Clinical characteristics and treatment patterns with histrelin acetate subcutaneous implants vs. leuprolide injections in children with precocious puberty: a real-world study using a US claims database.

OBJECTIVES: Gonadotropin-releasing hormone analogs are the treatment of choice for central precocious puberty (CPP). This study characterizes patients treated with histrelin implant or leuprolide injection. METHODS: A US claims database was used to identify patients aged ≤20 years with ≥1 histrelin or leuprolide claim (index treatment) between April 2010 and November 2017 and continuous enrollment ≥3 months before and ≥12 months after the index treatment date. RESULTS: Overall, 4,217 patients (histrelin, n=1,001; leuprolide, n=3,216) were identified. The percentage of patients with CPP diagnosis was greater in the histrelin (96.5%) vs. leuprolide (68.8%; p<0.0001) cohort. In patients with CPP (histrelin, n=966; leuprolide, n=2,214), mean age at treatment initiation was similar for histrelin (9.0 ± 2.0 years) and leuprolide (9.1 ± 2.3 years), with >50% of patients aged 6-9 years. Mean treatment duration was significantly longer for histrelin (26.7 ± 14.8 months) vs. leuprolide (14.1 ± 12.1 months; p<0.0001), and was longer in younger patient groups. More patients switched from leuprolide to histrelin (12.3%) than vice versa (3.6%; p<0.0001). Median annual total treatment costs were slightly lower for the histrelin cohort ($23,071 [interquartile range, $16,833-$31,050]) than the leuprolide cohort ($27,021 [interquartile range, $18,314-$34,995]; p<0.0001). CONCLUSIONS: Patients with CPP treated with histrelin had a longer duration of treatment, lower rates of index treatment discontinuation, and lower annual treatment costs vs. those treated with leuprolide.

An assessment of the protective effect of gonadotropin-releasing hormone agonist and antagonist on bleomycin-induced ovarian toxicity in rats.

The aim of this study is to evaluate the effect of GnRH agonist or GnRH antagonist therapy on bleomycin-administered rats by examining ovarian follicle counts and AMH levels. A total of 30 female Wistar albino rats aged 4-6 months were randomly divided into 4 groups. First, an intramuscular injection of bleomycin (30 mg/m2) was administered to all except the control group on the 1st, 8th and 15th days. The control group (Group I) was administered 0.1 mL intramuscular saline on those days. The bleomycin group (Group II) was followed up without any further treatment. The bleomycin + GnRH agonist group (Group III) was administered subcutaneous GnRH agonist triptorelin (1 mg/kg) at the same time as the bleomycin injections. The bleomycin + GnRH antagonist group (Group IV) was administered 1 mg/kg cetrorelix acetate subcutaneously, concurrently with the bleomycin. Although AMH levels were lower in the bleomycin group than in all the other groups, there was no statistically significant difference between the groups in terms of AMH levels (p > .05). In the bleomycin + cetrorelix acetate and bleomycin + triptorelin groups, significantly higher primordial, secondary and tertiary follicle counts were determined compared to the bleomycin group (p < .001). In conclusion the harmful effects of bleomycin on ovarian reserve can be reduced by the simultaneous administration of GnRH agonist or GnRH antagonist.

Pubertal Suppression for Transgender Youth and Risk of Suicidal Ideation.

