The hormonal sensitivity of prostate cancer has been exploited clinically since Huggins and Hodges established the suppressive effects of castration on prostate cancer. Despite over sixty years of research into alternate modalities, androgen deprivation therapy (ADT) has become the mainstay treatment for locally advanced and metastatic prostate cancer. Suppression of testosterone production, the primary goal of hormonal therapy, can be achieved by a multitude of treatments. The ideal timing, duration and composition of ADT remains undefined. At the present time, first-line therapy consists of orchiectomy, luteinizing hormone-releasing hormone (LHRH) analogues or complete androgen blockade (CAB). However, new combinations and treatment settings show promise for improving outcomes and decreasing toxicity. This article provides an overview of the hormonal therapies currently used in advanced prostate cancer.
Androgen Antagonists ; Castration ; Gonadotropin-Releasing Hormone ; Orchiectomy ; Prostatic Neoplasms ; Testosterone

Antidiuretic Hormone Receptor Antagonists ; Heart Failure ; drug therapy ; Humans

The highly unusual action of autoantibodies that stimulate TSH receptor is unique to the development of hyperthyroidism in Grave's disease. Assay of these antibodies has been used as a prognostic tool in monitoring response to antithyroid treatment, disease remission and relapse. The objective of this study was to evaluate the clinical value of TRab titre in terms of predicting responsiveness to antithyroid treatment by achieving a biochemical euthyroid status with minimum maintenance doses of antithyroid drugs. We followed up 28 patients (25 females, 3 males), 20 to 63 years old, who were newly diagnosed with Grave's disease. TSH receptor antibody (TRab) was measured prior to initiation of antithyroid medication. Based on TRab titres, patients were grouped into A (1.5-4.9 U/L), B(5-15 U/L) and C (>15 U/L). Our results showed that patients with lower levels of TRab (<5 U/L) before antithyroid drug therapy have statistically greater chance of achieving euthyroid status (33% in 6 months and 83.3% in 12 months) than those with higher TRab concentrations (combined B and C, 0% in 6 months and 18.8% in 12 months). This study suggests that TRab titre, detected by radioreceptor assay, is useful for predicting the outcome of antithyroid drug therapy in our patients with untreated Grave's hyperthyroidism.
Human ; Male ; Female ; Middle Aged ; Adult ; Young Adult ; RECEPTORS, THYROTROPIN ; GRAVES DISEASE ; ANTITHYROID AGENTS ; HORMONES, HORMONE SUBSTITUTES, AND HORMONE ANTAGONISTS ; HORMONE ANTAGONISTS

OBJECTIVETo evaluate the application of gonadotrophin-releasing hormone antagonist (GnRH-ant) in patients with risk of poor response to controlled ovarian stimulation in IVF-ET.

METHODSClinical data of 48 patients undergoing IVF with or without ICSI were retrospectively analyzed. Among them 24 patients were allocated to the GnRH-ant protocol and 24 to the long gonadotrophin-releasing hormone agonist (GnRH-a) protocol. The duration of down-regulation, duration of stimulation, amps of gonadotropin estradiol level on hCG day, number of oocytes retrieved, fertilization rate, total embryos obtained, high quality embryo obtained, embryos transferred, embryos frozen, implantation rate per transfer, clinical pregnancy rate per transfer, embryo survival rate, clinical pregnancy rate per frozen embryos transfer and per cycle were compared between two groups.

RESULTThe duration of down-regulation, duration of stimulation, the amps of gonadotropin were significantly lower in the antagonist group than those in agonist group (P <0.001, <0.05, <0.05), the estradiol level on hCG day, the number of oocytes retrieved were significantly lower in the antagonist group than those in the agonist group (P<0.05, <0.05). No significant differences were noted in fertilization rate, total embryos obtained, high quality embryo obtained, embryos transferred, embryos frozen, implantation rate per transfer, clinical pregnancy rate per transfer, embryo survival rate, clinical pregnancy rate per frozen embryos transfer and per cycle.

CONCLUSIONCompared with long GnRH-a protocol, the GnRH-ant protocol in patients with risk of poor response can reduce the dosage of gonadotropin and shorten the duration of stimulation, although the estradiol level on hCG day and the number of oocytes retrieved are lower, which does not affect the implantation rate and clinical pregnancy rate.

