Idiopathic Central Precocious Puberty Research Articles

Efficacy and safety of domestic leuprorelin in girls with idiopathic central precocious puberty: a multicenter, randomized, parallel, controlled trial.

Background:In central precocious puberty (CPP), the pulse secretion and release of gonadotropin-releasing hormone (GnRH) are increased due to early activation of the hypothalamic-pituitary-gonadal axis, resulting in developmental abnormalities with gonadal development and appearance of secondary sexual characteristics. The CPP without organic disease is known as idiopathic CPP (ICPP). The objective of the study was to evaluate the clinical efficacy and safety of domestic leuprorelin (GnRH analog) in girls with ICPP.Methods:A total of 236 girls with ICPP diagnosed from April 2012 to January 2014 were selected and were randomized into two groups. One hundred fifty-seven girls in the test group were treated with domestic leuprorelin acetate, 79 girls in the control group were treated with imported leuprorelin acetate. They all were treated and observed for 6 months. After 6-month treatment, the percentage of children with peak luteinizing hormone (LH) ≤3.3 U/L, the percentage of children with peak LH/peak follicle stimulating hormone (FSH) ratio <0.6, the improvements of secondary sexual characteristics, gonadal development and sex hormone levels, the change of growth rate of bone age (BA) and growth velocity, and drug adverse effects between two groups were compared.Results:After the treatment, the percentage of children with a suppressed LH response to GnRH, defined as a peak LH ≤3.3 U/L, at 6 months in test and control groups were 96.80% and 96.20%, respectively, and the percentage of children with peak LH/FSH ratio ≤0.6 at 6 months in test and control groups were 93.60% and 93.70%, respectively. The sizes of breast, uterus and ovary of children and the levels of estradiol (E2) were significantly reduced, and the growth rate of BA was also reduced. All the differences between pre- and post-treatment in each group were statistically significant (P < 0. 05), but the differences of the parameters between two groups were not significant (P > 0.05).Conclusions:Domestic leuprorelin is effective and safe in the treatment of Chinese girls with ICPP. Its effectiveness and safety are comparable with imported leuprorelin.

Test on kisspeptin levels in girls with idiopathic central precocious puberty and its significance

The aim of this study was to explore the signifi - cance of plasma kisspeptin levels in diagnosis and therapeutic evaluation through the analysis of the kisspeptin levels of girls diagnosed with idiopathic central precocious puberty (ICPP) prior to treatment and after 6-months of treatment and those with simple premature thelarche (PT). A total of 70 girls including 24 girls diagnosed with ICPP, 21 girls with PT and 25 normal girls were enrolled in the study. ELISA analysis was conducted to detect the plasma levels of kisspeptin. The kisspeptin level of the ICPP group prior to treatment (1.80±0.13 ng/ml) was significantly higher than those of the other two groups. The kisspeptin level of the ICPP group after 6 months of treatment (1.49±0.21 ng/ml) was signifi - cantly lower than that prior to treatment (P<0.05). It may be concluded that the plasma level of kisspeptin is associated with the initiation of pubertal development, and it may serve as an important parameter in the diagnosis of ICPP and the evalua- tion of therapeutic effects.

Effect of triptorelin 3.75 mg subcutaneously injection every 6 weeks on adult height in girls with idiopathic central precocious puberty

Methods Forty females with ICPP received triptorelin 3.75 mg every 6 weeks subcutaneously injection in our hospital from 2002 to December 2010 and reached final height were collected. These patients were divided into two groups according to whether there was presence of growth deceleration and rhGH used concomitantly during the treatment. Group A: triptorelin alone, n=17; group B: triptorelin + rhGH, n=23. During the treatment, height, weight, annual GV, sexual development, PAH and adverse effects were observed. BA and height SDS were monitored yearly. After discontinuation of treatment, follow-up was continued for 4~9 years till final height was attained, and age of menarche, time of menarche from discontinuation were recorded.

Paediatric endocrinology: Treatment of girls with central precocious puberty.

Gonadotropin-releasing hormone analogues (GnRHa) can improve adult height prospects in children with central precocious puberty (CPP). A recent report demonstrates that 50 mg histrelin subcutaneous implants are safe and effective when used yearly. However, questions remain regarding the use of GnRHa in girls with idiopathic CPP, who experience a slow progressive form of puberty.

