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The Oncologist 2000Prostate cancer has become the most common cancer among American men and is second only to lung cancer as a cause of male cancer-related death. Several treatment options... (Review)
Review
Prostate cancer has become the most common cancer among American men and is second only to lung cancer as a cause of male cancer-related death. Several treatment options exist for different stages of prostate cancer including observation, prostatectomy, radiation therapy, chemotherapy, and hormone therapy. Hormone therapy has evolved from the use of estrogens to gonadotropin-releasing hormone (GnRH) agonists and recently, investigational GnRH antagonists. GnRH receptor agonists such as leuprolide, bruserelin and goserelin have been used for the treatment of prostate cancer. These agonists eventually cause the inhibition of lutenizing hormone production, which in turn causes a suppression of testosterone and dihydrotestosterone, on which continued growth of prostate cancer cells depend. Several comparative studies of leuprorelin administered as daily injections or monthly depot injections have been reported. Disease progression was prevented in more than 72% of men administered daily leuprorelin, and in 82% to 89% of those receiving monthly depots. Another synthetic GnRH analog, goserelin, has been studied in a similar population of men with daily injections producing partial responses in 60% to 80% of men with previously untreated prostate cancer. Abarelix, a peptide antagonist of GnRH receptor, is also being studied for the treatment of prostate cancer. The discovery and development of GnRH antagonists may provide an important advance for patients with prostate cancer. Clearly the studies described herein, as well as many others, outline an exciting era of research to define the optimal use of hormonal therapy in prostate cancer.
Topics: Antineoplastic Agents, Hormonal; Buserelin; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Testosterone
PubMed: 10794807
DOI: 10.1634/theoncologist.5-2-162 -
Drug Design, Development and Therapy 2018Patients receiving androgen deprivation therapy experience secondary hypogonadism, associated bone loss, and increased fracture risk. It has been shown that tocotrienol...
BACKGROUND
Patients receiving androgen deprivation therapy experience secondary hypogonadism, associated bone loss, and increased fracture risk. It has been shown that tocotrienol from (annatto) prevents skeletal microstructural changes in rats experiencing primary hypogonadism. However, its potential in preventing bone loss due to androgen deprivation therapy has not been tested. This study aimed to evaluate the skeletal protective effects of annatto tocotrienol using a buserelin-induced osteoporotic rat model.
METHODS
Forty-six male Sprague Dawley rats aged 3 months were randomized into six groups. The baseline control (n=6) was sacrificed at the onset of the study. The normal control (n=8) received corn oil (the vehicle of tocotrienol) orally daily and normal saline (the vehicle of buserelin) subcutaneously daily. The buserelin control (n=8) received corn oil orally daily and subcutaneous buserelin injection (75 µg/kg) daily. The calcium control (n=8) was supplemented with 1% calcium in drinking water and daily subcutaneous buserelin injection (75 µg/kg). The remaining rats were given daily oral annatto tocotrienol at 60 mg/kg (n=8) or 100 mg/kg (n=8) plus daily subcutaneous buserelin injection (75 µg/kg) (n=8). At the end of the experiment, the rats were euthanized and their blood, tibia, and femur were harvested. Structural changes of the tibial trabecular and cortical bone were examined using X-ray micro-computed tomography. Femoral bone calcium content and biomechanical strength were also evaluated.
RESULTS
Annatto tocotrienol at 60 and 100 mg/kg significantly prevented the deterioration of trabecular bone and cortical thickness in buserelin-treated rats (<0.05). Both doses of annatto tocotrienol also improved femoral biomechanical strength and bone calcium content in buserelin-treated rats (<0.05). The effects of annatto tocotrienol were comparable to calcium supplementation.
CONCLUSION
Annatto tocotrienol supplementation is effective in preventing degeneration of the bone induced by buserelin. Therefore, it is a potential antiosteoporotic agent for men receiving androgen deprivation therapy.
Topics: Animals; Bixaceae; Bone and Bones; Buserelin; Calcium; Carotenoids; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Molecular Structure; Osteoporosis; Plant Extracts; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Tocotrienols
PubMed: 29588572
DOI: 10.2147/DDDT.S158410 -
Fertility and Sterility Sep 2001To compare the efficacy of a draw-back nafarelin acetate protocol with routine buserelin acetate administration for in vitro fertilization (IVF) and intracytoplasmic... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A prospective randomized comparison of routine buserelin acetate and a decreasing dosage of nafarelin acetate with a low-dose gonadotropin-releasing hormone agonist protocol for in vitro fertilization and intracytoplasmic sperm injection.
