Relationship between serum insulin-like growth factor-1, IGF binding protein-3 levels and body height before and after gonadotropin-releasing hormone agonist therapy.
Song Han Sol,Choi Won Bok,Song Joon Sup,Hwang Il Tae,Yang Seung
Annals of pediatric endocrinology & metabolism
PURPOSE:The gonadotropin-releasing hormone agonist (GnRHa) is widely used to treat patients with precocious puberty. However, its effect on growth is often difficult to predict because of the diverse nature of its causes and presentation. This study aims to show the impact of GnRHa treatment on insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP-3) secretion, growth, and on other parameters that may help estimate the height velocity. METHODS:Data from 60 girls (mean age, 8.8±0.7 years) treated with GnRHa were analyzed. Their height, bone age (BA), serum IGF-I, and IGFBP-3 concentrations were measured at the start and after a year of GnRHa treatment. To eliminate the confounding effect of chronological age (CA), the standard deviation scores (SDSs) of their height, IGF-I, and IGFBP-3 concentrations according to their CA at the start and after a year of GnRHa treatment were calculated. We looked for possible correlations between these variables and compared the subgroups based on their height velocities and midparental heights. RESULTS:During their one-year GnRHa therapy, height SDS for CA significantly decreased to 0.81±0.83 (P<0.001), but height SDS for BA increased to -0.28±0.68 (P<0.001). There was no significant change in serum IGF-I SDS, IGFBP-3 SDS, and IGF-I/IGFBP-3 ratio. The advanced BA was the factor most strongly correlated to the height velocity (R=0.265, P=0.041). CONCLUSION:These findings suggest that GnRHa treatment may affect the height velocity due to mechanisms other than suppression of the IGF-I and IGFBP-3 secretory axis.
10.6065/apem.2014.19.4.208
Adult height after spontaneous pubertal growth or GnRH analog treatment in girls with early puberty: a meta-analysis.
Bertelloni Silvano,Massart Francesco,Miccoli Mario,Baroncelli Giampiero I
European journal of pediatrics
Early puberty (EP) has been defined as the onset of puberty in the low-normal range; it may be a cause for concern regarding a possible impairment of adult height (AH). This paper meta-analysed data on AH after spontaneous growth or after gonadotropin-releasing hormone (GnRH) analog treatment in girls with EP. A computerized literature search was conducted from 1980 to June 30, 2016. Only published studies in English were considered. Eight papers were selected (483 cases). In untreated girls (n = 300), predicted adult height (PAH) at start of follow-up (-0.559 SDS (95%CI -1.110 to 0.001); P = 0.050) was close to mid-parental height (MPH) (-0.557 SDS (95%CI -0.736 to -0.419); P < 0.0001) and AH (-0.663 SDS (95%CI -0.803 to -0.524); P < 0.0001). In GnRH analog treated girls (n = 183), PAH before the start of treatment was slightly reduced (-0.939 SDS (95%CI -1.401 to -0.477; P < 0.0001) vs MPH (-0.678 SDS (95%CI -0.942 to -0.414); P < 0.0000), but AH (-0.604 SDS (95%CI -0.877 to -0.338); P < 0.0000) was close to MPH. CONCLUSION:Present meta-analysis indicates that girls with EP spontaneously reach their MPH and that GnRH analog treatment does not widely change growth outcome. Differences among the selected studies for definition of EP, inclusion criteria, treatment duration, age at discontinuation of therapy, definition of AH may affect results. What is Known: • Early puberty represents a main cause of consultation in paediatric endocrinology offices due to concerns of both practitioners and parents. • Treatment with GnRH analogs is sometimes attempted with the aim to improve adult height. What is New: • Untreated and GnRH analog treated girls with early puberty reached similar adult height. • Adult height was consistent with mid-parental height in both untreated and GnRH analog treated girls with early puberty.
10.1007/s00431-017-2898-8
Gonadotropin-Releasing Hormone Analogue Treatment in Females with Moderately Early Puberty: No Effect on Final Height.