Risk factors for idiopathic central precocious puberty of girls in Fujian province

Methods A case-control study was conducted in 566 girls who were diagnosed with ICPP at endocrinology department and 547 healthy girls for routine physical examination in Fuzhou Children’s Hospital of Fujian from October 2011 to October 2013. Parents were asked to fulfill the questionnaires on children’s diets, behaviors, parents and family conditions, and Logistic regression analysis was conducted for risk factors.

Models for predicting the adult height and age at first menstruation of girls with idiopathic central precocious puberty.

BackgroundIt is difficult to determine whether to treat a given girl who has idiopathic central precocious puberty (CPP) with gonadotropin-releasing hormone analog (GnRHa) in terms of adult height (AH). The objective was to provide an easy tool for predicting AH and age at first menstruation at initial evaluation to help guide the decision regarding whether to treat.MethodsData analysis using multiple linear regression models was performed in 134 girls with CPP. Among them 78 were given GnRHa because of low predicted AH (n=45), pubertal luteinising hormone (LH)/follicle-stimulating hormone peaks (FSH) ratio (n=50) and/or high plasma estradiol concentration (n=45). 56 girls were followed without treatment.ResultsIn the whole population, the actual AH (162.1±5.61 cm) was similar to target height (161.7±4.91 cm) and to AH predicted by the Bayley and Pinneau method (161.9±7.98 cm). Separated models for treated and untreated girls provide very close estimations, leading to a unique formula for both groups. The AH (cm) could be calculated at the initial evaluation: 2.21 (height at initial evaluation, SD) + 2.32 (target height, SD) – 1.83 (LH/FSH peaks ratio) + 159.68. The actual AH was lower than the calculated AH by more than 1 SD (5.6 cm) in 11 girls (8.0%). The time between onset of puberty and first menstruation (in untreated girls) can be estimated with: 10.9 - 0.57 (LH/FSH peaks ratio). The formulae are available at http://www.kamick.org/lemaire/med/girls-cpp15.html.ConclusionsWe established formulae that can be used at an initial evaluation to predict the AH, and the time between onset of puberty and first menstruation after spontaneous puberty. The similarity of the formulae for both groups suggests that the treatment had no significant effect on the AH. However, the criteria used to select treatment suggest that it prevents the deterioration of AH in cases with rapidly evolving form of CPP.

Testing of kisspeptin levels in girls with idiopathic central precocious puberty and its significance.

The aim of this study was to explore the significance of plasma kisspeptin levels in diagnosis and therapeutic evaluation through the analysis of the kisspeptin levels of girls diagnosed with idiopathic central precocious puberty (ICPP) prior to treatment and after 6-months of treatment and those with simple premature thelarche (PT). A total of 70 girls including 24 girls diagnosed with ICPP, 21 girls with PT and 25 normal girls were enrolled in the study. ELISA analysis was conducted to detect the plasma levels of kisspeptin. The kisspeptin level of the ICPP group prior to treatment (1.80±0.13 ng/ml) was significantly higher than those of the other two groups. The kisspeptin level of the ICPP group after 6 months of treatment (1.49±0.21 ng/ml) was significantly lower than that prior to treatment (P<0.05). It may be concluded that the plasma level of kisspeptin is associated with the initiation of pubertal development, and it may serve as an important parameter in the diagnosis of ICPP and the evaluation of therapeutic effects.

Histrelin for central precocious puberty—a single surgeon experience

BackgroundThe 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. MethodsThe 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. ResultsFifty-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. ConclusionsThis 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.

Changing Etiological Trends in Male Precocious Puberty: Evaluation of 100 Cases with Central Precocious Puberty over the Last Decade

Background/Aims: There are few studies in the literature that have evaluated the etiological factors in boys with central precocious puberty (CPP), and these studies are limited in terms of the sample size. In the present study, we aimed to evaluate the etiological factors in male CPP cases. Methods: One hundred male CPP subjects, aged between 9 months and 10.5 years, were included. The medical records were screened, and age at diagnosis, bone age, body weight, height, pubertal stage, imaging findings of the pituitary gland, testosterone, and basal and stimulated gonadotropin levels were recorded. Results: There was no underlying cause in 74% of the cases, and an organic cause was determined in only 26%. Most of the organic cases had been diagnosed before the age of 7 years, whereas most of the idiopathic cases had been diagnosed after the age of 7 years. Conclusion: An organic cause was determined in 26% of the male patients with CPP. This rate is one of the lowest rates in the literature and indicates that the number of idiopathic male CPP cases is increasing over time. When a boy is diagnosed with CPP above the age of 7 years, the odds of detecting an underlying pathology are very low, and these cases are mostly idiopathic.