BACKGROUND AND OBJECTIVES: Gonadotropin-releasing hormone analogues are commonly prescribed to suppress endogenous puberty for transgender adolescents. There are limited data regarding the mental health benefits of this treatment. Our objective for this study was to examine associations between access to pubertal suppression during adolescence and adult mental health outcomes. METHODS: Using a cross-sectional survey of 20 619 transgender adults aged 18 to 36 years, we examined self-reported history of pubertal suppression during adolescence. Using multivariable logistic regression, we examined associations between access to pubertal suppression and adult mental health outcomes, including multiple measures of suicidality. RESULTS: Of the sample, 16.9% reported that they ever wanted pubertal suppression as part of their gender-related care. Their mean age was 23.4 years, and 45.2% were assigned male sex at birth. Of them, 2.5% received pubertal suppression. After adjustment for demographic variables and level of family support for gender identity, those who received treatment with pubertal suppression, when compared with those who wanted pubertal suppression but did not receive it, had lower odds of lifetime suicidal ideation (adjusted odds ratio = 0.3; 95% confidence interval = 0.2-0.6). CONCLUSIONS: This is the first study in which associations between access to pubertal suppression and suicidality are examined. There is a significant inverse association between treatment with pubertal suppression during adolescence and lifetime suicidal ideation among transgender adults who ever wanted this treatment. These results align with past literature, suggesting that pubertal suppression for transgender adolescents who want this treatment is associated with favorable mental health outcomes.

Treatment patterns, health resource utilization and costs among central precocious puberty patients treated with leuprolide or histrelin: an examination of the commercial and Medicaid populations.

Aims: To compare treatment duration, healthcare resource utilization (HRU), and direct healthcare costs between patients with central precocious puberty (CPP) treated with leuprolide or histrelin, and between patients with Medicaid or commercial insurance. This information is important as it affects treatment choice and outcomes.Materials and methods: This retrospective cohort study identified commercial and Medicaid-insured CPP patients ≤12-years-old who were diagnosed between 1 January 2010 and 30 September 2014 and had ≥1 prescription for leuprolide or histrelin (first prescription = index date). Treatment patterns were measured for the duration of available data; whereas, all-cause and disease-monitoring HRU and all-cause costs were compared between treatment groups for the year following treatment initiation. Multivariable analysis was used to adjust healthcare costs for differences in baseline patient characteristics.Results: A total of 1,177 commercially-insured (907 leuprolide and 270 histrelin) and 658 Medicaid-insured (613 leuprolide and 45 histrelin) patients were identified. Mean age at treatment initiation ranged from 7.5-8.5-years-old, 11.1-20.5% of patients were male, and the mean treatment duration was over one year. Commercially-insured patients treated with histrelin used more services in general than those treated with leuprolide but had fewer office visits. Healthcare service utilization was similar between Medicaid-insured treatment groups. In both payer populations, costs were similar.Limitations: The number of Medicaid-insured patients who received a histrelin implant was low, and this may make the findings more sensitive to influence by outliers.Conclusions: Mean overall healthcare costs were similar between CPP patients treated with leuprolide and those treated with histrelin. Medicaid patients generally received less testing and were less likely to receive specialist care. Patients treated with histrelin had fewer office visits but also had a shorter overall treatment.

Health Care Utilization and Economic Burden in Patients with Central Precocious Puberty: An Assessment of the Commercially Insured and Medicaid Populations.

