leuprolide and histrelin

Precocious puberty is a common problem affecting up to 29 per 100,000 girls per year. The earliest identified neuroendocrine change in early puberty thus far is increased kisspeptin secretion from the arcuate nucleus and the anteroventral paraventricular nucleus of the hypothalamus. The regulation of kisspeptin secretion is not well understood, but neurokinin B and dynorphin provide autocrine regulation. The etiologies of precocious puberty may be subdivided into GnRH-dependent and GnRH-independent causes. GnRH-dependent precocious puberty, often called central precocious puberty (CPP), is usually treated with GnRH analogs. Newer developments in the treatment of CPP include expanded data on the safety and efficacy of the subdermal histrelin implant, which is useful for long-term treatment, although removal may be difficult in some cases. Preliminary data suggest that the implant may be left in place for up to 2 years without loss of biochemical suppression. In the last 2 years, more data have been published concerning extended-release leuprolide acetate injections that indicate that the 11.25-mg dose may not provide full biochemical suppression but may clinically suppress signs of puberty, including the accelerated growth velocity and advanced skeletal maturation seen in CPP. Treatment options for familial male-limited precocious puberty and McCune-Albright syndrome are expanding as well, although data are preliminary. Long-term outcome studies of CPP indicate overall good menstrual and reproductive function, but the prevalence of polycystic ovary syndrome may be higher than in the general population. Remarkably few studies have evaluated the behavioral and psychological outcomes of precocious puberty, in contrast to early normal maturation. Additional outcome studies of endocrine, metabolic, and psychological effects of CPP are clearly needed.

Topics: Delayed-Action Preparations; Drug Implants; Female; Gonadotropin-Releasing Hormone; Humans; Kisspeptins; Leuprolide; Male; Puberty; Puberty, Precocious; Treatment Outcome

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.. 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.. 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).. 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.

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Child; Child, Preschool; Databases, Factual; Drug Implants; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Injections, Intravenous; Insurance Claim Review; Leuprolide; Male; Prognosis; Puberty, Precocious; Retrospective Studies; Subcutaneous Tissue; United States; Young Adult

Topics: Child; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Health Care Costs; Health Resources; Humans; Insurance Coverage; Insurance, Health; Leuprolide; Male; Medicaid; Multivariate Analysis; Patient Acceptance of Health Care; Private Sector; Puberty, Precocious; Retrospective Studies; United States

There is no consensus on the association between the use of androgen deprivation therapy (ADT) and the risk of developing depression. This study investigated the association between ADT use and the development of depression, outpatient psychiatric services, inpatient psychiatric services, and suicide in a homogeneous group of men with prostate cancer (PC) treated with definitive radiation therapy (RT) after controlling for multiple sources of selection bias.. This was a retrospective, observational cohort study of 39,965 veterans with PC who were treated with definitive RT and were diagnosed by the US Department of Veterans Affairs health care system between January 1, 2001, and October 31, 2015. Exposure was ADT initiation within 1 year of the PC diagnosis. The primary outcome was new development of depression. Secondary outcomes were outpatient psychiatric use, inpatient psychiatric use, and suicide.. During follow-up, 934 patients were newly diagnosed with depression, 7825 patients used outpatient psychiatric services, 358 patients used inpatient psychiatric services, and 54 patients committed suicide. In the multivariable competing risks regression model, ADT was associated with the development of depression (subdistribution hazard ratio [SHR], 1.50; 95% confidence interval [CI], 1.32-1.71; P < .001). ADT was also associated with outpatient psychiatric utilization (SHR, 1.21; 95% CI, 1.16-1.27; P < .001). Finally, ADT was not associated with inpatient psychiatric utilization or suicide.. An increase in the risk of depression and the use of outpatient psychiatric services was observed in a large cohort of men with PC who received ADT with definitive RT. These results may provide further evidence for the long-term risks of ADT for psychiatric health in the treatment of PC.

Topics: Aged; Aged, 80 and over; Ambulatory Care; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Depression; Depressive Disorder; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Hospitalization; Humans; Imidazolidines; Leuprolide; Male; Mental Health Services; Middle Aged; Nitriles; Oligopeptides; Prostatic Neoplasms; Radiotherapy; Retrospective Studies; Suicide; Tosyl Compounds

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.. 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.. 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.. 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.. Patients with CPP have substantially more comorbidities and greater HRU and costs than their non-CPP peers.. 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)."

Topics: Child; Child, Preschool; Cohort Studies; Cost of Illness; Female; Gonadotropin-Releasing Hormone; Health Care Costs; Humans; Insurance, Health; Leuprolide; Male; Medicaid; Patient Acceptance of Health Care; Puberty, Precocious; Retrospective Studies; United States

Gonadotropin-releasing hormone (GnRH) agonists are FDA approved for the treatment of precocious puberty. The therapy consists of histrelin acetate (Supprelin), a surgically implanted device, or Lupron injections. In recent years, the use of these agents has been extended to include the off-label treatment of children with normally timed puberty. Trends in the off-label use of GnRH agonists in children across the U.S. have not been previously described in the literature.. We analyzed data on the use of Supprelin and Lupron reported to the Pediatric Health Information System (PHIS) from 2013 to 2016 to determine the trends in both the FDA-approved and off-label uses of these medications.. We identified a stable cohort of 39 children's hospitals administering GnRH agonist therapies from 2013 to 2016. During this period, the annual number of children treated with these medications for precocious puberty increased modestly, from 283 to 303; meanwhile, the fraction of children receiving therapy for an off-label indication more than doubled, from 12% (39 of 322 total patients) to 29% (125 of 428 total patients). Privately insured patients were more likely to be treated for an off-label indication (13%; 119 out of 883 patients) than Medicaid patients (8%; 58 out of 706 patients; χ. From 2013 to 2016, the proportion of children treated with GnRH agonists for an off-label indication notably increased. The number of children treated for precocious puberty modestly increased. Private insurance coverage was associated with higher rates of off-label use.

Topics: Adolescent; Child; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Off-Label Use; Retrospective Studies; United States

Topics: Child; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Nafarelin; Puberty, Precocious