Therapeutic Use of Pituitary Oesensitization With a Long-Acting LHRM Agonist: A Potential New Treatment for Idiopathic Precocious Puberty*

Crowley, William F.; Comite, Florence; Vale, Wylie; Rivier, J.; Loriaux, D. Lynn; Cutler, Gordon B.

doi:10.1210/jcem-52-2-370

Cited by 269 publications

(86 citation statements)

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“…The treatment to counteract early puberty was gonadotrophin releasing hormone analogues(GnRHa), intranasal preparations first and depot preparations subsequently (12)(13)(14)(15)(16)(17)(18)(19). Although this treatment effectively blocked the progress of pubertal development, it was found to be associated with a decrease in height velocity as well (20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Can Bone Age Determination Provide Criteria for Growth Hormone Treatment in Adopted Girls with Early Puberty?

Proos

Lönnerholm

Jonsson

et al. 2006

Upsala Journal of Medical Sciences

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In treatment of idiopathic central precocious puberty, GnRH analogues (GnRHa) have been accepted as the treatment of choice. Since growth velocity may be impaired with GnRHa treatment growth hormone (GH) treatment has been added in clinical trials. Recently, a study followed adopted girls with early or precocious puberty on GnRHa or combined GnRHa and GH treatment to final height. It was found that final height was significantly higher in the combined treatment group, although the difference was small. It was seen that patients that were extremely short at arrival and short at start of treatment seemed to be candidates for combined treatment. We have now analysed the data in order to define criteria for the subgroup in need of combined GnRHa-GH treatment in order to achieve normal final height, i.e. above -2 SDS.Bone ages of 46 patients at start of treatment, randomized to either GnRHa treatment or GnRHa treatment combined with GH, were examined blindly by the same radiologist and the PAH calculated. The methods according to Greulich-Pyle / Bayley-Pinneau (GP/BP) and Tanner-Whitehouse (TW2) were used. Predictions versus final height data were analysed.The accuracy of FH prediction was greatest for GnRHa treated group using the GP/BP method. The GP/BP method gave useful cut off limits for when combined treatment was necessary to possibly achieve normal height. If pre-treatment GP/PAH was > 157cm, the patients attained normal height with GnRHa treatment only. Ten out of 13 (77%) such girls could be correctly identified. Using TW2 with 117

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Section: Introductionmentioning

confidence: 99%

Can Bone Age Determination Provide Criteria for Growth Hormone Treatment in Adopted Girls with Early Puberty?

Proos

Lönnerholm

Jonsson

et al. 2006

Upsala Journal of Medical Sciences

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“…First, the pattern of GnRH presentation is critical since a pulsatile pattern of GnRH stimulation maintains normal gonadotropin secretion whereas continuous GnRH delivery causes profound pituitary desensitization (1,2). Secondly, the quantity of GnRH within each pulse is directly related to the magnitude of the ensuing luteinizing hormone (LH) response from the pituitary (3,4).…”

Section: Introductionmentioning

confidence: 99%

Effects of decreasing the frequency of gonadotropin-releasing hormone stimulation on gonadotropin secretion in gonadotropin-releasing hormone-deficient men and perifused rat pituitary cells.

