histrelin has been researched along with Puberty--Precocious* in 34 studies
7 review(s) available for histrelin and Puberty--Precocious
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Experience with the Histrelin Implant in Pediatric Patients.
The histrelin implant has emerged as a therapeutic option for the treatment of central precocious puberty that has been favorably received by patients and providers. Inserted subcutaneously, the 50-mg implant provides continuous release of the potent gonadotropin-releasing hormone analog (GnRHa) histrelin. Profound suppression of the hypothalamic-pituitary-gonadal (HPG) axis occurs within 1 month of its placement resulting in pubertal arrest, attenuation of skeletal advancement and a progressive increase in predicted adult height. Although marketed for annual use, suppression lasting 2 years from a single implant has been demonstrated. Placing and removing the device is a minor outpatient procedure easily accomplished by a pediatric surgeon using local anesthesia. The major downside to the implant is a ∼25% rate of breakage upon removal. Information about the recovery of the HPG axis following histrelin explantation is limited but suggests an average time to menarche comparable with depot GnRHa formulations albeit with wide individual variation. Topics: Child; Drug Implants; Gonadotropin-Releasing Hormone; Humans; Puberty, Precocious | 2016 |
Treatment and outcomes of precocious puberty: an update.
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 | 2013 |
Histrelin Hydrogel Implant--Valera: Histrelin implant, LHRH-Hydrogel implant, RL 0903, SPD 424.
Valera Pharmaceuticals, formerly Hydro Med Sciences, is developing a once-yearly Histrelin Hydrogel Implant [Histrelin implant, LHRH-Hydrogel implant, RL 0903, SPD 424, Vantas], a subcutaneous (s.c.) reservoir device capable of long-term delivery of histrelin at constant release rates for the treatment of prostate cancer. Histrelin is a luteinising hormone-releasing hormone agonist (LHRH). A different formulation of the LHRH implant is currently in development for the treatment of central precocious puberty (CPP). On 4 September 2003, Hydro Med Sciences announced that it had changed its name to Valera Pharmaceuticals. Shire Pharmaceuticals had an option to market and distribute the histrelin implant outside the US, but in a realigned agreement announced in January 2002, Shire stated that HydroMed (now Valera) would be responsible for concluding the phase III studies, filing for regulatory approval and producing the implant, while also gaining marketing rights in the US. Shire has no further involvement in development, but retains an option to market and distribute the product outside the US. The product is available for rest-of-the-world licensing through Valera Pharmaceuticals' business development division. Paladin Labs has received the exclusive rights for the sale and marketing of histrelin hydrogel implant in Canada. Valera Pharmaceuticals will have the responsibility for manufacturing and completing development of the product. In July 2004, Paladin announced it had filed for regulatory approval with Health Canada for the treatment of prostate cancer. Phase III trials have been conducted and initially involved two open-labelled, randomised, parallel studies that compared the hydrogel implant with the active comparators, leuprorelin acetate 22.5 mg depot (TAP Pharmaceutical's Lupron Depot) and a 3-month implant of goserelin acetate (Astra Zeneca's Zoladex). However, because of financial constraints, HydroMed discontinued recruitment in a phase II European study and could not rationalise keeping the comparator arm of the phase III study. The US FDA then gave permission to continue the US part of the programme without the comparator arm, but with appropriate increases in the patient sample size. Patient enrolment in the phase III trial (US and Canada) was completed in July 2002. Valera Pharmaceuticals believes the product may have advantages over standard prostate cancer treatments including reduced costly surgical procedures, lower dosing, increased pa Topics: Antineoplastic Agents; Drug Implants; Female; Gonadotropin-Releasing Hormone; Humans; Hydrogels; Injections, Subcutaneous; Male; Prostatic Neoplasms; Puberty, Precocious | 2005 |
Follow-up of children and young adults after GnRH-agonist therapy or central precocious puberty.
Topics: Adolescent; Body Mass Index; Child; Epilepsy; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Obesity; Ovary; Puberty, Precocious; Testis; Triptorelin Pamoate | 2001 |
Gonadotropin-releasing hormone agonists. Current uses for these increasingly important drugs.
Use of gonadotropin-releasing hormone (GnRH) agonists produces a transient increase and subsequent long-term reduction in concentrations of pituitary hormones, resulting in gonadal hormone suppression. This reversible suppression is useful in treating diseases dependent on these hormones. GnRH agonists have been approved for use in patients with endometriosis, advanced prostate cancer, and precocious puberty. As research continues, GnRH agonists are expected to change the clinical approach to the treatment of many other reproductive and nonreproductive diseases. Topics: Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Male; Prostatic Neoplasms; Puberty, Precocious | 1994 |
Histrelin. A review of its pharmacological properties and therapeutic role in central precocious puberty.
