Peak Follicle-stimulating Hormone Research Articles

Association between dietary behavior and puberty in girls

IntroductionOver the decades the trends of early onset of puberty have been observed in children, particularly in girls. Research evidence has reported diet to be among the most important risk factors for puberty onset. This study evaluated the association between dietary behavior and puberty in girls.MethodsWe enrolled 201 girls with the main complaints of breast development as the cases at the Endocrine Department of Nanjing Children's Hospital. The cases were divided into breast development with central priming and breast development without central priming groups and were matched with 223 normal health girls with no breast development (control group). We used the modified Child Eating Behavior Questionnaire (CEBQ) to conduct a face-to-face interview about dietary behavior. Sample t-test or Mann Whitney U test or Chi-square test, the analysis of variance or Kruskal Wallis test, and least significant difference (LSD) were used to compare differences between the groups, Bonferroni was used to correct the p-value, and logistic regression was used to analyze risk factors for puberty onset.ResultsA total of 424 girls participated in this study, among them, 136 were cases with breast development with central priming, 65 were cases with breast development without central priming, and 223 were normal health girls with no breast development. Age of the participants ranged from 4.5 to 9.3 years. There were significant differences in food response (p < 0.001), dietary restriction (p < 0.001), frequencies of vegetable intake (χ2 = 8.856, p = 0.012), drinking milk (χ2 = 23.099, p = 0.001), and borderline statistical difference in a total score of unhealthy dietary behavior (p = 0.053) among the cases and controls. However, in the post hoc analysis, these dietary behaviors were significant differences between the girls with breast development with central priming and the control groups. Moreover, girls in the breast development with central priming group had significantly higher bone age (BA), uterine body length, ovarian volume, basal luteinizing hormone (LH), basal follicle-stimulating hormone (FSH), peak LH, peak FSH, estradiol (E2), and free triiodothyronine (FT3) compared to those in the breast development without central priming group. In the multivariate logistic regression, only uterine body length was associated with increased risk of breast development with central priming (OR = 1.516, 95%CI: 1.243–1.850).ConclusionThere were significant differences in dietary behaviors among girls with breast development with central priming and normal health girls with no breast development, and uterine body length was associated with an increasing risk of breast development with central priming among girls with breast development.

Confirming the association between low serum 25OHD levels in girls with central precocious puberty and its severity

BackgroundTo assess the differences in vitamin D levels in girls with rapidly progressive (RP) or slowly progressive (SP) central precocious puberty (CPP) and to compare whether the factors related to RP-CPP influenced the vitamin D status. A cross-sectional study was performed among girls with CPP classified as RP-CPP or SP-CPP.MethodsThe baseline data, gonadotropin-releasing hormone (GnRH) stimulation test results, serum 25-hydroxyvitamin D (25OHD) levels, and season of sample collection were analyzed.ResultsThe mean 25OHD level in 340 girls was 15.89 ± 6.87 ng/mL, of whom only 10 (2.9%) had normal levels (≥ 30 ng/mL). A total of 114 girls in the SP-CPP group and 226 in the RP-CPP group had similar chronological age, disease course, height SDS, bone mineral density, baseline follicle-stimulating hormone (FSH), peak FSH, and 25OHD levels. Developmental age, body mass index (BMI), BMI SDS, peak luteinizing hormone (LH)/FSH, insulin-like growth factor 1 (IGF-1), and IGF-1 SDS were independent risk factors for RP-CPP. Significant differences were observed among the different serum 25OHD levels in terms of season, disease course, IGF1 level, and BMI SDS (P < 0.05). Moreover, the sampling season was strongly correlated with serum 25OHD levels (r = 0.402, P < 0.001).ConclusionThe vitamin D levels were generally deficient or insufficient in girls with CPP, but were not related to the different types of CPP. High BMI levels, IGF1 levels, or peak LH/FSH ratio, but not vitamin D levels, could promote the progression of RP-CPP. Seasonal factors mainly influenced the vitamin D levels.

Clinical significance of serum MBD3 detection in girls with central precocious puberty.