Clinical and laboratory findings in the differential diagnosis of central precocious puberty and premature thelarche

In this study, it was aimed to evaluate the clinical, antropometric and laboratory findings of female patients diagnosed with central precocious puberty and to determine the laboratory value with the best diagnostic accuracy in the diagnosis of central precocious puberty. Female patients whose breast development began before the age of 8 years were included in the study. The data of the patients were obtained by retrospectively examining file records. The chronogical age, age at the time of onset of the complaint, antropometric variables, bone age and hormonal tests were recorded. The patients whose bone age/chronological age ratio was >1 and in whom pubertal response was obtained to gonodotropin releasing hormone stimulation test were considered central precocious puberty and the patients who did not meet these criteria were considered premature thelarche. Receiver operating charecteristic curve (ROC) analysis was performed to determine the diagnostic accuracy of the laboratory variables. Fifty one patients with idiopathic central precocious puberty and 36 patients with premature thelarche were included in the study. In the patients with central precocious puberty, the height standard deviation score, bone age and bone age/chronological age ratio were found to be significantly higher compared to the patients with premature thelarche. The basal luteinizing hormone, basal follicle stimulating hormone, basal luteinizing hormone/follicle stimulating hormone, peak luteinizing hormone, peak follicle stimulating hormone and peak luteinizing hormone/follicle stimulating hormone values were found to be significantly higher in the patients with central precocious puberty. When the cut-off value for the peak luteinizing hormone/follicle stimulating hormone ratio was taken as >0.24, the sensitivity was found to be 100% and specificity was found to be 84%. When the cut-off value for the basal follicle stimulating hormone was taken as >1.9 IU/L, the sensitivity was found to be 71% and specificity was found to be 68%. When the cut-off value for the basal luteinizing hormone was taken as >0.1 IU/L, the sensitivity was found to be 71% and specificity was found to be 64%. In female children, a peak luteinizing hormone/follicle stimulating hormone ratio of >0.24 can be used in the diagnosis of central precocious puberty. However, the findings should be assessed in association with the clinical and antropometric variables.

Impact of BMI on gonadorelin-stimulated LH peak in premenarcheal girls with idiopathic central precocious puberty.

To clarify the impact of body mass index (BMI) on luteinizing hormone (LH) secretion in response to gonadorelin (GnRH) stimulation testing in girls diagnosed with idiopathic central precocious puberty (ICPP). Retrospective single-center cohort study was carried out in 865 confirmed ICPP girls who underwent GnRH stimulation tests. Pubertal development according to Tanner, sex hormone parameters, and LH secretion in response to GnRH-stimulation was compared. Around 609 girls were of normal weight (70.4%), while 168 children (19.4%) were overweight, and 88 (10.2%) were obese. Peak LH levels after GnRH were much higher in the normal-weight group, with a median of 9.1 mIU ml(-1) (interquartile 5.2-13.1), compared with the median peak LH in the overweight and obese groups (8.5 mIU ml(-1), interquartile 5.3-11.6, and 6.2 mIU ml(-1), interquartile 5.3-11.0, respectively P < 0.001 for all comparisons). Peak LH/FSH ratio was also lower in the obese group (median 0.6, interquartile 0.68-0.90) compared with the normal-weight (median 0.8, interquartile 0.61-1.11) and overweight (median 0.8, interquartile 0.64-0.92) groups. Higher BMI is associated with lower LH response to GnRH-stimulation testing in girls with ICPP. It is recommended that BMI should be considered when interpreting GnRH-stimulation tests.

