Leuprolide Research Articles

A Lipid-Based Depot Formulation with a Novel Non-lamellar Liquid Crystal Forming Lipid.

PurposeNon-lamellar liquid crystal (NLLC)-forming lipids have gained attention as a novel component because of their ability to self-assemble upon contact with body fluids. In this study, a novel NLLC-forming lipid, mono-O-(5, 9, 13-trimethyl-4-tetradecenyl) glycerol ester (C17MGE), and a model drug with a middle molecule weight, leuprolide acetate (LA), were used to confirm the usefulness of C17MGE as an excipient for depot formulations with sustained release properties.MethodsA self-constructed depot formulation was prepared by mixing C17MGE and different types of phospholipids. The constructed NLLC structure was evaluated using small angle X-ray analysis and cryo-transmission electron microscopy. In vitro release and blood concentration profiles of LA were investigated.ResultsThe NLLC structure was confirmed by small angle X-ray analysis. LA release was able to be modified by adding different ratios of various phospholipids to C17MGE. Formulations containing 1, 2-dioleoyl-sn-glycero-3-phosphoglycerol sodium salt with a mixing ratio of 12% or 24% (MDOPG12 or MDOPG24, respectively) exhibited sustained release profiles of LA. In addition, the blood concentration of LA was detected over 21 days or more after administration of MDOPG12, and the absolute bioavailability was calculated to be about 100%.ConclusionsA depot formulation using C17MGE was useful to achieve sustained release of LA.

Effectiveness and Distribution of Testosterone Levels within First Year of Androgen Deprivation Therapy in a Real-World Setting: Results from the Non-Interventional German Cohort LEAN Study

Background: Observational studies generate information on real-world therapy and complement data from prospective randomized trials. LEAN is an open-label, non-interventional, multi-centre, German cohort study on leuprorelin in routine clinical practice. Objectives: To extend knowledge on the use, effectiveness, and tolerability of HEXAL/Sandoz leuprorelin (in this article, the term Leuprone® HEXAL® covers Leuprorelin Sandoz® as well) solid implant in patients with prostate cancer (PCa) in a real-world setting. Methods: 959 PCa patients scheduled for androgen deprivation therapy (ADT) received leuprorelin acetate implant. Metabolism, serum prostate-specific antigen (PSA), and testosterone data, if available, were collected at baseline and follow-up visits for ≥12 months. Results: Of 694 patients in the modified full analysis set, 26.4% received GnRH analogues ≤6 months before enrolment. Fifty-one percent of patients were treated for locally advanced or metastatic PCa. In 19.6% of patients, ADT was used in neoadjuvant or adjuvant settings and in 28.5% with rising PSA after definite therapy. Testosterone levels <0.5 ng/mL were achieved in >90% of patients. Safety profile was in line with the summary of product characteristics. Therapy was well tolerated, with patient-triggered therapy discontinuation in 3.6%. Conclusions: This interim analysis confirmed previous efficacy findings for leuprorelin implant in a real-world setting. This contemporary cohort showed a shift in the use of ADT to non-metastatic PCa stages.

Myopic Progression in Girls with Gonadotrophin-Releasing Hormone Agonist Treatment for Central Precocious Puberty.

We sought to determine whether the myopic progression of patients with central precocious puberty (CPP) who were undergoing treatment differed from that of their healthy peers with normal pubertal onset and progression. Eighteen girls with CPP and 14 age-matched controls who underwent regular ophthalmic examinations for at least 1 year were included. All the CPP patients received a 3.75 mg leuprolide acetate depot subcutaneously every 28 days. The spherical equivalent (SE) and axial length (AL) for myopia progression and the pubertal parameters (height, body weight, body mass index, Tanner stage, and bone age) were compared between the two groups. Of 32 subjects with a mean age of 8.6 ± 0.7 years, the SEs and ALs did not differ at baseline between the two groups, which had similar weight and similar body mass index. After 1 year, both the CPP patients and controls showed myopic progression, with an average myopic shift of −0.73 ± 0.48 diopters (D) and AL elongation with a mean change of 0.44 ± 0.61 mm. The SE and AL changes over 1 year were greater in the controls than those in the CPP patients, which was not statistically significant (–0.85 ± 0.55 D vs. –0.64 ± 0.41 D and 0.55 ± 0.89 mm vs. 0.35 ± 0.22 mm, respectively). The change in AL correlated significantly with the change in the height (β = 0.691, p = 0.039). In this 1-year study, the CPP patients with treatments trended to show less myopic progression than the controls.