Diagnosis of central precocious puberty (CPP) in girls remains a huge challenge. The current study was to measure the serum expression of methyl-DNA bind protein 3 (MBD3) in CPP girls and assess its diagnostic efficacy. To begin with, we enrolled 109 CPP girls and 74 healthy pre-puberty girls. Then, MBD3 expression in their serum samples was measured via reverse transcription-quantitative polymerase chain reaction, and its diagnostic efficacy on CPP was assessed via the receiver operating characteristic (ROC) curve, followed by correlation analysis between serum MBD3 and patient age, gender, bone age, weight, height, body mass index, basal luteinizing hormone (LH), peak LH, basal follicle-stimulating hormone (FSH), peak FSH, and ovarian size using bivariate correlations method. Finally, independent predictors of MBD3 expression were confirmed using multivariate linear regression analysis. MBD3 was highly expressed in sera of CPP patients. The area under the ROC curve of MBD3 diagnosing CCP was 0.9309, with 1.475 cut-off value (92.66% sensitivity and 86.49% specificity). MBD3 expression positively correlated with basal LH, peak LH, basal FSH, and ovarian size, among which basal LH was considered the strongest independent predictor of MBD3, followed by basal FSH and peak LH. In summary, serum MBD3 could act as a biomarker in aiding CPP diagnosis.

Relationship between Body Mass Index and Bone Turnover Markers in Girls with Idiopathic Central Precocious Puberty.

This study aimed to determine the effect of body mass index (BMI) on bone turnover markers in girls with idiopathic central precocious puberty (ICPP) according to weight status at diagnosis. Two hundred and eleven girls with ICPP were divided according to their weight status at diagnosis into three groups: normal weight, overweight, and obese. The serum levels of total procollagen type 1 N-terminal propeptide (P1NP), N-terminal midfragment of osteocalcin, β-C-terminal telopeptide of type 1 collagen, and some biochemical indicators were measured. Associations between variables were evaluated by multiple regression analysis. Serum P1NP concentrations were significantly different among groups (p < 0.001). No other significant differences were noted in N-terminal midfragment of osteocalcin and β-C-terminal telopeptide of type 1 collagen. BMI was associated with estradiol (r = 0.155, p < 0.05) and inversely associated with P1NP (r = -0.251, p < 0.01), luteinizing hormone peak (r = -0.334, p < 0.01), follicle-stimulating hormone peak (r = -0.215, p < 0.01), and luteinizing hormone/follicle-stimulating hormone peak (r = -0.284, p < 0.01). Multiple regression analysis of factors associated with BMI showed that it was correlated with P1NP, follicle-stimulating hormone base, and luteinizing hormone peak in the overweight group and the obese group. Our findings showed that BMI was associated with P1NP, revealing the reduction of bone formation in overweight and obese girls with ICPP. During the diagnosis and treatment of girls with ICPP, attention should be paid to body weight and bone metabolism.

Clinical and hormonal characteristics and growth data of 45,X/46,XY mosaicism in 38 Chinese patients.

45,X/46,XY mosaicism is the most common type of sex chromosomal abnormality in disorders of sex development (DSD). We investigated the clinical manifestations, serum sex hormone levels and growth data of 38 45,X/46,XY mosaicism patients, which provides better insight into this disease. We prospectively evaluated 38 patients who were diagnosed with 45,X/46,XY mosaicism at the Department of Endocrinology of Shanghai Children's Hospital from 2010 to 2020. We analyzed clinical data from the patients, including hormone levels, height, weight, body mass index (BMI) and gonadal pathology results. Among the 38 cases of 45,X/46,XY mosaicism, 18 cases showed a female external genitalia phenotype (the female group) with an external masculinization score (EMS) of 1 (0-3) [median (range)], and 20 cases showed a male external genitalia phenotype (the male group) with an EMS of 7.63 (3-11) [median (range)]. The age at diagnosis ranged from 0.7 to 16.1 years. Under 2 years of age, the standard deviation scores of height (HtSDS) were in the normal range and then they gradually decreased. The inhibin B (INHB), anti-Mullerian hormone (AMH), and testosterone (T) levels after human chorionic gonadotropin (HCG) stimulation and the T:DHT ratio in the male group were significantly higher than those in the female group (P < 0.001). The basal luteinizing hormone (LH), basal follicle-stimulating hormone (FSH), peak LH and peak FSH in females were significantly higher than those in males (P < 0.05). Their height showed a positive correlation with T levels after HCG stimulation (r = 0.636, P < 0.01), T:DHT ratio (r = 0.724, P < 0.01), growth hormone (GH) (r = 0.827, P < 0.05), and insulin-like growth factor 1 (IGF-1) (r = 0.067, P > 0.05) and a negative correlation with gonadal pathology in ovarian tissue (r = -0.663, P < 0.05) and the number of chimaeric XY cells (r = -0.533, P < 0.05). Patients with 45,X/46,XY mosaicism have specific growth patterns. Their HtSDS was in the normal range during 0-2 years of age and then they began to show a short stature after 2 years of age. The probability of short stature in females was higher than that in males. WtSDS were all in the normal range, but below the median. BMISDS was in the normal range, and there was no evidence of obesity. The gonads in the male group retained a certain androgen secretion function, while the gonadal damage is more severe in the female group.