BACKGROUND: Central precocious puberty (CPP), early onset of puberty caused by the premature activation of the hypothalamic-pituitary-gonadal axis, is a rare disease affecting children of both sexes. There is limited evidence that quantifies the economic burden of CPP. OBJECTIVE: To characterize the health care resource utilization (HRU) and costs among patients with CPP who were treated with gonadotropinreleasing hormone (GnRH) agonists, for those insured commercially and with Medicaid. METHODS: Eligible CPP patients for this retrospective cohort analysis were aged ≤ 12 years; were diagnosed between January 1, 2010, and September 30, 2014; and had at least 1 prescription for an FDA-approved GnRH agonist: leuprolide or histrelin (first prescription = index date). CPP patients had to be continuously enrolled in the MarketScan Commercial or Medicaid Database for at least 12 months before and after the index date. Control patients were randomly selected from all eligible non-CPP patients and N:1 matched on demographic characteristics with up to 20 controls per case. Clinical comorbidities, HRU, and costs were compared between study cohorts. Health care costs were examined via multivariable analysis to adjust for baseline differences between patients and controls. Treatment patterns among CPP patients were also characterized. RESULTS: There were 1,236 CPP patients and 24,206 controls with commercial insurance and 673 CPP patients and 11,965 controls with Medicaid insurance who met the inclusion criteria. Across payers, the mean age of CPP patients ranged from 7.6 years (Medicaid) to 8.5 (commercial), and 80%-87% were female. The mean observed duration (SD) of treatment with any approved GnRH agonist was 1.51 (0.98) years for commercial patients and 1.22 (1.04) for Medicaid patients. The mean age of discontinuation among patients who ceased GnRH agonist treatment ranged from 8.7 to 9.6 years. In the first year post-index, CPP patients had a greater number of unique diagnosis codes, unique medications, and comorbid conditions than controls. They also had significantly higher all-cause and diseasemonitoring related HRU. After adjusting for baseline characteristics, CPP patients with Medicaid insurance spent 6.42 times more ($16,768 [$31,460] vs. $2,610 [$4,897]), and patients with commercial insurance spent 12.25 times more ($19,940 [$20,132] vs. $1,628 [$1,645]) on health care in the year following treatment initiation than matched controls. CONCLUSIONS: Patients with CPP have substantially more comorbidities and greater HRU and costs than their non-CPP peers. DISCLOSURES: All funding for this study was provided by AbbVie, which participated in analysis and interpretation of data, drafting, reviewing, and approving the publication. All authors contributed to the development of the publication and maintained control over the final content. Soliman and Grubb are employed by AbbVie and hold stock in AbbVie. Bonafede and Nelson are employed by IBM Watson Health, which received funding from AbbVie to conduct this study. Klein is a paid consultant of AbbVie but was not compensated for any work on development of this manuscript for publication. Portions of this work were presented at Pediatric Academic Societies (PAS) 2018 Meeting, May 5-8, 2018, in Toronto, Canada, as a poster presentation titled "Examination of Economic Burden Among Commercially Insured Patients with Central Precocious Puberty (CPP)."

Evaluation of the cost-effectiveness of ovulation suppression with progestins compared with GnRH analogs in assisted reproduction cycles.

RESEARCH QUESTION: Is ovulation suppression with progestins, requiring a freeze-all approach and subsequent frozen embryo transfer resulting from progestenic endometrial changes, cost-effective compared with gonadotropin releasing hormone analogues (GnRH) during assisted reproduction cycles. DESIGN: Cost-effectiveness analysis derived from a PubMed literature search of average US costs of GnRH agonist and antagonist IVF cycles. RESULTS: In all fresh IVF cycle models, progestin cycles were more expensive owing to the additional costs of increased gonadotropin use, embryo freezing and subsequent frozen embryo transfer (FET). The average cost per live birth with progestins ($32,466-$56,194) was higher than fresh IVF cycles with short (flare) GnRH agonist ($4,447-$12,797 higher) and GnRH antagonist ($1,542-$9,893 higher). When analyzing an initial embryo transfer plus additional FET in patients not initially pregnant, progestin cycles were still more expensive per live birth compared with conventional protocols. When planned freeze only cycles were analyzed, progestins became more cost-effective per live birth compared with antagonist cycles ($2,079 lower) but remained more expensive than short agonist cycles ($823 more expensive). CONCLUSIONS: Ovulation inhibition in IVF using progestins requires a freeze-only approach of embryos, and thus progestin use was not cost-effective compared with fresh embryo transfer cycles. Progestins, however, may be cost-effective compared with GnRH antagonist in planned freeze only cycles such as in preimplantation genetic testing or fertility preservation.

Population-based estimate of the use of intermittent androgen deprivation therapy in prostate cancer patients in Catalonia, Spain.