OBJECTIVE
To compare the efficacy of a draw-back nafarelin acetate protocol with routine buserelin acetate administration for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).
DESIGN
Prospective clinical study.
SETTING
Mie University School of Medicine, Tsu, Mie, Japan.
PATIENT(S)
One hundred sixty-nine women treated with IVF and 183 women treated with ICSI.
INTERVENTION(S)
Nafarelin acetate and buserelin acetate in ovarian hyperstimulation in IVF and ICSI were administered.
MAIN OUTCOME MEASURE(S)
The concentrations of estradiol (E(2)), FSH, LH, gonadotropin dosages; the number of oocytes retrieved, oocytes fertilized, and embryos; and pregnancy rates.
RESULT(S)
A prospective study was conducted with 44 cycles for 34 couples with nafarelin acetate (group 1) and 47 cycles for 40 couples with buserelin acetate (group 2) with a long IVF protocol; 68 cycles for 46 couples with nafarelin acetate (group 3) and 56 cycles for 39 couples with buserelin acetate (group 4) with a short IVF protocol; 39 cycles for 32 couples with nafarelin acetate (group 5) and 50 cycles for 30 couples with buserelin acetate (group 6) with a long ICSI protocol; and 87 cycles for 60 couples with nafarelin acetate (group 7) and 81 cycles for 61 couples with buserelin acetate (group 8) with a short ICSI protocol. Patients were randomized to receive either full-dose nafarelin acetate (200 microg b.i.d.) treatment for 7 days followed by half-dose nafarelin acetate (200 microg daily) or buserelin acetate (300 microg t.i.d.). There were no statistically significant differences in baseline concentrations of E(2) and FSH, concentrations of E(2), P4, FSH, LH on hCG administration, gonadotropin dosage, the number of oocytes retrieved and embryos transferred, or pregnancy rates between groups 1 and 2, groups 3 and 4, groups 5 and 6, and groups 7 and 8.
CONCLUSION(S)
Full-dose nafarelin acetate treatment for 7 days followed by half-dose nafarelin acetate ("draw-back" protocol) is an effective new protocol for IVF and ICSI.
Topics: Abortion, Spontaneous; Adult; Buserelin; Chorionic Gonadotropin; Embryo Implantation; Embryo Transfer; Endometrium; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Hormones; Humans; Luteinizing Hormone; Male; Nafarelin; Pregnancy; Progesterone; Prospective Studies; Sperm Injections, Intracytoplasmic; Time Factors
PubMed: 11532477
DOI: 10.1016/s0015-0282(01)01977-x -
Reproduction in Domestic Animals =... Oct 2022The aim was to assess the reproductive efficiency of different techniques used to preserve spermatozoa in artificial insemination semen doses (AI-doses) by evaluating...
The aim was to assess the reproductive efficiency of different techniques used to preserve spermatozoa in artificial insemination semen doses (AI-doses) by evaluating refrigeration at 15°C, cryopreservation and encapsulation. Forty-two hyperprolific sows were treated with buserelin and inseminated once at a single fixed time. The fertility rate, embryonic vesicles viability and the early embryonic mortality (arrested conceptuses) evaluated post-mortem at 24th day of pregnancy, were analysed in order to assess the effectiveness of each proposed technique. Results show an overall reduction on fertility using the three proposal sperm preservation techniques (69.27%, 60.00% and 78.75% for refrigerated, frozen-thawed and encapsulated AI-doses, respectively). Total number of embryonic vesicles was very similar among the three treatments; yet, the number of viable vesicles was numerically different among groups, and thus, embryonic viability was 79.25%, 80.0% and 87.15% for refrigerated, frozen-thawed and encapsulated AI-doses, respectively.