Türkiye’nin Trakya bölgesinde erken prepubertal gelişim ile takip edilen 367 çocuğun biyokimyasal klinik ve etiyolojik özellikleri

Background: Appearance of menarche before nine years of age, secondary sex characteristics before 8 in girls and 9 in boys is defined as Precocious Puberty (PP).&#x0D; Objective: The aim of this study was to describe etiologies, clinical findings, and compare anthropometric properties and biochemical characteristics of children with PP.&#x0D; Methods: In this single-centre study, 367 patients of whom medical records were reviewed diagnosed as premature thelarche (PT), premature adrenarche (PA), Central PP (CPP), and peripheral PP (PPP). The diagnosis was based on clinical, laboratory, and radiologic investigations and their follow-up.&#x0D; Results: During six years, 349 girls (%95,1) and 18 boys (%4,9) diagnosed as PP. The most common etiologies were CPP;127 (%34,6), PT;117 (%31,9), PA;112(%30,5) and PPP 11(%3), respectively. CPP group had significantly higher levels of height, weight, body mass index (BMI) and obesity/overweight incidence, estradiol (E2), basal luteinizing hormone (LH), peak LH, and peak LH/ follicle-stimulating hormone (FSH) ratio and higher uterine dimensions compared to the PT group while the PT group had significantly higher levels of peak FSH compared to the CPP group (p

A single blood sample for stimulated LH assayed by ICMA is useful for monitoring the treatment efficacy of triptorelin depot in girls

Background: There is still no consensus on the optimal monitoring method to evaluate the hypothalamic-pituitary-gonadal axis (HPGA) inhibition. Methods: There were 124 girls treated with triptorelin depot due to puberty disorders, including 77 central precocious puberty and 47 early puberty. After treatment, triptorelin stimulation tests were performed, and blood samples were collected at 0, 20, 40 and 60 min. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured by immunochemiluminometric assay (ICMA). Results: Peak LH (PLH), peak FSH and estradiol in 124 girls were significantly decreased after treatment, while 2 cases had inadequate treatment efficacy. Areas under the receiver operating characteristic curves (AUC) of PLH and peak FSH after stimulation for the diagnosis of HPGA suppression were 0.984 and 0.121. When the cut-off value of PLH was ≤ 2.25 IU/L, the sensitivity was 96.7% and specificity was 100.0%. There was no difference in AUC between PLH and a single LH at 20, 40, or 60 min (p > 0.05). When LH were ≤ 2.34 IU/L, ≤ 2.21 IU/L and ≤ 2.00 IU/L at 20, 40 and 60 min, respectively, the sensitivity were 99.1%, 96.7% and 98.4%, and the specificity were all 100.0%. The correlation coefficients between PLH and LH at 20, 40 or 60 min were 0.947, 0.975 and 0.961. Conclusion: A single blood sample for stimulated LH at 20 min, 40 min, or 60 min assayed by ICMA during triptorelin stimulation test is useful for monitoring the treatment efficacy of triptorelin depot in girls with puberty disorders.

Gene Polymorphisms Associated with Central Precocious Puberty and Hormone Levels in Chinese Girls.