PURPOSE: To estimate the use of intermittent androgen deprivation (IAD) therapy in patients with prostate cancer (PCa). METHODS: Retrospective, non-interventional study based on electronic pharmacy dispensation data of luteinizing hormone-releasing hormone (LHRH) analogs and anti-androgens in Catalonia (Spain). Intermittency was defined as the percentage of time off treatment (%IAD), which was calculated for the whole sample by dividing the sum of all off-IAD periods by the total time on any LHRH analog regimen. The prevalence of patients on an IAD regimen (PIAD ) was also estimated. A small validation study based on data from clinical records confirmed the excellent sensitivity and specificity of this approach. RESULTS: A total of 515 803 prescriptions for LHRH analog were dispensed over a 5-year period (2008 to 2012) to 35 089 PCa patients. The mean age (±SD) was 77 years (±9). The %IAD in the cohort was 1.7% whereas the 5-year prevalence (PIAD ) was 4.2%. Only 2.5% of patients on IAD were on IAD for >6 months. Of the physicians (n = 1638) who prescribed hormonal treatment, 24% used IAD at least once. Total expenditures for LHRH analogs were 1.2% of total drug expenditure in this population. CONCLUSIONS: This study confirms the validity of the method developed to estimate IAD use based on electronic pharmacy dispensation data. Given the large potential clinical and economic benefits that greater use of IAD could provide, future studies are needed to confirm these findings and to identify new strategies to increase the use of IAD.

[Assessment of the suppression of puberty in children with gender identity problems]. / Valoración de la supresión de la pubertad en menores con problemas de identidad de género.

The objective of this article is to reflect on the opportunity and risk of the proposed treatments to address gender identity problems in that sector of the population. In most of the protocols for the care of minors with gender identity problems, the abolition of puberty is proposed as a method of choice. This technique consists in the administration of reversible agonists of GnRH to provoke a suppression of the hormonal expression of the minor and, thus, the development of the sexual characters of their gender. The opportunity or adequacy of the systematic use of reversible GnRH agonists may be questioned for several reasons. The first, because the diagnosis of transsexualism in minors carries a great complexity and difficulty, so there is a wide margin of error. The second, because the suppression of puberty has direct consequences in the development of the child. Thirdly, because the aforementioned treatments have some risks and side effects in minors, some of them not studied and unknown, which, without a doubt, should be weighted. Finally, because the drugs used are neither designed nor experienced, for the care of minors with gender identity problems. Therefore, they are used without being approved by the regulatory agencies of the medicinal product for that purpose. These issues need to be addressed and also transmitted in the information provided to the stakeholders.

Neonate female to male ratio after assisted reproduction following antagonist and agonist protocols.

We retrospectively compared neonatal sex after antagonist- versus long-stimulation protocols followed by fresh in vitro fertilization (IVF) or fresh intracytoplasmic sperm injection (ICSI) with either protocol. We reviewed data for 762 IVF/ICSI cycles in 2015, including 23 IVF procedures. We summarized sex outcomes in the entire cohort, and for the additional subgroups: embryo transfer day and number of embryos transferred, and number of oocytes recovered and maternal age. Among 169 live births for all protocols combined, 50.9% of babies were male, and we saw no difference between the antagonist versus long-stimulation groups (52.3% vs 48.3% male babies, respectively; P = .740). Our results also showed no significant difference in sex proportion when comparing IVF versus ICSI, although a higher proportion of babies were male with the antagonist-ICSI protocol. Differences between the additional subgroups were also neither clinically nor statistically significant.

Patterns of Bicalutamide Use in Prostate Cancer Treatment: A U.S. Real-World Analysis Using the SEER-Medicare Database.

INTRODUCTION: Bicalutamide (BIC), a non-steroidal anti-androgen, is FDA-indicated for use in combination with a luteinizing hormone-releasing hormone (LHRH) analog for treatment of Stage D2 metastatic carcinoma of the prostate. Lack of consensus exists regarding the clinical benefit of BIC use, either alone or combined use of BIC with an LHRH analog or antagonist (combined androgen blockade or CAB), versus treatment with androgen deprivation therapy (ADT) alone. METHODS: The SEER-Medicare database was used to identify prostate cancer patients aged ≥ 66 years diagnosed between 2007 and 2011 and who filled at least one prescription for BIC. Duration of BIC treatment was assessed in relation to ADT use; either alone (monotherapy), as part of CAB only, and as part of CAB followed by monotherapy. Additionally, we assessed use of BIC during or outside a potential testosterone flare prevention period (initiation within 2 months of an LHRH agonist). RESULTS: A total of 7521 prostate cancer patients who filled a prescription for BIC were identified. Eighteen percent of the cohort used BIC alone, over half the patients (54%) used BIC as part of CAB and 27% used BIC as part of CAB followed by monotherapy. Among men treated with BIC as part of CAB, 58% received BIC only within the potential flare period. CONCLUSIONS: Although there is no FDA indication for BIC use as monotherapy, > 44% of patients in this study used BIC alone or as part of CAB followed by monotherapy. Further research is necessary to understand the outcomes of BIC utilization in these settings, particularly compared with newer second-generation anti-androgens. FUNDING: Medivation LLC, a Pfizer company, and Astellas, Pharma, Inc.

