the gonadotropin-releasing hormone (GnRH) stimulation test are inconsistent in girls with early breast development and bone age advancement. We aimed to investigate the factors predicting positive results of the GnRH stimulation test in girls with suspected central precocious puberty (CPP). We reviewed the records of 574 girls who developed breast budding before the age of 8 yr and underwent the GnRH stimulation test under the age of 9 yr. Positive results of the GnRH stimulated peak luteinizing hormone (LH) level were defined as 5 IU/L and over. Girls with the initial positive results (n = 375) showed accelerated growth, advanced bone age and higher serum basal LH, follicle-stimulating hormone, and estradiol levels, compared to those with the initial negative results (n = 199). Girls with the follow-up positive results (n = 64) showed accelerated growth and advanced bone age, compared to those with the follow-up negative results. In the binary logistic regression, the growth velocity ratio was the most significant predictive factor of positive results. We suggest that the rapid growth velocity is the most useful predictive factor for positive results in the GnRH stimulation test in girls with suspected precocious puberty.
Age Determination by Skeleton ; Breast/growth & development ; Child ; Estradiol/blood ; Female ; Follicle Stimulating Hormone/blood ; Follow-Up Studies ; Gonadotropin-Releasing Hormone/*analysis ; Humans ; Logistic Models ; Luteinizing Hormone/blood ; Predictive Value of Tests ; Puberty, Precocious/*diagnosis ; ROC Curve ; Retrospective Studies

OBJECTIVE: This study was designed to assess the actual circumstances of post-operative anemia and associating factors, during the laparoscopic myomectomy. METHODS: A retrospective chart review of 172 patients who underwent laparoscopic myomectomy from 2008 to 2009 was performed. Characteristics of patients (age, parity, body mass index, and preoperative gonadotropin releasing hormone agonists injection) and fibroids (the largest diameter, number, width, type and location), and surgical outcomes (operating time, pre- and post-operative hemoglobin level, blood loss, hospital stay, and complications, including transfusion) were retrieved. RESULTS: One patient (0.6 %) required transfusion and significant hemoglobin change (> or =2.0 g/dL) occurred in 45 patients, after laparoscopic myomectomy. The largest diameter, width, type, and location of fibroids, and pre-operative gonadotropin releasing hormone agonist injection were not associated with the hemoglobin change (p=0.193, 0.172, 0.764, 0.741, and 0.954 respectively). Multivariate analysis revealed that nulliparity (p=0.195, 95% confidence interval (CI): 0.286-1.291) was not a risk factor, but long operating time (> or =90 min; p=0.048, 95% CI: 1.008-5.054) and multiple myoma (> or =3 in number; p=0.009, 95% CI: 1.320-6.717) were independent risk factors for significant hemoglobin change. CONCLUSION: In our data, symptomatic anemia after laparoscopic myomectomy was uncommon. In addition, the only useful predictive factor for hemoglobin change during the laparoscopic myomectomy was a multiplicity of myoma.
Anemia ; Body Mass Index ; Female ; Gonadotropin-Releasing Hormone ; Hemoglobins ; Humans ; Leiomyoma ; Length of Stay ; Multivariate Analysis ; Myoma ; Parity ; Retrospective Studies ; Risk Factors

PURPOSE: The aim of this study was to investigate the influence of body mass index (BMI) on the level of peak luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) stimulation in girls with central precocious puberty (CPP) and advanced puberty (AP). METHODS: This study conducted a retrospective review of the medical records of 113 girls (7 to 9 years old; 24 CPP, 89 AP) who underwent a GnRH stimulation test. The following parameters were evaluated: chronologic age (CA), bone age (BA), the difference between BA and CA (BA-CA), height, weight, BMI, and the levels of basal LH, peak LH, basal follicle stimulating hormone (FSH), peak FSH, and basal estradiol. RESULTS: The peak LH level was negatively correlated with weight-standard deviation score (SDS) and BMI-SDS; furthermore, the peak LH level was positively correlated with both basal and peak FSH levels. Using multivariate analysis, BMI-SDS was found to be a significant factor in predicting peak LH levels after GnRH administration. When the subjects were divided into four groups by quartile of peak LH level, the mean BMI-SDS of the highest LH group was significantly lower than the mean BMI-SDS of the lowest LH group. CONCLUSION: LH levels rise after GnRH administration is blunted in precocious and advanced pubertal girls with high BMI. The impact of BMI on the GnRH stimulation test should be considered when evaluating sexual precocity in girls.
Body Mass Index ; Follicle Stimulating Hormone ; Gonadotropin-Releasing Hormone ; Lutein ; Luteinizing Hormone ; Medical Records ; Multivariate Analysis ; Piperazines ; Puberty ; Puberty, Precocious ; Retrospective Studies