Central precocious puberty (CPP) is associated with adverse health outcomes in females; however, CPP pathogenesis remains unclear. In this study, we investigated the association of 20 single nucleotide polymorphisms (SNPs) in eight genes with CPP risk and hormone levels. A case-control study on 247 and 243 girls with and without CPP, respectively, was conducted at Kunming Children's Hospital, China, from September 2019 to August 2020. The genotype of the SNPs and their haplotypes were identified. Additionally, the effects of the polymorphisms on hormone levels were investigated. Three variants (rs10159082, rs7538038, and rs5780218) in KISS1 and two variants (rs7895833 and rs3758391) in SIRT1 were related to an increased CPP risk (odds ratio (OR) = 1.524, 1.507, 1.409, 1.348, and 1.737; 95% confidence interval (CI) = 1.176–1.974, 1.152–1.970, 1.089–1.824, 1.023–1.777, and 1.242–2.430, respectively). Rs3740051in SIRT1 and rs1544410 in VDR reduced CPP risk (OR = 0.689, 0.464; 95% CI, 0.511–0.928, 0.232–0.925, respectively). Rs1544410, rs7975232, and rs731236 in VDR were negatively correlated with peak follicle-stimulating hormone (FSH; β = −2.181; P=0.045), basal FSH (β = −0.391; P=0.010), and insulin-like growth factor (β = −50.360; P=0.041) levels, respectively. KISS1, SIRT1, and VDR variants were associated with CPP susceptibility, and VDR SNPs influenced hormonal levels in Chinese females with CPP. In particular, VDR polymorphism rs1544410 was associated with both CPP risk and GnRH-stimulated peak FSH levels. Further functional research and large-scale genetic studies of these loci and genes are required to confirm our findings.

Diagnostic Value of LH Peak Value of the GnRH Stimulation Test for Girls with Precocious Puberty and Its Correlation with Body Mass Index.

Objective To analyze the diagnostic value of luteinizing hormone (LH) peak value of the gonadotropin-releasing hormone (GnRH) stimulation test for girls with precocious puberty and its correlation with body mass index (BMI). Methods A total of 230 girls with precocious puberty who came to our hospital for testing from June 2019 to June 2021 were selected and divided into a true group (n = 130) and sham group (n = 100) according to the results of the GnRH stimulation test. According to the BMI, the true group was further divided into a normal group (48 cases), overweight group (43 cases), and obese group (39 cases). The GnRH stimulation test was performed on all subjects, and the basal value and peak value of LH and the basal value and peak value of follicle-stimulating hormone (FSH) were recorded. The general data and serological indexes of the true group and the sham group were compared. Indicators of the GnRH stimulation test, breast stage, bone age, BMI, uterine volume, ovarian volume, and serological indicators (leptin, sex hormone-binding protein (SHBG), and adiponectin (APN)) were compared among the normal group, the overweight group, and the obese group. Results There were no significant differences in age and breast stage between the true group and the sham group (P > 0.05). There were statistically significant differences in bone age, BMI, uterine volume, and ovarian volume between the two groups (P < 0.05). The LH base value, LH peak value, FSH base value, and FSH peak value in the true group were higher than those in the sham group, and the differences were statistically significant (P < 0.05). ROC curve analysis showed that the AUC of LH peak value in diagnosing girls with precocious puberty was 0.973, which was higher than 0.895, 0.875, and 0.912 of LH base value, FSH base value, and FSH peak value, respectively. There were statistically significant differences in LH base value, LH peak value, FSH base value, breast development stage, bone age, BMI, SHBG, leptin, and APN among the normal group, overweight group, and obese group (P < 0.05), but there were no significant differences in FSH peak value, uterine volume, and ovarian volume among the three groups (P > 0.05). There was a negative correlation between BMI, LH peak value, and FSH base value (P < 0.05), but there was no significant correlation between BMI and FSH peak value (P > 0.05). Conclusion The LH peak value of the GnRH stimulation test has high diagnostic value for girls with precocious puberty, and BMI is negatively correlated with the LH peak value of CPP children.

Combined diagnostic value of insulin-like growth factor-1, insulin-like growth factor binding protein-3, and baseline luteinizing hormone levels for central precocious puberty in girls.

The golden standard test for diagnosing central precocious puberty (CPP) is the gonadotropin releasing hormone stimulation test, which has many limitations. This study aimed to investigate the value of insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), and basal luteinizing hormone (LH) levels in diagnosing CPP. Cross-sectional study of the levels of IGF-1, IGFBP-3, and basal LH in girls with a chief complaint of premature breast development. Seventy-nine girls with CPP and 37 girls with premature thelarche (PT) diagnosed at West China Second University Hospital from January 2016 to October 2018 were recruited. All patients underwent physical examination, laboratory tests, uterine and ovarian ultrasound, and bone age tests, only CPP patients underwent pituitary magnetic resonance imaging (MRI). Statistical analysis was performed using the SPSS software 21.0. A receiver operating characteristic curve was used to determine diagnostic value. The anthropometric data and hormone indicators between CPP and PT were statistically different (p<0.001), except for peak follicle stimulating hormone (FSH) levels (p=0.181). IGF-1, IGFBP-3, and basal LH levels were significantly higher in the subjects with CPP than in those with PT; IGF-1 and basal LH were positively correlated with peak LH and LH/FSH (peak) (p<0.001). The area under the curve (AUC) of IGF-1, IGFBP-3, and basal LH were 0.880, 0.853, and 0.915, respectively. When combined, the AUC reached the highest value of 0.978. IGF-1, IGFBP-3, and baseline LH levels were useful in diagnosing CPP. The combined analysis improved the diagnostic effectiveness.

