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Minerva Pediatrica Dec 2014Recently, it was reported that the development of breast tissue and secondary sex characteristics in girls occurred at much younger age and the incidences of premature...
AIM
Recently, it was reported that the development of breast tissue and secondary sex characteristics in girls occurred at much younger age and the incidences of premature thelarce (PT) and central idiopathic precocious puberty (ICPP) are increasing. In this context, we wanted to evaluate the mycoestrogen exposure as triggering factor for premature sexual development.
METHODS
The girls living in Mediterranean region of Turkey were divided in to three groups: control (N.=25; mean age: 6.45 ± 1), PT (N.=28; mean age: 6.86 ± 0.95) and ICPP (N.=25; mean age: 6.97 ± 0.87). Urinary ZEN levels were measured by using ELISA technique and were normalized by urinary creatinine levels. Body Mass Index (BMI) was evaluated and sex hormone levels were also measured.
RESULTS
We found that urinary ZEN was detectable in ~81% of all samples and observed an increase of ~2-fold in PT and a significant increase ~2.8-fold in ICPP group vs. control. We did not find any significant correlations between urinary ZEN levels and BMI and sex hormones in any of the groups.
CONCLUSION
To our knowledge, this is the first study evaluating urinary ZEN levels in PT and ICPP Turkish patients. We can postulate that ZEN exposure can contribute to the etiology of PT and PP; however further studies on large number of subjects are needed to confirm the present data.
Topics: Body Mass Index; Breast; Case-Control Studies; Child; Child, Preschool; Environmental Exposure; Enzyme-Linked Immunosorbent Assay; Female; Humans; Puberty, Precocious; Turkey; Zearalenone
PubMed: 25336100
DOI: No ID Found -
JAMA Network Open Sep 2020A growing body of literature suggests that exposure to early-life adversity (ELA) is associated with accelerated biological aging, offering 1 mechanism through which ELA...
IMPORTANCE
A growing body of literature suggests that exposure to early-life adversity (ELA) is associated with accelerated biological aging, offering 1 mechanism through which ELA may be associated with an increased risk for age-related disease. These investigations, however, have been predominantly cross-sectional and focused on adults and females.
OBJECTIVE
To evaluate associations of threat-related (ie, physical abuse) and deprivation-related (ie, emotional neglect) ELA exposure with cellular and reproductive strategy metrics of biological aging among boys and girls with specific genetic backgrounds around the period of pubertal onset.
DESIGN, SETTING, AND PARTICIPANTS
In this cohort study, 997 boys and girls in grade 1 to grade 3 from 3 large elementary schools were recruited from Bengbu, Anhui Province, China, and were followed up from March 21, 2016 (baseline; wave 1), for 4 consecutive years, through March 25, 2019.
MAIN OUTCOMES AND MEASURES
The outcome was accelerated biological aging in both cellular and reproductive strategy metrics: telomere attrition and age at thelarche (for girls) and testicular maturation (for boys). Multi-informant assessment of exposure to threat-related and deprivation-related ELA was done at baseline (wave 1) and 1-year follow-up (wave 2). The polygenic risk score (PRS) was computed based on 17 single-nucleotide variations for early pubertal timing.
RESULTS
Of the 997 participants (579 girls [58.1%]; mean [SD] age at baseline, 8.0 [0.8] years), 550 (55.2%) reported exposure to threat-related ELA and 443 (44.4%) reported exposure to deprivation-related ELA. Threat-related ELA was associated with onset of thelarche 2.6 months earlier and deprivation-related ELA with onset of thelarche 3.3 months earlier in exposed girls than in unexposed peers; these associations were observed only among girls with a low PRS. Among boys, a similar pattern was found. Threat-related ELA was associated with testicular volume of 4 mL or more 1.4 months earlier and deprivation-related ELA was associated with testicular volume of 4 mL or more 2.3 months earlier than in unexposed peers but only among those with a low PRS. Boys and girls with greater exposure to threats showed a significantly higher percentage of telomere length change during 1-year follow-up, but only among those with low PRS (boys: β = 1.50; 95% CI, 0.80-2.21; P < .001; girls: β = 2.40; 95% CI, 1.78-3.05; P < .001) and moderate PRS (boys: β = 1.09; 95% CI, 0.43-1.75; P = .001; and girls: β = 1.27; 95% CI, 0.77-1.77; P < .001). No associations of deprivation-related ELA with percentage of telomere length change were found.
CONCLUSIONS AND RELEVANCE
This study suggests that the accelerating association of ELA with biological aging might occur at an earlier age and in a genetic background-dependent and dimension-specific manner.