Savaş-Erdeve Şenay,Şıklar Zeynep,Hacıhamdioğlu Bülent,Kocaay Pınar,Çamtosun Emine,Öcal Gönül,Berberoğlu Merih
Journal of clinical research in pediatric endocrinology
OBJECTIVE:To investigate the effects of treatment with gonadotropin-releasing hormone analog (GnRHa) on final height in girls who experienced moderately early puberty with symptoms beginning at 7-8.5 years of age. METHODS:Female cases diagnosed with moderately early puberty which had started between ages 7 to 8.5 years were included in the study. In the treatment groups, all cases with a bone age ≤10.5 years constituted group 1 (n=18) and those with a bone age >10.5 years constituted group 2 (n=23). The 8 patients for which treatment approval could not be obtained constituted group 3. The 49 cases in all three groups were observed until they reached their final height. RESULTS:Target height, target height standard deviation score (SDS), final height, and final height SDS values were similar in all 3 groups. Final height showed a significant positive correlation with target height (p=0.000, r=0.54) and height at diagnosis (p=0.003, r=0.467) in all groups. Linear regression analysis revealed that a 1 cm longer height at diagnosis increased the final height 0.213 fold, and a 1 cm longer target height at diagnosis increased the final height 0.459 fold. CONCLUSION:We found that GnRHa did not make a positive contribution to final height in cases of moderately early puberty.
10.4274/jcrpe.2356
BIRD'S-EYE VIEW OF GnRH ANALOG USE IN A PEDIATRIC ENDOCRINOLOGY REFERRAL CENTER.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
OBJECTIVE:Gonadotropin-releasing hormone analogs (GnRHa) are standard of care for the treatment of central precocious puberty (CPP). GnRHa have also been prescribed in other clinical settings with the hope of increasing adult stature, although evidence to support this practice is lacking. The degree to which GnRHa are being prescribed for indications other than CPP in routine clinical care has not been described. We sought to systematically examine GnRHa prescribing practices among the pediatric endocrinologists at our academic medical center. METHODS:We reviewed medical records of children treated with GnRHa during a 6-year interval. Variables analyzed included gender, age at start of treatment, indication for therapy, and use of growth hormone as adjunctive treatment. Nonparametric analyses were utilized to compare treatment characteristics of those with CPP versus those without. RESULTS:A total of 260 patients (82% female) aged 8.06 ± 2.68 years were identified. Of these, 191 (73.5%) were treated for CPP, whereas 69 (26.5%) were treated for normally timed puberty in the context of idiopathic short stature/poor predicted height (n = 37), growth hormone deficiency (n = 17), congenital adrenal hyperplasia (n = 10), primary hypothyroidism (n = 4), and developmental delay (n = 1). Of the 161 girls with CPP, GnRHa therapy was initiated at ≥8 years of age in 62 (39%). CONCLUSION:Whereas most patients were treated for CPP, ~27% were treated for other indications. Of girls with CPP, 39% were treated at an age when benefit in terms of height is unlikely. This highlights the need for rigorous studies of GnRHa use for indications beyond CPP.
10.4158/EP14412.OR
Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age.
Tinggaard Jeanette,Jensen Rikke Beck,Sundberg Karin,Birkebæk Niels,Christiansen Peter,Ellermann Annie,Holm Kirsten,Jeppesen Eva Mosfeldt,Kremke Britta,Marcinski Pawel,Pedersen Carsten,Saurbrey Nina,Thisted Ebbe,Main Katharina M,Juul Anders
Fertility and sterility
OBJECTIVE:To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls. DESIGN:A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA. SETTING:Not applicable. PATIENT(S):A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS). INTERVENTION(S):One year of GH treatment (67 μg/kg/day) followed by 2 years of randomized GH treatment (67 μg/kg/day, 35 μg/kg/day, or IGF-I titrated). MAIN OUTCOME MEASURE(S):Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment. RESULT(S):Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries. CONCLUSION(S):GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown. CLINICAL TRIAL REGISTRATION NUMBER:EudraCT 2005-001507-19.