Deep Learning-Based Ultrasound Imaging Diagnosis for Gonadotropin-Releasing Hormone Agonists Treatment of Central Precocious Puberty

To explore the adoption of ultrasound imaging diagnosis based on deep learning of convolutional neural networks (CNNs) in the treatment of central precocious puberty (CPP) by gonadotropin-releasing hormone agonists (GnRHa), ultrasound imaging based on CNN was utilized to treat CPP. The bone age, uterine and ovarian volume, and breast development of incomplete precocious puberty (IPP) group and CPP group were observed and recorded. The peak values of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured. The uterine and ovarian volume before and after GnRHa treatment of CPP were compared. The results showed that the bone age (9.03 ± 1.07), uterine volume (2.37 ± 1.52), ovarian volume (2.36 ± 0.82 mL), and breast development of the CPP group were considerably higher in contrast to the IPP group and control group ( P &lt; 0.05 ). The LH peak (11.97 ± 5.63) and FSH peak (12.89 ± 3.15) of the CPP group were substantially higher relative to the IPP group ( P &lt; 0.05 ). The uterine volume (1.06 ± 0.42) and ovarian volume (1.12 ± 0.49) after treatment were inferior to those before treatment ( P &lt; 0.05 ). In short, ultrasound images based on deep learning could diagnose precocious puberty, which could also provide a certain basis for GnRHa treatment of CPP, as well as an important basis for clinical diagnosis and treatment of precocious puberty.

Interactions of circulating estradiol and progesterone on changes in endometrial area and pituitary responsiveness to GnRH†.

Changes in circulating progesterone (P4) and estradiol (E2) during proestrus produce dynamic changes in endometrial function and pituitary release of gonadotropins. Independent and combined effects of P4 and E2 on endometrium and pituitary were evaluated. In a preliminary study, an exogenous hormone model of proestrus was created by removal of corpus luteum and follicles ≥5mm followed by gradual removal of intravaginal P4 implants during 18h and treatment with increasing doses of estradiol benzoate during 48h to mimic proestrus using high E2 (n=9) or low E2 (n=9). Decreased P4, increased E2, and increased endometrial area (EA) simulated proestrus in high-E2 cows and this was used subsequently. The main experiment used a 2×2 factorial design with: high E2 and low P4 (n=11); high E2 and high P4 (n=11); low E2 and high P4 (n=11); low E2 and low P4 (n=10). At 48h, gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) and follicle stimulating hormone (FSH) release was determined. Variables were analyzed using PROCMIXED of Statistical Analysis System. The EA increased dramatically during 48h only in high-E2 and low-P4 cows. For FSH, high-E2 cows had greater area under the curve (AUC) and FSH peak after GnRH than low E2, with mild negative effects of high P4. For LH, concentration at peak and AUC were 2-fold greater in high E2 compared to low-E2 groups, with low P4 also 2-fold greater than high-P4 groups. Thus, maximal changes in uterus and pituitary during proestrus depend on both low P4 and high E2, but different physiologic responses are regulated differently by E2 and P4. Changes in endometrium depend on low P4 and high E2, whereas GnRH-induced FSH secretion primarily depends on high E2, and GnRH-induced LH secretion is independently increased by high E2 or reduced by high P4.