Abiraterone decanoate (AD): Potent and long-acting activity of a novel intramuscular (IM) abiraterone prodrug depot in a castrate monkey model.

78 Background: Oral abiraterone acetate (AA) is a standard of care for castration-resistant (CRPC) and castration-sensitive prostate cancer (CSPC). Due to poor oral bioavailability, the recommended AA dose is 1,000 mg (4 x 250mg) once-daily on an empty stomach. The daily oral regimen produces high peak plasma concentrations that may be associated with safety issues (e.g., hepatotoxicity) and low trough concentrations that may be associated with inadequate CYP17 inhibition. AD is one of a series of novel abiraterone prodrugs that were designed to provide a controlled release of abiraterone and long-acting CYP17 inhibition with IM delivery. Following successful preclinical pilot studies, AD was further developed into a clinically acceptable formulation (PRL-02) and its PK/PD characteristics were evaluated and compared to oral AA in a castrate monkey pharmacology model in support of future clinical development. Methods: Sexually mature male cynomolgus monkeys underwent chemical castration using Lupron depot. Plasma samples were analyzed for prodrug, abiraterone and steroid concentrations following a single oral AA dose (5, 15 or 45 mg/kg) and a single IM AD injection (10, 30 or 100 mg/kg) (n=3/dose group). The combined activity of IM AD plus glucocorticoid replacement (single 0.5 mg/kg IM dexamethasone (DEX) dose or weekly doses of 1.29 mg/kg IM methylprednisolone acetate (MPA)) was also evaluated. AD, abiraterone and adrenal steroid levels were evaluated by LC-MS/MS. Results: Chemical castration resulted in a plasma testosterone (T) decrease of 72% from intact. T was further reduced to sub-castrate levels by both AA and AD (98.6% and 99.7% maximum decrease from castrate baseline, respectively). All dose levels of AD were highly effective in reducing plasma T yet led to abiraterone plasma concentrations (Cmax, AUC, Cmin) that were much less than those associated with steady-state clinical levels from oral AA. Sustained T suppression was observed following all single AD IM doses for 14 weeks, the last timepoint tested.The addition of a glucocorticoid replacement (DEX or MPA) starting at week 9 further reduced T in all AD groups. Conclusions: Single-dose IM AD suppressed T to the same or greater extent than single-dose oral AA in castrate monkeys, while providing much lower abiraterone exposures than the oral acetate prodrug. As such, IM AD may offer an improved risk-benefit profile due to the consistently lower abiraterone levels. The durable, profound T reductions provided by all AD doses are consistent with a 3-month clinical regimen that can be given in conjunction with Lupron. IM AD may thus offer patients with CSPC and CRPC a more convenient, safe and effective alternative than daily oral AA.

Oocyte cryopreservation in a transgender man on long-term testosterone therapy: a case report

ObjectiveTo report a case of ovarian stimulation for the purposes of oocyte cryopreservation in a transgender man without cessation of long-term testosterone therapy.DesignReport of a unique case of fertility preservation through ovarian stimulation and oocyte cryopreservation in a transgender man who had been on testosterone therapy for 18 months before treatment. The patient elected to continue testosterone therapy throughout ovarian stimulation and oocyte retrieval. To our knowledge, there have not been any published reports of patients undergoing oocyte cryopreservation while continuing long-term testosterone therapy.SettingPrivate fertility clinic with university affiliation.Patient(s)A 20-year-old transgender man undergoing oocyte cryopreservation before gonadectomy.Intervention(s)Fertility preservation through oocyte cryopreservation.Main Outcome Measure(s)This patient had a robust response to ovarian gonadotropin stimulation. Leuprolide acetate was used for final oocyte maturation to minimize ovarian hyperstimulation syndrome risk.Result(s)Cryopreservation of 22 mature oocytes.Conclusion(s)Cryopreservation of mature oocytes is possible for patients on continued long-term testosterone therapy. The impact of long-term testosterone therapy on markers of ovarian reserve, reproductive potential, and long-term reproductive outcomes have yet to be elucidated and further studies are needed in this area.