Topics: Adverse Childhood Experiences; Aging; Aging, Premature; Causality; Child; Child Abuse; Child Development; China; Female; Gene-Environment Interaction; Humans; Male; Puberty; Risk Assessment; Sex Factors; Sexual Maturation; Telomere Homeostasis
PubMed: 32955573
DOI: 10.1001/jamanetworkopen.2020.13588 -
Frontiers in Pediatrics 2019Puberty is a sensitive period of life characterized by the appearance of secondary sex characteristics which leads to a complete sexual maturation. It physiologically... (Review)
Review
Puberty is a sensitive period of life characterized by the appearance of secondary sex characteristics which leads to a complete sexual maturation. It physiologically starts between the age of 8 and 13 years in girls and 9 and 14 years in boys. In the last two decades, several studies have showed that start of puberty has moved up to younger ages by 12-18 months, and some of the hypotheses trying to explain this change include the role of nutritional status and obesity and the influence of extrinsic factors such as exposure to endocrine-disrupting chemicals (EDCs), as well. The hypothalamic-hypophysis-gonadal axis develops during embryogenesis, and except for a period of activation immediately after birth, remains suppressed until the onset of pubertal development. At the beginning of puberty, the pulse generator is reactivated, probably due to progressive stimulatory influences on GnRH neurons from glial signals and neurotrasmitters. Kisspeptin and its receptor play a fundamental role in this phase. Premature Pubarche/Adrenarche, Premature Thelarche, and Premature Menarche are incomplete forms of precocious pubertal development that have their origin in endocrine mechanisms that only recently have started to be understood. It is important to distinguish these forms from the complete ones in order to reassure patients and parents about the non-evolution of pubertal progression and avoid non-useful treatments with analogous LHRH.
PubMed: 31139600
DOI: 10.3389/fped.2019.00147 -
Clinical Endocrinology Apr 2024This study aimed to investigate the quality of life of patients with central precocious puberty (CPP) who required treatment and premature thelarche (PT) followed up...
OBJECTIVE
This study aimed to investigate the quality of life of patients with central precocious puberty (CPP) who required treatment and premature thelarche (PT) followed up without treatment and to compare the groups with and without treatment among themselves and with healthy children.
DESIGN, PATIENTS AND MEASUREMENT
This study is designed as a case-control study. A total of 193 children including 59 children with CPP, 53 children with PT, 81 healthy children and their parents were included in the study. A questionnaire was applied to evaluate the sociodemographic characteristics that would affect the quality of life. The 'Pediatric Quality of Life Inventory (PedsQL)' was used to assess the quality of life.
RESULTS
The PedsQL total scale score was 78.10 ± 17.13, 79.35 ± 11.54 and 79.52 ± 14.65, the psychosocial health summary score was 78.86 ± 16.83, 79.40 ± 12.54 and 79.94 ± 14.94 and physical health summary score was 75.81 ± 20.69, 79.41 ± 15.04 and 78.25 ± 17.52 in CPP, PT and control groups, respectively; however, there was no statistical difference (p > .05). In the scale administered to the parents, scores were similar in the three groups. No difference was found between CPP, PT and control groups in terms of sociodemographic data in the study (p > .05).
CONCLUSION
Unlike previous studies, in this study the effects of sociodemographic characteristics and whether treatment was initiated or not on quality of life were investigated. Although the scale scores of the CPP group were lower than the PT and control group, there was no statistically significant difference, indicating that quality of life was not negatively affected in the CPP group receiving treatment.
Topics: Child; Humans; Puberty, Precocious; Quality of Life; Case-Control Studies; Surveys and Questionnaires
PubMed: 38375881
DOI: 10.1111/cen.15033 -
Indian Journal of Endocrinology and... 2023In this study, it was aimed to examine the clinical and laboratory findings that can be used to predict central precocious puberty (CPP) in cases whose breast...
AIM
In this study, it was aimed to examine the clinical and laboratory findings that can be used to predict central precocious puberty (CPP) in cases whose breast development started before the age of 8.
MATERIALS AND METHODS
The chronological age, anthropometric measurements, bone age (BA), hormone test results and pelvic ultrasonography findings of the cases were recorded. Those with a peak luteinizing hormone (LH) level of ≥5 IU/L in the gonadotropin-releasing hormone (GnRH) stimulation test were classified as CPP and those with a peak LH level of <5 IU/L were classified as prepubertal cases. A receiver operating characteristic (ROC) analysis was performed to determine the diagnostic accuracy of laboratory variables.
FINDINGS
A total of 297 female cases were included in the study. The age at the time of admission, height-standard deviation score (SDS), BA, the long axis of the uterus and the volumes of the right and left ovaries of the cases diagnosed with CPP were found to be significantly higher than those of the prepubertal group. The cut-off value providing the best sensitivity (99%) and specificity (99%) for the peak LH was found to be 4.55; the cut-off value providing the best sensitivity (94%) and specificity (85%) for the peak LH/follicle-stimulating hormone (FSH) ratio was found to be 0.32 and the cut-off value providing the best sensitivity (47%) and specificity (93%) for the basal LH was found to be 0.13.