Cost-effectiveness comparison between neoadjuvant chemohormonal therapy and extended pelvic lymph node dissection in high-risk prostate cancer patients treated with radical prostatectomy: a multi-institutional analysis.

The aim of the present study was to assess the cost-effectiveness of extended pelvic lymph node dissection (ePLND) compared to neoadjuvant chemohormonal therapy using gonadotropin-releasing hormone agonist/antagonist and estramustine. We retrospectively analyzed data within Michinoku Urological Cancer Study Group database containing 2971 PC patients treated with radical prostatectomy (RP) at four institutes between July 1996 and July 2017. We identified 237 and 403 high-risk patients who underwent RP and ePLND (ePLND group), and neoadjuvant chemohormonal therapy followed by RP and limited PLND (neoadjuvant group), respectively. The oncological outcomes and cost-effectiveness were compared between groups. Medical cost calculation focused on PC-related medication and adjuvant radiotherapy. Biochemical recurrence-free and overall survival rates in the neoadjuvant group were significantly higher than those in the ePLND group. Significantly higher number of patients progressed to castration-resistant PC in the ePLND group than in the neoadjuvant group. Background-adjusted multivariate Cox regression analysis using inverse probability of treatment weighting (IPTW) revealed that neoadjuvant chemohormonal therapy independently reduced the risk of biochemical recurrence after RP. The 5-year cost per person was significantly higher in the ePLND group than in the neoadjuvant group. Although the present study was retrospective, neoadjuvant chemohormonal therapy followed by RP as a concurrent strategy has potential to improve oncological outcome and cost-effectiveness.

Bilateral Salpingo-Oophorectomy Versus GnRH Analogue in the Adjuvant Treatment of Premenopausal Breast Cancer Patients: Cost-Effectiveness Evaluation of Breast Cancer Outcome, Ovarian Cancer Prevention and Treatment.

BACKGROUND AND OBJECTIVE: There is no available evidence to recommend gonadotropin-releasing hormone (GnRH) analogue-based ovarian suppression versus bilateral salpingo-oophorectomy (BSO) in the adjuvant treatment of early breast cancer, since the two approaches are considered equivalent in terms of oncologic outcome. The role of surgical ovarian ablation has been revitalized based on the advances of minimally invasive surgery, and a better understanding of clinical and molecular basis of hereditary breast/ovarian cancer syndromes. The aim of this study is to analyze the cost-effectiveness of laparoscopic BSO and GnRH analogue administration in patients aged 40-49 years with hormone-sensitive breast cancer. METHODS: A probabilistic decision tree model was developed to evaluate costs and outcomes of ovarian ablation through laparoscopic BSO, or ovarian suppression through monthly injections of GnRH analogue. Results were expressed as incremental costs per quality-adjusted life years (QALYs) gained. RESULTS: Laparoscopic BSO strategy was associated with a lower mean total cost per patient than GnRH treatment, and considering the difference in terms of QALYs, the incremental effectiveness did not demonstrate a notable difference between the two approaches. From the National Health Service perspective, and for a time horizon of 5 years, laparoscopic BSO was the dominant option compared to GnRH treatment; laparoscopic BSO was less expensive than GnRH, €2385 [95% confidence interval (CI) = 2044, 2753] vs €7093 (95% CI = 3409, 12,105), respectively, and more effective. CONCLUSION: Surgical ovarian ablation is more cost-effective than GnRH administration in the adjuvant treatment of hormone-sensitive breast cancer patients aged 40-49 years, and the advantage of preventing ovarian cancer through laparoscopic BSO should be considered.