Development of intravaginal rod insert bearing liposomal raloxifene hydrochloride and Leuprolide acetate as a potential carrier for uterine targeting

This project aimed at the formulation of dual drug entrapped liposomes held as freeze-dried intravaginal rod insert (IVR), to be administered by vaginal route for uterine targeting. Liposomes were formulated by dehydration-rehydration method using 3 : 1 molar ratio of1,2-distearoyl-sn-glycero-3-phosphocholine : Cholesterol. Characterization was done for vesicle size, zeta potential, entrapment efficiency, surface morphology and % loading. Spherical and discrete vesicles of size 354 nm were observed in transmission electron microscopy (TEM) image. The entrapment efficiency of 90.91% and 74.3% w/w was obtained for Raloxifene Hydrochloride (RLX) and Leuprolide acetate (LA) respectively. Drug release was sustained for 6 days. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results showed that dual drug entrapped liposomal formulation show significant cytotoxicity, as also confirmed by higher apoptosis in cell cycle analysis and apoptosis studies (FACS) analysis. Pharmacodynamic studies in New Zealand white female rabbits revealed that intravaginal administration of RLX-LA entrapped liposomal formulation shows considerable fibroid regression. Uterine targeting of liposomal RLX-LA suggests its potential to solve the limitations of the presently available therapeutic options.

Development and Characterization of Leuprolide Acetate Encapsulated PLGA Microspheres for Parenteral Controlled Release Depot Injection

Abstract: Objectives: Polylactic acid (PLA) and copolymer polylactic-co-glycolic acid (PLGA) are the most versatile drug carriers for long acting release injectable (LAI) formulations for small molecules, peptides and macromolecules such as proteins and nucleic acids. The present research work consists of a PLGA based one-month release microsphere formulation of GnRH agonist leuprolide acetate, using double emulsion (W1/O/W2) technique. Materials and Methods: Microparticles were prepared by double emulsion solvent evaporation technique and critical quality attributes of finished products such as drug loading, entrapment efficiency, particle size distribution (PSD), surface porosity, drug distribution within microparticles were analysed. Results and Conclusion: The microspheres have shown the mean particle size of 15.2 μm and suitable particle size distribution pattern ideal for syringe ability. The microparticles were spherical in shape with uniform pore distribution and uniform distribution of API in the polymer matrix. The drug release has been sustained over a month for the microsphere formulation and could be correlated with the testosterone suppression. Key words: Leuprolide, PLGA Microspheres, Double-emulsion technique, Prostate cancer, Controlled release depot Injection.

Therapeutic Potentials of Cyclic Peptides as Promising Anticancer Drugs

This review focuses on studying the pharmacological effect of cyclic peptides as anti-cancer drugs. There are many examples which are already used to treat cancer, either directly or in the treatment of episodes associated with cancer tumors. Goserelin acetate; is an anti-cancer drug, trade name Zoladex, is an injectable gonadotropin releasing hormone superagonist. Leuprolide acetate; is a gonadotropin-releasing hormone or luteinizing-hormone-releasing hormone analog used in the treatment of hormone-responsive cancers such as prostate cancer or breast cancer. Somatostatin, (SST), is a peptide hormone; the peptide hormone somatostatin regulates the endocrine system, affects neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin receptors and inhibits the release of numerous secondary hormones. Octreotide: is a somatostatin mimic, trade name sandostatin, Octreotide is also a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. On the other hand there are many natural bioactive peptides: derived from different foods represent another source of health-enhancing or cancer fighting compounds. Different studies indicate that it is possible that many of these peptides may be released during digestion in the human stomach or during food processing from various plant and animal proteins, especially milk, soy, and fish proteins, for examples Depsipeptides and Argyrins.