Histrelin is a synthetic gonadotrophin-releasing hormone (GnRH) agonist which, when administered over a prolonged period, suppresses the release of gonadotrophins from the anterior pituitary. Data from clinical trials undertaken in small numbers of patients with idiopathic central precocious puberty have demonstrated that histrelin 8 to 10 micrograms/kg/day administered subcutaneously desensitises the anterior pituitary to gonadotrophin secretion within 3 months, ablating the pubertal gonadotrophin response to GnRH stimulation and reducing circulating gonadal sex steroid levels. When histrelin is administered to treat central precocious puberty, the rate of secondary sexual maturation is slowed and in some cases there is a reversal of maturation which occurs before initiation of treatment. Of equal importance, histrelin therapy appears to have decelerating effects on skeletal maturation, allowing more statural growth; an increase in final adult height is predicted from available data, but will need to be confirmed in long term follow-up studies currently being undertaken. The most common adverse event reported during histrelin therapy was a skin reaction at the site of subcutaneous injection. Few patients have discontinued therapy because of any adverse event. Although experience with histrelin is limited, the absence of effective clinically available alternatives and the demonstrated efficacy of histrelin justifies its place as a first-line therapy for patients with central precocious puberty. Topics: Amino Acid Sequence; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Male; Molecular Sequence Data; Puberty, Precocious | 1993 |
Effects of luteinizing hormone-releasing hormone agonists on final height in luteinizing hormone-releasing hormone-dependent precocious puberty.
Topics: Adult; Age Determination by Skeleton; Age Factors; Body Height; Buserelin; Child; Clinical Trials as Topic; Female; Gonadotropin-Releasing Hormone; Humans; Male; Nafarelin; Prognosis; Puberty, Precocious; Triptorelin Pamoate | 1993 |
4 trial(s) available for histrelin and Puberty--Precocious
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Long-Term Continuous Suppression With Once-Yearly Histrelin Subcutaneous Implants for the Treatment of Central Precocious Puberty: A Final Report of a Phase 3 Multicenter Trial.
The histrelin implant has proven to be an effective method of delivering GnRH analog (GnRHa) therapy to children with central precocious puberty (CPP), yet there are limited data available regarding hormonal suppression and auxological changes during an extended course of therapy.. This was a phase 3, prospective, open-label study.. Thirty-six children with CPP who participated in a phase 3, open-label study and required further GnRHa therapy were eligible to continue treatment receiving a new implant upon removal of the prior 12-month histrelin implant during a long-term extension phase.. Hormone levels and auxologic parameters were measured periodically for up to 6 years of treatment and up to 1 year of posttreatment follow-up.. Hormonal suppression was maintained throughout the study in patients who had prior GnRHa therapy (n = 16) and in treatment-naive patients (n = 20). Bone age to chronological age ratio decreased from 1.417 (n = 20) at baseline to 1.18 (n = 8) at 48 months in treatment-naive children (P < .01). Predicted adult height in girls increased from 151.9 cm at baseline to 166.5 cm at month 60 (n = 6; P < .05), with a 10.7-cm height gain observed among treatment-naive children (n = 5). No adverse effect on growth or recovery of the hypothalamic-pituitary-gonadal axis was observed with hormonal suppression. The histrelin implant was generally well tolerated during long-term therapy.. Long-term histrelin implant therapy provided sustained gonadotropin suppression safely and effectively and improved predicted adult height in children with CPP. Topics: Body Height; Child; Child, Preschool; Down-Regulation; Drug Administration Schedule; Drug Implants; Female; Gonadotropin-Releasing Hormone; Gonads; Humans; Hypothalamo-Hypophyseal System; Injections, Subcutaneous; Male; Puberty; Puberty, Precocious; Time Factors | 2015 |
Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial.
GnRH analog (GnRHa) therapy for central precocious puberty (CPP) typically involves im injections. The histrelin implant is a new treatment that provides a continuous slow release of the GnRHa histrelin.. The objective of the study was to investigate the safety and efficacy of the subdermal histrelin implant for the treatment of CPP in treatment naive and previously treated children.. This was a phase III, open-label, prospective study of 1-yr duration.. The study was conducted at nine U.S. medical centers.. Girls ages 2-8 yr (naive) or 2-10 yr (previously treated) and boys 2-9 yr (naive) or 2-11 yr (previously treated) with clinical evidence of CPP and a pretreatment pubertal response to leuprolide stimulation were eligible.. A 50-mg histrelin implant was inserted sc in the inner upper arm.. Peak LH after GnRHa stimulation testing and estradiol (girls) and testosterone (boys) were the main outcome measures.. Thirty-six subjects (20 naive) were enrolled. By 1 month, peak LH fell from 28.2 +/- 19.97 (naive) to 0.8 +/- 0.39 mIU/ml (P < 0.0001) and from 2.1 +/- 2.15 (previously treated) to 0.5 +/- 0.32 mIU/ml (P < 0.0056). Estradiol suppressed from 24.5 +/- 22.27 (naive) to 5.9 +/- 2.37 pg/ml (P = 0.0016) and remained suppressed in previously treated subjects, as did testosterone. Suppression was maintained throughout the study. No significant adverse events occurred.. The subdermal histrelin implant achieves and maintains excellent suppression of peak LH and sex steroid levels for 1 yr in children with CPP. The treatment is well tolerated. Long-term studies are needed to confirm these results. Topics: Age Determination by Skeleton; Body Mass Index; Bone and Bones; Breast; Child; Child, Preschool; Drug Implants; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Growth; Humans; Luteinizing Hormone; Male; Prospective Studies; Puberty, Precocious; Testosterone | 2007 |
The histrelin implant: a novel treatment for central precocious puberty.