Topics: Animals; Buserelin; Cryopreservation; Female; Fertility; Insemination, Artificial; Male; Pregnancy; Semen; Semen Preservation; Spermatozoa; Swine
PubMed: 35699357
DOI: 10.1111/rda.14179 -
Reproductive Biology and Endocrinology... Jun 2015Although a large number of studies have been dedicated to ovarian hyperstimulation syndrome (OHSS) none gave full embryological and clinical outcomes comparing oocyte...
BACKGROUND
Although a large number of studies have been dedicated to ovarian hyperstimulation syndrome (OHSS) none gave full embryological and clinical outcomes comparing oocyte trigger with human chorionic gonadotrophin (HCG) versus with a gonadotrophin-releasing hormone (GnRH) agonist (Buserelin) in cases with suspicious OHSS. The aim of the present study was thus to analyze 4894 consecutive assisted reproductive treatment cycles to undercover associated risk factors for development of OHSS, and the effects of the use of Buserelin as ovulation trigger on embryological and clinical outcomes.
METHODS
In the 51 cases that developed OHSS, ovulation trigger was performed with HCG as indicators were not suspicious for OHSS. These were compared against two types of groups: 71 cases where Buserelin was used for ovulation induction due to suspicious development of OHSS; and those remaining 4772 cases where ovulation trigger was currently performed with HCG (control).
RESULTS
Of the cases treated with Buserelin the oocyte maturation rate and the ongoing pregnancy rate were significantly lower, with higher rates of ectopic pregnancy and newborn malformations, but none developed OHSS. Of the OHSS cases, 23 needed hospitalization, with no major complications.
CONCLUSIONS
Young age, lower time of infertility, lower basal follicle stimulating hormone levels, higher number of cases with female factor and polycystic ovarian syndrome, high number of follicles and higher estradiol concentrations were the risk factors found associated with OHSS. Cases with OHSS also presented higher follicle count but the estradiol levels were within the normal range. It thus remains to develop more strict criteria to avoid all cases with OHSS.
Topics: Buserelin; Chorionic Gonadotropin; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Retrospective Studies
PubMed: 26100393
DOI: 10.1186/s12958-015-0067-3 -
European Journal of Drug Metabolism and... Apr 2017Although many synthetic gonadoliberin analogs have been developed, only a few of them, including buserelin, were introduced into clinical practice. Dalarelin, which... (Comparative Study)
Comparative Study
BACKGROUND AND OBJECTIVES
Although many synthetic gonadoliberin analogs have been developed, only a few of them, including buserelin, were introduced into clinical practice. Dalarelin, which differs from buserelin by just one aminoacid in the position 6 (D-Ala), is not widely used so far. Gonadotropin-releasing hormone (GnRH) analogs are used to treat many different illnesses and are available in different forms like solution for injection, nasal spray, microspheres, etc. Unfortunately, none of the above drug formulations can release the hormones for 24 h. We assumed that classical suspension could solve this problem.
METHODS
Two sets of experiments were performed. In the first one, buserelin and dalarelin were injected into mature female rats in two forms: suspension, in which the analogs are bounded by Zn ions and solution. The pharmacokinetic parameters and bioavailability of the analogs were calculated, based on their concentration in the plasma measured by high-performance liquid chromatography method (HPLC). In the second experiment, the hormones in two different forms were injected into superovulated immature female rats and then the concentration of Luteinizing hormone (LH), Follicle-stimulating hormone (FSH) and 17β-estradiol in the serum was measured by radioimmunological method.
RESULTS
The Extent of Biological Availability (EBA), calculated on the base of AUC, showed that in the form of solution buserelin and dalarelin display, respectively, only 13 and 8 % of biological availability of their suspension counterparts. Comparing both analogs, the EBA of dalarelin was half (53 %) that of buserelin delivered in the form of solution and 83 % when they were delivered in the form of suspension. The injection of buserelin or dalarelin, in the form of solution or suspension, into superovulated female rats increased LH, FSH and estradiol concentration in the serum. However, after injection of the analogs in the form of suspension, the high concentration of LH and FSH in the serum persisted longer.
CONCLUSION
Performed studies indicate that GnRH analogs in the form of suspension have higher bioavailability than their solution counterparts. It influences the effects of their action, especially in relation to LH and FSH.