Finkelstein¹,

Badger²,

O’Dea³

et al. 1988

J. Clin. Invest.

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The effects of decreasing the frequency of pulsatile gonadotropin-releasing hormone (GnRH) stimulation on pituitary responsiveness were studied in (a) men with isolated GnRH deficiency who had achieved normal sex steroid levels during prior long-term pulsatile GnRH replacement and (b) perifused dispersed pituitary cells from male rats in the absence of sex steroids. In three groups of four GnRH-deficient men, the frequency of GnRH stimulation was decreased at weekly intervals from (a) every 2-34 h (group I), (b) every 2-8 h without testosterone replacement (group II), or (c) every 2-8 h with testosterone replacement (group III). In three groups of three columns of perifused dispersed pituitary cells, pulses of GnRH were administered every 2, 4, or 8 h.In groups I and II, mean area under the luteinizing hormone (LH) curve increased (P < 0.025) and serum testosterone levels fell (P < 0.035) as the frequency of GnRH stimulation was decreased. In group III, the area under the LH curve also increased (P < 0.01) although serum testosterone levels were constant, thereby demonstrating that the increase in pituitary responsiveness to slow frequencies of GnRH stimulation occurs independently of changes in the sex steroid hormonal milieu. The area under the LH curve also increased in the perifused dispersed rat pituitary cells when the frequency of GnRH administration was decreased to every 8 h (P < 0.05), thus demonstrating that the enhanced pituitary responsiveness to slow frequencies of GnRH stimulation is maintained even in the complete absence of gonadal steroids.Nadir LH levels fell in all three groups (P < 0.01) as the frequency of GnRH stimulation was decreased. In contrast, mean peak LH levels, the rate of LH rise, and the rate of endogenous LH decay were constant as the frequency ofGnRH stimulation was decreased. Finally, as the GnRH interpulse interval increased, mean LH levels fell, and mean follicle-stimulating hormone levels were stable or fell.

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“…A long-acting GnRH, when used for a long duration, induces desensitization of pituitary GnRH receptors and final block of secretion after a short period of LH release. With adequate therapy, secondary sexual maturation is suppressed in a reversible manner, taking about 3 to 12 months after discontinuation (2,3). Several side effects, including sexual dysfunction, gastrointestinal upset, mood disorders, breast swelling, graying of hair, dry skin, alterations in liver function, menopausal symptoms, rash, tumor flare, urticaria, acne, and hair loss have been reported (1,3,4).…”

Section: Introductionmentioning

confidence: 99%

“…With adequate therapy, secondary sexual maturation is suppressed in a reversible manner, taking about 3 to 12 months after discontinuation (2,3). Several side effects, including sexual dysfunction, gastrointestinal upset, mood disorders, breast swelling, graying of hair, dry skin, alterations in liver function, menopausal symptoms, rash, tumor flare, urticaria, acne, and hair loss have been reported (1,3,4). The occurrence of these side effects is assumed to be directly related to the dose of the drug, thus, every effort should be made to reduce the dose with noticeable influence on the final outcome (5).…”

Section: Introductionmentioning

confidence: 99%

Comparison of Continuous Versus Intermittent Administration of Triptorelin on the Final Height of Girls with Idiopathic Precocious Puberty

et al. 2017

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Background: It has long been reported that gonadotropin releasing hormone (GnRH) analogs can improve final height of patients with idiopathic precocious puberty (IPP). This study aimed at comparing 2 different doses of GnRH agonist, triptorelin, on the adult height of girls with IPP. Methods: From July 2013, sixteen girls with IPP were randomly divided to 2 groups. The first Group received 1 intramuscular injection of triptorelin 0.3 mg/kg of body weight on a monthly basis, and the second group received this at months 1 to 6, 10 to 15, and 19 to 24. They did not receive triptorelin at months 7 to 9 and 16 to 18. Results: Patients in Group 1 received a total of 7.2 mg/kg of triptorelin during a 2-year follow up while the Group 2 received 5.4 mg/kg triptorelin or about 39.6 mg less than the other group during the same period of follow up. No side effects were noted in Group 2 receiving lower dose of triptorelin, yet, 2 cases with gray hair and 1 case with mild rash were reported in the group receiving the higher dose. No statistically significant difference was found between the 2 groups regarding height after 2 years. Conclusions: Treatment of IPP can be performed with triptorelin doses of less than 0.3 mg/kg per month, with the same height increment and lower side effects.

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Therapeutic Use of Pituitary Oesensitization With a Long-Acting LHRM Agonist: A Potential New Treatment for Idiopathic Precocious Puberty*

Cited by 269 publications

References 0 publications

Can Bone Age Determination Provide Criteria for Growth Hormone Treatment in Adopted Girls with Early Puberty?

Can Bone Age Determination Provide Criteria for Growth Hormone Treatment in Adopted Girls with Early Puberty?

Effects of decreasing the frequency of gonadotropin-releasing hormone stimulation on gonadotropin secretion in gonadotropin-releasing hormone-deficient men and perifused rat pituitary cells.

Comparison of Continuous Versus Intermittent Administration of Triptorelin on the Final Height of Girls with Idiopathic Precocious Puberty

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