The increased survival of patients with breast cancer has given rise to other problems associated with the complications of chemotherapy. One major complication is premature ovarian failure, an especially harmful outcome for women of reproductive age. This study was performed to evaluate the efficacy of GnRH agonist (GnRHa) treatment on protecting ovarian function in young breast cancer patients (30.59+/-5.1 yr) receiving chemotherapy after surgery. Twenty-two women were enrolled and given subcutaneous injections of leuprolide acetate (3.75 mg) every 4 weeks during chemotherapy. Follow-up laboratory tests (luteinizing hormone [LH], follicle stimulating hormone [FSH], and estradiol) were performed 1, 3, and 6 months after chemotherapy. Menstruation patterns and clinical symptoms were followed up for a mean duration of 35.6+/-1.7 months. FSH and LH levels were normal in all patients 6 months after completing chemotherapy (8.0+/-5.3, 4.4+/-2.7 mIU/mL, respectively). During follow-up, none of the patients complained of menopausal symptoms and 81.8% experienced recovery of menstruation. This report is the first trial of GnRHa as a treatment modality to protect ovarian function during adjuvant chemotherapy in young Korean breast cancer patients.
Adult ; Antineoplastic Agents/adverse effects/therapeutic use ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/diagnosis/*drug therapy/surgery ; Combined Modality Therapy ; Cyclophosphamide/adverse effects/therapeutic use ; Doxorubicin/adverse effects/therapeutic use ; Female ; Follicle Stimulating Hormone/analysis ; Gonadotropin-Releasing Hormone/*agonists ; Humans ; Leuprolide/administration & dosage ; Luteinizing Hormone/analysis ; Menstruation ; Ovarian Function Tests ; Primary Ovarian Insufficiency/etiology/*prevention & control ; Republic of Korea ; Tamoxifen/therapeutic use ; Time Factors

OBJECTIVEThis study aimed to investigate the possible role of Orphanin FQ (OFQ) in the regulation of hypo-thalamic gonadotropin-releasing hormone (GnRH) secretion.

METHODSThe method of push-pull perfusion and radioimmuno-assay (RIA) were adopted to examine the secretory profile of GnRH in the median eminence (ME) in freely moving ovari-ectomized (OVX) rats after intracerebroventricular (icv) injection of OFQ and/or [Nphe(1)]NC(1-13)NH(2) (NC13), a competitive antagonists of the opioid receptor-like 1 receptor (ORL1 receptor).

RESULTSGnRH release from ME significantly decreased from 40 min to 80 min after the administration of 20 and 200 nmol OFQ in OVX rats (P < 0.05). This inhibitory effect of 20 nmol OFQ could be abolished by pretreatment with equal dose of NC13. More interestingly, GnRH secretion from ME was increased markedly 60 min after icv injection of 100 and 200 nmol NC13 (P < 0.05).

CONCLUSIONOur results suggested central administration of OFQ could inhibit the release of GnRH in the ME of hypothalamus through ORL1 receptor, providing further in vivo evidence supporting the role of OFQ in the control of GnRH secretion.

Analysis of Variance ; Animals ; Dose-Response Relationship, Drug ; Female ; Gonadotropin-Releasing Hormone ; metabolism ; Median Eminence ; metabolism ; Narcotic Antagonists ; Opioid Peptides ; pharmacology ; Ovariectomy ; methods ; Peptide Fragments ; pharmacology ; Radioimmunoassay ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid ; metabolism ; Secretory Pathway ; drug effects ; Vasodilator Agents ; pharmacology ; Wakefulness ; physiology

OBJECTIVE: To explore the different effect of short 7-day gonadotropin releasing hormone agonist (GnRHa) protocol and GnRHa long protocol on the insulin-like growth factor II(IGF-II) and insulin-like growth factor binding protein-4 (IGFBP-4) levels in follicular fluid. METHODS: Eighty-eight infertile patients due to tubal factors were included in this study. They were randomly divided into a short 7-day GnRHa protocol group and a GnRHa long protocol group (n = 44). Follicular fluid was obtained from dominant follicles during oocyte retrieval. Levels of IGF-II and IGFBP-4 in the follicular fluid were detected by radioimmunoassay and enzyme-linked immunosorbent assay respectively. RESULTS: Duration of controlled ovarian stimulation was significantly shorter and the injected dosages of gonadotropin were significantly lower in the short 7-day protocol group. The differences in serum levels of estradiol and estradiol per mature follicle on the day of human chorionic gonadotropin injection between the two groups were not significant. The concentrations of IGF-II and IGFBP-4 in the follicular fluid of the short 7-day protocol group were significantly lower,while the difference of the ratio of IGF-II/IGFBP-4 between the two groups was not significant. Linear correlation analysis showed that IGF-II level in the follicular fluid was positively correlated to the total dose of gonadotropin. CONCLUSION The short 7-day and long GnRHa protocols may affect the concentrations of IGF-II and IGFBP-4 in the follicular fluid. However, changes of IGF-II and IGFBP-4 concentrations do not contribute to different clinical outcomes.
Embryo Transfer ; Female ; Fertilization in Vitro ; methods ; Follicular Fluid ; chemistry ; Gonadotropin-Releasing Hormone ; administration & dosage ; agonists ; Humans ; Insulin-Like Growth Factor Binding Protein 4 ; analysis ; Insulin-Like Growth Factor II ; analysis ; Ovulation Induction ; methods