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BACKGROUND: This study examined the clinical effects of leuprolide acetate in sexual offenders with paraphilic disorders evaluated by means of objective psychiatric assessment. METHODS: The subjects of this study were seven sexual offenders who were being treated by means of an injection for sexual impulse control by a court order. They had been diagnosed with paraphilia by a psychiatrist based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and had been put on probation by the Ministry of Justice between January 2016 and December 2016. RESULTS: After twelve months, we observed significant improvement in symptoms, as decrease of abnormal sexual interest and activity, sexual fantasy, Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Impulsivity (GCI-I). There were a mild feminization of the body shape, feelings of fatigue, and mild hot flushes. No other adverse effect was reported. CONCLUSION: These results suggested that the clinical effects of leuprolide acetate in sexual offenders might be an effective treatment and safety strategy.
Subject(s)
Humans , Criminals , Diagnostic and Statistical Manual of Mental Disorders , Fantasy , Fatigue , Feminization , Leuprolide , Paraphilic Disorders , Psychiatry , Sexual Behavior , Social Justice , Therapeutic UsesABSTRACT
Objetivo: Comparar los protocolos de microdosis de acetato de leuprolide y priming de estradiol. Métodos: Estudio retrospectivo de 115 pacientes bajas respondedoras (según criterios de Bologna), evaluadas en UNIFERTES desde enero 2010 a diciembre 2012, sometidas a hiperestimulación ovárica controlada según protocolo. La inducción ovárica constó de pauta fija con gonadotropinas (hormona folículo estimulante recombinante 450 UI/día + Gonadotropina menopaúsica humana 150 UI/día); realizando disparo de ovulación con 10.000 UI gonadotropina coriónica humana urinaria al obtener 2 o 3 folículos entre 17-18 mm de diámetro. Se realizó aspiración folicular con aguja bilumen a las 35 horas del disparo, fecundación in vitro en medios secuenciales y transferencia embrionaria al día 3. El soporte de fase lútea constó de progesterona natural micronizada 600 mg/día y valerato de estradiol 4 mg/día. Se realizó prueba de embarazo cuantitativa a los quince días y verificación de embriocardia al mes. Se compara: tasa de cancelación, días de estimulación, número de ovocitos aspirados, tasa de embarazo clínico por transferencia y tasa de aborto. Resultados: Se incluyeron 115 pacientes: 69 al protocolo de microdosis y 46 al de priming de estradiol. No hubo diferencias estadísticas entre ambos protocolos en cuanto a: número de ovocitos aspirados, tasa de embarazo clínico y aborto. Los días de estimulación y la dosis total de gonadotropinas fue mayor con microdosis. Conclusiones: Aunque no hubo diferencias estadísticamente significativas entre ambos protocolos, el de priming de estradiol por tener menos días de estimulación y dosis totales de gonadotropinas menores, implica mayor bienestar de la paciente.
Objective: To compare microdose leuprolide acetate protocols and Estradiol Priming. Methods: Retrospective study of 115 low-responding patients (according to Bologna Criteria), evaluated at UNIFERTES from January 2010 to December 2012, who underwent controlled ovarian hyperstimulation as per Microdose leuprolide acetate protocol or Estradiol Priming Protocols. Ovarian induction consisted of a set standard with gonadotropins, 450UI/day recombinant follicle-stimulating hormone + 150UI/day Human Menopausal Gonadotropin; performing an ovulation trigger shot with 10,000UI urinary human chorionic gonadotropin when obtaining 2 to 3 follicles of 17-18mm diameter. Follicular aspiration is performed with double lumen needle, 35 hours from trigger shot with in vitro fertilization in sequential media, and embryo transfer on day 3. Luteal phase support consisted of 600mg/day micronized natural progesterone and 4mg/day of estradiol valerate. Quantitative pregnancy test was carried out at fifteen days and embryo cardiac activity validation at one month. The following are compared: cancellation rate, stimulation days, number of aspirated oocytes, rate of clinical pregnancy by transfer and abortion rate. Results: 115 patients were included: 69 underwent microdose leuprolide acetate protocol flare and 46 underwent estradiol priming. There were no statistical differences between both protocols with regards to: number of aspirated oocytes, rate of clinical pregnancy by transfer and abortion rate. Stimulation days and therefore, gonadotropins total dosage was greater with microdose leuprolide acetate protocol. Conclusions: Even though there were no significant statistical differences between both protocols, estradiol priming entails greater patients wellbeing, since it requires less stimulation days and less gonadotropin total dosages.