10.1016/j.fertnstert.2014.09.014
Efficacy and Safety of Gonadotropin-Releasing Hormone Agonist Treatment to Suppress Puberty in Gender Dysphoric Adolescents.
Schagen Sebastian E E,Cohen-Kettenis Peggy T,Delemarre-van de Waal Henriette A,Hannema Sabine E
The journal of sexual medicine
INTRODUCTION:Puberty suppression using gonadotropin-releasing hormone agonists (GnRHas) is recommended by current guidelines as the treatment of choice for gender dysphoric adolescents. Although GnRHas have long been used to treat precocious puberty, there are few data on the efficacy and safety in gender dysphoric adolescents. Therefore, the Endocrine Society guideline recommends frequent monitoring of gonadotropins, sex steroids, and renal and liver function. AIM:To evaluate the efficacy and safety of GnRHa treatment to suppress puberty in gender dysphoric adolescents. METHODS:Forty-nine male-to-female and 67 female-to-male gender dysphoric adolescents treated with triptorelin were included in the analysis. MAIN OUTCOME MEASURES:Physical examination, including assessment of Tanner stage, took place every 3 months and blood samples were drawn at 0, 3, and 6 months and then every 6 months. Body composition was evaluated using dual energy x-ray absorptiometry. RESULTS:GnRHa treatment caused a decrease in testicular volume in 43 of 49 male-to-female subjects. In one of four female-to-male subjects who presented at Tanner breast stage 2, breast development completely regressed. Gonadotropins and sex steroid levels were suppressed within 3 months. Treatment did not have to be adjusted because of insufficient suppression in any subject. No sustained abnormalities of liver enzymes or creatinine were encountered. Alkaline phosphatase decreased, probably related to a slower growth velocity, because height SD score decreased in boys and girls. Lean body mass percentage significantly decreased during the first year of treatment in girls and boys, whereas fat percentage significantly increased. CONCLUSION:Triptorelin effectively suppresses puberty in gender dysphoric adolescents. These data suggest routine monitoring of gonadotropins, sex steroids, creatinine, and liver function is not necessary during treatment with triptorelin. Further studies should evaluate the extent to which changes in height SD score and body composition that occur during GnRHa treatment can be reversed during subsequent cross-sex hormone treatment.
10.1016/j.jsxm.2016.05.004
The Beneficial Effect of Combined GH/GnRHa Therapy in Increasing Adult Height Outcome in Children With ISS.
Lazar Liora,Levy Sigal,Oron Tal,Meyerovitch Joseph,de Vries Liat,Shalitin Shlomit,Tenenbaum Ariel,Phillip Moshe,Lebenthal Yael
The Journal of clinical endocrinology and metabolism
CONTEXT:Management of GH-treated children with idiopathic short stature (ISS) with early puberty and adolescents in midpuberty at initiation of treatment is challenging. OBJECTIVE:To assess the effect of combined GH/GnRHa therapy during puberty on achieved adult height (AHt) in these children with ISS and to determine whether outcome depended on sex and pubertal status at initiation of GH therapy. DESIGN:Retrospective, single-center observational study from 2003-2018. SETTING:Tertiary endocrine center. PATIENTS:One hundred ninety-two GH-treated children with ISS; 58 of 192 were treated by GH/GnRHa during puberty; 31 of 58 were prepubertal (19 girls) and 27 of 58 pubertal (19 girls) at initiation of GH. MAIN OUTCOME MEASURES:AHt, gain-in-height standard deviation score (SDS), AHt vs predicted adult height (PAHt), AHt vs target height (THt). RESULTS:Most boys and girls attained AHt SDS within the normal range (-0.73 ± 0.60 and -0.85 ± 0.65, respectively). Treatment modality, pubertal status, and sex were tested for their joint effect on growth outcome measures. Combined GH/GnRHa therapy increased AHt vs PAHt (P < 0.001) and AHt vs THt (P = 0.035). Prepubertal status at onset of GH treatment increased AHt (P = 0.049), gain-in-height SDS (P < 0.001), AHt vs PAHt (P < 0.001), and AHt vs THt (P = 0.042). Female sex increased AHt vs PAHt (P < 0.001). CONCLUSIONS:Our study demonstrated a beneficial effect of combined GH/GnRHa therapy in increasing AHt outcome in children with ISS with early/normal puberty and in adolescents naïve to GH treatment who are in midpuberty at initiation of therapy. This effect was more pronounced in the prepubertal group and in girls. Prospective randomized controlled trials are needed to assess whether GnRHa can increase AHt in GH-treated children with ISS.
