Precocious Puberty Research Articles

Diagnostic Value of Single LH and LH/FSH Ratio at 60-minute after GnRHa Stimulation Test for Central Precocious Puberty.

To evaluate the diagnostic value of luteinizing hormone (LH) and LH/follicle stimulating hormone (FSH) ratio at 60 min after gonadotropin-releasing hormone analogs (GnRHa) stimulation test for central precocious puberty (CPP) in girls. Two hundred and fifty-seven girls, aged 3 to 7.5 y, suspected of precocious puberty at authors' hospital from April 2020 through November 2023 were enrolled in the study. The blood was taken at 0, 30, 60 min after GnRHa stimulation test, and LH and LH/FSH were detected by chemiluminescence assay. The diagnostic efficacy was analysed by Mann-Whitney U test, spearman's correlation analysis and receiver operating characteristic (ROC) analysis. The proportion of obesity was analysed by Chi-square test. LH and LH/FSH at different times were statistically significantly different (P <0.05) between the CPP and non-CPP groups. Spearman's correlation analysis showed that the level of LH and LH/FSH at 60 min had the strongest consistency with the peak of LH (r = 0.9988, P <0.001) and LH/FSH (r = 0.9981, P <0.001). ROC curve analysis showed that the area under the ROC curves at 60 min of LH and LH/FSH were 0.975 and 0.997 with a cut-off value of 5.70 IU/L and 0.609, respectively. The peak of LH and LH/FSH in the diagnosis of CPP can be determined by LH and LH/FSH at 60 min after the triptorelin acetate is injected. This will reduce the number of blood draws required compared with the traditional stimulation test, which is more effective and acceptable for children.

Association between BMI and age at menarche or spermarche among both sexes: Findings from six successive national surveys in China.

To explore trends of the association between body mass index (BMI) and age at menarche or spermarche and its urban-rural disparities from 1995 to 2019. A total of 912 753 children and adolescents - including 519 940 9-18 years old girls and 392 813 11-18 years old boys - were involved in six successive cross-sectional surveys conducted across 30 provinces in China from 1995 to 2019. Data on menarche and spermarche was collected using the status quo method, where same-gender physicians conducted face-to-face interviews to determine if children and adolescents had experienced their first menstrual cycle or ejaculation (yes/no). The median age at menarche or spermarche was estimated by probit analysis. Anthropometric measurements measured the height and weight of the study subjects. Children and adolescents were classified into thinness, normal range of weight, overweight, and obesity. t test was used to compare the differences in BMI between premenarchal and postmenarchal girls or prespermarcheal and postspermarcheal boys. Logistic regression was used to explore the associations between BMI/nutritional status and menarche or spermarche stratified by urban or rural residency status. From 1995 to 2019, BMI in all age groups growth over time, and the values of BMI among children and adolescents under 15 who had menarche or spermarche were more significant than those without menarche or spermarche. In 2019, for girls, thinness was associated with delayed menarche (odds ratio (OR) = 0.26; 95% confidence interval (CI) = 0.24-0.28), while overweight (OR = 1.99; 95% CI = 1.85-2.14) and obesity (OR = 2.20; 95% CI = 1.92-2.53) was associated with advanced menarche. For boys, thinness was associated with delayed spermarche (OR = 0.71; 95% CI = 0.65-0.78), overweight was associated with advanced spermarche (OR = 1.08; 95% CI = 1.01-1.15) while obesity had no association with spermarche. The OR between BMI and menarche in 1995 was 1.35 (95% CI = 1.33-1.37), which decreased to 1.19 (95% CI = 1.18-1.20) by 2019. The OR between BMI and spermarche in 1995 was 1.10 (95% CI = 1.09-1.11), which decreased to 1.02 (95% CI = 1.02-1.03) by 2019. The trends by urban-rural stratification were consistent with the total sample. We have established a dose-response relationship between BMI and menarche in girls, whereas the association appears to be nonlinear in boys, and the associations were diminishing. Similar findings were observed in both urban and rural areas. Considering the dual adverse effects of obesity and early puberty on health, the results of this study suggest that sexual health education should be strengthened, especially among obese girls. Further research on the influencing factors and biological mechanisms of early puberty will be beneficial.

Evaluating breast ultrasonography as a complementary diagnostic method in girls with central precocious puberty.

