Comparison of Complete and Incomplete Suppression of Pituitary-Gonadal Activity in Girls with Central Precocious Puberty: Influence on Growth and Predicted Final Height

Partsch, C. J.; Hümmelink, R.; Peter, Michael; Sippell, Wolfgang G.; Oostdijk, Wilma; Odink, Roelof J.; Drop, S. L. S.

doi:10.1159/000182709

Cited by 35 publications

(24 citation statements)

References 6 publications

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“…injection once monthly (group 2) than in girls treated with short-acting GnRH agonist administered intranasally several times daily given in combination with cyproterone acetate (group 1). This is in accordance with other reports of short-acting GnRH agonist being less effective than long-acting when comparing similar treatment regimens [13, 14]. Thus, it seems that greater suppression of gonadotropin levels is reflected in lower levels of inhibin B, also supported by the positive correlation between peak LH levels and inhibin B during treatment.…”

Section: Discussionsupporting

confidence: 92%

Serum Inhibin A and Inhibin B in Central Precocious Puberty before and during Treatment with GnRH Agonists

et al. 2000

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Serum levels of the gonadal hormones inhibin A and inhibin B are undetectable or low in prepubertal girls, and rise during puberty. In girls with central precocious puberty (CPP) the hypothalamic-pituitary-gonadal axis is prematurely activated, if the girl is thereafter treated with GnRH agonists both gonadotropins and estradiol levels become suppressed. We therefore investigated serum levels of inhibin A and inhibin B in girls with CPP at diagnosis and during treatment in order to test the hypothesis that inhibin secretion would increase and decrease in parallel with the activation and suppression of the hypothalamic-pituitary-gonadal axis. Serum levels of inhibin A and inhibin B were significantly (p < 0.0005) elevated in 42 girls at diagnosis of CPP (inhibin A: 7 pg/ml (<7–139), inhibin B: 80 pg/ml (<20–294) (median, range)) compared to levels in age-matched healthy schoolgirls (inhibin A: all values <7 pg/ml, inhibin B: 21 pg/ml (<20–122) (median, range)), but were appropriate for Tanner stage. During treatment with GnRH agonist (intranasal buserelin and oral cyproterone acetate, treatment group 1, n = 23, or triptorelin depot injections, treatment group 2, n = 19) levels of both hormones fell significantly (p = 0.002). There was a significantly (p = 0.003) greater fall in inhibin B levels during treatment in group 2 compared to group 1, with inhibin B levels now lying below (group 2: <20 pg/ml (<20–68)) rather than within (group 1: 34.5 pg/ml (<20–93)) the age-appropriate range. It is concluded that levels of inhibin A and inhibin B are elevated and suppressed in concert with activation and suppression of the hypothalamo-pituitary-gonadal axis in girls with CPP, supporting the concept that ovarian inhibin secretion is dynamically regulated by gonadotropin stimulation.

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Section: Discussionsupporting

confidence: 92%

Serum Inhibin A and Inhibin B in Central Precocious Puberty before and during Treatment with GnRH Agonists

et al. 2000

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“…The dose needed to adequately suppress puberty varies considerably. 8,15 Inadequate therapy can lead to clinical progression and continued advancement of bone maturation. 8,9 On the other hand, excessive dosing is costly: recent pharmacy retail pricing at our hospital shows that a 3.75-mg dose of depot leuprolide costs a patient $643, 7.5 mg costs $855, and 11.25 mg costs $1598.…”

Section: Discussionmentioning

confidence: 99%

“…8,15 Inadequate therapy can lead to clinical progression and continued advancement of bone maturation. 8,9 On the other hand, excessive dosing is costly: recent pharmacy retail pricing at our hospital shows that a 3.75-mg dose of depot leuprolide costs a patient $643, 7.5 mg costs $855, and 11.25 mg costs $1598. More importantly, overtreatment may suppress endogenous growth hormone secretion and decrease growth velocity and bone density accrual below that expected in the prepubertal period.…”

Section: Discussionmentioning

confidence: 99%

“…Insufficient doses can be counterproductive, as the waxing and waning of hormone levels may actually mimic the stimulatory GnRH pulses that advance puberty. 8,9 Frequent testing to ensure adequacy of therapy and to optimize the dose is important in monitoring treated patients. 3 Patients receiving depot leuprolide therapy are monitored clinically, through assessment of linear growth, sexual maturation, and bone age.…”

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confidence: 99%

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Serum Luteinizing Hormone Rises Within Minutes After Depot Leuprolide Injection: Implications for Monitoring Therapy