ANALEPTIC APPLICATIONS OF PEPTIDES

Bioactive peptides are protein parts which positively affect the capacities and states of living creatures. Peptides have demonstrated a few helpful properties for human wellbeing, including antimicrobial, antifungal, antiviral, and antitumor exercises. These mixes are delivered by practically all types of life. Notwithstanding, they are delivered in restricted amounts in nature. Subsequently, scientists have attempted to integrate bioactive peptides to contemplate their properties and applications in different zones. This review delivers a concise portrayal of the applications utilized by peptides: Triptorelin Acetate, Thymosin Alpha 1, Leuprolide acetate, Liraglutide, Desmopressin Acetate, Teduglutide, Pramlintide, Oxytocin, Calcitonin, Octreotide and Triptorelin.&#x0D; Keywords: Triptorelin Acetate, Thymosin Alpha 1, Leuprolide acetate

Modeling the synergistic properties of drugs in hormonal treatment for prostate cancer

Prostate cancer is one of the most prevalent cancers in men, with increasing incidence worldwide. This public health concern has inspired considerable effort to study various aspects of prostate cancer treatment using dynamical models, especially in clinical settings. The standard of care for metastatic prostate cancer is hormonal therapy, which reduces the production of androgen that fuels the growth of prostate tumor cells prior to treatment resistance. Existing population models often use patients’ prostate-specific antigen levels as a biomarker for model validation and for finding optimal treatment schedules; however, the synergistic effects of drugs used in hormonal therapy have not been well-examined. This paper describes the first mathematical model that explicitly incorporates the synergistic effects of two drugs used to inhibit androgen production in hormonal therapy. The drugs are cyproterone acetate, representing the drug family of anti-androgens that affect luteinizing hormones, and leuprolide acetate, representing the drug family of gonadotropin-releasing hormone analogs. By fitting the model to clinical data, we show that the proposed model can capture the dynamics of serum androgen levels during intermittent hormonal therapy better than previously published models. Our results highlight the importance of considering the synergistic effects of drugs in cancer treatment, thus suggesting that the dynamics of the drugs should be taken into account in optimal treatment studies, particularly for adaptive therapy. Otherwise, an unrealistic treatment schedule may be prescribed and render the treatment less effective. Furthermore, the drug dynamics allow our model to explain the delay in the relapse of androgen the moment a patient is taken off treatment, which supports that this delay is due to the residual effects of the drugs.

Chemoprevention Agents to Reduce Mammographic Breast Density in Premenopausal Women: A Systematic Review of Clinical Trials.

BackgroundHigher mammographic breast density (MBD) is associated with an increased risk of breast cancer when compared with lower MBD, especially in premenopausal women. However, little is known about the effectiveness of chemoprevention agents in reducing MBD in premenopausal women without a history of breast cancer. Findings from this review should provide insight on how to target MBD in breast cancer prevention in premenopausal women with dense breasts.MethodsWe searched 9 electronic databases for clinical trials in English, Spanish, French, or German published until January 2020. Articles evaluating the association of pharmacological agents and MBD were included. Data were extracted on methods, type and dose of intervention, outcomes, side effects, and follow up. Quality of the studies was assessed using the US Preventive Services Task Force criteria.ResultsWe identified 7 clinical trials evaluating the associations of 6 chemoprevention agents with changes in MBD in premenopausal women without history of breast cancer. The studies evaluated selective estrogen-receptor modulators (n = 1); gonadotropin-releasing hormone agonists (n = 2); isoflavones (n = 1); vitamin D (n = 1); and Boswellia, betaine, and mayo-inositol compound (n = 1). Hormonal interventions were associated with net reductions in percent density (tamoxifen [13.4%], leuprolide acetate [8.9%], and goserelin [2.7%]), whereas nonhormonal (vitamin D and isoflavone) interventions were not. However, MBD returned to preintervention baseline levels after cessation of gonadotropin-releasing hormone agonists.ConclusionsA limited number of chemoprevention agents have been shown to reduce MBD in premenopausal women. Identification of new and well-tolerated chemoprevention agents targeting MBD and larger studies to confirm agents that have been studied in small trials are urgent priorities for primary breast cancer prevention in premenopausal women with dense breasts.

Dydrogesterone in the treatment of endometriosis: evidence mapping and meta-analysis