Assessment of breast development by physical examination can be difficult in the early stages and in overweight girls. To investigate ultrasonography (US) for evaluation of early breast development. In a prospective study, 125 girls (age 7.1 ± 1.5years) with breast development before 8years underwent US breast staging, breast volume, and elastography, in addition to clinical/hormonal evaluation for precocious puberty. Accuracy of US for determining breast development and predicting progression to central precocious puberty was investigated. Physical examination revealed glandular breast enlargement in 100 and predominantly lipomastia in 25. Breast US in the former confirmed glandular breast development in 92 (group 1, physical examination and US positive), but not in 8 (group 2, physical examination positive, US negative). Comparison of the two groups demonstrated lower Tanner and US staging, bone age/chronological age, basal luteinizing hormone (LH), breast volume, and uterine volume in group 2. In the 25 lipomastia patients, US demonstrated no breast tissue in 19 (group 3, physical examination and US negative), but US stage ≥ II in 6 (group 4, physical examination negative, US positive) without differences in clinical parameters. After follow-up of 19.8 ± 4.2months, 46/125 subjects were diagnosed with precocious puberty. US stage, total breast volume, and shear-wave speeds were significantly higher in these 46 patients. Multivariate analyses demonstrated breast volume > 3.4cc had odds ratio of 11.0, sensitivity of 62%, and specificity of 89, in predicting progression to precocious puberty, being second only to stimulated LH for all variables. Breast US is a useful predictive tool for diagnosis of precocious puberty in girls. Higher US stages and higher breast volume on US increased the likelihood of eventual diagnosis of precocious puberty.

Precocious Puberty and GnRH analogs: Current treatment practices and perspectives amongst US pediatric endocrinologists.

GnRHas are used for treatment of precocious puberty. Over the last decade, several new formulations have been approved. The Drugs & Therapeutics subcommittee of the Pediatric Endocrine Society (PES) undertook a review to ascertain the current treatment options, prescribing behaviors, and practices of GnRHas among pediatric endocrinologists practicing within the United States. The survey consisted of four main subsections: 1. Description of clinical practice; 2. Self-assessment of knowledge base of pediatric and adult GnRHa formulations; 3. Current practice for treating CPP; and 4. Utilization of healthcare resources. There were 223 survey respondents. Pediatric endocrine practitioners were most familiar with the pediatric one-monthly preparation, the three-month preparation, and the histrelin implant (Supprelin®) (61.9%, 71.7%, and 34.5%, respectively), with lower familiarity for 24-week triptorelin intramuscular (Triptodur®) and 22.9% and six-month subcutaneous leuprolide (Fensolvi®). Only 23% of the respondents reported being extremely familiar with the availability of adult formulations, and 25% reported being completely unaware of cost differences between pediatric and adult GnRHa preparations. The implant was the most preferred therapy (44.4%), but in practice, respondents reported a higher percentage of patients were treated with 3-month preparation. While family preference/ease of treatment (87%) was the key determinant for using a particular GnRHa preparation, insurance coverage also played a significant role in the decision (65.5%). Responses regarding assessment for efficacy of treatment were inconsistent, as were practices and criteria for obtaining an MRI. The survey indicated there is more familiarity with older, shorter-acting GnRHas, which are prescribed in greater numbers than newer, longer-acting formulations. There is lack of consensus on the need for CNS imaging in girls presenting with CPP between 6-8 years of age and use of laboratory testing to monitor response to treatment. Insurance requirements regarding CNS imaging and laboratory monitoring are highly variable. Despite having similar constituents and bioavailability there are substantial cost differences between the pediatric and adult formulations and lack of evidence for safe use of these formulations in children. The survey-based analysis highlights the challenges faced by prescribers, while reflecting on areas where further research is needed to provide evidence-based practice guidelines for pediatric endocrinologists.

Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome

BackgroundTemple syndrome (TS14) is a rare imprinting disorder caused by maternal UPD14, imprinting defects or paternal microdeletions which lead to an increase in the maternal expressed genes and a silencing the paternally expressed genes in the 14q32 imprinted domain. Classical TS14 phenotypic features include pre- and postnatal short stature, small hands and feet, muscular hypotonia, motor delay, feeding difficulties, weight gain, premature puberty along and precocious puberty.MethodsAn exon array comparative genomic hybridization was performed on a patient affected by psychomotor and language delay, muscular hypotonia, relative macrocephaly, and small hand and feet at two years old. At 6 years of age, the proband presented with precocious thelarche. Genes dosage and methylation within the 14q32 region were analyzed by MS-MLPA. Bisulfite PCR and pyrosequencing were employed to quantification methylation at the four known imprinted differentially methylated regions (DMR) within the 14q32 domain: DLK1 DMR, IG-DMR, MEG3 DMR and MEG8 DMR.ResultsThe patient had inherited a 69 Kb deletion, encompassing the entire DLK1 gene, on the paternal allele. Relative hypermethylation of the two maternally methylated intervals, DLK1 and MEG8 DMRs, was observed along with normal methylation level at IG-DMR and MEG3 DMR, resulting in a phenotype consistent with TS14. Additional family members with the deletion showed modest methylation changes at both the DLK1 and MEG8 DMRs consistent with parental transmission.ConclusionWe describe a girl with clinical presentation suggestive of Temple syndrome resulting from a small paternal 14q32 deletion that led to DLK1 whole-gene deletion, as well as hypermethylation of the maternally methylated DLK1-DMR.

Precocious puberty and skyrocketing obesity rates among children: a contemporary clinical perspective on the co-occurrence

Precocious puberty and skyrocketing obesity rates among children: a contemporary clinical perspective on the co-occurrence

Precocious puberty: etiology and treatement

Precocious puberty: etiology and treatement

Early puberty and abnormal bone health: a comprehensive review

Early puberty and abnormal bone health: a comprehensive review

A zebra among horses - testotoxicosis as a rare cause of peripheral precocious puberty

A zebra among horses - testotoxicosis as a rare cause of peripheral precocious puberty

Smaller subcortical volume relates to greater weight gain in girls with initially healthy weight.

Among 3614 youth who were 9 to 12 years old and initially did not have overweight or obesity (12% [n = 385] developed overweight or obesity), we examined the natural progression of weight gain and brain structure development during a 2-year period with a high risk for obesity (e.g., pre- and early adolescence) to determine the following: 1) whether variation in maturational trajectories of the brain regions contributes to weight gain; and/or 2) whether weight gain contributes to altered brain development. Data were gathered from the Adolescent Brain Cognitive Development (ABCD) Study. Linear mixed-effects regression models controlled for puberty, caregiver education, handedness, and intracranial volume (random effects: magnetic resonance scanner [MRI] scanner and participant). Because pubertal development occurs earlier in girls, analyses were stratified by sex. For girls, but not boys, independent of puberty, greater increases in BMI were driven by smaller volumes over time in the bilateral accumbens, amygdala, hippocampus, and thalamus, right caudate and ventral diencephalon, and left pallidum (all p < 0.05). The results suggest a potential phenotype for identifying obesity risk because underlying differences among regions involved in food intake were related to greater weight gain in girls, but not in boys. Importantly, 2 years of weight gain may not be sufficient to alter brain development, highlighting early puberty as a critical time to prevent negative neurological outcomes.

Pubertal Suppression in Early Puberty Followed by Testosterone Mildly Increases Final Height in Transmasculine Youth

Abstract Purpose Treatment for transmasculine youth (TMY) can involve testosterone (T) treatment and is sometimes preceded by gonadotropin-releasing hormone agonist (GnRHa) treatment for puberty blockade. GnRHa can increase final height in birth-assigned females with central precocious puberty. Maximizing final adult height (FAH) is an important outcome for many TMY. Our objective was to determine how GnRHa treatment before testosterone impacts FAH. Methods Retrospective cohort study at 5 U.S. transgender health clinics. Participants were 32 TMY treated with GnRHa in early-to-mid-puberty before testosterone (GnRHa+T group) and 62 late/post-pubertal TMY treated with only testosterone (T-only group). Results The difference between FAH minus mid-parental target height (MPTH) was +2.3 ± 5.7cm and -2.2 ± 5.6cm in the GnRHa+T and T-only groups, respectively (p&amp;lt;0.01). In the GnRHa+T group, FAH was 1.8 ± 3.4cm greater than predicted adult height (PAH) (p&amp;lt;0.05) and FAH vs. initial height (IH) z-score was 0.5 ± 1.2 vs. 0.16 ± 1.0 (p&amp;lt;0.05). After adjusting for patient characteristics, each additional month of GnRHa monotherapy increased FAH by 0.59cm (95% CI: 0.31,0.9 cm), stage 3 breast development at start of GnRHa was associated with 6.5cm lower FAH compared to stage 2 (95% CI: -10.43, -2.55), and FAH was 7.95cm greater in the GnRHa+T group compared to T-only group (95% CI: -10.85, -5.06). Conclusions Treatment with GnRHa in TMY in early puberty before testosterone increases FAH compared with MPTH, PAH, IH, and TMY who only received testosterone in late/post-puberty. TMY considering GnRHa should be counseled that GnRHa may mildly increase their FAH if started early.