10.1210/jc.2019-00233
Expensive therapies in children: benefit versus cost of combined treatment of recombinant human growth hormone and gonadotropin-releasing hormone analogue in girls with poor height potential.
Toumba Meropi,Kokotsis Vasilis,Savva Savvas C,Skordis Nicos
Journal of pediatric endocrinology & metabolism : JPEM
OBJECTIVE:The combination therapy of gonadotropin-releasing hormone analogues (GnRHa) and recombinant human growth hormone (rhGH) has been used to increase growth in children with premature sexual maturation and attenuated growth. The aim of this report was to study the benefit over cost of combined treatment in girls with central precocious puberty (CPP) and poor height prognosis and in girls with idiopathic short stature (ISS) and early puberty. Should this expensive treatment be given to such patients? SUBJECTS AND METHODS:Two patient groups were included: five girls with central precocious puberty (CPP) who reached final height (FH) at 16.3±1.2 years and eight girls with ISS who reached FH at 14.7±0.8 years. Patients were treated for 3.5±0.6 years. RESULTS:In both groups, FH improved significantly; in CPP from -1.3 to -0.5 standard deviation score (SDS) (p=0.030) and in ISS from -2.6 to -1.7 SDS (p=0.012). Only girls with CPP reached their target height (-0.5 vs. -0.6 SDS) (p=0.500). CONCLUSIONS:Both groups had a total height gain of 5 cm. Each centimetre cost about €2700 per patient. This treatment should be considered only in patients with extremely low height prediction and very early pubertal onset.
10.1515/jpem-2013-0210
Evaluation and Referral of Children With Signs of Early Puberty.
Kaplowitz Paul,Bloch Clifford,
Pediatrics
Concerns about possible early pubertal development are a common cause for referral to pediatric medical subspecialists. Several recent studies have suggested that onset of breast and/or pubic hair development may be occurring earlier than in the past. Although there is a chance of finding pathology in girls with signs of puberty before 8 years of age and in boys before 9 years of age, the vast majority of these children with signs of apparent puberty have variations of normal growth and physical development and do not require laboratory testing, bone age radiographs, or intervention. The most common of these signs of early puberty are premature adrenarche (early onset of pubic hair and/or body odor), premature thelarche (nonprogressive breast development, usually occurring before 2 years of age), and lipomastia, in which girls have apparent breast development which, on careful palpation, is determined to be adipose tissue. Indicators that the signs of sexual maturation may represent true, central precocious puberty include progressive breast development over a 4- to 6-month period of observation or progressive penis and testicular enlargement, especially if accompanied by rapid linear growth. Children exhibiting these true indicators of early puberty need prompt evaluation by the appropriate pediatric medical subspecialist. Therapy with a gonadotropin-releasing hormone agonist may be indicated, as discussed in this report.
10.1542/peds.2015-3732
Pros and cons of GnRHa treatment for early puberty in girls.