Topics: Animals; Area Under Curve; Biological Availability; Buserelin; Chromatography, High Pressure Liquid; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Injections, Subcutaneous; Luteinizing Hormone; Pharmaceutical Solutions; Rats; Rats, Wistar; Suspensions; Time Factors; Zinc
PubMed: 27180066
DOI: 10.1007/s13318-016-0342-5 -
Molecules (Basel, Switzerland) Nov 2022A novel HPLC-ESI-MS/MS method for simultaneous gonadotropin-releasing hormone (GnRH) analogs and somatostatin analog quantitation was developed and validated. The...
A novel HPLC-ESI-MS/MS method for simultaneous gonadotropin-releasing hormone (GnRH) analogs and somatostatin analog quantitation was developed and validated. The developed method was successfully applied to pharmacokinetic studies. The sample preparation process included solid-phase extraction (SPE). Effective chromatographic separation of the analytes and internal standard (dalargin) was achieved with a C18 column, using a gradient elution with two mobile phases: 0.1% / formic acid (aqueous solution) and 0.1% / formic acid (acetonitrile solution). The linearity of the method was demonstrated within a concentration range of 0.5-20 ng/mL, with correlation coefficients between 0.998-0.999 for goserelin, buserelin, triptorelin, and octreotide, respectively. The relative standard deviation (RSD, %) values for method accuracy and precision did not exceed 20% at the lower level of quantitation (LLOQ) or 15% at other concentration levels.
Topics: Humans; Chromatography, Liquid; Tandem Mass Spectrometry; Reproducibility of Results; Plasma; Peptides
PubMed: 36431933
DOI: 10.3390/molecules27227831 -
Evidence Report/technology Assessment... May 1999With 184,500 new cases and 39,200 deaths anticipated in 1998, prostate cancer is second only to lung cancer in cancer mortality for men. This report is a systematic... (Review)
Review
OBJECTIVES
With 184,500 new cases and 39,200 deaths anticipated in 1998, prostate cancer is second only to lung cancer in cancer mortality for men. This report is a systematic review of the evidence from randomized controlled trials on the relative effectiveness of alternative strategies for androgen suppression as treatment of advanced prostate cancer. Three key issues are addressed: (1) the relative effectiveness of the available methods for monotherapy (orchiectomy, luteinizing hormone-releasing hormone [LHRH] agonists, and antiandrogens), (2) the effectiveness of combined androgen blockade compared to monotherapy, and (3) the effectiveness of immediate androgen suppression compared to androgen suppression deferred until clinical progression. Outcomes of interest are overall, cancer-specific, and progression-free survival; time to treatment failure; adverse effects; and quality of life. Two supplementary analyses were conducted for each key question: (1) meta-analysis of overall survival at 2 years (questions 1 and 2) and 5 years (questions 2 and 3), and (2) cost-effectiveness analysis.
SEARCH STRATEGY
The MEDLINE, CANCERLIT, and EMBASE databases were searched from 1966 to March 1998, and Current Contents to August 24, 1998, for the terms: leuprolide (Lupron); goserelin (Zoladex); buserelin (Suprefact); flutamide (Eulexin); nilutamide (Anandron, Nilandron); bicalutamide (Casodex); cyproterone acetate (Androcur); diethylstilbestrol (DES); and orchiectomy (castration, orchidectomy). The search was then limited to human studies indexed under the MeSH term "prostatic neoplasms" and by the UK Cochrane Center search strategy for randomized controlled trials. Total yield was 1,477 references.
SELECTION CRITERIA
We Reports of efficacy outcomes were limited to randomized controlled trials. Phase II studies that reported on withdrawals from therapy and all studies reporting on quality of life were also included.
DATA COLLECTION AND ANALYSIS
The systematic review used a prospectively designed protocol conducted by two independent reviewers, with disagreements resolved by consensus. The meta-analysis combined data on overall survival using a random effects model. The cost-effectiveness analysis used a decision analysis model of advanced prostate cancer with health states and transitions derived from the literature and estimates of effectiveness derived from the meta-analysis. The cost-effectiveness analysis is conducted from a societal perspective, consistent with the guidelines of the U.S. Public Health Service Panel on Cost-Effectiveness in Health and Medicine.