Adult ; Embryo Transfer ; Female ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone ; agonists ; antagonists & inhibitors ; Hormone Antagonists ; pharmacology ; therapeutic use ; Humans ; Infertility, Female ; therapy ; Ovulation Induction ; methods ; Retrospective Studies

OBJECTIVE: Immune alternation is related to the pathogenesis and progression of endometriosis. Helixor-A, mistletoe extract, has been known that it has immune modulation effect. Therefore the purpose of this study is to determine the effects of Helixor-A for pain of endometriosis by intraperitoneal instillation of mistletoe extract during the diagnostic laparoscopy. METHODS: Among the paitients who visited to outpatient clinic due to chronic pelvic pain, 30 patients who had laparoscopically-confirmed endometriosis were included in this study. Helixor-A 5 mg was instilled into the posterior cul-de-sac during the diagnostic laparoscopy. Before diagnostic laparoscopy and one month after laparoscopy, the patients recorded pain scores. RESULTS: In 11 of 30 patients (36.7%), pelvic pain of endometriosis improved after laparoscopy. In 2 of 30 patients, the side-effect of Helixor- A appeared and they were easily controlled by antihistamines. CONCLUSION: The instillation of Helixor-A during diagnostic laparoscopy, that is essential for confirmation of endometriosis, may be helpful as a supportive treatment for treatment of pelvic pain due to endometriosis with classical treatment such as GnRH agonist therapy.
Ambulatory Care Facilities ; Endometriosis* ; Female ; Gonadotropin-Releasing Hormone ; Histamine Antagonists ; Humans ; Laparoscopy* ; Mistletoe* ; Pelvic Pain

This study was performed to analyze retrospectively outcomes of stimulated in vitro fertilization (IVF) cycles where the gonadotropin-releasing hormone (GnRH) antagonist was omitted on ovulation triggering day. A total of 92 consecutive IVF cycles were included in 65 women who are undergoing ovarian stimulation with recombinant FSH. A GnRH antagonist, cetrorelix 0.25 mg/day, was started when leading follicle reached 14 mm in diameter until the day of hCG administration (Group A, 66 cycles) or until the day before hCG administration (Group B, 26 cycles). The duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and the number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in Group B compared to Group A (2.7+/-0.8 vs. 3.2+/-0.9 ampoules). There was no premature luteinization in the subjects. The proportion of mature oocytes (71.4% vs. 61.7%) and fertilization rate of mature (86.3+/-19.7% vs. 71.8+/-31.7%) was significantly higher in Group B. There were no significant differences in embryo quality and clinical pregnancy rates. Our results suggest that cessation of the GnRH antagonist on the day of hCG administration during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising IVF results.
Adult ; Chorionic Gonadotropin/administration & dosage ; Drug Administration Schedule ; Estradiol/blood ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone/administration & dosage/blood ; Gonadotropin-Releasing Hormone/*antagonists & inhibitors ; Hormone Antagonists/*administration & dosage ; Humans ; Ovulation Induction/*methods ; Recombinant Proteins/therapeutic use ; Retrospective Studies

OBJECTIVETo analyze the clinical characteristics and cycle outcome of Chinese women with gonadotropin-releasing hormone (GnRH) antagonist treatment during controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET).

METHODSA retrospective review was conducted in patients who completed 54 consecutive cycles of IVF-ET with GnRH antagonist treatment for luteinizing hormone (LH) surge prevention. Descriptive statistics were recorded for the patients' age, GnRH treatment duration (days) and dose, timing and duration of GnRH antagonist treatment, serum E2 and LH level on the day of antagonist use and hCG injection, number of oocytes retrieved, and clinical pregnancy rate.

RESULTSThe clinical pregnancy rate was 46.2% per ET cycle for GnRH antagonist group and 56.8% in GnRH agonist group, showing no significant difference between the two protocols. The age of the patients with GnRH antagonist averaged 35.7-/+3.8 years. Gn and GnRH antagonist treatment lasted for 8.5-/+1.6 and 4.5-/+1.1 days, respectively. On the day of ovulation triggered by hCG, the serum estradiol level was 1616.7-/+721.1 pg/ml, and a mean of 7.4-/+4.6 oocytes was collected per retrieval. The number of the embryos transferred was 2.4-/+0.6, with an implantation rate of 27.7%, resulting in a clinical pregnancy rate of 50.0% in the fixed protocol (antagonist initiation on day 4 or 5 of stimulation) and 37.5% in the flexible protocol (antagonist treatment initiated for a follicle of 12-15 mm, on day 6 to 9 of stimulation).

CONCLUSIONSGnRH antagonists treatment results in good outcomes and can be safe, short, convenient and effective for Chinese women undergoing COH for IVF. GnRH antagonist treatment can be initiated on day 4 to 9 of Gn stimulation to obtain comparable pregnancy rate.