Significance of serum neurokinin B and kisspeptin levels in the differential diagnosis of premature thelarche and idiopathic central precocious puberty

The aim of the present study was to investigate the diagnostic role of serum neurokinin B level and its relationship with kisspeptin and leptin, which are known to be involved in the initiation of pubertal process. Girls who presented with breast development (<8 years) were included in the study. All patients underwent bone age assessment. Basal levels of serum follicle stimulating hormone and luteinizing hormone were measured and gonadotropin releasing hormone stimulation test was performed. Patients with a bone age/chronological age ratio >1 and a peak luteinizing hormone response in gonadotropin releasing hormone stimulation test >5mIU/L were included in the central precocious puberty group, while patients who did not meet these criteria were included in the premature thelarche group. Patients with organic pathologies were excluded. Healthy prepubertal girls with similar age were included as the control group. Leptin, kisspeptin and neurokinin B levels were measured by ELISA method. The study included 20 girls with idiopathic central precocious puberty 22 girls with premature thelarche and 24 prepubertal controls. While serum kisspeptin, leptin and neurokinin B levels were significantly higher in central precocious puberty and premature thelarche groups compared to controls, no significant difference was found between central precocious puberty and premature thelarche groups. Increased serum levels of leptin, kisspeptin and neurokinin B in patients with premature thelarche and central precocious puberty suggest that they take part during the initiation of pubertal process, however, these markers are not able to differentiate patients with central precocious puberty from premature thelarche.

Mutation of kisspeptin 1 gene in children with precocious puberty in isfahan city.

Background:Considering the role of kisspeptin (KISS) in the process of puberty, this study aimed to determine the mutation of KISS1 gene among a group of patients with idiopathic central precocious puberty (ICPP).Methods:In this case control study, a group of children with diagnosed ICPP and a group of healthy children were selected. Genomic DNA was extracted from peripheral blood of selected population. After proving the quality and quantity of extracted DNA samples by nano-drop instrument, PCR was performed using 3 set of primers to amplify all coding exons and flanking intron region of Kiss1 gene.Results:In this study, 33 patients with idiopathic PP and 30 control age and sex matched children were studied. Genetic analysis indicated that there was not any polymorphism or mutation in studied participants of the control group. Among patients with ICPP, 4 single nucleotide polymorphisms within the promoter and coding regions of KISS1 gene were determined in 9 patients (5 boys and 4 girls). Among them, the c.-148 T > A was novel variant.Conclusions:The results of the current study identified one novel polymorphism and three reported polymorphism in KISS gene among patients with ICPP. It is recommended to design further studies for analysis other genes related to ICPP in accordance with more complementary biochemical evaluations is recommended also.

Effect of gonadotropin-releasing hormone agonist therapy on body mass index and growth in girls with idiopathic central precocious puberty.

Objective:The study aimed to assess the effect of gonadotropin-releasing hormone (GnRH) agonist therapy on body mass index (BMI) and growth in girls diagnosed with idiopathic central precocious puberty (CPP).Materials and Methods:Hospital records of 32 girls with idiopathic CPP who have been receiving GnRH agonist therapy for at least 12 months were retrospectively reviewed and auxological, clinical and laboratory parameters of the patients were recorded. BMI, body mass index standard deviation score (BMI SDS) for chronological age body mass index standard deviation score (CA-BMI SDS), BMI SDS for bone age body mass index standard deviation score (BA-BMI SDS), ratios of obesity and overweight were assessed before treatment and on the 12th month of therapy in patients diagnosed with idiopathic CPP.Results:The study comprised of 32 girls diagnosed with idiopathic CPP. BMI values showed statistically significant increase in the 1st year of treatment (19.16 ± 2.8 vs. 20.7 ± 3.4, P = 0.001). Despite a mild increase in CA-BMI SDS in the 1st year of treatment versus before treatment, it was no statistically significant (1.0 ± 0.8 vs. 1.1 ± 0.9, P = 0.061). However, significant increase was observed in BA-BMI SDS in the 1st year of treatment versus before treatment (0.8 ± 0.7 vs. 0.4 ± 0.8, P < 0.001). Before treatment, 37.5% (12/32) of the patients were overweight and 21.9% (5/32) were obese, whereas in the 1st year, 34.4% (11/32) of the patients were overweight and 31.3% were obese (P = 0.001).Conclusion:Whilst 1/3 of the cases diagnosed with idiopathic CPP were overweight and obese at the time of diagnosis, GnRH agonist therapy caused statistically significant weight gain in patients diagnosed with CPP. Therefore, these patients should be closely monitored and weight control should be provided by diet and exercise programs in the course of treatment.