Precocious puberty in a patient diagnosed with neonatal steinert syndrome: A case report

Precocious puberty in a patient diagnosed with neonatal steinert syndrome: A case report

Safety and efficacy of cinacalcet in children below 3 years of age on maintenance dialysis

BackgroundSecondary hyperparathyroidism (sHPT) is particularly severe in rapidly growing infants in dialysis. While cinacalcet is effective and licensed in dialysis above 3 years, its efficacy and safety below 3 years is unknown. MethodsWe identified 26 children on dialysis below three years treated with cinacalcet between 2009 and 2021 in 8 European pediatric centers. ResultsMedian (IQR) age at start of cinacalcet was 18[IQR 11–27] months, serum parathyroid hormone (PTH) was 792[411–1397] pg/mL, corresponding to 11.6[5.9–19.8] times the upper limit of normal (ULN). Serum calcium was 2.56[2.43–2.75] mmol/L, and serum phosphate 1.47[1.16-1.71] mmol/L. Serum 25-OHD was 70[60–89] nmol/L, three children were vitamin D deficient (<50nmol/L). The initial cinacalcet dose was 0.4[0.2–0.8] mg/kg/day and the maximum dose was 1.1[0.6–1.2] mg/kg/day. The median follow-up under cinacalcet was 1.2[0.7-2.0] years. PTH decreased to 4.3[2.2–7.8] times the ULN after 6 months, to 2.0[1.0–5.3] times ULN after 12 months and to 1.6[0.5–3.4] times thereafter (p=0.017/ 0.003/<0.0001, log-transformed PTH). Seven of the 26 infants developed 10 hypocalcemic episodes <2.10 mmol/L. Oral calcium intake was 84[66-117] % of recommended nutrient intake at start, 100[64-142] % at 3 months and declined to 78[65-102] % at 12 months of therapy. Three children developed clinical signs of precocious puberty. ConclusionCinacalcet efficiently controlled severe sHPT in children below 3 years of age and was associated with hypocalcemic episodes (similarly, to what is observed in older children) and precious puberty, mandating meticulous control of calcium (taking into account nutrition, supplementation and dialysate) and endocrine changes.

Effectiveness of the triptorelin stimulation test compared with the classic gonadotropin-releasing hormone stimulation test in diagnosing central precocious puberty in girls.

The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). Gonadorelin (Relefact) is used for the test but is not always readily available; triptorelin is used as an alternative. The purpose of this study was to evaluate the diagnostic validity of the triptorelin test compared with the GnRH test in the diagnosis of CPP in girls. This retrospective study included 100 girls with premature thelarche (PT) who underwent a hypothalamic-pituitary-gonadal axis evaluation. In the overall group, 50 girls were tested with intravenous gonadorelin (Relefact) and 50 girls were tested with subcutaneous triptorelin acetate (Decapeptyl). Luteinizing hormone (LH) and follicle-stimulating hormone levels were measured at baseline and 30, 45, 60, and 90 minutes after gonadorelin injection or 30, 60, 90, and 120 minutes after triptorelin injection. Clinical characteristics of age, height, weight, body mass index, and bone age were similar between the 2 groups. The highest LH level was reached 60 minutes after stimulation in both groups. Approximately 20% of the gonadorelin group and 24% of the triptorelin group were diagnosed with CPP (P=0.52). Among those diagnosed with CPP, the mean peak LH concentrations were 8.15 mIU/mL and 9.73 mIU/mL in the gonadorelin and triptorelin groups, respectively. The triptorelin test showed similar trends of LH elevation and diagnostic rate compared with the traditional GnRH test for diagnosing CPP. This suggests that the triptorelin test may be a valid alternative to the GnRH test for differentiating CPP from self-limiting PT. Our study also demonstrated that a triptorelin stimulation test for up to 120 minutes was sufficient to diagnose CPP.