Standard treatment of central precocious puberty (CPP) consists of intramuscular or subcutaneous administration of a gonadotropin-releasing hormone (GnRH) agonist (GnRHa) at 3- to 4-week intervals. Although generally effective in suppressing clinical and laboratory parameters of puberty, GnRHa injections are painful, and the need for monthly clinic visits may contribute to poor compliance. Recently, a subcutaneous implant was developed that releases the GnRHa histrelin at an average rate of 65 microg/day. The aims of this study were to determine if a histrelin implant would suppress gonadotropin and estradiol (E2) in girls with CPP for 1 year and to compare the suppression to standard treatment.. We studied 11 girls with CPP to determine if the histrelin implant can maintain long-term gonadotropin suppression. Mean age at diagnosis was 6 years (range: 2-9 years). GnRH (100 microg intravenously) stimulation tests (GnRH-STs) showed peak luteinizing hormone and follicle-stimulating hormone responses of 23 +/- 28 (mean +/- SD) and 20 +/- 25 mIU/mL, respectively. All subjects were initially treated with depot intramuscular GnRHa triptorelin embonate. Implants were inserted subcutaneously under local anesthesia, and depot GnRHa treatment was discontinued. Six girls were followed for 15 months after insertion (group A). For the remaining 5 girls, the implant was removed after 9 months, and a new implant was inserted at the same incision site (group B). GnRH-STs were performed before depot GnRHa treatment, immediately before implant insertion, at the 6- and 9-month visits for each patient and the 12- and 15-month visit for those girls followed for 15 months.. In all girls, breast development regressed, growth velocity decreased, and bone-age advancement was slowed. Basal gonadotropins and their responses to GnRH-STs and E2 levels were suppressed. Peak luteinizing hormone and follicle-stimulating hormone responses to GnRH-STs at preinsertion versus 9 months were 1.30 +/- 1.34 vs 0.25 +/- 0.08 and 1.68 +/- 1.08 vs 1.13 +/- 0.55 mIU/mL, respectively. Basal and stimulated gonadotropin levels and E2 level remained suppressed in all 6 patients followed for 15 months after implant insertion. Patients and parents reported less pain and discomfort and less interference with school activity and work with the implant compared with standard monthly injections.. The histrelin implant consistently suppresses clinical and laboratory parameters of puberty for 1 year and is a promising new technique for treating CPP without the pain and inconvenience of monthly injections. Topics: Child; Drug Implants; Female; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Humans; Injections; Puberty, Precocious | 2005 |
Is obesity an outcome of gonadotropin-releasing hormone agonist administration? Analysis of growth and body composition in 110 patients with central precocious puberty.
Concern has been raised that children with central precocious puberty (CPP) are prone to the development of obesity. Here we report longitudinal height, weight, and body mass index (BMI) data from 96 girls and 14 boys with CPP before, during, and after GnRH agonist (GnRHa) administration. Skinfold thickness (n = 46) and percent body fat by dual energy x-ray absorptiometry (n = 21) were determined in subsets for more accurate assessment of body composition and to validate the use of the BMI SD score as an index of body fatness in our subjects. Before the initiation of therapy (PRE), the girls with CPP had a mean BMI SD score for chronological age (CA) of 1.1+/-0.1 and for bone age (BA) of 0.1+/-0.1. By the end of the study, 12-24 months after the discontinuation of GnRHa, the mean BMI SD score was 0.9+/-0.1 for CA and 0.6+/-0.1 for BA. At the visit when GnRHa was discontinued, 41% and 22% of the girls had a BMI SD score for CA more than the 85th and 95th percentiles, respectively, indicating that obesity was present at a high rate among our subjects; the BMI SD score for CA at the PRE visit was its strongest predictor. Indeed, 86% of the girls with BMI SD score for CA above the 85th percentile when GnRHa was discontinued also had BMI SD score for CA above the 85th percentile at the PRE visit. The proportion of boys with elevated BMI SD score for CA was also high. Fifty-four percent and 31% of the SD scores were greater than the 85th and 95th percentiles after 36 months of GnRHa therapy; the BMI SD score for CA PRE had been above the 85th percentile in 71% of these overweight subjects. Obesity occurs at a high rate among children with CPP, but does not appear to be related to long term pituitary-gonadal suppression induced by GnRHa administration. Children with CPP should have a baseline BMI SD score calculated, and those at risk for obesity should be counseled appropriately. Topics: Adolescent; Body Composition; Body Height; Body Mass Index; Child; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Humans; Male; Obesity; Puberty, Precocious; Skinfold Thickness; Triptorelin Pamoate; Weight Gain | 1999 |
23 other study(ies) available for histrelin and Puberty--Precocious
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Long-term experience with the use of a single histrelin implant beyond one year in patients with central precocious puberty.
The histrelin implant has been used to treat central precocious puberty (CPP) for more than 15 years. Although approved for annual use, limited published reports suggest that a single implant is efficacious well beyond a year. Our objective was to report our long-term experience using a single histrelin implant for more than 12 months in children with CPP.. We performed a retrospective study of 170 children with central precocious puberty treated with a single histrelin implant for more than 1 year.. Implants were left. A single histrelin implant provides excellent pubertal suppression well beyond a year. Extended use of a single histrelin implant should be considered standard of care in children with CPP. Topics: Child; Drug Implants; Gonadotropin-Releasing Hormone; Humans; Puberty, Precocious; Retrospective Studies | 2023 |
Trends in Histrelin Implantation at a Pediatric Tertiary Care Center.