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Objective To explore the clinical efficacy of Danzhi Xiaoyao capsule combined with leuprolide acetate for treatment of central precocious puberty(CPP) in children.Methods One hundred and six female children with CPP in Xinyang Central Hospital from March 2015 to December 2016 were selected and divided into control group and observation group by random digits table,with 53 children in each group.The children in the control group were given leuprolide acetate subcutaneously;based on this,the children in the observation group were given Danzhi Xiaoyao capsule.After treatment,the ovarian volume,uterine volume,bone age index,sex hormone,height change,clinical efficacy and adverse reactions of children were compared between the two groups.Results Before treatment,there was no statistic difference in the ovarian volume,uterine volume and bone age index of children between the two groups (P ＞ 0.05);the ovarian volume,uterine volume and bone age index of children in the two groups after treatment were significantly lower than those before treatment (P ＜ 0.05);the ovarian volume,uterine volume and bone age index of children in the observation group were significantly lower than those in the control group (P ＜ 0.05).Before treatment,there was no statistic difference in the luteotropic hormone (LH),follicle-stimulating hormone (FSH) and estradiol(E2) levels of children between the two groups (P ＞ 0.05);the LH,FSH and E2 levels of children in the two groups after treatment were significantly lower than those before treatment (P ＜ 0.05);the LH,FSH and E2 levels of children in the observation group were significantly lower than those in the control group (P ＜ 0.05).The height growth speed of children in observation group [(4.52 + 0.83) cm · a-1] was significantly lower than that in control group [(7.35 ± 1.02) cm · a-1] (P ＜ 0.05).The total effective rate of children in observation group (92.45％) was significantly higher than that of control group (73.58％) (x2 =6.692,P ＜ 0.05).There was no adverse effects in the two groups during treatment.Conclusion Danzhi Xiaoyao capsule combined with leuprolide acetate for treatment of central precocious puberty in children has evident effect,less adverse reactions;it can effectively regulate the sex hormones levels of body,and delay the growth time.
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Objective To establish a determination method for leuprolide acetate microspheres. Methods HPLC was performed on Inertsil ODS-SP (150×4.6 mm×5μm) with mobile phase consist of 0.1 mol/L of Ammonium Dihydrogen Phosphate(adjust its pH to 7.00±0.05 with Ammonium Hydroxide) and Acetonitrile in ratio of 3:1(V/V),and the flow rate was 1.0 mL/min.The wavelength was 220 nm and column temperature was 30℃. The injection volume was 20 μL. Results The linear range of leuprolide acetate was 20.0-160.0μg/mL (r=0.9999) with an average recovery of 99.80%,RSD=0.63%(n=9). Conclusion The method of HPLC was accurate,reliable and specific, which could be used to determinate the assay of leuprolide acetate microspheres and for quality control of microspheres.
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A phospholipid-based injectable gel was developed for the sustained delivery of leuprolide acetate (LA). The gel system was prepared using biocompatible materials (SPME), including soya phosphatidyl choline (SPC), medium chain triglyceride (MCT) and ethanol. The system displayed a sol state with low viscosity in vitro and underwent in situ gelation in vivo after subcutaneous injection. An in vitro release study was performed using a dialysis setup with different release media containing different percentages of ethanol. The stability of LA in the SPME system was investigated under different temperatures and in the presence of various antioxidants. In vivo studies in male rats were performed to elucidate the pharmacokinetic profiles and pharmacodynamic efficacy. A sustained release of LA for 28 days was observed without obvious initial burst in vivo. The pharmacodynamic study showed that once-a-month injection of LA-loaded SPME (SPME-LA) led to comparable suppression effects on the serum testosterone level as observed in LA solution except for the onset time. These findings demonstrate excellent potential for this novel SPME system as a sustained release delivery system for LA.
