Cost-Effectiveness Analysis of Triptorelin, Goserelin, and Leuprolide in the Treatment of Patients With Metastatic Prostate Cancer: A Societal Perspective.

OBJECTIVES: Metastatic prostate cancer is the most common malignant cancer and the second leading cause of death due to various types of cancer among men after lung cancer. This study aimed to analyze the cost-effectiveness of triptorelin, goserelin, and leuprolide in the treatment of the patients with metastatic prostate cancer from the societal perspective in Iran in 2020. METHODS: This is a cost-effectiveness study in which a 20-year Markov transition modeling was applied. In this study, local cost and quality-of-life data of each health state were gathered from cohort of patients. The TreeAge pro 2020 and Microsoft Excel 2016 software were used to simulate cost-effectiveness of each treatment in the long term. The one-way and probabilistic sensitivity analyses were also performed to measure robustness of the model outputs. RESULTS: The findings indicated that the mean costs and utility gained over a 20-year horizon for goserelin, triptorelin, and leuprolide treatments were $ 13 539.13 and 6.365 quality-adjusted life-years (QALY), $ 18 124.75 and 6.658 QALY, and $ 26 006.92 and 6.856 QALY, respectively. Goserelin was considered as a superior treatment option, given the estimated incremental cost-effectiveness ratio. The one-way and probabilistic sensitivity analyses confirmed the robustness of the study outcomes. CONCLUSIONS: According to the results of the present study, goserelin was the most effective and cost-effective strategy versus 2 other options. It could be recommended to policy makers of the Iran healthcare system to prioritize it in clinical guidelines and reimbursement policies.

Triptorelina para uso en púberes con necesidad de terapia hormonal para alcanzar su libre desarrollo personal / Triptorelin for use in puberty with need of hormonal therapy to achieve their free personal development

CONTEXTO: El Sistema de Salud Pública de Neuquén cuenta con Leuprolide en su Formulario Terapéutico Provincial (FTP) para tratamiento de estas indicaciones. Desde el Ministerio de Salud de Nación se comenzó a enviar Triptorelina, lo que motivó la realización del presente informe, buscando responder las siguientes preguntas: 1. ¿Es eficaz el tratamiento con triptorelina en púberes con necesidad de terapia hormonal para alcanzar su libre desarrollo personal comparado con medicamentos alternativos disponibles en el FTP (leuprolide)? 2. ¿Es seguro el tratamiento con triptorelina en púberes necesidad de terapia hormonal para alcanzar su libre desarrollo personal comparado con medicamentos alternativos disponibles en el FTP (leuprolide)? 3. ¿Cuál es el costo por tratamiento y el potencial impacto presupuestario del tratamiento con triptorelina a necesidad de terapia hormonal para alcanzar su libre desarrollo personal? 4. ¿Cuál es el potencial impacto en la equidad de la incorporación de la tecnología? TECNOLOGÍA: Triptorelina es un análogo de la GnRH que se utiliza para inhibir el eje hipotálamo-hipofiso-gonadal. MÉTODOS: un equipo multidisciplinario e independiente realizó una búsqueda sistemática de bibliografía científica priorizando la inclusión de revisiones sistemáticas y metanálisis, evaluaciones de tecnologías sanitarias e informes de seguridad, Guías de Práctica Clínica basadas en la evidencia que fueran independientes. RESULTADOS: No se encontraron comparaciones cabeza a cabeza entre Leuprolide y Triptorelina. Triptorelina ha demostrado eficacia en suprimir el eje hipotálamo-hipofiso-gonadal en púberes, tanto en aplicaciones mensuales y trimestrales. Presenta un perfil de efectos adversos similares a otros análogos disponibles en el Formulario Terapéutico Provincial. Es una medicación que no es de mayor costo a otros análogos disponibles en el Formulario Terapéutico Provincial. RECOMENDACIONES: Se recomienda la aprobación de Triptorelina para inhibición del eje hipotálamo-hipófiso-gonadal en puberes con necesidad de terapia hormonal para alcanzar su libre desarrollo personal. CONCLUSIONES: Se concluye que la triptorelina es eficaz y segura para inhibir el eje hipotálamo-hipófiso-gonadal. No se hallaron estudios en la bibliografía que comparen específicamente la triptorelina con los medicamentos disponibles en el FTP para esta indicación o población particular.. No representan una alternativa que implique mayores costos al sistema de salud de la Provincia de Neuquén, ni un potencial impacto negativo en la equidad.

New approaches to non-surgical sterilization for dogs and cats: Opportunities and challenges.