Determine procedural outcomes and identify changing trends of utilization among patients undergoing histrelin implantation at a large pediatric tertiary care center over 15 y.. Retrospective review of all patients undergoing histrelin implantation between January 2008 and April 2022.. A total of 746 patients underwent 1794 unique procedures (1364 placements/replacements, 430 removals). Procedures were performed in the clinic (1071, 60%), sedation unit (630, 35%), and operating room (93, 5%). A total of 14 (0.8%) complications were identified, including two patients that required early implant removal and one patient requiring antibiotics. Implants were placed for central precocious puberty (CPP, 579) or gender dysphoria (GD, 167). Cohort included 25.9% males and 74.1% females with mean age of implantation of 9.48 y (SD: 2.34, range: 1.05-17.34). The GD group is comprised of 52.4% males and 47.6% females, compared to 18.3% males and 81.7% females in the CPP. Significant difference was identified for mean age at placement by indication (CPP 8.65 y versus GD 12.34, P < 0.001). New patient referrals and implant procedures increased significantly over 14 y. Yearly frequency of patients receiving implants for CPP and GD increased significantly (P < 0.001), with proportion of GD patients increasing from 7% to 32%.. Histrelin procedures have increased in frequency overall with the greater increase noted in the GD cohort. The development of a streamlined process and a dedicated team have enabled histrelin procedures to be safely performed in the clinic setting for most, with a very low complication rate. Topics: Child; Drug Implants; Female; Gonadotropin-Releasing Hormone; Humans; Male; Puberty, Precocious; Retrospective Studies; Tertiary Care Centers | 2023 |
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.
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 | 2021 |
Optimizing pediatric histrelin implantation to improve success rates in clinic without sedation.
The purpose of this study was to review our success rate performing the histrelin implant procedure in clinic without sedation.. A retrospective study was performed for histrelin implant procedures done at our institution from 2008 to 2020. Wilcoxon rank-sum test or Fisher's exact test was utilized to identify significant differences (p<0.05).. A total of 73 patients underwent 184 histrelin implant procedures from 2008 to 2020. In the past few years, there has been a decrease in procedures for precocious puberty and an increase for gender dysphoria. The majority of procedures were performed in clinic without sedation (82%). The only risk factor associated with requiring sedation was younger age (median 9 vs. 10 years; p<0.003). Complications (i.e. implant fracture or need for counter-incision) were noted in 10 of the procedures (5%). The only risk factor identified for a procedural complication during implant removal/replacement was interval time from insertion (21 vs. 13 months; p<0.01). The only documented wound problem reported was dermatitis in 1 patient (no suture granuloma, dehiscence, or implant extravasation).. Procedural refinements and distraction therapy have enabled us to perform the majority of procedures in clinic without sedation. In our experience, procedural difficulty and complications appear to increase with prolonged implant duration. Histrelin implantation is increasingly being performed for gender dysphoria. Topics: Adolescent; Child; Child, Preschool; Drug Implants; Female; Gender Dysphoria; Gonadotropin-Releasing Hormone; Humans; Male; Puberty, Precocious; Retrospective Studies; Risk Factors; Treatment Outcome | 2021 |
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.
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 | 2020 |
Histrelin implantation in the pediatric population: A 10-year institutional experience.
To perform the largest review of the safety and clinical management practices of histrelin implantation in children.. A retrospective cohort study was performed including all patients (age ≤ 20) that underwent histrelin implant insertion, replacement, or removal by a single surgeon at a large pediatric tertiary care center (2008-2017). Data analyzed included patient demographics, procedure details, and complications.. A total of 377 patients, with a mean age of 9.3 ± 2.4 years, underwent 866 unique procedures (352 insertions, 329 replacements, and 185 removals) for a diagnosis of either central precocious puberty (343 patients, 821 cases) or gender identity disorder (34 patients, 45 cases). There were 271 (72%) female patients, 72 (19%) male patients, and 34 (9%) children in gender transition. Procedures were performed in three settings: 415 (47.9%) in the outpatient clinic, 401 (46.3%) in a sedation unit, and 50 (5.8%) in the operating room. The preferred setting shifted over time to more clinic-based procedures (9.4% vs. 62.9% in the first five vs. second five years, respectively). Complications were rare (1% of cases).. Histrelin implantation in the pediatric population is safe, with minimal morbidity. Implantation and removal in the clinic setting are appropriate for the majority of patients.. Treatment study; Level IV. Topics: Ambulatory Care Facilities; Child; Drug Implants; Female; Gender Dysphoria; Gender Identity; Gonadotropin-Releasing Hormone; Humans; Male; Operating Rooms; Puberty, Precocious; Retrospective Studies | 2019 |
Health Care Utilization and Economic Burden in Patients with Central Precocious Puberty: An Assessment of the Commercially Insured and Medicaid Populations.
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 | 2019 |
Trends in the use of puberty blockers among transgender children in the United States.