MAIN RESULTS
Survival after treatment with an LHRH agonist is equivalent to survival after orchiectomy. The available LHRH agonists are equally effective, and no LHRH agonist is superior to the other when adverse effects are considered. Survival may be somewhat lower with use of a nonsteroidal antiandrogen. There is no statistically significant difference in survival at 2 years between patients treated with combined androgen blockade or monotherapy. Meta-analysis of the limited data available shows a statistically significant difference in survival at 5 years that favors combined androgen blockade. However, the magnitude of this difference is of questionable clinical significance. For the subgroup of patients with good prognosis, there is no statistically significant difference in survival. Adverse effects leading to withdrawal from therapy occurred more often with combined androgen blockade. No evidence is yet available from randomized controlled trials of androgen suppression initiated at prostate-specific antigen (PSA) rise after definitive therapy for clinically localized disease. For patients who are newly diagnosed with locally advanced or asymptomatic metastatic disease, the evidence is insufficient to determine whether primary androgen suppression initiated at diagnosis improves outcomes. (ABSTRACT TRUNCATED)
Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Cost-Benefit Analysis; Evidence-Based Medicine; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 11098244
DOI: No ID Found -
Advanced Pharmaceutical Bulletin Nov 2023In this study, we prepared inhalable buserelin microparticles using the spray freeze-drying (SFD) method for pulmonary drug delivery. Raffinose as a cryoprotectant...
PURPOSE
In this study, we prepared inhalable buserelin microparticles using the spray freeze-drying (SFD) method for pulmonary drug delivery. Raffinose as a cryoprotectant carrier was combined with two levels of five different cyclodextrins (CDs) and then processed by SFD.
METHODS
Dry powder diameters were evaluated by laser light scattering and morphology was determined by scanning electron microscopy (SEM). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis were utilized for the determination of crystalline structures. The aerodynamic properties of the spray freeze-dried powders were evaluated by twin stage impinger (TSI) and the stability of prepared samples was assessed under normal and accelerated conditions.
RESULTS
The prepared powders were mostly porous spheres and the size of microparticles ranged from 9.08 to 13.53 μm, which are suitable as spray-freeze dried particles. All formulations showed amorphous structure confirmed by DSC and XRD. The aerosolization performance of the formulation containing buserelin, raffinose and 5% beta-cyclodextrin (β-CD), was the highest and its fine particle fraction (FPF) was 69.38%. The more circular and separated structures were observed in higher concentrations of CDs, which were compatible with FPFs. The highest stability was obtained in the formulation containing hydroxypropyl beta-cyclodextrin (HP-β-16. CD) 5%. On the contrary, sulfobutylether beta-cyclodextrin (SBE-β-CD) 5% bearing particles showed the least stability.
CONCLUSION
By adjusting the type and ratio of CDs in the presence of raffinose, the prepared formulations could effectively enhance the aerosolization and stability of buserelin. Therefore, they can be proposed as a suitable career for lung drug delivery.
PubMed: 38022810
DOI: 10.34172/apb.2023.086 -
Endocrinology, Diabetes & Metabolism... Nov 2019Cantu syndrome, or hypertrichotic osteochondrodysplasia, is a rare, autosomal dominant genetically heterogeneous disorder. It is characterized by hypertrichosis, cardiac...
SUMMARY
Cantu syndrome, or hypertrichotic osteochondrodysplasia, is a rare, autosomal dominant genetically heterogeneous disorder. It is characterized by hypertrichosis, cardiac and skeletal anomalies and distinctive coarse facial features. We report a case where slowed growth velocity at 13 years led to identification of multiple pituitary hormone deficiencies. This adds to other reports of pituitary abnormalities in this condition and supports inclusion of endocrine monitoring in the clinical surveillance of patients with Cantu syndrome.
LEARNING POINTS
Cantu syndrome is a rare genetic disorder caused by pathogenic variants in the ABCC9 and KCNJ8 genes, which result in gain of function of the SUR2 or Kir6.1 subunits of widely expressed KATP channels. The main manifestations of the syndrome are varied, but most commonly include hypertrichosis, macrosomia, macrocephaly, coarse 'acromegaloid' facies, and a range of cardiac defects. Anterior pituitary dysfunction may be implicated in this disorder, and we propose that routine screening should be included in the clinical and biochemical surveillance of patients with Cantu syndrome.
PubMed: 31743099
DOI: 10.1530/EDM-19-0103