Over the last 40 years, researchers have explored methods to non-surgically suppress fertility in animals. Immunocontraception has been used to control wildlife populations but does not confer long-term immunity. The gonadotropin-releasing hormone (GnRH) agonist deslorelin, formulated as an implant to provide 6-month to 1-year suppression of fertility in male dogs, is available commercially in some countries. Neither of these approaches provide permanent sterility. A single-dose, permanent treatment would be a valuable tool in dog and cat population control. The Michelson Prize and Grants (MPG) programme was initiated "to eliminate shelter euthanasia of healthy, adoptable companion animals and reduce populations of feral and free-roaming cats and dogs" offering a $25 million US prize for a non-surgical sterilant that is effective as a single treatment in both male and female dogs and cats. Michelson Prize and Grants programme has offered US $50 million in grant money for research and has attracted scientists worldwide. Approaches under study include gene therapy, small interfering RNA to inhibit reproductive targets and delivery of cytotoxins to pituitary gonadotrophs or GnRH producing neurons in the hypothalamus. Research in implant technology that could deliver compounds over an animal's lifetime is also underway. Details of funded grants and results to date can be found at: http://www.michelsonprizeandgrants.org/michelson-grants/research-findings. The next steps are translating the most promising research into products. The Alliance for Contraception of Cats and Dogs (ACC&D) is helping to research practical methods of marking sterilized animals to avoid costly retreatment and population modelling that will help guide field workers in use of resources for sterilization programmes.

Assessment of Estradiol Response after Depot Triptorelin Administration in Girls with Central Precocious Puberty.

BACKGROUND: Estradiol at baseline or after a classical gonadotropin-releasing hormone test did not reflect ovarian steroidogenesis in central precocious puberty (CPP) girls. AIMS: To evaluate estradiol response to depot triptorelin, both at start and during therapy to determine how active ovarian steroidogenesis is at pubertal stage and under therapy. METHODS: A prospective study was performed in 43 CPP girls. Serum luteinizing hormone and follicle-stimulating hormone at 3 h (LH-3h, FSH-3h) and estradiol at 24 h (E2-24h) after injection of depot triptorelin 3.75 mg were measured, at first dose and at 3, 6, 12, 18 and 24 months of treatment. RESULTS: E2-24h after depot triptorelin was >100 pg/ml after the first dose. Estradiol response (E2-24h) fell to levels <14 pg/ml in 78 out of 82 follow-up visits along 2 years of therapy. Concomitantly, LH-3h and FSH-3h were <4.0 and <6.3 IU/l, respectively. In 4 patients with inadequate treatment, E2-24h, LH-3h and FSH-3h rose to pubertal values similar to those observed at first dose. CONCLUSION: Estradiol (<14 pg/ml) assessment 24 h after depot triptorelin administration is a reliable and simple manner to confirm ovarian suppression in CPP girls during treatment.

Cost-effectiveness comparison between pituitary down-regulation with a gonadotropin-releasing hormone agonist short regimen on alternate days and an antagonist protocol for assisted fertilization treatments.

OBJECTIVE: To compare cost-effectiveness between pituitary down-regulation with a GnRH agonist (GnRHa) short regimen on alternate days and GnRH antagonist (GnRHant) multidose protocol on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcome. DESIGN: Prospective, randomized. SETTING: A private center. PATIENT(S): Patients were randomized into GnRHa (n = 48) and GnRHant (n = 48) groups. INTERVENTION(S): GnRHa stimulation protocol: administration of triptorelin on alternate days starting on the first day of the cycle, recombinant FSH (rFSH), and recombinant hCG (rhCG) microdose. GnRHant protocol: administration of a daily dose of rFSH, cetrorelix, and rhCG microdose. MAIN OUTCOME MEASURE(S): ICSI outcomes and treatment costs. RESULT(S): A significantly lower number of patients underwent embryo transfer in the GnRHa group. Clinical pregnancy rate was significantly lower and miscarriage rate was significantly higher in the GnRHa group. It was observed a significant lower cost per cycle in the GnRHa group compared with the GnRHant group ($5,327.80 ± 387.30 vs. $5,900.40 ± 472.50). However, mean cost per pregnancy in the GnRHa was higher than in the GnRHant group ($19,671.80 ± 1,430.00 vs. $11,328.70 ± 907.20). CONCLUSION(S): Although the short controlled ovarian stimulation protocol with GnRHa on alternate days, rFSH, and rhCG microdose may lower the cost of an individual IVF cycle, it requires more cycles to achieve pregnancy. CLINICAL TRIAL REGISTRATION NUMBER: NCT01468441.

Experimental manipulation of fertility reveals potential lactation costs in a free-ranging marsupial.

Lactation is the most energetically expensive component of reproduction in mammals. Theory predicts that reproducing females will adjust their behaviour to compensate for increased nutritional demands. However, experimental tests are required, since comparisons of the behaviour of naturally reproducing and non-reproducing females cannot distinguish between true costs of reproduction, individual differences or seasonal variation. We experimentally manipulated reproduction in free-ranging, eastern grey kangaroos (Macropus giganteus), using a fertility control agent. Our novel field experiment revealed that females altered their behaviour in direct response to the energetic demands of reproduction: reproducing females increased bite rates, and thus food intake, when the energetic demands of lactation were highest. Reproducing females did not reduce the time spent on vigilance for predators, but increased their forage intake on faecal-contaminated pasture, thereby increasing the risk of infection by gastrointestinal parasites-a largely unrecognized potential cost of reproduction.

Cost-effectiveness analysis of LHRH agonists in the treatment of metastatic prostate cancer in Italy.