Adult ; China ; Embryo Transfer ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone, Human ; administration & dosage ; Gonadotropin-Releasing Hormone ; administration & dosage ; antagonists & inhibitors ; Hormone Antagonists ; administration & dosage ; Humans ; Ovarian Hyperstimulation Syndrome ; drug therapy ; prevention & control ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Time Factors

To determine whether exocrine pancreatic secretion is regulated by endogenous somatostatin, somatostatin deficiency was induced by cysteamine. Rats were subcutaneously administered a single dose of cysteamine (30 mg/100 g body weight) 12 hr before experiment. Anesthetized rats were prepared with cannulation into bile duct, pancreatic duct, duodenum, and jugular vein and pancreatic juice was collected. For in vitro study, isolated pancreata of rats, pretreated with cysteamine, were perfused with an intraarterial infusion of Krebs-Henseleit solution (37 degrees C) at 1.2 mL/min, and pancreatic juice was collected in 15-min samples. In vivo experiment of the rat, the mean basal pancreatic secretions, including volume, bicarbonate, and protein output were significantly increased from 18.4+/-0.5 microL/30 min, 0.58+/-0.05 microEq/30 min, and 214.0+/-26.1 microg/30 min to 51.6+/-3.7 microL/30 min, 1.52+/-0.11 microEq/30 min, and 569.8+/-128.9 microg/30 min, respectively (p<0.05). In the isolated perfused pancreas, cysteamine also resulted in a significant increase in basal pancreatic secretion (p<0.05). Simultaneous intraarterial infusion of octreotide (10 pmol/hr) to isolated pancreata partially reversed the effect of cysteamine on basal pancreatic secretion. These findings suggest that endogenous somatostatin play an important role on the regulation of basal pancreatic exocrine secretion.
Animal ; Cysteamine/pharmacology* ; Hormone Antagonists/pharmacology* ; Hormones, Synthetic/pharmacology ; In Vitro ; Male ; Octreotide/pharmacology ; Pancreas/secretion ; Pancreas/drug effects* ; Perfusion ; Rats ; Rats, Sprague-Dawley ; Somatostatin/antagonists & inhibitors*

PURPOSE: High-risk prostate cancer patients undergoing treatment often experience biochemical recurrence. The use of bisphosphonates as an adjuvant treatment delays skeletal events, yet whether or not bisphosphonates also delay metastastic development remains to be determined. MATERIALS AND METHODS: A total of 140 high-risk prostate cancer patients who were undergoing definitive treatment and who had clinically organ-confined disease and who suffered from biochemical recurrence were administered intravenous (IV) clodronate. The patients were treated with a radical retropubic prostatectomy (RP) or curative radiotherapy (RTx). Upon androgen deprivation therapy initiation, tri-monthly IV clodronate was added to the treatment to prevent bone demineralization. Twenty-six out of 60 operated cases and 45 out of 80 irradiated cases received bisphosphonate. The length of time until the first bone metastasis was recorded and analyzed. RESULTS: No statistical difference was found for the type of primary treatment (RP or RTx) on the time to the first bone metastasis (95% confidence interval [CI], 0.40 to 2.43; p=0.98). However, there was a clear advantage favoring the group that received bisphosphonate (p<0.001). The addition of bisphosphonate delayed the appearance of the first bone metastasis by seven-fold (95% CI, 3.1 to 15.4; p<0.001). CONCLUSION: Treatment with tri-monthly IV clodronate delayed the time to the first bone metastasis in high-risk prostate cancer patients who were experiencing an increase in the prostate specific antigen level after definitive treatment.
Androgen Antagonists ; Clodronic Acid ; Diphosphonates ; Hormone Antagonists ; Humans ; Imidazoles ; Neoplasm Metastasis ; Nitro Compounds ; Osteoporosis ; Prospective Studies ; Prostate ; Prostate-Specific Antigen ; Prostatectomy ; Prostatic Neoplasms ; Recurrence

AIMIn order to explore the mechanism of central motilin-induced feeding behavior, the effects of erythromycin, a motilin receptor agonist, on glucose responsive neurons in hypothalamus were observed.

METHODSExtracellular recordings were made from single neurons in region of lateral hypothalamic area (LHA) and ventromedial hypothalamic nucleus (VMH) in anesthetized rats. On the basis of their responsiveness to intracarotid injection of 0.58 mol/L glucose solution 0.2 ml, glucose-sensitive neurons (GSNs) in LHA and glucoreceptor neurons (GRNs) in VMH were recognized. Effects of intracerebroventricularly (i. c. v.) administration of 4 microg erythromycin on neural activities of glucose responsive neurons and non-glucose responsive neurons were examined. The mixture of EM and GM-109 1 microl were used to GSNs and GRNs which were sensitive to i. c. v. administration of EM.

RESULTSIn LHA, EM increased activity of GSNs significantly (P < 0.05 vs non-glucose-sensitive neurons group). Whereas in VMH, EM significantly decreased the activities of GRNs (P < 0.01 vs non-glucoreceptor neurons group). The mixture of EM and GM-109 had no effect on GSNs and GRNs.

CONCLUSIONEM, a motilin receptor agonist, can stimulate GSNs in LHA and suppress GRNs in VMH and this may contribute to central motilin's effect on feeding behavior.

Animals ; Erythromycin ; pharmacology ; Hypothalamus ; cytology ; Neurons ; cytology ; drug effects ; Rats ; Rats, Wistar ; Receptors, Cell Surface ; metabolism ; Receptors, Gastrointestinal Hormone ; antagonists & inhibitors ; Receptors, Neuropeptide ; antagonists & inhibitors