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OBJECTIVE:To discuss clinical efficacy and safety of leuprolide acetate in the treatment of endometriosis. METH-ODS:66 endometriosis patients were divided into observation group(37 cases)and control group(29 cases)according to random number table method. Observation group was treated with Leuprolide acetate microsphere for injection,3.75 mg/time,on the upper arm,abdomen or buttocks since the first-fifth day of menstrual cycle(administration time was available at hysterectomized patients disposal),and then every 4 weeks;one administration was recognized as a treatment course. Control group was treated with Ethi-nyl estradiol cyproterone tablet orally,1 tablets per day for 3 weeks,one week drug withdrawal,as a treatment course. 2 groups were given 3-5 courses of treatment according to their tolerance or the improvement of clinical symptoms. The improvement of clini-cal symptoms were compared between 2 groups,and the levels of FSH,LH and E2 were compared before and after treatment;the occurrence of ADR and the time of the return of menses were recorded. RESULTS:2 patients in observation group and 1 patient in control group withdrew from the test. After treatment,total effective rate was 97.14% in observation group,which was significant-ly higher than 75.00% in control group,with statistical significance (P0.05). After treatment,the levels of FSH,LH and E2 were de-creased significantly,and the observation group was more significant than the control group,with statistical significance (P0.05). The time of the return of menses in observation group was (89.75 ± 3.34) d after drug withdrawal,com-pared to control group [(88.46±2.94)d],there was no statistical significance(P>0.05). CONCLUSIONS:Leuprolide acetate can effectively improve clinical symptoms of patients with endometriosis,and reduce the levels of FSH,LH and E2 with slight ADR, and it doesn’t influence the time of the return of menses.
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OBJECTIVE:To observe the efficacy and safety of Guizhi fuling capsule combined with leuprolide acetate in the treatment of endometriosis (EMS) after laparoscopicsurgery. METHODS:87 EMS patients were randomly divided into control group(44 cases)and observation group(43 cases). Control group received EMS resection under laparoscope,3.75 mg Leuprolide acetate for injection was given in the first day of postoperative first menstruation by intramuscular injection,once a day. Observa-tion group additionally received 0.93 g Guizhi fuling capsule,3 times a day. The treatment course for both groups was 6 months. Clinical efficacy,estradiol(E2),follicle stimulating hormone(FSH),luteinizing hormone(LH)and prolactin(PRL)levels before and after treatment,recurrence after 6 months and the incidence of adverse reactions in 2 groups were observed. RESULTS:The to-tal effective rate in observation group was significantly higher than control group,recurrence rate was significantly lower than con-trol group,the differences were statistically significant (P0.05);after treatment,E2,FSH,LH and PRL in 2 groups were significantly lower than be-fore,and E2,FSH and LH in observation group were lower than control group,the differences were statistically significant (P0.05). And there was no significant difference in the inci-dence of adverse reactions in 2 groups (P>0.05). CONCLUSIONS:After laparoscope resection,Guizhi fuling capsule combined with leuprolide acetate can effectively improve efficacy,reduce sex hormone level and recurrence rate,and do not increase the inci-dence of adverse reactions in the treatment of EMS.