Ovarian follicle dynamics and hormonal changes during early pregnancy in Saanen goats

This study is aimed at describing the ovarian follicular dynamics, corpora lutea and their hormonal control during early pregnancy in Saanen goats. The ovaries of pregnant goats (n = 10) were monitored daily for follicles (≥ 2 mm) and corpora lutea by transrectal ultrasound over the 35 days after mating. Blood samples were collected by jugular venipuncture at the time of ultrasonography and were analysed for the concentrations of oestradiol (E&lt;sub&gt;2&lt;/sub&gt;) and progesterone (P&lt;sub&gt;4&lt;/sub&gt;), inhibin, FSH (follicle-stimulating hormone) and LH (luteinizing hormone). The pattern of follicular growth was characterised by five (n = 2; 20 %), six (n = 5; 50 %) and seven (n = 3; 30 %) follicular waves during early pregnancy. The first corpora lutea (size 6.8 ± 0.4 mm, mean + SEM) were detected at 5.0 ± 0.3 days after the mating with a maximum diameter (12.2 ± 0.3 mm) observed on day 24.0 ± 1.1 of pregnancy. The dominant follicle diameter of waves 1 and 4, and the duration of waves 1–4 and 7 were maximal during the early pregnancy period (P &amp;lt; 0.05). In addition, the inter-wave interval of the 5 waves was significantly (P &amp;lt; 0.05) longer compared to the six and seven inter-wave intervals (7.0 ± 0.1, 5.8 ± 0.1 and 5.0 ± 0.2 days, respectively). Although the number of small and medium-sized follicles did not differ with the days post-breeding, the number of large-sized follicles in the same period significantly decreased between 16 and 26 days and was negatively correlated with the period of pregnancy (P &amp;lt; 0.05). The plasma LH and E&lt;sub&gt;2&lt;/sub&gt; concentrations were negatively correlated with the P&lt;sub&gt;4&lt;/sub&gt; concentration. The inhibin concentrations were negatively correlated with FSH, but positively correlated with the number of large-sized follicles. These results indicate that ovarian follicular growth during the first 35 days of pregnancy in goats was characterised by a wave-like pattern and there was a close relationship between the number of FSH peaks and the number of follicular waves.

Altered Brain Structure and Functional Connectivity Associated with Pubertal Hormones in Girls with Precocious Puberty

Pubertal hormones play an important role in brain and psychosocial development. However, the role of abnormal HPG axis states in altering brain function and structure remains unclear. The present study is aimed at determining whether there were significant differences in gray matter volume (GMV) and resting state (RS) functional connectivity (FC) patterns in girls with idiopathic central precocious puberty (CPP) and peripheral precocious puberty (PPP). We further explored the correlation between these differences and serum pubertal hormone levels. To assess this, we recruited 29 idiopathic CPP girls and 38 age-matched PPP girls. A gonadotropin-releasing hormone (GnRH) stimulation test was performed, and pubertal hormone levels (including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin, and cortisol) were assessed. All subjects underwent multimodal magnetic resonance imaging of brain structure and function. Voxel-based morphometry (VBM) analysis was paired with seed-to-voxel whole-brain RS-FC analysis to calculate the GMV and RS-FC in idiopathic CPP and PPP girls. Correlation analyses were used to assess the effects of pubertal hormones on brain regions with structural and functional differences between the groups. We found that girls with CPP exhibited decreased GMV in the left insula and left fusiform gyrus, while connectivity between the left and right insula and the right middle frontal gyrus (MFG), as well as the left fusiform gyrus and right amygdala, was reduced in girls with CPP. Furthermore, the GMV of the left insula and peak FSH levels were negatively correlated while higher basal and peak E2 levels were associated with increased bilateral insula RS-FC. These findings suggest that premature activation of the HPG axis and pubertal hormone fluctuations alter brain structure and function involved in the cognitive and emotional process in early childhood. These findings provide vital insights into the early pathophysiology of idiopathic CPP.

Analysis of the cut point of peak level of luteinizing hormone in gonadotropin-releasing hormone agonist test in obese girls with precocious puberty