Nature reviews. Endocrinology
The timing of puberty has considerable biological, psychosocial and long-term health implications. Secular trends in age at pubertal development, the effects of obesity and the potential effects of environmental endocrine disruptors challenge the standard definitions of precocious puberty and the indications for intervention with gonadotropin-releasing hormone agonists (GnRHa) in girls with precocious puberty. GnRHa therapy is effective in improving adult height in patients who present with classic central precocious puberty (at <8 years old), without causing adverse effects on body composition, BMD and reproductive function. However, its benefits in patients with atypical forms of early puberty not driven by luteinising hormone are not well defined. The role of GnRHa in these patients and the potential benefits in terms of later growth, psychosocial functioning and long-term risk of adult diseases that are associated with early menarche, such as breast cancer and the metabolic syndrome, have not been established.
10.1038/nrendo.2014.40
Is a Combination of a GnRH Agonist and Recombinant Growth Hormone an Effective Treatment to Increase the Final Adult Height of Girls with Precocious or Early Puberty?
Song Wei,Zhao Fei,Liang Shuang,Li Guimei,Xue Jiang
International journal of endocrinology
The aim of treatment for idiopathic central precocious puberty (ICPP) is to increase final adult stature, for which gonadotropin-releasing hormone agonist (GnRHa) is the gold standard. Early puberty is frequently similar to ICPP, with pubertal onset only slightly advanced. Short stature may result from early pubertal onset. Some studies have suggested that recombinant human growth hormone (rhGH) should be combined with a GnRHa to improve adult height, while others have not. Here, the aim was to compare the efficacy of combined GnRHa and rhGH treatment with GnRHa or rhGH treatment alone, or no therapy, for the improvement of the final height of girls with ICPP or early puberty. Electronic databases of randomized and quasi-randomized controlled trials, in which the efficacy of GnRHa preparations was compared with that of rhGH for the treatment of children with precocious or early puberty, were searched and a meta-analysis conducted. Five studies of early puberty and four studies of ICPP were identified. There were no statistically significant differences between final adult height standard deviation score and initial height standard deviation score in the treatment of early puberty (GnRHa and rhGH versus rhGH alone or no treatment). The overall analysis of the data failed to indicate any benefit of combined therapy, while individual reports suggested that in specific instances combined therapy may be beneficial in preserving or reclaiming growth potential and improving adult height.
10.1155/2018/1708650
MANAGEMENT OF ENDOCRINE DISEASE: Long-term outcomes of the treatment of central precocious puberty.
Guaraldi Federica,Beccuti Guglielmo,Gori Davide,Ghizzoni Lucia
European journal of endocrinology
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 long-term 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.
10.1530/EJE-15-0590
The Efficacy of GnRHa Alone or in Combination with rhGH for the Treatment of Chinese Children with Central Precocious Puberty.
Wang Mengjie,Zhang Youjie,Lan Dan,Hill Jennifer W
Scientific reports
The addition of recombinant human growth hormone (rhGH) to GnRH agonist (GnRHa) to treat central precocious puberty (CPP) is controversial. We systemically reviewed and evaluated the efficacy and safety of the rhGH and GnRHa adjunctive therapy in Chinese children with CPP and assessed the influence of age and therapy duration on the efficacy of the combined treatment. A total of 464 patients were included from 14 studies. Compared with baseline, administration of GnRHa plus rhGH led to a significant increase in height, predicted adult height (PAH) and height standard deviation for bone age (HtSDS-BA), corresponding to a weighted mean difference (WMD) (95%CI) of 9.06 cm (6.41, 11.70), 6.5 cm (4.47, 8.52), and 0.86 (0.58, 1.14) respectively. Subgroup analysis showed the combined therapy had increased efficacy in subjects with initial treatment age younger than 10 years old or with treatment lasting over 12 months. Compared with GnRHa alone treatment, the combined treatment led to a significant increase in height, PAH and HtSDS-BA, corresponding to a WMD (95% CI) of 3.56 cm (2.54, 4.57), 3.76 cm (3.19, 4.34) and 0.56 (0.43, 0.69). The combined treatment exhibited no safety concerns. Our findings may aid clinicians in making treatment decisions for children with CPP.