CONCLUSION
We believe that in female cases with early breast development, a peak LH level of ≥4.55 may possibly indicate CPP and a basal LH level of <0.13 can significantly rule out CPP.
PubMed: 37583412
DOI: 10.4103/ijem.ijem_245_22 -
The British Journal of Dermatology Dec 2015Multiple congenital melanocytic naevi (CMN) is a rare mosaic RASopathy, caused by postzygotic activating mutations in NRAS. Growth and hormonal disturbances are...
BACKGROUND
Multiple congenital melanocytic naevi (CMN) is a rare mosaic RASopathy, caused by postzygotic activating mutations in NRAS. Growth and hormonal disturbances are described in germline RASopathies, but growth and hormone status have not previously been investigated in individuals with CMN.
OBJECTIVES
To explore premature thelarche, undescended testes, and a clinically abnormal fat distribution with CMN through prospective endocrinological assessment of a cohort of subjects with CMN, and a retrospective review of longitudinal growth of a larger group of patients with CMN from outpatient clinics (which included all subjects in the endocrinological assessment group).
PATIENTS AND METHODS
Longitudinal growth in a cohort of 202 patients with single or multiple CMN was compared with the U.K. National Child Measurement Programme 2010. Forty-seven children had hormonal profiling including measurement of circulating luteinizing hormone, follicle-stimulating hormone, thyroid stimulating hormone, adrenocorticotrophic hormone, growth hormone, prolactin, pro-opiomelanocortin, estradiol, testosterone, cortisol, thyroxine, insulin-like growth factor-1 and leptin; 10 had oral glucose tolerance testing 25 had dual-energy X-ray absorptiometry scans for body composition.
RESULTS
Body mass index increased markedly with age (coefficient 0·119, SE 0·016 standard deviation scores per year), at twice the rate of the U.K. population, due to increased adiposity. Three per cent of girls had premature thelarche variant and 6% of boys had persistent undescended testes. Both fat and muscle mass were reduced in areas underlying large naevi, resulting in limb asymmetry and abnormal truncal fat distribution. Anterior pituitary hormone profiling revealed subtle and variable abnormalities. Oral glucose tolerance tests revealed moderate-severe insulin insensitivity in five of 10, and impaired glucose tolerance in one.
CONCLUSIONS
Interpersonal variation may reflect the mosaic nature of this disease and patients should be considered individually. Postnatal weight gain is potentially related to the underlying genetic defect; however, environmental reasons cannot be excluded. Naevus-related reduction of fat and muscle mass suggests local hormonal or metabolic effects on development or growth of adjacent tissues, or mosaic involvement of these tissues at the genetic level. Premature thelarche and undescended testes should be looked for, and investigated, as for any child.
Topics: Absorptiometry, Photon; Adolescent; Case-Control Studies; Child; Child, Preschool; Cryptorchidism; Female; Glucose Tolerance Test; Growth Disorders; Hormones; Humans; Infant; Male; Nevus, Pigmented; Prospective Studies; Puberty; Puberty, Precocious
PubMed: 26286459
DOI: 10.1111/bjd.14091 -
Asian Biomedicine : Research, Reviews... Feb 2021The criterion standard gonadotropin-releasing hormone (GnRH) stimulation tests to diagnose central precocious puberty (CPP) are time-consuming, inconvenient, and...
BACKGROUND
The criterion standard gonadotropin-releasing hormone (GnRH) stimulation tests to diagnose central precocious puberty (CPP) are time-consuming, inconvenient, and expensive.
OBJECTIVES
To determine predictive cut-off values codetermined by ultrasonographic parameters and basal gonadotropin levels in girls with premature sexual development and compare them results of criterion standard tests in a study of diagnostic accuracy.
METHODS
Retrospective review of hormonal investigations and ultrasonographic uterine and ovarian parameters in a consecutive sample of girls at a single center, tertiary care hospital in Bangkok, Thailand.
RESULTS
We separated data from 68 girls (age range 2-12 years) into 2 groups based on their response to a GnRH analogue agonist stimulation test. A "prepubertal response" group included girls with premature thelarche and thelarche variants (n = 18, 6.37 ± 1.77 years) and a "pubertal response" group, including girls with CPP (n = 50, 8.46 ± 1.46 years); excluding patients with pathological causes (n = 0). The basal level of luteinizing hormone (LH) had the largest area under receiver operating characteristic curves (AUC) of 0.84; 95% confidence interval [CI] 0.74-0.93) compared with basal levels of follicle stimulating hormone (AUC 0.77; 95% CI 0.64-0.90) or estradiol (0.70; 95% CI 0.56-0.85). An optimal cut-off of 0.25 IU/L LH was related to a pubertal response to GnRH analogue agonist stimulation tests with 75.0% sensitivity, 88.9% specificity, 94.7% positive predictive value (PPV), and 57.1% negative predictive value. Uterine and ovarian cut-off volumes of 3.5 cm and 1.5 cm were related to a pubertal response with 88.6% and 76.2% PPV, respectively. A uterine width cut-off of 1.7 cm combined with a basal LH cut-off of 0.25 IU/L increased specificity and PPV to 100%.