PurposeEndometriosis is a common, chronic gynecological disease that affects women’s fertility potential. Dydrogesterone is an effective and safe drug that is under-utilized due to limited clinical research. The purpose of this evidence mapping is to identify, describe, and analyze the current available evidence regarding dydrogesterone for the treatment of endometriosis.Materials and methodsWe performed a search in electronic databases: Medline, The Cochrane Library, EMBASE, PubMed, CNKI, Wanfang, VIP, and CBM. We also hand-searched google for relevant studies. Our primary outcomes included changes in pain relief including pelvic pain, dysmenorrhea, and dyspareunia. Secondary outcomes included pregnancy rate, frequency of analgesic use, and other reported outcomes according to specific settings in the studies.ResultsOf 377 references screened, 19 studies were included in the data synthesis involving 1709 female participants. Nearly three-quarters were either randomized control trials or clinical control trials. Compared with gestrinone, dydrogesterone relieved dysmenorrhea, increased the pregnancy rate, and reduced the risk of certain adverse events. Compared with GnRH-a, dydrogesterone also lowered the risk of endometriosis recurrence and elevated transaminase levels. Whether there was any difference in efficacy between dydrogesterone and leuprolide acetate, letrozole or traditional Chinese medicine remains unclear due to insufficient data.ConclusionsThe amount and quality of evidence evaluating the effects of dydrogesterone for the treatment of endometriosis is generally very low. Limited evidence suggests that dydrogesterone may have some advantages over gestrinone, GnRH agonists, and other therapeutic interventions in treating endometriosis. However, this conclusion should be interpreted with caution.

Evaluation of hypersensitivity reactions with leuprolide acetate and triptorelin acetate in children

Introduction:Gonadotropin releasing hormone analogues (GnRHa) are commonly used to treat central precocious puberty (CPP). Generally, they are well-tolerated; however adverse reactions have been reported. Local adverse events occur in 10-15% of the patients who were treated with GnRHa. Anaphylactoid reactions with GnRHa are very rarely seen. The aim of this study is to report our clinical experience with hypersensitivity reactions seen in pediatric patients receiving leuprolide acetate (LA) and triptorelin acetate (TA) in CPP at the single pediatric tertiary medical center and to evaluate the incidence rate of hypersensitivity reactions.Methods:This retrospective study included children with CPP who were treated with GnRHa (LA and TA) at our hospital between January 2013 and December 2020. We analyzed clinical characteristics of patients who experienced adverse reactions and analyzed the incidence rate.Results:Seven side effects (adverse reactions) (0.69%) were observed among total of 1010 CPP patients who were treated with TA and LA. Sterile abscesses were observed in 3 patients (0.29%). None of the patients had an anaphylaxis. Tremors of both hands, a vomiting episode, an urticarial rash, and musculoskeletal stiffness were observed in one patient each.Conclusion:In our study, mild reactions were seen in 7 patients. GnRHa can be safely used and well-tolerated medications; but exceedingly rare, severe reactions can be developed.

Evaluation of Dual Trigger with Combination of Gonadotropin-Releasing Hormone Agonist and Human Chorionic Gonadotropin in İmproving Oocyte-Follicle Ratio in Normo-Responder Patients

Our aim was to compare the efficacy of two triggering method one with dual triggering with gonadotropin-realising hormon (GnRH) agonist plus standard dosage human chorionic gonadotropin (hCG) and the other with hCG only for final oocyte maturation on oocyte/follicle ratio and pregnancy rates in normoresponders in GnRH antagonist cycles in invitro fertilization-intrastoplasmic sperm injection (IVF-ICSI). In this retrospective study, all patients underwent GnRH antagonist protocol. When at least ≥3 follicles reached ≥17 mm diameter, 116 patients received dual trigger with GnRH agonist plus hCG (1mg Leuprolide acetate plus 10.000 IU uhCG) and 178 patients received uhCG (10.000 IU u hCG) for final oocyte maturation. All follicles ≥10 mm diameter were aspirated. Number of oocytes and metaphase II oocytes retrieved per aspirated follicles, implantation rate, and clinical pregnancy rate per cycle was recorded. There was no statistically significant difference in terms of metaphase II oocyte ratio per aspirated follicle, implantation rate and clinical pregnancy rate between the dual trigger group and hCG only group (45.7% vs. 51%; 35.4% vs.30.3% and 45%vs. 40% respectively). Oocyte/ follicle ratio was significantly higher in dual trigger group (68.2%vs 63.8% p=0,028). Dual triggering in normal responders with a GnRH-agonist and a standard dosage of hCG is superior to hCG only protocol in terms of oocyte/follicle ratio but does not improve metaphase II oocyte, implantation and clinical pregnancy rates in GnRH-antagonist cycles. Dual triggering method may be beneficial in patients with immature oocytes and emty follicle syndrome.