10.1038/srep24259
Pelvic Ultrasound in Diagnosing and Evaluating the Efficacy of Gonadotropin-Releasing Hormone Agonist Therapy in Girls With Idiopathic Central Precocious Puberty.
Yu Hong-Kui,Liu Xiao,Chen Jia-Kun,Wang Shan,Quan Xian-Yue
Frontiers in pharmacology
Idiopathic central precocious puberty (ICPP) is characterized by early pubertal changes, the acceleration of growth velocity, and rapid bone maturation that often results in reduced adult height. Gonadotrophin-releasing hormone agonist (GnRHa) is currently considered to be an effective therapeutic agent. At present, GnRH stimulation test is adopted as a gold standard for the diagnosis of ICPP and the efficacy evaluation of GnRHa therapy. However, it is difficult to operate in practice due to the cumbersome procedures and multiple blood samples required. This study was conducted to establish the value of pelvic ultrasound in diagnosing ICPP and evaluating the efficacy of GnRHa therapy. One hundred and twenty-two girls with ICPP (ICPP group) were enrolled in the study. Pelvic ultrasound and levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were examined before and after GnRHa therapy for 3 months. Eighty normal prepubertal girls were enrolled as the control group. The difference in pelvic ultrasound parameters between the ICPP group before GnRHa therapy and the control group was compared by independent-sample -test, while paired -test for ICPP group before and after GnRHa therapy. Receiver operating characteristic (ROC) curve was used to explore the optimal pelvic ultrasound parameters for diagnosing ICPP. Pearson correlation analysis was performed between the pelvic ultrasound parameters and serum sexual hormone level. The pelvic ultrasound parameters (length of the uterine body, anteroposterior diameter of the uterine body, transverse diameter of the uterine body, volume of the uterine body, uterine body-cervix ratio, length of the ovary, transverse diameter of the ovary, anteroposterior diameter of the ovary, volume of the ovary, number of increased follicles and maximum diameter of the follicle) in the ICPP group before GnRHa therapy were significantly larger than those of the control group ( < 0.05). All the above pelvic ultrasound parameters in the ICPP group were significantly decreased after GnRHa therapy compared with those before treatment ( < 0.05). The volume of the uterine body had the largest area under the ROC curve in differentiating between patients with ICCP and the control group. Pelvic ultrasound parameters were significantly correlated with serum sexual hormone levels ( < 0.05). This study indicates pelvic ultrasound is a simple and reliable tool to diagnose ICPP and evaluates the efficacy of GnRHa therapy by dynamically observing the morphology of internal genitalia. The volume of uterine body was the best ultrasound parameter to distinguish patients with ICPP from normal girls.
10.3389/fphar.2019.00104
Gonadotropin releasing hormone analog treatment in children with congenital adrenal hyperplasia complicated by central precocious puberty.
Güven Ayla,Nurcan Cebeci Ayşe,Hancili Suna
Hormones (Athens, Greece)
OBJECTIVE:Congenital adrenal hyperplasia (CAH) can be complicated by central precocious puberty (CPP) in children, which may compromise final height. We aimed to evaluate the effect of gonadotropin-releasing hormone analog (GnRHa) therapy on growth in children with CAH. DESIGN:Twelve children with CAH were enrolled in a follow-up study. Eight patients underwent the GnRH stimulation test. GnRHa-treatment was administered at 3.75 mg every 4 weeks; the dose had to be increased to 7.5 mg in three patients. Bone age, growth velocities and body mass index of the patients were monitored during treatment. RESULTS:Median chronologic age and bone age at diagnosis were 6.8 (3.5) years and 11 (1.2) years, respectively. Median follow-up was 4.4 (4.9) years. A significant difference was found in the median ratio of bone age to chronological age between diagnosis and last visit (p=0.005) and between the beginning of GnRHa treatment and last visit (p=0.004). Median growth velocity was 4 (2.5) cm, 3.4 (5.2) cm and 5.5 (5.5) cm at the end of the first, second and third years of the therapy, respectively. Second-year growth velocity was inversely correlated with median bone age at diagnosis (rho:-0.758, p=0.004) and at the initiation of therapy (rho:-0.876, p<0.001). CONCLUSION:GnRHa therapy should be considered for augmentation of linear growth and diminishment of bone age advancement in children with CAH complicated by CPP, particularly in children who do not have extremely advanced bone age for chronological age.