The objective of the study was to identify national trends in the utilization of histrelin acetate implants among transgender children in the United States.. We analyzed demographic, diagnostic and treatment data from 2004 to 2016 on the use of histrelin acetate reported to the Pediatric Health Information System (PHIS) to determine the temporal trends in its use for transgender-related billing diagnoses, e.g. "gender identity disorder". Demographic and payer status data on this patient population were also collected.. Between 2004 and 2016, the annual number of implants placed for a transgender-related diagnosis increased from 0 to 63. The average age for placement was 14 years. Compared to natal females, natal males were more likely to receive implants (57 vs. 46) and more likely to have implants placed at an older age (62% of natal males vs. 50% of natal females were ≥;13 years; p<0.04). The majority of children were White non-Hispanic (White: 60, minority: 21). When compared to the distribution of patients treated for precocious puberty (White: 1428, minority: 1421), White non-Hispanic patients were more likely to be treated with a histrelin acetate implant for a transgender-related diagnosis than minority patients (p<0.001). This disparity was present even among minority patients with commercial insurance (p<0.001).. Utilization of histrelin acetate implants among transgender children has increased dramatically. Compared to natal females, natal males are more likely to receive implants and also more likely to receive implants at an older age. Treated transgender patients are more likely to be White when compared to the larger cohort of patients being treated with histrelin acetate for central precocious puberty (CPP), thus identifying a potential racial disparity in access to medically appropriate transgender care. Topics: Adolescent; Child; Child, Preschool; Drug Implants; Female; Gender Dysphoria; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infant; Male; Puberty; Puberty, Delayed; Puberty, Precocious; Retrospective Studies; Transgender Persons; United States | 2018 |
Use of Gonadotropin-Releasing Hormone for Intractable Seizures in a Girl with Precocious Puberty without Hypothalamic Hamartoma.
The use of gonadotropin-releasing hormone analogs has been reported in the treatment of gelastic seizures and precocious puberty associated with hypothalamic hamartomas, but not in other seizure types without hypothalamic hamartoma. We describe a 7.5 year-old girl whose seizures subsided after gonadotropin-releasing hormone analog implant, administered for precocious puberty. Topics: Anticonvulsants; Child; Female; Gonadotropin-Releasing Hormone; Humans; Magnetic Resonance Imaging; Positron-Emission Tomography; Puberty, Precocious; Seizures | 2016 |
Histrelin for central precocious puberty-a single surgeon experience.
The most common cause of precocious puberty is idiopathic central precocious puberty (CPP), which is usually treated with monthly injections. An alternative treatment of precious puberty is a subcutaneous implant that contains histrelin acetate, which is continuously released for more than 1 y and then removed or replaced with a new implant.. The aim of this study was to conduct a retrospective review of one surgeon's experience with the histrelin implant and to examine patient satisfaction. After obtaining institutional review board approval, the charts of all children who had undergone at least one implant were reviewed.. Fifty-eight children, average age 8.4 y old (range 7-14), underwent at least one histrelin implant insertion for treatment of CPP. Parents of 44 patients were able to be reached by telephone for this study and rated the histrelin implant treatment highly. All implants were placed, replaced, or removed without significant difficulty, and there were no complications.. This study suggests that the use of a histrelin subcutaneous implant for control of CPP is a safe and effective method for the treatment of this condition. Topics: Adolescent; Child; Conscious Sedation; Gonadotropin-Releasing Hormone; Humans; Patient Satisfaction; Puberty, Precocious; Retrospective Studies | 2015 |
Resumption of puberty in girls and boys following removal of the histrelin implant.
To determine time to menarche in girls and testicular volume increase in boys after removal of a histrelin implant, which causes profound hypothalamic-pituitary-gonadal axis suppression.. Medical records of patients treated with a histrelin implant were reviewed. Seventy-one patients (56 girls) treated with the histrelin implant were identified, of these patients, 37 explanted girls (68% naïve) and 6 explanted boys (83% naïve) were included in the analysis. Time to menarche after explantation in girls and time to testicular volume increase after explantation in boys were determined. Additional variables investigated included indication for and duration of treatment, history of menarche (girls), previous therapy, and age at beginning and end of histrelin treatment.. Of the girls, 30 were treated for central precocious puberty (CPP), 26 had menarche at an average of 12.75 months after explantation. Of the 30, 7 were treated for other indications, of whom 6 had reached menarche. In girls with CPP, older age at explantation correlated with sooner menarche (P = .04). All boys achieved spontaneous testicular enlargement within 1 year of explantation.. This study documented resumption of puberty after histrelin explantation in treatment naïve and non-naïve boys and girls with and without CPP. Menarche in girls with CPP occurs within a similar timeframe to that observed after other treatment approaches. Topics: Child; Device Removal; Drug Implants; Female; Gonadotropin-Releasing Hormone; Humans; Male; Menarche; Puberty; Puberty, Precocious; Retrospective Studies; Testis | 2014 |
Surgical and anesthetic considerations in histrelin capsule implantation for the treatment of precocious puberty.