Análisis de impacto presupuestal de hormonoterapia para el tratamiento de cáncer de próstata en Colombia / Budget impact analysis of hormone therapy for the treatment of prostate cancer in Colombia

INTRODUCCIÓN: El análisis de impacto presupuestal (AIP) de hormonoterapia para el tratamiento de cáncer de próstata en Colombia, se desarrolló en el marco del mecanismo técnico-científico para la ampliación progresiva del Plan de Beneficios en Salud (PBSUPC) y la definición de la lista de exclusiones, establecido en el artículo 15 de la Ley 1751 de 2015. Estas tecnologías fueron seleccionadas por la Dirección de Beneficios, Costos y Tarifas del Aseguramiento en Salud del Ministerio de Salud y Protección Social (MinSalud), y remitidas al Instituto de Evaluación Tecnológica en Salud (IETS) para su evaluación. El cáncer de próstata corresponde al crecimiento anormal de células de la glándula prostática, principalmente en células basales de la glándula, el cual se ha relacionado con factores genéticos y hormonales. Según estimaciones de Globocan en 2012, en el mundo la tasa de incidencia estandarizada por edad fue de 30.7 x 100.000 hombres, aportando el 14.8% del total de los nuevos casos de c

Discovery of LHRH and development of LHRH analogs for prostate cancer treatment.

The discovery, isolation, elucidation of structure, synthesis, and initial testing of the neuropeptide hypothalamic luteinizing hormone-releasing hormone (LHRH), which regulates reproduction, is briefly described. The design, synthesis, and experimental and clinical testing of agonistic analogs of LHRH is extensively reviewed focusing on the development of new methods for the treatment of prostate cancer. Subsequent development of antagonistic analogs of LHRH is then faithfully recounted with special emphasis on therapy of prostate cancer and BPH. The concepts of targeted therapy to peptide receptors on tumors are re-examined and the development of the cytotoxic analogs of LHRH and their status is reviewed. The endeavor to develop better therapies for prostate cancer, based on LHRH analogs, guided much of our work.

Importance of bone assessment and prevention of osteoporotic fracture in patients with prostate cancer in the gonadotropic hormone analogues use.

The antiandrogenic therapy (ADT) for prostate cancer represents an additional risk factor for the development of osteoporosis and fragility fractures. Still, bone health of patients on ADT is often not evaluated. After literature research we found that simple preventive measures can prevent bone loss in these patients, resulting in more cost-effective solutions to the public health system and family when compared to the treatment of fractures.

Infertility in reproductive-age female cancer survivors.

Improved survival rates among reproductive-age females diagnosed with cancer have increased the focus on long-term quality of life, including maintenance of the ability to conceive biological children. Cancer-directed therapies such as high-dose alkylating agents and radiation to the pelvis, which deplete ovarian reserve, radiation to the brain, which affects the hypothalamic-pituitary-gonadal axis, and surgical resection of reproductive structures can decrease the likelihood of having biological children. Standard fertility preservation strategies such as embryo and oocyte cryopreservation before the onset of therapy offer the opportunity to conserve fertility, but they may not be feasible because of the urgency to start cancer therapy, financial limitations, and a lack of access to reproductive endocrinologists. Ovarian tissue freezing is considered experimental, with limited data related to pregnancies, but it minimizes treatment delay. Studies evaluating gonadotropin-releasing hormone analogues have had mixed results, although a recent randomized, prospective study in women with breast cancer demonstrated a protective effect. Fertility preservation programs are increasingly being developed within cancer programs. In this article, we describe risks to infertility and options for preservation, raise psychosocial and ethical issues, and propose elements for establishing an effective fertility preservation program.