OBJECTIVES: Luteinizing hormone-releasing hormone (LHRH) agonists represent one of the main cost factors in the management of patients with metastatic prostate cancer. We compared the cost-effectiveness of the five different 3-month formulations of LHRH agonists currently available for advanced prostate cancer in Italy, because these differ both in their capacity to suppress testosterone and in their acquisition costs. METHODS: A probabilistic, patient-level simulation model was developed to compare the cost-effectiveness, from the perspective of the Italian National Health Service (INHS), of leuprorelin 11.25 mg and 22.5 mg, triptorelin 11.25 mg, buserelin 9.9 mg, and goserelin 10.8 mg. The model incorporated testosterone-dependent progression-free and cancer-specific survival functions, LHRH agonist effectiveness data, and national costs and tariffs. Cox's proportional hazard models were used to compute total and progression-free survival functions based on clinical data from 129 patients with metastatic prostate cancer treated in an Italian center. Bayesian random effects models were employed to summarize evidence from published literature on testosterone suppression obtained with the available LHRH agonists. RESULTS: Estimated total survival was ≈5 years, with a maximum difference between treatment options of ≈2 months. There was a mean difference of almost €2,500 in lifetime total costs between the least costly option (leuprorelin 22.5 mg) and the most expensive (goserelin). In the incremental cost-effectiveness analysis, leuprorelin 22.5 mg dominated all alternatives except buserelin, which had an incremental cost-effectiveness ratio versus leuprorelin 22.5 mg of ≈€12,000 per life-month gained. CONCLUSIONS: Based on modelling with meta-analysis of comparative survival data, leuprorelin 22.5 mg was the most cost-effective treatment of the available depot formulation LHRH agonists.

Administration of alternate day triptorelin for controlled ovarian hyperstimulation is cost effective.

Gonadotropin-releasing hormone agonists in an alternate-day dosage resulted in similar clinical pregnancy rates as the daily protocol. No premature luteinization was reported in either group. Total GnRH agonist dosage in the alternate-day protocol was significantly reduced.

An open and randomized study comparing the efficacy of standard danazol and modified triptorelin regimens for postoperative disease management of moderate to severe endometriosis.

OBJECTIVE: To compare the efficacy of danazol and triptorelin (Decapeptyl CR, Ferring, Kiel, Germany) in the management of moderate and severe endometriosis in terms of symptom control and revised American Fertility Society (AFS) score reduction, and to evaluate the hormonal profile of patients treated with triptorelin every 6 weeks. DESIGN: Open and randomized trial. SETTING: Kwong Wah Hospital, a large public hospital in an urban location (Hong Kong). PATIENT(S): Forty patients after their first conservative operation for endometriosis, with surgical confirmation of revised AFS stage III or IV endometriosis. INTERVENTION(S): Postoperative 6 months' therapy of danazol or triptorelin every 6 weeks, postmedical therapy second-look laparoscopy. MAIN OUTCOME MEASURE(S): Symptom control and patients' tolerance during medical therapy, posttherapy revised AFS score, hormonal profile during triptorelin therapy. RESULT(S): Pain control was similar between danazol and triptorelin therapy. There was less breakthrough bleeding with triptorelin. More patients failed to complete the whole course of danazol because of its side effects. The revised AFS score at second-look laparoscopy did not show a significant difference between the two medications. Adequate pituitary suppression was observed with injection of triptorelin every 6 weeks. CONCLUSION(S): Lengthening of triptorelin administration intervals from 4 weeks to 6 weeks is effective in maintaining a hypoestrogenic state. Patients were more compliant with triptorelin than danazol. Thus, triptorelin injection every 6 weeks is more cost-effective than conventional regimens.

The use of clomiphene citrate/human menopausal gonadotrophins in conjunction with GnRH antagonist in an IVF/ICSI program is not a cost effective protocol.

OBJECTIVE: To evaluate the cost effectiveness of a clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/GnRH antagonist protocol versus a long-acting GnRH agonist/hMG protocol. PARTICIPANTS AND METHODS: One hundred eighty nine couples having their first trial of ICSI for male factor infertility were divided into two groups. Group I (no = 33) received CC 100-150 mg/day for five days starting from day 2 of the cycle and 150 IU of hMG/day on days 6-10. GnRH antagonist (Centrorelix) 0.25 mg/day was started when the leading follicle reached 16 mm in the absence of an LH surge. Group II (no = 156) received 0.1 mg Deacapeptyl/day as our standard long protocol. RESULTS: Clinical pregnancy was observed in 8 out of the 33 cases in group I (24%) while in group II, 92 out of 156 achieved clinical pregnancy (59%), the difference was statistically significant (P = 0.019). The cost of medications/cycle was estimated to be 1110+/-492 E.P in group I, while it was 1928+/-456 E.P. in group II. However, the total cost per pregnancy was 19653 EP in group I and 10047 EP in group II. CONCLUSION: The use of the clomid/hMG/antagonist protocol is not a cost effective strategy and should not be recommended in IVF-ICSI cycles.