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.. All cases from one surgeon at a tertiary pediatric hospital were reviewed for patient age, anesthetic type, technical difficulties, and complications.. 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).. 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. Topics: Anesthesia, General; Anesthesia, Local; Anesthetics, Inhalation; Capsules; Child; Conscious Sedation; Cost Savings; Device Removal; Drug Implants; Equipment Failure; Female; Gonadotropin-Releasing Hormone; Humans; Hypersensitivity; Infections; Male; Nitrous Oxide; Puberty, Precocious; Retrospective Studies; Risk Factors | 2014 |
Time to menarche and final height after histrelin implant treatment for central precocious puberty.
To compare final height, change in body mass index (BMI), and time from end of treatment until menarche in girls with central precocious puberty treated with the histrelin implant versus depot gonadotropin releasing hormone agonist injections.. Chart review, interview, and final height measurements of 2 groups of girls with central precocious puberty; triptorelin depot (TD) group: 23 girls were treated from age 8.4 ± 0.3 with monthly injections of TD, for 26.7 ± 2.5 months; histrelin implant group: 11 girls were treated from age 8.7 ± 0.3 years for 28.4 ± 3.7 months, of whom 9 initially received monthly TD injections for 1.5-39 months. Final height, BMI (pretreatment vs recent), and time between either implant removal or last injection to menarche were compared.. Time between removal of implant or last injection and menarche was 9.3 ± 1.5 (histrelin implant group) versus 16.1 ± 1.7 (TD group) months (P = .02). Predicted height at implant insertion was 156.8 ± 2.6 cm, and final height was 161.1 ± 2.0 cm (not significant [NS]). Predicted height for TD was 155.2 ± 1.9 cm and final height was 157.9 ± 1.7 cm (NS). Change from onset of treatment to final BMI-SDS for histrelin implant was -0.41 ± 0.3, and for TD was -0.03 ± 0.2 (NS).. Menarche occurred sooner after implant removal. There was no difference in final height or BMI outcomes between the 2 treatment modalities. Topics: Age Factors; Body Height; Body Mass Index; Child; Delayed-Action Preparations; Drug Implants; Female; Gonadotropin-Releasing Hormone; Humans; Menarche; Puberty, Precocious; Triptorelin Pamoate | 2013 |
A single histrelin implant is effective for 2 years for treatment of central precocious puberty.
We investigated whether a "yearly" histrelin implant would provide pubertal suppression when left in place for 2 years. Equivalent suppression was observed when comparing 12 and 24 months in 33 children with central precocious puberty. A single implant for 2 years reduces cost and number of implant procedures. Topics: Child; Child, Preschool; Drug Implants; Female; Gonadotropin-Releasing Hormone; Humans; Hypothalamo-Hypophyseal System; Luteinizing Hormone; Male; Puberty, Precocious; Sex Factors; Time Factors | 2013 |
Random luteinizing hormone often remains pubertal in children treated with the histrelin implant for central precocious puberty.
To investigate the use of random ultrasensitive (US) luteinizing hormone (LH) levels to monitor children being treated with a histrelin implant for central precocious puberty (CPP).. This was a prospective, uncontrolled, observational study at a pediatric endocrinology tertiary center. Thirty-three children (26 girls; mean age 7.2 ± 2.5 years) treated with a histrelin implant for CPP were enrolled. A random US LH measurement was obtained at 6 months, and a gonadotropin-releasing hormone analog stimulation test was performed at 12 months. Clinic visits occurred at baseline and at 6-month intervals.. In 59% of the patients (17 of 29), the 6-month random US LH exceeded the prepubertal range of ≤0.3 IU/L. In contrast, gonadotropin-releasing hormone analog stimulation tests revealed complete hypothalamic-pituitary-gonadal axis suppression (peak LH <4 IU/L) in all 31 patients who underwent testing. US LH levels were highly correlated with peak stimulated LH levels. The mean peak stimulated LH level was higher in patients with a pubertal random LH than in those with a prepubertal random LH (1.2 ± 0.5 IU/L vs 0.5 ± 0.1 IU/L; P < .01). No patient had clinical evidence of pubertal progression.. The random US LH level does not revert to a prepubertal range in more than one-half of patients with a histrelin implant and documented hypothalamic-pituitary-gonadal axis suppression. Long-term studies are needed to elucidate the optimal strategy for monitoring treatment in children with CPP. Topics: Child; Child, Preschool; Drug Implants; Drug Monitoring; Female; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Prospective Studies; Puberty, Precocious | 2013 |
Intraoperative sonographic localization of a fractured Supprelin implant in a pediatric patient: a case report.
The subdermal implant is an effective delivery system for the gonadotropin-releasing hormone analog histrelin in the treatment of central precocious puberty. In younger patients, implantation and replacement of the implant is performed under general anesthesia. This obviates the need for frequent intramuscular injections and has been shown to be preferable to patients and families. However, the implantation procedures have been complicated by fracture during surgical withdrawal. This paper discusses one such case and the intraoperative technique that led to effective withdrawal of the fractured implant. Topics: Administration, Cutaneous; Child; Drug Implants; Gonadotropin-Releasing Hormone; Humans; Male; Puberty, Precocious | 2012 |
Free alpha-subunit is the most sensitive marker of gonadotropin recovery after treatment of central precocious puberty with the histrelin implant.