Objective To explore the significance of the cut point of peak level of luteinizing hormone(LH) in gonadotropin-releasing hormone (GnRH) agonist test in the diagnosis of precocious puberty in obese girls. Methods According to the diagnostic criteria of children′s central precocious puberty diagnosis consensus (2015), 796 cases of precocious puberty (peak level of LH ≥3.3 IU/L) in Children′s Hospital of Zhejiang University School of Medicine from January 2014 to December 2015 were divided into normal weight group (573 cases), overweight group (170 cases) and obesity group (53 cases). The 3 groups were compared in terms of basic level of LH, basic level of follicle stimulating hormone (FSH), peak level of LH and FSH, ratio of LH(peak)/FSH(peak), sex hormone binding protein (SHBG), and children with 3.3 IU/L ≤peak level of LH <5.0 IU/L were followed up.The accuracy of the diagnosis of central precocious puberty using peak level of LH was analyzed by using receiver operating characteristic (ROC) curve. Results The median of LH (peak) in the obese group was 6.92 IU/L, the median of SHBG was 46.52 nmol/L, the median of LH (peak) in normal weight group was 8.92 IU/L, and the median of SHBG was 87.28 nmol/L.There were significant differences between the 2 groups (P<0.05, 0.001). A total of 89 cases in normal weight group and 65 cases of obesity/overweight group (3.3 IU/L ≤peak level of LH <5.0 IU/L) were followed up for 1 year, and 18 cases in normal weight group and 33 cases in obesity/overweight group developed to central precocious puberty, while the number of cases in the 2 groups was significantly different (P<0.001). The ROC curve analysis showed that the cut point of peak level of LH was 4.16 IU/L, the sensitivity was 0.606, the specificity was 0.656, and the Jordan index was the largest (0.344). Conclusions The peak level of LH in GnRH agonist test is important for the diagnosis of central precocious puberty in girls, but the effect of body mass index on its cut point needs to be considered. Key words: Body mass index; Precocious puberty; Gonadotropin-releasing hormone agonist test; Receiver operating characteristic curve

The effect of overweight on the luteinizing hormone level after gonadorelin stimulation test in girls with idiopathic central precocious puberty.

PurposeWe investigated the effect of overweight on luteinizing hormone (LH) levels after a gonadorelin stimulation test in Korean girls with idiopathic central precocious puberty (CPP).MethodsMedical records of 234 girls diagnosed with idiopathic CPP were reviewed retrospectively. CPP was diagnosed when the peak LH levels after gonadorelin stimulation was >5.0 U/L. The enrolled girls had a peak LH level >5.0 U/L after a gonadorelin stimulation test. Selected girls were classified as normoweight (body mass index [BMI] below the 85th percentile with respect to age) and overweight (BMI greater than the 85th percentile with respect to age).ResultsThe peak LH (8.95±2.85 U/L vs. 11.97±8.42 U/L, P<0.01) and peak follicle-stimulating hormone (9.60±2.91 U/L vs. 11.17±7.77 U/L, P=0.04) after gonadorelin stimulation were lower in overweight girls with idiopathic CPP than in normoweight girls with idiopathic CPP. Being overweight was negatively associated with peak LH levels after gonadorelin stimulation test (odds ratio, 0.89; 95 % confidence interval, 0.81–0.98, P=0.02).ConclusionsIn girls with idiopathic CPP, being overweight led to a lower LH peak after gonadorelin stimulation. Further research is needed to better understand the role of overweight on gonadotropin secretion in precocious puberty.

Association between bisphenol a exposure and idiopathic central precocious puberty (ICPP) among school-aged girls in Shanghai, China

BackgroundBisphenol A (BPA) is a well-known and widely used endocrine disrupter, but data on its association with childhood reproductive development are limited. ObjectivesWe investigated the possible relationship between exposure to BPA and idiopathic central precocious puberty (ICPP) in school-aged girls. MethodsWe conducted a 1:1 matched case-control study in Shanghai, China, between July 2011 and September 2012. This study included 136 school-aged (6 to 9 years old) girls diagnosed with ICPP and 136 controls matched for age and body mass index (BMI). We measured the urinary BPA concentrations of all the girls and examined the association with odds of having ICPP. Laboratory examinations including serum estradiol (E2) levels, basal and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels, bone ages (BA), and uterine and ovarian sizes were conducted in the ICPP girls. ResultsMedian concentrations of urinary BPA in the ICPP and control groups were 6.35 and 1.17 μg/g creatinine (Cr), respectively (p < 0.001). After adjustment for confounders, compared to those with the lowest concentrations of BPA, the highest concentrations were associated with a 9.08-fold increased odds of having ICPP [odds ratio (OR) = 9.08, (95% confidence interval (CI): 2.83–29.15)]. In the ICPP group, modest negative correlation was present between urinary BPA concentrations (μg/g Cr) and peak FSH levels [β = −0.090 (95% CI: −0.178, −0.003), p = 0.044]. ConclusionsOur findings suggest that BPA exposure is associated with increased odds of having ICPP in school-aged girls, and the potential mechanism may be attributable to the relatively low FSH levels.