10.14310/horm.2002.1555
Long-term effects and significant Adverse Drug Reactions (ADRs) associated with the use of Gonadotropin-Releasing Hormone analogs (GnRHa) for central precocious puberty: a brief review of literature.
De Sanctis Vincenzo,Soliman Ashraf T,Di Maio Salvatore,Soliman Nada,Elsedfy Heba
Acta bio-medica : Atenei Parmensis
Central precocious puberty (CPP) is defined as an early pubertal development that occurs before the age of 9 years in boys and 8 years in girls. It results from premature activation of the hypothalamic-pituitary-gonadal axis. Gonadotropin-releasing hormone agonists (GnRHa) have been the gold standard therapy for CPP for more than 30 years. These compounds have a high affinity for the pituitary LHRH receptor and are resistant to enzymatic degradation. Through continuous stimulation, GnRHa inhibit the pulsatile secretion of gonadotropin, resulting in hormonal suppression, cessation of pubertal development, and normalization of growth and skeletal maturation rates. The goal of therapy is to halt pubertal progression and delay epiphyseal maturation that leads to improvement of final adult height. There are no widely accepted guidelines for how long to continue treatment with a GnRHa for CPP, and individual practice varies widely. Furthermore, conflicting results have been published on the long-term effects of GnRHa therapy in patients with CPP. Therefore, we reviewed the current literature focusing our attention on the long-term effects and the significant adverse drug reactions (ADRs) observed during treatment with GnRHa in patients with CPP. Our review may provide the necessary data to enable clinicians to administer GnRHa in the safest and most appropriate way. Further studies are necessary to identify the mechanisms of development of potential adverse drug reactions related to GnRHa therapy in CPP.
10.23750/abm.v90i3.8736
COMPARATIVE EFFICACY AND SAFETY OF THREE CURRENT CLINICAL TREATMENTS FOR GIRLS WITH CENTRAL PRECOCIOUS PUBERTY: A NETWORK META-ANALYSIS.
Gu Qiuyun,Luo Yi,Ye Jun,Shen Xiuhua
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
The optimal treatment for girls with central precocious puberty (CPP) is unknown. We conducted a network meta-analysis to evaluate the efficacy and safety of existing treatments to provide credible clinical guidelines. We compared gonadotropin-releasing hormone analogue (GnRHa) therapy, GnRHa plus growth hormone (GH) combination therapy, and no-treatment therapy for girls with CPP by performing an electronic search for studies in PubMed, Embase, Chinese National Knowledge Infrastructure databases, and Wanfang Data from their inception until September 30, 2018. Six outcomes, including bone maturation ratio, final height, final height compared with target height, growth velocity, height gain, and gain in predicted adult height (ΔPAH), were expressed as the mean difference with 95% confidence interval. The surface under the cumulative ranking curve (SUCRA) value illustrated the rank probability of each treatment under different outcomes. Twenty-two studies with 1,268 patients were included. GnRHa plus GH had the best performance on final height, final height compared with target height, growth velocity, height gain, and ΔPAH, with the highest SUCRA values of 0.919, 0.975, 0.909, 0.999, and 0.957, respectively. For bone maturation ratio, GnRHa ranked the highest, with a SUCRA value of 0.663. No severe adverse effects were reported. For girls with CPP, GnRHa plus GH had the highest probability of being the optimal therapy for improving final height, and no severe adverse effects were reported. = body mass index; = confidence interval; = central precocious puberty; = growth hormone; = gonadotropin-releasing hormone analogue; = hypothalamic-pituitary-gonadal; = luteinizing hormone; = network meta-analysis; = predicted adult height; = polycystic ovary syndrome; = randomized controlled trial; = surface under the cumulative ranking curve.