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Leuprolide acetate is an established luteinizing hormone-releasing hormone (LHRH) agonist used as a first-line treatment in advanced prostate cancer. An 80-year-old man presented with a localized erythematous patch with an indurated plaque and nodule and pustules on the left upper arm. The patient had been treated for metastatic prostate cancer with subcutaneous injections of leuprolide acetate 18 months previously. Histopathologic findings revealed granulomas with multinucleated giant cells from the dermis to the subcutaneous fat layer. The granuloma contained numerous round vacuoles. Cultures from the tissue for bacteria, fungi, and mycobacteria were all negative. The diagnosis of leuprolide acetate-induced foreign body granuloma was made by clinicopathologic findings. Various theories on the mechanism of local reactions to leuprolide have been suggested. The formation of granulomas may be related to the poly (lactic-co-glycolic acid) polymers or leuprolide itself. The depth of injection could have also contributed; therefore, intramuscular injection is recommended to minimize granuloma formation. To the best of our knowledge, there has been no reported case of leuprolide-induced foreign body granuloma in a patient with prostate cancer in the Korean literature. Dermatologists need to know that leuprolide acetate depot injection may cause a granulomatous reaction.
Subject(s)
Aged, 80 and over , Humans , Arm , Bacteria , Dermis , Diagnosis , Foreign Bodies , Fungi , Giant Cells , Gonadotropin-Releasing Hormone , Granuloma , Granuloma, Foreign-Body , Injections, Intramuscular , Injections, Subcutaneous , Leuprolide , Polymers , Prostate , Prostatic Neoplasms , Subcutaneous Fat , VacuolesABSTRACT
Leuprolide acetate is an established luteinizing hormone-releasing hormone (LHRH) agonist used as a first-line treatment in advanced prostate cancer. An 80-year-old man presented with a localized erythematous patch with an indurated plaque and nodule and pustules on the left upper arm. The patient had been treated for metastatic prostate cancer with subcutaneous injections of leuprolide acetate 18 months previously. Histopathologic findings revealed granulomas with multinucleated giant cells from the dermis to the subcutaneous fat layer. The granuloma contained numerous round vacuoles. Cultures from the tissue for bacteria, fungi, and mycobacteria were all negative. The diagnosis of leuprolide acetate-induced foreign body granuloma was made by clinicopathologic findings. Various theories on the mechanism of local reactions to leuprolide have been suggested. The formation of granulomas may be related to the poly (lactic-co-glycolic acid) polymers or leuprolide itself. The depth of injection could have also contributed; therefore, intramuscular injection is recommended to minimize granuloma formation. To the best of our knowledge, there has been no reported case of leuprolide-induced foreign body granuloma in a patient with prostate cancer in the Korean literature. Dermatologists need to know that leuprolide acetate depot injection may cause a granulomatous reaction.
Subject(s)
Aged, 80 and over , Humans , Arm , Bacteria , Dermis , Diagnosis , Foreign Bodies , Fungi , Giant Cells , Gonadotropin-Releasing Hormone , Granuloma , Granuloma, Foreign-Body , Injections, Intramuscular , Injections, Subcutaneous , Leuprolide , Polymers , Prostate , Prostatic Neoplasms , Subcutaneous Fat , VacuolesABSTRACT
Introdução: O acetato de leuprorrelina, substância ativa do medicamento Eligard®, é um análogo sintético não peptídeo do hormônio liberador do hormônio luteinizante (LHRH) que está bem estabelecido para o tratamento de primeira linha para pacientes com câncer de próstata avançado. Diversas opções de análogos LHRH estão disponíveis no Brasil, com diferentes formulações e periodicidade entre as aplicações. O Eligard® 45mg, de administração semestral, pode trazer vantagens clínicas e econômicas pela sua maior duração de efeito. Objetivo: Realizar uma avaliação econômica comparando diferentes apresentações de Eligard® e outros análogos LHRH no tratamento de pacientes com câncer de próstata avançado ou metastático no Brasil, sob as perspectivas do SUS, serviços públicos e saúde suplementar. Método: Modelos de Markov foram desenvolvidos para avaliar custos e desfechos em coortes de pacientes com câncer de próstata metastático, sem tratamento prévio, submetidos à terapia de privação androgênica e tratamentos subsequentes. Eligard® 45 mg, em sua forma de depósito semestral, foi colocado em perspectiva econômica com outras seis apresentações de análogos de LHRH disponíveis no mercado nacional. Resultados: O bloqueio androgênico, com qualquer um dos análogos LHRH avaliados, resultou em uma expectativa de vida média de 31,44 meses em todas as perspectivas analisadas...