Gonadotropin free alpha-subunit (FAS) levels paradoxically increase during GnRH agonist (GnRHa) treatment of central precocious puberty (CPP). The histrelin implant suppresses gonadotropins and estradiol (E(2)) levels for 1 yr, but effects on FAS have not been described.. We aimed to determine whether FAS levels remain elevated during treatment with the implant, to assess the dynamics of FAS after removal, and to ascertain the reliability of FAS for monitoring gonadotropin secretion.. Ten girls with CPP were studied. In eight, monthly im GnRHa preparations were given until implant insertion. Two naive girls did not receive prior GnRHa. Duration of implant treatment ranged from 18-63 months with repeated implant removals and insertions of new implants. LH, FSH, E(2), and FAS were measured before implant insertion in the two naive patients and during treatment, and in all girls before and after implant removal.. FAS levels were 0.2 and 0.4 ng/ml (normal, <0.6 ng/ml) in the two naive girls and increased to 2.4 and 5.1 ng/ml within 2-5 d of insertion. FAS level (mean +/- SD) in all 10 girls during histrelin implant treatment was 1.19 +/- 0.49 ng/ml and rapidly decreased to 0.31 +/- 0.12 ng/ml within 1 wk of implant removal (P < 0.03). In contrast, significant increases in LH (P < 0.05) and FSH (P < 0.02) were observed at 3 wk and E(2) (P < 0.05) at 6 wk after implant removal.. Compared to LH, FSH, and E(2), FAS responds more rapidly to implant removal and represents the most sensitive indicator of gonadotropin recovery after histrelin implant treatment. Topics: Child; Delayed-Action Preparations; Drug Implants; Estradiol; Female; Follicle Stimulating Hormone; Follicle Stimulating Hormone, Human; Glycoprotein Hormones, alpha Subunit; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Hydrogels; Luteinizing Hormone; Puberty, Precocious; Recovery of Function | 2010 |
Determinants of growth during gonadotropin-releasing hormone analog therapy for precocious puberty.
In children with precocious puberty (PP), treatment with GnRH analogs (GnRHa) often decreases height velocity below normal. Based on previous animal studies, we hypothesized that this impaired growth is due to excessive advancement in growth plate senescence induced by the prior estrogen exposure. This hypothesis predicts that the height velocity during treatment will be inversely related to the severity of prior estrogen exposure. We analyzed data from 100 girls (age, 5.8 +/- 2.1 yr; mean +/- SD) with central PP who were treated with GnRHa. During GnRHa therapy, height velocity was low for age (-1.6 +/- 1.7 SD score; mean +/- SD). The absolute height velocity correlated most strongly with the bone age (BA), which we used as a surrogate marker for growth plate senescence (r = -0.727, P < 0.001). The severity of the growth abnormality (height velocity SD score for age) correlated inversely with markers of the severity of prior estrogen exposure, including duration of PP (r = -0.375, P < 0.001), Tanner breast stage (r = -0.220, P < 0.05), and BA advancement (r = -0.283, P < 0.01). Stepwise regression confirmed that BA was the best independent predictor of growth during GnRHa therapy. The findings are consistent with our hypothesis that impaired growth during GnRHa therapy is due, at least in part, to premature growth plate senescence induced by the prior estrogen exposure. Topics: Age Determination by Skeleton; Body Height; Child; Child, Preschool; Estrogens; Female; Gonadotropin-Releasing Hormone; Growth Disorders; Growth Plate; Humans; Puberty; Puberty, Precocious; Regression Analysis; Time Factors; Triptorelin Pamoate | 2004 |
Increased final height in precocious puberty after long-term treatment with LHRH agonists: the National Institutes of Health experience.
We report 98 children who have reached final adult height in a long-term trial of LHRH agonist treatment. These children were 5.3 +/- 2.1 yr old at the start of treatment and were treated with either deslorelin (4 microg/kg.d sc) or histrelin (4-10 microg/kg.d) for an average of 6.1 +/- 2.5 yr. Final height averaged 159.8 +/- 7.6 cm in the 80 girls, which was significantly greater than pretreatment predicted height (149.3 +/- 9.6 cm) but still significantly less than midparental height (MPH) (163.7 +/- 5.6). Final height averaged 171.1 +/- 8.7 cm in the 18 boys, which was significantly greater than pretreatment predicted height (156.1 +/- 14.2 cm) but still significantly less than MPH (178.3 +/- 5.2 cm). However, the average adult height of the 54 children who had less than a 2-yr delay in the onset of treatment was not significantly different from their MPH, and 21 children exceeded MPH. Final height SD score correlated positively with duration of treatment (P < 0.01), midparental height (P < 0.001), predicted height at the start of treatment (P < 0.001), and growth velocity during the last year of treatment (P < 0.001) and correlated inversely with delay in the onset of treatment (P < 0.001), age at the start of treatment (P < 0.001), bone age at the start of treatment (P < 0.001), bone age at the end of treatment (P < 0.001), breast stage at the start of treatment (P = 0.02), and bone age minus chronological age at the start of treatment (P = 0.001). We conclude that LHRH agonist treatment improves the final height for children with rapidly progressing precocious puberty treated before the age of 8 yr for girls or 9 yr for boys. Less delay in the onset of treatment, longer duration of treatment, and lower chronological and bone age at the onset of treatment all lead to greater final height. All children with onset of pubertal symptoms before age 8 in girls and age 9 in boys should be evaluated for possible treatment. Treatment is appropriate in children with rapidly progressing puberty, accelerated bone maturation, and compromise of adult height prediction, regardless of bone age or chronological age at time of evaluation. However, once treatment is considered appropriate, it should be initiated quickly, because longer delays lead to shorter final height. In addition, the longer the treatment is continued, the greater is the final height outcome. Topics: Age Factors; Body Height; Child; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Humans; Infant; Male; Puberty, Precocious; Triptorelin Pamoate | 2001 |
Reproductive axis after discontinuation of gonadotropin-releasing hormone analog treatment of girls with precocious puberty: long term follow-up comparing girls with hypothalamic hamartoma to those with idiopathic precocious puberty.