2002

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ABSTRACT. Objective. To find the time of the serum gonadotropin peak after depot leuprolide injection in children and to show that depot leuprolide therapy can be monitored by measuring serum luteinizing hormone (LH) immediately after injections.Study Design. We measured concentrations of leuprolide, LH, and follicle-stimulating hormone (FSH) at multiple time points before and after the first dose of depot leuprolide in 14 pubertal children beginning therapy. Gonadotropins and sex steroids were measured again after the fourth dose.Results. Serum leuprolide, LH, and FSH levels rose rapidly after initial injection, reaching sustained elevations at 30 to 120 minutes. The median LH level increased from 2.1 mIU/mL at baseline to a peak of 27.5 mIU/mL at 45 minutes, and FSH increased from 5.2 to 16.5 mIU/mL. After 3 months on therapy, median serum LH after depot leuprolide injection was only 0.83 mIU/mL, similar to levels observed after intravenous or subcutaneous gonadotropin-releasing hormone stimulation in comparable subjects on depot leuprolide.Conclusion. Our pharmacokinetic data demonstrate that free leuprolide present in a depot leuprolide injection is equivalent to gonadotropin-releasing hormone in stimulating a rapid rise in serum gonadotropin concentrations. We propose that a single serum sample for LH obtained 30 to 60 minutes after depot leuprolide injection in children provides a convenient and accurate assessment of treatment efficacy. Pediatrics 2002;109(2). URL: http://www.pediatrics.org/cgi/content/full/109/2/e30; puberty, leuprolide, luteinizing hormone, follicle-stimulating hormone, gonadotropin, gonadotropin-releasing hormone.ABBREVIATIONS. CPP, central precocious puberty; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone; IM, intramuscular; IV, intravenous; SQ, subcutaneous. C entral precocious puberty (CPP) is the early onset of pubertal development attributable to premature gonadotropin release by the pituitary. Most commonly idiopathic, CPP can also result from central nervous system trauma or tumors. Untreated, precocious puberty can result in short stature and significant social problems for children undergoing sexual maturation years before their peers. 1,2 Pulsatile secretion of endogenous gonadotropin-releasing hormone (GnRH) results in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release from the pituitary and progression of puberty, 3 whereas the tonic stimulus of a long-acting GnRH analog causes an initial surge of gonadotropin release, followed by suppression of pituitary gonadotropin production and release. 4,5 Depot leuprolide (Depot-Lupron, TAP Pharmaceuticals, Deerfield, IL), a commonly used long-acting GnRH analog, is given by monthly intramuscular (IM) injection and is slowly released into the circulation to provide such tonic suppressive levels.Depot leuprolide consists of leuprolide encased in microspheres of a glycolic and lactic acid copolymer. Free leuprolide is also present in the preparation 6 and is absorbe...

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“…Funhrrmore, significant improvement of growth parameters and final height were shown (Ocrter ct al. , Partsch et al 1993, Sippcll 1994.…”

mentioning

confidence: 99%

Precocious puberty in children with myelomeningocele: treatment with gonadotropin‐releasing hormone analogues

Trollmann

Strehl

Dörr

1998

Develop Med Child Neuro

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In patients with myelomeningocele (MMC), growth is influenced by a large number of growth‐retarding factors due to the neurological defect. Moreover, endocrine disorders have been found to contribute to short stature in MMC patients. Central precocious puberty (CPP) is a common problem. Due to growth disturbances and difficulties in obtaining standardized measurements, MMC patients have been excluded from gonadotropin‐releasing hormone (GnRH) analogue studies in the past. We report on eight patients (six female, two male) with MMC, hydrocephalus, and CPP who were treated with GnRH analogues: triptorelin intramuscularly (N=5) or leuprorelin subcutaneously (N=3). Auxological data and hormone levels were assessed before treatment and every 6 months during treatment. The median chronological ages (CA) at the start of treatment were 8.6 years (females) and 8.4 years (males). Bone age (BA) was accelerated in all cases prior to treatment and two girls were already menstruating. Elevated gonadotropin serum levels and sex steroid levels decreased during treatment, although no complete suppression to prepubertal levels was reached. Progression of pubertal development and menses stopped in all patients. The tempo of BA acceleration (ΔBA:ΔCA) decreased, but no significant improvement in height standard deviation score BA and predicted adult height resulted. No side effects during treatment were observed. CPP in MMC patients has to be considered as early as possible to enable an early diagnosis and corresponding treatment. Further prospective studies on the effects of GnRH analogues in MMC patients are necessary.

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Comparison of Complete and Incomplete Suppression of Pituitary-Gonadal Activity in Girls with Central Precocious Puberty: Influence on Growth and Predicted Final Height

Cited by 35 publications

References 6 publications

Serum Inhibin A and Inhibin B in Central Precocious Puberty before and during Treatment with GnRH Agonists

Serum Inhibin A and Inhibin B in Central Precocious Puberty before and during Treatment with GnRH Agonists

Serum Luteinizing Hormone Rises Within Minutes After Depot Leuprolide Injection: Implications for Monitoring Therapy

Precocious puberty in children with myelomeningocele: treatment with gonadotropin‐releasing hormone analogues

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