Dual Trigger Compared with Human Chorionic Gonadotropin Alone and Effects on Clinical Outcome of Intracytoplasmic Sperm Injection.

BackgroundThis study compared outcomes of the standard 6000 IU human chorionic gonadotropin (hCG) trigger with a dual trigger comprised of 6000 IU hCG and 1 mg leuprolide acetate for final oocyte maturation in an intracyto- plasmic sperm injection (ICSI) cycle. By convention, ICSI was performed in most cases at the clinic.Materials and MethodsIn this retrospective study, a total of 50 women were included in each arm. Participants were matched for age, indication and number of prior assisted reproduction technology (ART) cycles. Women at risk for ovarian hyperstimulation syndrome (OHSS) were excluded. A flexible gonadotropin releasing hormone (GnRH) antagonist protocol was used and final oocyte maturation was triggered when two leading follicles were >17 mm. Distribution of variables was evaluated visually with histograms. Continuous variables were defined by mean (stand- ard deviation) or median (25th-75th percentile) depending on distribution characteristics. Categorical variables were defined by numbers and percentages. Continuous variables were compared between the groups with the t test or Mann-Whitney U test as appropriate. Categorical variables were compared by the chi-square test and its derivatives as appropriate. A two-sided P<0.05 indicated statistical significance.ResultsBoth groups had similar antral follicle counts, median parity (0) and number of previous failed cycles (0). The median number of oocytes (8 vs. 7), metaphase-two oocytes (6 vs. 5.5), blastocysts (1 vs. 1), clinical pregnancy rates (CPR) (28% vs. 22%), ongoing pregnancy rates (OPR) (22% vs. 20%) and pregnancy rate per transfer (53.3% vs 53.8%) were similar between the dual trigger and hCG only groups, respectively.ConclusionDual trigger for oocyte maturation stimulation failed to improve the ICSI outcome.

Effects of Lupron and surgical castration on fecal androgen metabolite concentrations and intermale aggression in capybaras (Hydrochoerus hydrochaeris).

To curb agonistic interactions in a bachelor group of three male capybaras (Hydrochoerus hydrochaeris), a single dose of leuprolide acetate (Lupron®) was used in an attempt to chemically sterilize the males. Concurrently, fecal androgen metabolite (FAM) concentrations were quantified via enzyme immunoassay to monitor changes in testosterone production after injection of the gonadotropin-releasing hormone agonist. When Lupron proved ineffective in suppressing intraspecific aggression, surgical castration was performed on two males, with continued noninvasive endocrine monitoring. In all three capybaras, FAM concentrations increased initially as a result of the luteinizing hormone surge, but then decreased significantly following chemical sterilization. Surgical castration resulted in further, persistent declines in FAM concentrations in two males, while the third, intact male demonstrated a rise in FAM to pre-Lupron concentrations at 8.5 and 9.5-month postadministration. Despite successful suppression of sperm and testosterone production, intermale aggression continued, ultimately necessitating separation of the animals and transfer to other holding institutions. Under this set of conditions, a single Lupron dose was inadequate for suppressing intraspecific aggression in a group of three males with a pre-established history of aggression.

Case Report: A castration-resistant terminal prostate cancer patient’s survival prolonged after practicing Falun Gong

Background: Most metastatic prostate cancer patients receive combined androgen blockade (CAB) as the mainstay of treatment. Unfortunately, patients ultimately progress to castration resistance. Clinical finding and diagnosis: We describe a man in his eighties who developed stage IV, M1b prostate cancer, multiple (≥5) bone metastases, and required the aid of a walker to ambulate. Without treatment, his treating physician predicted he would survive 6 months. Interventions and outcomes: The patient initially responded well to treatment with CAB, but during the 68-80th week of treatment he developed castration resistance. Bicalutamide was then discontinued. He chose to begin practicing Falun Gong (FLG) at week 89 as an alternative form of care while continuing two doses of leuprolide acetate. His PSA decreased by 86% within five weeks, he walked independently at 17 weeks and bone metastases disappeared in 41-43 weeks after beginning to practice Falun Gong. He also reported better psychosocial functioning. His treating physician assessed that his prostate malignancy was “clinically, under control” and “his overall functional status is excellent.” The patient survived a total of 263 weeks (61.4 months) post-diagnosis, including 183 weeks (42.3 months) after developing castration resistance. Conclusion: This castration-resistant terminal prostate cancer patient gained significant clinical benefits after practicing Falun Gong.