CONCLUSION
Combining uterine and ovarian ultrasonographic parameters with basal gonadotropin levels, especially uterine width and basal LH level, appears useful for diagnosis of CPP.
PubMed: 37551300
DOI: 10.2478/abm-2021-0004 -
Peptides Feb 2015The 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...
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.
Topics: Biomarkers; Child; Child, Preschool; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Humans; Kisspeptins; Leptin; Neurokinin B; Puberty, Precocious
PubMed: 25572302
DOI: 10.1016/j.peptides.2014.12.011 -
Journal of Pediatric Endocrinology &... Nov 2015The possible difference of antimüllerian hormone (AMH) levels at central precocious puberty (CPP) and premature thelarche (PT) has not been properly evaluated.
BACKGROUND
The possible difference of antimüllerian hormone (AMH) levels at central precocious puberty (CPP) and premature thelarche (PT) has not been properly evaluated.
OBJECTIVE/HYPOTHESIS
By evaluating AMH levels in girls with diagnosed CPP and PT, we aim to show the change of AMH levels at the pubertal onset.
SUBJECTS
Sixty-five girls who have breast development before the age of 8 years and 25 healthy girls were enrolled in the study.
METHODS
The subjects were divided into two groups as CPP and PT, according to results of GnRH test. AMH levels were determined in the two groups.
RESULTS
The mean AMH levels of the CPP group were significantly lower than those in the PT group (13.57±9.85 pmol/L and 58.42±12.78 pmol/L, respectively, p=0.022).
CONCLUSION
These results suggest that the AMH levels decrease in the duration of the hypothalamus-pituitary-ovarian axis activation. We thought that AMH might/may be a marker for distinguishing between CPP and PT.
Topics: Anti-Mullerian Hormone; Biomarkers; Breast; Child; Child, Preschool; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Puberty, Precocious
PubMed: 26226120
DOI: 10.1515/jpem-2014-0521 -
Frontiers in Endocrinology 2022To investigate the associations between physical and pubertal development based on the breast development outcomes in girls.
OBJECTIVE
To investigate the associations between physical and pubertal development based on the breast development outcomes in girls.
METHODS
This was a retrospective study. A total of 452 girls aged 6~8 years were included. Based on their breast development outcomes, the patients were divided into an idiopathic central precocious puberty (ICPP) group and a premature thelarche (PT) group. Anthropometry included measurements of height, weight, and BMI. ICPP was diagnosed when five diagnostic criteria from the current guidelines were met.
RESULTS
The girls with breast development at initial evaluation had a median age of 6.9 years. In total, 31.4% of patients were diagnosed with ICPP, and ICPP was rare in girls <7 years old (19%). Patients who presented with recurrence of breast development in the PT group accounted for 38.4%. At initial evaluation, the height, weight, BMI and bone age (BA) of the girls in the PT group corresponded to those of a normally developing girl at ages 7.8 years, 8.2 years, 8.6 years and 7.6 years, respectively. The girls in the ICPP group had a mean age of 7.3 years, and their mean height, weight, and BMI were 129.6 cm, 28.4 kg, and 17.0 kg/m, which corresponded to the mean of a normally developing girl at ages 8.5 years, 9.1 years, and 10.5 years, respectively; these patients had BA of 9.2 years. Additionally, based on receiver operating characteristic (ROC) curve analysis, when the basal luteinizing hormone (LH) level was 0.32 IU/L and BMI reached 16.4 kg/m, CPP was diagnosed in patients meeting all five diagnostic criteria for CPP, and the specificity and sensitivity were 71.9% and 88.2%, respectively.
CONCLUSIONS
Girls with breast development before 8 years old had a high proportion of recurrence of breast development. The physical development of these girls at the time of breast development preceded that of normally developing girls by 1-2 years. BMI is an independent risk factor for early pubertal development, and is a simple and clear predictor of ICPP. In addition to the five classic diagnostic criteria, CPP is diagnosed when physical development corresponds to the mean for a 10.5 years old girl.
Topics: Female; Humans; Child; Body Mass Index; Luteinizing Hormone; Retrospective Studies; Puberty, Precocious; Body Height
PubMed: 36339403
DOI: 10.3389/fendo.2022.991908