Diagnostic value of stimulated urine luteinizing hormone after triptorelin stimulation test in girls with CPP.

To investigate the diagnostic value of urine luteinizing hormone (ULH) after triptorelin stimulation test detected by immunochemiluminometric assay (ICMA) in girls with central precocious puberty (CPP). The girls with precocious puberty were involved. The triptorelin stimulation test at 8:30 a.m.were performed. Two consecutive 12-hour urine samples were collected after the test, defined as first 12-hour and second 12-hour urine, respectively. ICMA measured ULH. Urine creatinine (Cr) concentration was measured. CPP and peripheral precocious puberty (PPP) were diagnosed by the same pediatric endocrinologist based on clinical symptoms, signs, and progression of clinical development. A total of 97 cases (CPP n=69; PPP n=28) were included, with 12 cases not meeting the receiver operating characteristic analysis criteria. The first and second 12-hour ULH/Cr in CPP group were higher than those in PPP group. When first 12-hour ULH/Cr was ≥ 287.252 IU/mol, the sensitivity and specificity for diagnosing CPP were 87.3% and 90.9%, respectively. When second 12-hour ULH/Cr was ≥ 152.769 IU/mol, the sensitivity and specificity for diagnosing CPP were 92.1% and 90.9%, respectively. The area under the curve of first and second 12-hour ULH/Cr were 0.933 and 0.954, respectively. The ULH detection method after the triptorelin stimulation test has clinical significance for diagnosing CPP in girls. When the compliance of blood sampling in girls with precocious puberty is poor, first 12-hour ULH/Cr ≥ 288 IU/mol (or second 12-hour ≥ 153 IU/mol) after the triptorelin stimulation test can serve as a laboratory indicator for diagnosis of CPP.

Unstimulated Luteinizing Hormone for Assessment of Suppression During Treatment of Central Precocious Puberty with 6-Month Subcutaneous Leuprolide Acetate: Correlations with Clinical Response.

Phase 3 trial of 6-month subcutaneous leuprolide acetate (SC-LA) in children with central precocious puberty (CPP) demonstrated efficacy and safety. Aims of this secondary analysis: evaluate unstimulated luteinizing hormone (LH) as efficacy measure; assess clinical suppression metrics; and present biochemical and clinical data for subgroups not achieving hormone suppression. 62 children with treatment-naïve CPP received 2 doses of 45 mg SC-LA at 24-week intervals. Unstimulated and GnRH-stimulated LH, E2, and T concentrations were measured. Clinical measures included bone age (BA) and predicted adult height (PAH). 84% and 86% of children achieved unstimulated LH&lt;1IU/L at weeks 24 and 48, respectively. Of 8 children not achieving unstimulated LH&lt;1IU/L at week 24 that completed the study, all showed lack of pubertal stage progression and stable/decreased BA to chronological age ratio (BA/CA). Received operating characteristic (ROC) analyses suggested unstimulated LH is a good diagnostic predictor of GnRH-stimulated LH&lt;4IU/L at week 24 and 48 (AUC=0.88). Across all children, mean BA/CA improved from 1.4 (screening) to 1.3 (week 48) and mean PAH increased by 3cm. Of 7 girls not achieving stimulated LH&lt;4IU/L at week 24, all achieved E2&lt;10pg/mL, showed lack of pubertal stage progression, and had stable or decreased BA/CA by week 48. Additionally, 6/7 had increased PAH by week 48 and 4 had unstimulated LH&lt;1IU/L. Unstimulated LH has value as an efficacy measure and concentrations &lt;1IU/L may be an adequate surrogate of treatment response in children with CPP. All children who completed the study had evidence of pubertal suppression.

