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

Silverman, Lawrence; Neely, E. Kirk; Kletter, Gad B.; Lewis, Katherine; Chitra, Surya; Terleckyj, Oksana; Eugster, Erica A.

doi:10.1210/jc.2014-3031

Cited by 56 publications

(29 citation statements)

References 37 publications

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“…A subdermal implant of prolonged action that releases therapeutic doses of GnRHa for 12 to 24 months (histrelin 50 mg) has advantages and disadvantages over 1-month and 3-month depot GnRHa (52). The advantages include the abolishment of periodic subcutaneous or intramuscular administration, but the risk of reactions at the implant site, spontaneous extrusion, and local infection are the main undesirable side effects of this therapy.…”

Section: Treatment Of Central Precocious Pubertymentioning

confidence: 99%

Central precocious puberty: revisiting the diagnosis and therapeutic management

Brito

Spinola-Castro

Kochi

et al. 2016

Arch. Endocrinol. Metab.

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Clinical and laboratory diagnosis and treatment of central precocious puberty (CPP) remain challenging due to lack of standardization. The aim of this revision was to address the diagnostic and therapeutic features of CPP in Brazil based on relevant international literature and availability of the existing therapies in the country. The diagnosis of CPP is based mainly on clinical and biochemical parameters, and a period of follow-up is desirable to define the "progressive" form of sexual precocity. This occurs due to the broad spectrum of pubertal development, including isolated premature thelarche, constitutional growth and puberty acceleration, progressive and nonprogressive CPP, and early puberty. Measurement of basal and stimulated LH levels remains challenging, considering that the levels are not always in the pubertal range at baseline, short-acting GnRH is not readily available in Brazil, and the cutoff values differ according to the laboratory assay. When CPP is suspected but basal LH values are at prepubertal range, a stimulation test with short-acting or long-acting monthly GnRH is a diagnostic option. In Brazil, the treatment of choice for progressive CPP and early puberty is a long-acting GnRH analog (GnRHa) administered once a month or every 3 months. In Brazil, formulations of GnRHa (leuprorelin and triptorelin) are available and commonly administered, including 1-month depot leuprorelin 3.75 mg and 7.5 mg, 1-month depot triptorelin 3.75 mg, and 3-month depot leuprorelin 11.25 mg. Monthly or 3-month depot GnRHa are effective and safe to treat CPP. Arch Endocrinol Metab. 2016;60(2):163-72

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Section: Treatment Of Central Precocious Pubertymentioning

confidence: 99%

Central precocious puberty: revisiting the diagnosis and therapeutic management

Brito

Spinola-Castro

Kochi

et al. 2016

Arch. Endocrinol. Metab.

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“…Fisher et al (41) reported the resumption of puberty in 26 of the 30 girls treated with the histrelin implant, with occurrence of menarche 2-36 months after explantation in treatment-naïve and -nonnaïve CPP girls, with an older age at explantation correlating with earlier menarche. In a recent study by Silverman et al (43), menarche occurred in two patients, 9 and 2 months after the final explant respectively.…”

Section: Reproductive Function and Risk Of Polycystic Ovarian Syndromementioning

confidence: 91%

“…The highest prevalence of regular cycles (96%) was observed in 87 treated idiopathic-CPP girls during a 7-year follow-up period after the discontinuation of treatment (15). Jay et al (43) described menstrual cycle lengths as becoming increasingly regular, from 41% in the first year post-menarche to 65% at 3 or more years post-menarche (44).…”

Section: Reproductive Function and Risk Of Polycystic Ovarian Syndromementioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Long-term outcomes of the treatment of central precocious puberty

Guaraldi

Beccuti

Gori

et al. 2016

European Journal of Endocrinology

113

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GnRH analogues (GnRHa) are the treatment of choice for central precocious puberty (CPP), with the main objective to recover the height potential compromised by the premature fusion of growth cartilages. The aim of this review was to analyze longterm effects of GnRHa on height, body weight, reproductive function, and bone mineral density (BMD) in patients with CPP, as well as the potential predictors of outcome. Because randomized controlled trials on the effectiveness and long-term outcomes of treatment are not available, only qualified conclusions about the efficacy of interventions can be drawn. GnRHa treatment appears to improve adult height in girls with CPP, especially if diagnosed before the age of 6, whereas a real benefit in terms of adult height is still controversial in patients with the onset of puberty between 6 and 8 years of age. No height benefit was shown in patients treated after 8 years. Gonadal function is promptly restored in girls after cessation of treatment, and reproductive potential appears normal in young adulthood. Data are conflicting on the long-term risk of polycystic ovarian syndrome in both treated and untreated women. Fat mass is increased at the start of treatment but normalizes thereafter, and GnRHa itself does not seem to have any long-term effect on BMI. Similarly, analogue treatment does not appear to have a negative impact on BMD. Owing to the paucity of data available, no conclusions can be drawn on the repercussions of CPP and/or its treatment on the timing of menopause and on the health of the offspring.

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“…2 Recently, a subcutaneous implant releasing the GnRHa histrelin at an average rate of 65 microg/day was developed, with encouraging results. 3,4 Monitoring of adequate suppression is usually based on an assessment of physical growth and puberty and the frequency of injections is often increased when these clinical parameters suggest inadequate suppression. Although there may be scope for further personalization of therapy, this has been difficult to achieve in the absence of objective and reliable tools that are simple, inexpensive and lend themselves to repeat measurements.…”

Section: Introductionmentioning

confidence: 99%

The measurement of urinary gonadotropins for assessment and management of pubertal disorder

Lucaccioni

McNeilly

Mason

et al. 2016

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ObJECTIvE: measurement of urinary lh (ulh) and FSh (uFSh) may facilitate non-invasive pubertal assessment but there is a need for further validation by studying children and adolescents with disorders of puberty. DESIgN: 65 cases (male: 25) with a median age of 12 years (2.9-18.1) supplied at least one non-timed urine sample for uLH and uFSH measurement by immunoassay and corrected for creatinine excretion. 25 cases were receiving gnRh-agonist (gnRh-a) at the time of sample collection. In 41 cases, urine samples were collected prior to a lhRh test and in 12 cases matched serum samples for basal lh (slh) and FSh (sFSh) were also available. RESUlTS: There was a significant correlation between slh and ulh:uCr (r=0.82; p-value <0.001) and sFSH and uFSH:uCr (r=0.93; p-value <0.001). Based on receiver operator characteristics analysis, a ulh:uCr value of 0.05 IU/mmol as a cut-off would detect a lh peak >5U I/l with a sensitivity of 86% and a specificity of 72% with a positive predictive value of 93%. In pubertal boys (6) and girls (22)

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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

Abstract: Long-term histrelin implant therapy provided sustained gonadotropin suppression safely and effectively and improved predicted adult height in children with CPP.

Cited by 56 publications

References 37 publications

Central precocious puberty: revisiting the diagnosis and therapeutic management

Central precocious puberty: revisiting the diagnosis and therapeutic management

MANAGEMENT OF ENDOCRINE DISEASE: Long-term outcomes of the treatment of central precocious puberty

The measurement of urinary gonadotropins for assessment and management of pubertal disorder

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