Pilot study on the dietary habits and lifestyles of girls with idiopathic precocious puberty from the city of Rome: potential impact of exposure to flame retardant polybrominated diphenyl ethers.

Puberty is regulated by the endocrine system, which when disrupted can affect reproductive health. Endocrine disrupters (ED) are involved in the pathogenesis of idiopathic central precocious puberty (ICPP). Polybrominated diphenyl ethers (PBDE) are lipophilic, persistent ED used as flame retardants in several products; thus, human population is exposed through food and domestic dust. PBDE exposure during the peripubertal period is suspected to interfere with reproductive development. The study aimed to investigate PBDE serum concentration in 31 girls with ICPP as well as describe their dietary habits and lifestyles. The PBDE median level was 59 ng/g of lipids, higher than in healthy girls in comparable studies. Interestingly, elder girls and girls with higher body mass index (BMI) showed higher PBDE serum levels. Considering the relevance of altered puberty onset as a risk factor for reproductive health, studies on food contribution to PBDE exposure in Italian children, and efforts to ameliorate risk assessment for emerging chemicals are suggested.

Routine screening by brain magnetic resonance imaging is not indicated in every girl with onset of puberty between the ages of 6 and 8 years.

It is still controversial whether all girls with central precocious puberty (CPP) should undergo brain magnetic resonance imaging (MRI) for unveiling intracranial pathology. The objectives of the study were to determine the prevalence and type of intracranial lesions in otherwise normal girls with central precocious puberty (idiopathic CPP) and to identify the clinical and biochemical predictors of brain abnormalities. This was a retrospective study conducted at the Endocrine Unit of "Bambino Gesù" Children's Hospital (Rome, Italy) from 1990 to 2012. One hundred eighty-two girls were consecutively diagnosed with CPP. All girls underwent a thorough endocrine assessment and brain MRI with a detailed examination of the hypothalamic-pituitary area. None of them had a history of neurological diseases, endocrine disorders, neurofibromatosis or other genetic syndromes, or previous hormonal therapies. Prevalence of brain abnormalities at MRI scan was measured. Brain MRI showed no alteration in 157 (86%), incidentalomas of the hypothalamic-pituitary area unrelated to CPP in 19 (11%), and hamartomas in six girls (3%). Girls with hamartomas were younger than 6 years and had significantly higher mean baseline and stimulated LH values (P < .001), LH to FSH ratio (P < .001), serum 17β-estradiol levels (P < .001), and uterine length (P < .05). However, all the parameters overlapped extensively in girls with or without cerebral alterations. Our data cast doubt on the need of routine screening by brain MRI in girls with idiopathic CPP older than 6 years. Evidence-based criteria to drive clinical decision making about the use of MRI are lacking.

Mutational analysis of the genes encoding RFamide-related peptide-3, the human orthologue of gonadotrophin-inhibitory hormone, and its receptor (GPR147) in patients with gonadotrophin-releasing hormone-dependent pubertal disorders.

RFamide-related peptide-3 (RFRP-3), the orthologue of avian gonadotrophin-inhibitory hormone, and its receptor GPR147 have been recently identified in the human hypothalamus, and their roles in the regulation of reproductive axis has been studied. The present study aimed to investigate whether the presence of variants in the genes encoding human RFRP-3 (NPVF gene) and its receptor, GPR147 (NPFFR1 gene), is associated with the occurrence of gonadotrophin-releasing hormone-dependent pubertal disorders. Seventy-eight patients with idiopathic central precocious puberty (CPP) and 51 with normosmic isolated hypogonadotrophic hypogonadism (nIHH) were investigated. Fifty healthy subjects comprised the control group. The coding sequences of the NPVF and NPFFR1 genes were amplified and sequenced. Odds ratios (OR) were used to estimate the likelihood of CPP or nIHH in the presence of the described polymorphisms. All such polymorphisms have already been registered in the National Center for Biotechnology Information database. A three-nucleotide in frame deletion was identified in the NPVF gene (p.I71_K72), with a smaller proportion in the CPP (5%) compared to the nIHH (15%) group (P = 0.06). This results in the deletion of the isoleucine at position 71, adjacent to lysine at an endoproteolytic cleavage site of the precursor peptide. This polymorphism was associated with a lower risk of CPP (OR = 0.33; 95% confidence interval = 0.08-0.88); interestingly, only two men with nIHH were homozygotes for this variant. A total of five missense polymorphisms were found in the NPFFR1 gene, which encodes GPR147, with similar frequencies among groups and no association with pubertal timing. Our data suggest that RFRP-3/GPR147 may play secondary, modulatory roles on the regulation of pubertal development; a restraining modulatory effect of the NPVF p.I71_K72 variant on the activation of the gonadotrophic axis cannot be ruled out and deserves further investigation.