Irisin combined index to diagnose central precocious puberty in girls: a cross-sectional study

BackgroundTo investigate serum irisin levels in girls at different developmental status and explore the significance of irisin for the diagnosis of central precocious puberty (CPP) in girls.MethodsIn this cross-sectional study 111 girls were enrolled, including 43 cases of CPP, 44 cases of peripheral precocious puberty (PPP) and 24 cases of girls with normal sexual development as controls. The data on age, weight and height, measured blood levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, and irisin were collected. Pelvic Doppler ultrasound was performed to evaluate uterine length, transverse diameter, anteroposterior diameter. The girls were divided into non-CPP group and CPP group according to gonadotropin-releasing hormone (GnRH) stimulation test.ResultsSerum irisin levels were significantly higher in CPP group than in PPP group and normal control group. Serum irisin level was positively correlated with basal LH level, basal FSH level, peak LH level, peak LH /FSH ratio, uterine volume, bone age, and bone age index. The area under the curve, cut-off value, sensitivity and specificity of serum irisin were 0.958, 219.255 pg/ml, 100% and 80.6%. The combined diagnosis of CPP in girls by serum irisin and serum basal LH combined with uterine volume had an AUC, sensitivity, and specificity of 0.994, 97.6%, and 100%, superior to that of the single index.ConclusionsSerum irisin level in girls with CPP is significantly increased. An irisin combined index could help the diagnosis of CPP in girls.

Effectiveness of leuprolide acetate administered monthly compared to three-monthly in the treatment of central precocious puberty: evaluation at the end of treatment.

Gonadotropin-releasing hormone (GnRH) analogs are the standard treatment for central precocious puberty (CPP). Although there are numerous varieties of GnRH agonists, the effectiveness of 1-monthly compared with 3-monthly Leuprolide acetate is still restricted. The objective of this study was to evaluate the outcomes of CPP treatment with Leuprolide acetate at a 1-monthly dosage of 3.75 mg, in comparison to a dosage of 11.25 mg administered every 3 months. This retrospective cohort study involved 143 girls diagnosed with CPP with 72 of them receiving the monthly treatment regimen and 71 receiving the 3-monthly treatment regimen. Anthropometric measurements were compared at the start and end of the therapy. The rates and level of LH suppression were assessed six months after therapy. The regimen administered every 3 months showed more significant suppression of LH. The 3-monthly group showed lower actual height and degree of bone age advancement at the end of therapy. However, the predicted adult height (PAH) remained comparable in both groups. The 3-monthly treatment showed greater hormonal and growth suppression effects, but there was no significant difference in PAH between the two groups.

Atypical Congenital Adrenal Hyperplasia (CAH) Presentation of A Patient, Resulting in A Similar Diagnosis for His Sibling

Introduction: Congenital adrenal hyperplasia (CAH) is the commonest cause of primary adrenal insufficiency and is known to be transmitted in an autosomal recessive manner. We report two cases of male siblings with CAH. Cases: The elder sibling was diagnosed late at 4 years old with signs of virilization, complicated with central precocious puberty (CPP). The younger sibling was diagnosed after baseline screening and stimulation test. Treatment with both hydrocortisone and fludrocortisone were commenced for both siblings once the diagnosis was made. The elder sibling however, required treatment with gonadotropin analogues to treat the CPP.  Conclusion: These cases illustrate the importance of an early diagnosis of CAH and the benefit of screening siblings to prevent late presentations of CAH in high-risk families.

Voice aspects in children with precocious puberty

PurposeIn this prospective study, we aimed to investigate the difference in voice acoustic parameters between girls with idiopathic central precocious puberty (ICPP) and those who developed normally during prepuberty. Materials and methodsOur study recruited 54 girls diagnosed with ICPP and randomly sampled 51 healthy prepubertal girls as the control. Tanner stages, circulating hormone levels and bone ages of the girls with ICPP and the age and body mass index (BMI) of all participants were recorded. Acoustic analyses were performed using PRAAT computer-based voice analysis software and the mean pitch (F0), jitter, shimmer, noise-to harmonic-ratio (NHR) and harmonic-to-noise ratio (HNR) values were compared in the patient and control groups. ResultsThe two groups did not significantly differ in age or BMI. In the evaluation of the F0 and jitter values, we were found to be lower in the control group than in the patient group. However, we did not find a statistical significance. The mean shimmer values of the patient group were significantly higher than those of the control group. In addition, a statistically significant difference was noted for the mean HNR and NHR values (P < 0.001). A moderate negative correlation was found between shimmer and hormone levels in the patient group. ConclusionsVoice acoustic parameters one of the defining features of girls with ICPP. Voice changes in acoustic parameters could reflect hormonal changes during puberty. Clinicians should suspect ICPP when there is a change in the voice.