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Humans , Economics, Pharmaceutical , Gonadotropin-Releasing Hormone , Prostatic NeoplasmsABSTRACT
This study investigated the effect of leuprolide acetate treatment on sex offenders' sexual fantasies and behaviors, as well as on their criminogenic psychological character and the risk of second conviction. The study participants consisted of 22 sex offenders who were confined to the National Institute of Forensic Psychiatry. Among them, 9 patients were given off-label leuprolide acetate for three months to inhibit sexual impulses, whereas the others were not given any medication. All sex offenders underwent two psychological evaluations; the first evaluation was conducted before starting medication, and the second was conducted after medication. Wilson's Sex Fantasy Questionnaire (WSFQ), the Rape Myth Acceptance Scale (RMAS), and the Endorsement of Violence Scale (EVS) were used for evaluation. Leuprolide acetate-treated sex offenders showed a statistically significant decline in the total WSFQ score (p < 0.05). However, the RMAS and EVS scores did not differ after leuprolide acetate treatment, indicating that cognitive distortions like rape myth acceptance and endorsement of violence were unchanged after leuprolide medication. Leuprolide acetate may reduce deviant sexual impulses and fantasies, as suggested by previous research form Korea and other countries. However, it probably cannot alter cognitive distortion. On the basis of these findings, we recommend a combination of leuprolide medication and other therapies, like cognitive behavioral therapy, for the treatment of paraphilic sex offenders.
Subject(s)
Humans , Cognitive Behavioral Therapy , Criminals , Fantasy , Forensic Psychiatry , Korea , Leuprolide , Paraphilic Disorders , Rape , Violence , Surveys and QuestionnairesABSTRACT
PURPOSE: We evaluated the efficacy, safety and psychological aspect of monthly administrations of the gonadotropin-releasing hormone agonists (GnRHa), leuprolide acetate depot (Luphere depot 3.75 mg), in patients with precocious puberty. METHODS: A total of 54 girls with central precocious puberty were administered with leuprolide acetate (Luphere depot 3.75 mg) every four weeks over 24 weeks. We evaluated the percentage of children exhibiting a suppressed luteinizing hormone (LH) response to GnRH (LH peak< or =3 IU/L), peak LH/follicle stimulating hormone (FSH) ratio of GnRH stimulation test less than 1, change in bone age/chronologic age ratio, change in the Tanner stage and change in eating habit and psychological aspect. RESULTS: (1) The percentage of children exhibiting a suppressed LH response to GnRH, defined as an LH peak< or =3 IU/L at 24 weeks was 96.3 % (52/54). (2) The percentage of children exhibiting peak LH/FSH ratio<1 at 24 weeks of the study was 94.4 % (51/54). (3) The ratio of bone age and chronological age significantly declined from 1.27+/-0.07 to 1.24+/-0.01 after the 6 months of the study. (4) The mean Tanner stage manifested a significant change 2.3+/-0.48 at baseline, down to 1.70+/-0.61 at 24 weeks. (5) Based on the questionnaires, the score for eating habits showed a significant change from the baseline 34.0+/-6.8 to 31.3+/-6.8. (6) The psychological assessment did not exhibit a significant difference except with scores for sociability, problem behavior total score and other problems. CONCLUSION: The leuprolide 3.75 mg (Luphere depot) is useful and safety for treating children with central precocious puberty.