Long-term outcomes after gonadotropin-releasing hormone agonist treatment in boys with central precocious puberty.

ObjectiveGonadotropin-releasing hormone agonist (GnRHa) treatment improves the potential for gaining height in patients with central precocious puberty (CPP). However, most studies have focused on girls because CPP in boys is relatively rare. Therefore, we aimed to determine the effect of GnRHa treatment on auxological outcomes in boys with CPP.MethodsEighty-five boys with CPP were treated with leuprolide or triptorelin acetate 3.75 mg over 2 years. Anthropometry, bone age, sexual maturity rating, and predicted adult height (PAH) were assessed every 6 months. Furthermore, 20 boys were followed up after treatment discontinuation until achievement of the final adult height (FAH).ResultsThe mean chronological age (CA) and bone age (BA) of the patients with CPP at treatment initiation were 9.5 ± 0.5 years and 11.7 ± 0.9 years, respectively. The mean duration of treatment was 2.87 ± 0.63 years. The PAH at treatment initiation was 172.1 cm (-0.23 ± 1.05 PAH standard deviation score). The PAH at treatment discontinuation (176.2 ± 6.6 cm) was significantly higher than the pretreatment PAH. In addition, the mean final adult height in the 20 boys who were followed up after discontinuation of treatment was 173.4 ± 5.8 cm, which was significantly higher than the initial PAH (170.1 ± 4.5 cm; p = 0.006). In multivariate analysis, the height gain (the difference between the FAH and PAH at treatment initiation) significantly correlated with the target height.ConclusionLong-term GnRHa treatment significantly improved the growth potential and FAH in boys with CPP.

Pseudotumor cerebri in patient on leuprolide acetate for central precocious puberty

BackgroundGonadotropin releasing hormone agonists (GnRHa) are well established as a standard of care for the treatment of central precocious puberty (CPP) worldwide. While numerous delivery systems and routes of administration exist, depot intramuscular injections or sustained-release preparations have been most widely used. Leuprolide acetate is well tolerated among children though some can develop some complications.Case presentationWe present a case report of a 6.5 year old girl with central precocious puberty who developed signs of pseudotumor cerebri after 2 doses of leuprolide acetate 3.75 mg given monthly. Systemic exam and other tests to look for the cause did not yield anything. However, fundoscopy showed marked papilloedema with blurred disc margins. After six weeks’ treatment with acetazolamide and withdrawal of the GRNHa the papilloedema resolved.ConclusionsIf a patient presents with complaints such as headache, nausea, vomiting, and double vision in pediatric patients treated with GnRH analogue one should highly consider the presence of pseudotumor cerebri and fundus examination be performed.

The LUCINDA trial: Leuprolide + cholinesterase inhibition to reduce neurologic decline in Alzheimer's

AbstractBackgroundLeuprolide Acetate has been used for decades to treat hormone‐sensitive conditions such as prostate cancer and endometriosis. In animal models of AD, leuprolide preserves cognition and decreases amyloid deposition and tau phosphorylation by decreasing levels of Luteinizing Hormone. A subgroup analysis of a prior human trial (Bowen, 2016) showed that leuprolide benefited cognition and function in women who were also taking donepezil. Here we describe an ongoing clinical trial of leuprolide to confirm and extend these results.MethodA three‐site, double‐blind, randomized trial of Leuprolide Acetate (22.5 mg/12 weeks) compared with placebo to evaluate the changes over 48 weeks in cognition, function, brain MRI measures (volume, hippocampal blood flow) and blood biomarkers of inflammation in women (n=150) with mild‐moderate AD who are also taking a stable dose of donepezil. This trial is enrolling at three US sites: Weill Cornell in NYC, University of Miami in Southern FL and University of Wisconsin, Madison.ResultResults are expected in 2025.ConclusionBy re‐purposing an existing medication, in combination with a current AD treatment, we will be able to build upon extensive previous research and development efforts, reducing the time frame and costs of making this promising therapy available to patients with AD. Re‐purposing an existing drug likely represents the only realistic option for meeting the HHS goal to “Prevent and Effectively Treat Alzheimer's Disease and Related Dementias by 2025."