10.4158/EP-2019-0008
Comparing adult height gain and menarcheal age between girls with central precocious puberty treated with gonadotropin-releasing hormone agonist alone and those treated with combined growth hormone therapy.
Kim Min Sub,Koh Hyo Jung,Lee Gwang Yeon,Kang Dong Hee,Kim Se Young
Annals of pediatric endocrinology & metabolism
PURPOSE:This study aimed to investigate the outcomes of gonadotropin-releasing hormone agonist (GnRHa) therapy with or without growth hormone (GH) therapy for girls with idiopathic central precocious puberty (CPP). METHODS:The medical records of 166 girls diagnosed with CPP from 2002 to 2017 were retrospectively reviewed. All included patients were treated with GnRHa for ≥36 months. Changes in height standard deviation score (SDS) for bone age, chronological age (CA), and predicted adult height (PAH) were assessed for the first three years of treatment. The final height gain SDS was calculated as the difference between the initial PAH SDS and adult height (AH) SDS; these were then compared between the GnRHa group (group A, n=135) and the combined GnRHa/GH group (group B, n=31). RESULTS:The initial mean CA was 7.89 years. The mean menarcheal age was 13.12 years (group A, 13.1±0.99; group B, 13.18±0.58 years; P=0.755). PAH SDS at the start of GnRHa treatment and AH SDS were significantly lower in group B than in group A (PAH SDS: -2.20±0.83 vs. -3.19±0.84, P<0.001; AH SDS: 0.18±084 vs. -0.30±0.66, P=0.021). The increase in PAH SDS was higher in group B than in group A for the first three years of GnRHa treatment (1.66±0.66 vs. 2.35±0.93, P<0.001). The height gain SDS was significantly higher in group B than in group A (2.5±0.75 vs. 2.93±1.02, P=0.048). Younger age, higher PAH at the start of treatment, and a greater increase in PAH SDS during the first year of GnRHa treatment positively affected AH. CONCLUSION:The combined GH group had more additional height gain than the GnRHa-alone group.
10.6065/apem.2019.24.2.116
The clinical effects of gonadotropin-releasing hormone agonists for the treatment of children patients with central precocious puberty.
Xue Y,Wang P,Wang S-Q,Gao Y-Q
European review for medical and pharmacological sciences
OBJECTIVE:We explored the clinical effect of gonadotropin-releasing hormone agonists for the treatment of children patients with central precocious puberty. PATIENTS AND METHODS:From March 2012 to October 2015, 100 cases of children patients with central precocious puberty were enrolled in this study. Intramuscular injection of acetic acid triptorelin (50 to 100 pLg/kg) was made once every 4 weeks, and the treatment lasted for 4 months. Patients' bone age/height differentials (DBA/DCA), bone age (BA), growth velocity (GV) and predicted adult height (PAH) were determined before and after treatment (after 6, 12, 24, 36 months). Differences before and after treatment were analyzed. DBA/DCA, BA and PAH values 6, 12, 24, 36 months after treatment were significantly different compared with those before treatment. RESULTS:Sexual development symptoms in children patients were significantly improved 4 months after treatment (p<0.05). All patients completed the treatment, without any adverse drug reaction or severe complication. After one course of treatment (4 months), patients' uterus and ovarian volumes shrank, FSH level peaked, and LH level was reduced, compared to those before treatment. CONCLUSIONS:Acetate acid triptorelin is safe and reliable for treating central precocious puberty. We achieved the excellent clinical curative effect and were able to delay the growth rate in children patients. The predicted height and final height were improved.
10.26355/eurrev_201808_15643