Subject(s)
Child , Female , Humans , Eating , Gonadotropin-Releasing Hormone , Leuprolide , Luteinizing Hormone , Puberty, Precocious , Treatment Outcome , Surveys and QuestionnairesABSTRACT
PURPOSE: The goal of this study was to investigate the effects of luteinizing hormone-releasing hormone(LHRH) agonist treatment on erectile function in an animal model. MATERIALS AND METHODS: New Zealand White male rabbits were either kept intact(control), surgically orchiectomized, or treated for 2, 4, or 8 weeks with the LHRH agonist leuprolide acetate(107microgram/kg/mo). Plasma testosterone levels were measured by enzyme-linked immunosorbent assay. Nitric oxide synthase activity in the total tissue extract was determined by measuring conversion of L-[14C(U)]arginine to [14C]citrulline and nitric oxide. Arginase activity in cytosolic extract was assessed by the Ruegg and Russel method. Erectile function was assessed by continuously recording systemic arterial pressure(SAP) and intracavernosal blood pressure(ICP) and determining the ICP:SAP ratios in response to electrical stimulation of the pelvic nerve at frequencies of 2.5 to 32 Hz. RESULTS: At 2 weeks, plasma testosterone levels of the orchiectomized and leuprolide acetate-treated animals were 12.8% and 57.4% of those in intact control animals, respectively. Androgen deprivation by orchiectomy or leuprolide acetate treatment reduced ICP at all frequencies tested but did not alter SAP. Administration of the phosphodiesterase type 5 inhibitor vardenafil(10microgram/kg) did not enhance ICP in orchiectomized or leuprolide acetate-treated animals. Nitric oxide synthase and arginase activities in the corpus cavernosum were not significantly altered by orchiectomy or leuprolide acetate. Masson trichrome staining of erectile tissue from androgen-ablated animals showed a reduction in smooth muscle content. CONCLUSIONS: Androgen deprivation achieved by orchiectomy or leuprolide acetate treatment adversely affects penile hemodynamics and erectile function without producing significant changes in the activities of nitric oxide synthase or arginase. We conclude that androgen deprivation by LHRH agonist produces structural alterations in the corpus cavernosum leading to corporal veno-occlusive dysfunction.
Subject(s)
Animals , Humans , Male , Rabbits , Androgens , Arginase , Cytosol , Electric Stimulation , Enzyme-Linked Immunosorbent Assay , Erectile Dysfunction , Gonadotropin-Releasing Hormone , Hemodynamics , Leuprolide , Lutein , Models, Animal , Muscle, Smooth , New Zealand , Nitric Oxide , Nitric Oxide Synthase , Orchiectomy , Plasma , TestosteroneABSTRACT
We performed this study to observe the effects of chronic administration of leuprolide acetate(potent synthetic LHRH analog) to the testicular histopathology of prostatic cancer patient and to the spermatogenesis in cryptochism treatment. Ten out of fifty healthy male rats whose body weight ranged 250-300gm were selected as a control group and the other forty as a study group. Two hundred micro-gram of leuprolide acetate was injected daily into the peritoneal cavity of study group, and ten rats were sacrificed at each first, second, third and sixth week, respectively. Then the changes of testicular weight and histopathological readings under light microscope of both control and study group were recorded and analyzed. The results of experimental data can be summarized as follows : 1. The average testicular weight of control group increased progressively until sixth week to 1. 1.43gm from the initial value of 1.26gm, while the weight of study group decreased to 0.96gm which was 67.1 % of age-matched control group. 2. There were almost no remarkable changes between both groups in terms of number, size and cellularity of seminiferous tubules. We observed the degenerative and regenerative changes simultaneously in spermatogonia and spermatocytes. During the first three weeks, degenerative changes took place while the regenerative changes started from the second week and have fully recovered at the sixth week. And, the number of spermatids and spermatozoa slightly decreased at the first week, but have recovered to normal value from the second week. 3. There were noticeable changes neither in the interstitium of testes except the minimal edema nor in terms of size and number of Leydig cell. The results using rats showed the discordance with those of human study of prostatic cancer patient. This conflict can be attributed to the functional differences of leuprolide action between two species, age of sacrificed rats and insufficiency of dose and time of administration. However, we can draw another conclusion that the leuprolide acetate is expected to have no significant adverse effects to the spermatogenesis in cryptorchism treatment.