Meta-Analysis of Paediatric Patients with Central Precocious Puberty Treated with Intramuscular Triptorelin 11.25 mg 3-Month Prolonged-Release Formulation

Background/Aims: A meta-analysis was undertaken to assess the effect of triptorelin 11.25 mg 3-month prolonged-release formulation in central precocious puberty (CPP). Methods: All available clinical studies with triptorelin 11.25 mg were included. The primary outcome was the proportion of children with suppressed luteinising hormone (LH) response (peak LH ≤3 IU/L) to the gonadotrophin-releasing hormone (GnRH) test 3 months after triptorelin 11.25 mg injection. Secondary outcomes included: the proportion with suppressed peak LH response at 6 months and the proportion with suppressed peak follicle-stimulating hormone (FSH) response (≤3 IU/L), suppressed oestradiol (≤20 pmol/L) in girls or suppressed testosterone (≤30 ng/dL) in boys at 3 months. Results: 153 children (13 boys, 140 girls) were included. The proportion with a suppressed peak LH response to the GnRH test was 87.6% (95% CI: 81.3–92.4, p < 0.0001, for a proportion >70%) and 92.8% (95% CI: 87.5–96.4, p < 0.0001, for a proportion >70%) at 3 and 6 months, respectively. FSH peak, oestradiol, and testosterone were suppressed in 86.7% (95% CI: 79.1–92.4), 97.1% (95% CI: 91.6–99.4), and 72.7% (95% CI: 39.0–94.0) of children at 3 months, respectively. Conclusion: Triptorelin 11.25 mg 3-month formulation is efficacious in suppressing LH peak and other gonadal hormones and in slowing the progression of CPP in children.

Transcriptional regulation of follicle-stimulating hormone β-subunit in marmoset by an alternate distal promoter

Follicle-stimulating hormone (FSH) is essential for mammalian folliculogenesis and spermatogenesis. Common marmoset (Callithrix jacchus) is a New World primate which exhibits an unusual FSH profile across the ovarian cycle with a mid-follicular FSH peak that is not observed in Catarrhini primates like humans. Since transcription of FSH β-subunit gene (FSHβ) is a rate-limiting step in the production of mature FSH, this study aimed to investigate the regulation of marmoset FSHβ gene expression in comparison to human. In silico analysis of the FSHβ promoter sequences identified a TATA box element upstream of the conventional TATA box element in marmoset but not in human sequence. FSHβ mRNA transcript longer than the conventional transcript was detected in marmoset pituitary implying presence of a distal transcription start site. In luciferase reporter assays, the marmoset putative distal promoter had higher activity than the corresponding human region even in absence of the conventional proximal promoter. Indeed higher affinity binding of TATA box-binding protein to the putative distal TATA box element was obtained in electrophoretic mobility shift assay. This suggests existence of a differential regulation of FSHβ transcription in marmoset compared to humans.

Serum nesfatin-1 and leptin levels in non-obese girls with premature thelarche.

We aimed to investigate serum nesfatin-1 level in girls with premature thelarche (PT) and its relationship with anthropometric parameters and leptin, which are involved in the initiation of pubertal process. Non-obese girls who presented with the complaint of early (2-8 years) and isolated breast development were included in the study. The control group consisted of age-matched healthy prepubertal girls. Auxological measurements were performed in all subjects. Gonadotropin-releasing hormone (GnRH) stimulation test and bone age assessment were conducted in subjects with early breast development. Girls with a bone age/chronologic age ratio <1.2 and a peak luteinizing hormone (LH) response to GnRH stimulation <5 mIU/L were included in the PT group. The study included 22 non-obese girls with PT and 24 healthy prepubertal controls. Body mass index (BMI), BMI-standard deviation score (SDS) and height SDS were similar between the groups (p > 0.05). Serum leptin and nesfatin-1 levels were found significantly higher in the PT group compared to controls (p < 0.05). No correlation was detected between nesfatin-1 and basal LH, basal follicle stimulating hormone (FSH), stimulated peak LH, peak FSH, leptin levels and anthropometric parameters in the PT group (p > 0.05). Results of the present study showed that serum nesfatin-1 and leptin levels are significantly higher in girls with PT than in prepubertal controls. This finding suggests that similar to leptin, nesfatin-1 may also have a central or peripheral role in the initiation of pubertal process and may be related to PT pathogenesis.