Although the GnRH agonist analogs have become an established treatment for precocious puberty, there have been few long term studies of reproductive function and general health after discontinuation of therapy. To this end, we compared peak LH and FSH after 100 microg sc GnRH, estradiol, mean ovarian volume (MOV), age of onset and frequency of menses, body mass (BMI), and incidence of neurological and psychiatric problems in 2 groups of girls: those with precocious puberty due to hypothalamic hamartoma (HH; n 18) and those with idiopathic precocious puberty (IPP; n = 32) who had been treated with deslorelin (4-8 microg/kg x day, s.c.) or histrelin (10 microg/kg x day, s.c.) for 3.1-10.3 yr and were observed at 1, 2, 3, and 4-5 yr after discontinuation of treatment. The endocrine findings were also compared to those in 14 normal perimenarcheal girls. There were no differences between the HH and IPP groups in age or bone age at the start of treatment, at the end of treatment, or during GnRH analog therapy. We found that whereas the peak LH level was higher in HH than in IPP girls before (165.5 +/- 129 vs. 97.5 +/- 55.7; P < 0.02) and at the end (6.8 +/- 6.0 vs. 3.9 +/- 1.8 mIU/mL; P < 0.05) of therapy, this difference did not persist at any of the posttherapy time points. LH, FSH, and estradiol rose into the pubertal range by 1 yr posttherapy in both HH and IPP. However, the mean posttherapy peak LH levels in both HH and IPP groups tended to be lower than normal, whereas the peak FSH levels were not different from normal, so that the overall posttherapy LH/FSH ratio was decreased compared to that in the normal girls (HH, 2.7 +/- 0.3; IPP, 2.6 +/- 0.1; normal, 5.2 +/- 4.8; P < 0.05). The MOV was larger in HH than IPP at the end of treatment (3.7 +/- 3.5 vs. 2.0 +/- 1.2 mL; P < 0.05) and tended to increase in both groups over time to become larger than that in normal girls by 4-5 yr posttherapy (HH, 14.9 +/- 12.9; IPP, 7.6 +/- 2.2; normal, 5.4 +/- 2.5 mL; P < 0.05). Whereas the onset of spontaneous menses varied widely in both groups, once menses had started, the HH group had a higher incidence of oligomenorrhea. Pelvic ultrasonography revealed more than 10-mm hypoechoic regions in 4 HH patients, 15 IPP patients, and 3 normal girls, all of whom were reporting regular menses. Live births of normal infants were reported by 2 HH and 2 IPP patients, and elective terminations of pregnancy were reported by 1 HH and 2 IPP patients. BMI was greater than normal in HH Topics: Adolescent; Child; Child, Preschool; Estradiol; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadotropin-Releasing Hormone; Hamartoma; Humans; Hypothalamic Diseases; Luteinizing Hormone; Pregnancy; Puberty, Precocious; Reproduction; Triptorelin Pamoate | 1999 |
Selection of children with precocious puberty for treatment with gonadotropin releasing hormone analogs.
Topics: Child; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Nafarelin; Puberty, Precocious | 1994 |
From the Food and Drug Administration.
Topics: Child; Facility Regulation and Control; Female; Gonadotropin-Releasing Hormone; Humans; Laboratories; Male; Orphan Drug Production; Puberty, Precocious; United States; United States Food and Drug Administration | 1992 |
Nocturnal melatonin levels are unaltered by ovarian suppression in girls with central precocious puberty.
Girls with central precocious puberty were utilized as a model in which to study the melatonin secretory response to ovarian suppression. Eight girls with central precocious puberty documented by clinical and endocrine characteristics, including sleep-entrained augmentation of luteinizing hormone (LH) pulsatility, were investigated. Nocturnal (6:00 P.M. to 9:00 A.M.) plasma melatonin levels were measured hourly by a sensitive and specific radioimmunoassay before and after gonadotropin-ovarian downregulation with gonadotropin-releasing hormone (GnRH)-agonist. Although nocturnal melatonin elevations varied widely between girls, patterns within the same individual were remarkably reproducible and unaltered before and after treatment. Although estrogens have been shown to modulate melatonin synthesis and secretion, in this model, reduction of estrogen levels was not associated with alterations in plasma melatonin concentrations. Topics: Child; Child, Preschool; Circadian Rhythm; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hydrocortisone; Luteinizing Hormone; Melatonin; Puberty, Precocious; Testosterone | 1989 |