The usefulness of the leuprolide stimulation test as a diagnostic method of idiopathic central precocious puberty in girls.

Central precocious puberty (CPP) diagnosis is based on clinical evaluation, but hormonal evaluation is crucial. The aim of the study was to evaluate the usefulness of the leuprolide stimulation test for diagnosis of idiopathic CPP. Sixty-one girls, aged 5-8 years, were evaluated retrospectively for premature breast development. According to clinical evolution, 28 had progressive puberty and 33 nonprogressive puberty. All underwent a leuprolide stimulation test. Cutoff points, sensitivity, and specificity for gonadotropins and estradiol were determined by receiver operating characteristic (ROC) curves. Cutoff points for CPP were: baseline LH: > 0.1 mUI/l, FSH: > 2.3 mUI/l, LH/FSH ratio: > 0.23, estradiol: > 12 pg/ml; and stimulated LH: > 5.5 mUI/l, LH/FSH ratio: > 0.24, estradiol: > 79.67 pg/ml. The best diagnostic efficiency for progressive puberty were stimulated LH/FSH ratio (sensitivity: 100%, specificity 94%) followed by stimulated LH (sensitivity: 93%, specificity: 100%). Stimulated LH/FSH ratio and LH resulted in the most useful parameters for the diagnosis of CPP. Stimulated estradiol did not add more information.

Use of a Gonadotropin-releasing Hormone Analog to Treat Idiopathic Central Precocious Puberty Is Not Associated with Changes in Bone Structure in Postmenarchal Adolescents

Study ObjectivesTo evaluate bone quantity and quality in postmenarchal adolescents treated for idiopathic central precocious puberty (CPP) in childhood with a gonadotropin-releasing hormone analog (GnRHa) and to determine the serum concentrations of bone remodeling markers. Design and ParticipantsThis cross-sectional study included 53 postmenarchal adolescent girls who were divided into 2 groups: 27 adolescents who were treated with GnRHa in childhood for idiopathic CPP (the CPP group) and 26 women who presented with physiological development of secondary sex traits (the control group). Interventions: None. Main Outcome MeasuresWeight, height, body mass index, age at menarche, time since menarche, body composition, bone mineral density (BMD), bone quality, and serum insulin, glucose, osteocalcin, and carboxyl-terminal telopeptide of type I collagen concentrations were compared in the 2 groups. BMD data were analyzed by using both dual-energy x-ray absorptiometry (DXA) and osteosonography, and body composition was measure with the use of DXA and electrical bioimpedance. ResultsBMD and bone quality did not differ significantly between the CPP and control groups when analyzed by using DXA or osteosonography. Serum osteocalcin concentration was significantly lower (P = .02) in the CPP than in the control group. Insulin was higher in the CPP group, and hyperinsulinemia was an independent predictor of bone quantity and quality assessed by using osteosonography. Body mass index and percent fat were determined by using DXA, and the duration of use of GnRHa treatment and the time since GnRHa discontinuation were not independent predictors of bone quantity and quality. ConclusionPostmenarchal adolescents treated with GnRHa for CPP in childhood did not show a reduction in bone quantity or quality.

Idiopathic central precocious puberty associated with an enlarged pituitary gland

Official Journal of the Endocrine Society of Sri Lanka. The Sri Lanka Journal of Diabetes Endocrinology and Metabolism (SJDEM) publishes original research articles, reviews, and other special features related to diabetes, endocrinology and metabolism in humans and human tissue.