[Direct and indirect costs of luteinising hormone-releasing hormone analogues in the treatment of locally advanced or metastatic prostate cancer in Italy]. / Analoghi sintetici dell'ormone di rilascio dell'ormone luteinizzante per il trattamento del carcinoma prostatico localmente avanzato o metastatico: analisi dei costi diretti e indiretti nello scenario italiano

BACKGROUND: When analyzing the use of luteinizing hormone-releasing hormone (LHRH) analogues for different clinical indications, current available evidence does not support a presumed drug class effect among the various LHRH in the treatment of prostate cancer. METHODS: The following search key words were entered in the PubMed database and the NICE and FDA websites: "LHRH agonist AND prostatic cancer", "androgen deprivation therapy", "androgen suppression", "buserelin", "leuprorelin", "goserelin","triptorelin", "degarelix". The direct costs included the following items: follow-up visits, diagnostic exams (e.g. prostate-specific antigen PSA) and drug costs. The indirect costs included working days lost by the patient. RESULTS: With intermittent therapy as a reference, leuprorelin injectable solution of 22,25 mg was associated with the lowest cost and degarelix with the highest cost. However, given the mandatory presence of a nurse for drug injection, the buserelin depot formulation was associated with the lowest cost. If the costs for hospital visits were added to drug costs, differences between the various therapeutic strategies were less remarkable. CONCLUSIONS: Our study showed how various factors (e.g. route of administration, frequency of administration, presence of a nurse for drug reconstitution and injection) should be taken into account by decision makers in addition to the price of drugs.

Surgical and anesthetic considerations in histrelin capsule implantation for the treatment of precocious puberty.

BACKGROUND: Precocious puberty treatment traditionally meant anxiety-provoking monthly depot injections until the advent of the annually implanted histrelin capsule. This study is the first to evaluate the surgical and anesthetic aspects of histrelin implantation for precocious puberty. METHODS: All cases from one surgeon at a tertiary pediatric hospital were reviewed for patient age, anesthetic type, technical difficulties, and complications. RESULTS: From 12/2007 to 3/2013, 114 cases (49% implantations, 25% removals/re-implantations, 25% removals) were performed. Local anesthesia was employed in 100% of non-general anesthesia cases (n=109, 96%), augmented by inhaled N2O in 49%. Five patients (4%) underwent general anesthesia: three neurologically-impaired and two coordinated with scheduled MRIs. Procedural difficulties (n=18, 16%) included implant fracture during removal (n=16/58 removals, 28%). Fracture never occurred during implantation. Three children (3%) suffered complications. One infection was treated with antibiotics, and two implants were removed for systemic allergic reaction. Six children (5%) had unscheduled post-operative checks for pain (n=3, 3%), allergy to elastic dressing (n=2, 2%), or rash (n=1, 1%). Mean charges for general anesthesia were $10,188±1292 versus $528±147 for N2O or local alone (p<0.0001). CONCLUSION: While histrelin implantation is straightforward, removal presents technical challenges. Local anesthesia, with possible N2O supplementation, is well-tolerated and introduces substantial resource and cost savings.

Clinical pharmacology and regulatory consequences of GnRH analogues in prostate cancer.

INTRODUCTION: GnRH (gonadotropin-releasing hormone) analogues are long-term known to be safe and effective in the clinical management of hormone-dependent advanced prostate cancer. However, their unusual mechanism of action of de-sensitizing pituitary receptors makes generic market entry challenging. In addition, safety aspects like initial flare-up, breakthrough escape, and miniflares render planning and organization of clinical registration trials a complex project. REGULATORY REQUIREMENTS THERAPEUTIC EQUIVALENCE: Regulatory requirements are high as these medicines are compared to bilateral surgical castration with a 100% success rate. GnRH analogues will be used probably even wider in the near future due to demographic development and extension of indications. However, they are challenged by their antagonistic counterparts, which are avoiding flare-up phenomena. The following article deals with regulatory requirements of GnRH analogues in regard to their clinical characteristics.