-
Clinical and Experimental Pediatrics Jun 2024Kisspeptin and delta-like 1 homolog (DLK1) are neuropeptides that reportedly play an important role in pubertal timing by activating and inhibiting the...
BACKGROUND
Kisspeptin and delta-like 1 homolog (DLK1) are neuropeptides that reportedly play an important role in pubertal timing by activating and inhibiting the hypothalamic-pituitary-gonadal axis, respectively. Consequently, serum kisspeptin and DLK1 levels may be novel biomarkers for differentiating between central precocious puberty (CPP) and premature thelarche (PT) in girls and used to monitor CPP treatment.
PURPOSE
To compare baseline serum kisspeptin and DLK1 levels in girls with CPP at diagnosis and after treatment to age-matched girls with PT.
METHODS
This prospective longitudinal study included girls with precocious puberty and girls with PT who experienced breast development before 8 years of age and peak luteinizing hormone levels of ≥6 versus <6 IU/L after a gonadotropin-releasing hormone (GnRH) stimulation test. Serum kisspeptin and DLK1 levels were determined in both groups at baseline and after 6 months of GnRH analog treatment in the CPP group and analyzed by enzyme-linked immunosorbent assay.
RESULTS
The study divided a total of 48 girls into CPP (n=24; mean age, 7.7±0.7 years) and PT (n=24; mean age, 7.4±0.8 years) groups. The baseline median serum kisspeptin levels were 50.5 pg/mL (range, 38.2-77 pg/mL) and 49.5 pg/mL (range, 39.7-67.6 pg/mL), respectively (P=0.89), while the baseline median serum DLK1 levels were 6.5 ng/mL (range, 5.9-7.5 ng/mL) and 6 ng/mL (4.4-14.4 ng/mL), respectively (P=0.68). After 6 months of GnRH analog treatment in the CPP group, the median serum kisspeptin level was lower (46.4 ng/mL; range, 37.1-60 ng/mL) than that at baseline (P=0.002), while the median serum DLK1 level was higher (7 ng/mL; range, 6.7-8.9) than that at baseline (P=0.002).
CONCLUSION
Our findings suggest that baseline serum kisspeptin and DLK1 levels are not reliable biomarkers for differentiating between CPP and PT. However, significant changes in serum kisspeptin and DLK1 levels may be used to monitor CPP treatment.
PubMed: 38772409
DOI: 10.3345/cep.2023.01361 -
European Review For Medical and... Oct 2023Although there is a relationship between earlier onset of puberty and increased adiposity tissue. Publications in the literature on adiposis in patients with central...
OBJECTIVE
Although there is a relationship between earlier onset of puberty and increased adiposity tissue. Publications in the literature on adiposis in patients with central precocious puberty (CPP) and visceral fat thickness (VFT) have conflicting results. So, in this study, we aimed to evaluate the relationship between sexual maturation and obesity in the development of early puberty and to examine their relationship with pelvic sonographic parameters.
PATIENTS AND METHODS
A total of 126 girls [patients - premature thelarche (PT) and CPP - and controls] were included in this study. Anthropometric and ultrasonographic evaluations were made by the same pediatric endocrinologist and pediatric radiologist, respectively. Pubertal stages were made according to the Tanner stages. Height, weight, and body mass index were measured as anthropometric measurements, and visceral, subcutaneous, and transabdominal fat thicknesses were measured in sonographic evaluation.
RESULTS
The study population was divided into three groups: 44 healthy subjects to Group 1, 23 patients with PT to Group 2, and 59 patients with CPP to Group 3. When we evaluated the anthropometric and ultrasonographic parameters according to pubertal status, significant differences, especially between Group 1 and Group 3, were observed in all data. In the multiple logistic regression analysis, the endometrial thickness (OR = 7.521, p < 0.001) and VFT (OR = 1.530, p < 0.001) were found to be independent predictors of precocious puberty.
CONCLUSIONS
It has been found that VFT and endometrial thickness measurements, which are evaluated quickly and accurately by USG, are important predictors of prepubertal precociousness.
Topics: Child; Female; Humans; Puberty, Precocious; Intra-Abdominal Fat; Puberty; Anthropometry; Obesity
PubMed: 37843336
DOI: 10.26355/eurrev_202310_33950 -
Italian Journal of Pediatrics Aug 2023Diagnosing central precocious puberty (CPP) requires an integrated approach based on clinical, biochemical and instrumental data. The diagnostic gold standard is...
BACKGROUND
Diagnosing central precocious puberty (CPP) requires an integrated approach based on clinical, biochemical and instrumental data. The diagnostic gold standard is represented by GnRH (gonadotropin-releasing hormone) stimulation test. Some undoubted limitations of this procedure led the international scientific community to look for cheaper and less invasive alternative diagnostic methods, such as luteinizing hormone urinary levels (uLH) measurement. This study aims to define the reliability of urinary LH levels as a biomarker of pubertal development, both concerning the initial diagnostic management and the monitoring of patients with central precocious puberty undergoing therapy with GnRH analogues. Furthermore, the study plans to detect the potential association between LH peak serum (pLH) and urinary LH in patients undergoing diagnostic tests with GnRH and to identify a possible cut-off of uLH that may be suggestive of ensued successful hormonal stimulation.
METHODS
The study includes 130 female patients with suspected precocious puberty or in follow-up during suppressive therapy. After the collection of the informed consent, the patients underwent clinical evaluation, auxological assessment, and hormone assays (basal levels of LH, FSH, and oestradiol; GnRH stimulating test in patients with suspected precocious puberty; urinary LH assay on the first-morning urine sample, collected after waking up).
RESULTS
Two uLH cut-off values have been identified: the first of 0.25 UI/L [C.I. 95% 0.23-0.27], able to distinguish between pubertal and pre-pubertal patients, the second of 0.45 UI/L [C.I. 95% 0,20 - 0,70] suggestive of occurred hormonal stimulation in patients with diagnosis of CPP at GnRH test. All 30 patients with CPP in follow-up during suppressive therapy presented uLH values ≤ 0.45 IU/L (p < 0.05), and uLH collected in prepubertal group control.
CONCLUSIONS
uLH assays on the first morning urine specimen could be considered a low-cost and minimally invasive tool for precocious puberty diagnosing and monitoring, making possible to be easily performed even by a general pediatrician. Thus, this could help referring only selected patients to pediatric endocrinologists. After an appropriate validation, this approach could reasonably reduce hospital attendance and costs of performing more invasive procedures, with a more significant emotional impact on the pediatric patient.
Topics: Humans; Child; Female; Puberty, Precocious; Reproducibility of Results; Urinary Tract; Gonadotropin-Releasing Hormone; Luteinizing Hormone
PubMed: 37605205
DOI: 10.1186/s13052-023-01506-8 -
Journal of Hazardous Materials Jan 2024The prevalence of precocious puberty and the consumption of nonnutritive sweeteners (NNS) is rapidly growing worldwide. However, the effects of NNSs on precocious...
The prevalence of precocious puberty and the consumption of nonnutritive sweeteners (NNS) is rapidly growing worldwide. However, the effects of NNSs on precocious puberty remain unclear. We examined the impact of acesulfame potassium (AceK), one of the most widely used NNS, on central precocious puberty (CPP) development using ex vivo and in vitro studies. 884 girls aged 6-12 were enrolled with complete AceK consumption data and CPP outcome assessment in the Taiwan Pubertal Longitudinal Study from 2018 to 2022. After adjustment for confounders, compared with no AceK consumption, AceK consumption at more than the median dose was associated with higher CPP risk in girls (odds ratio = 1.88, 95% confidence interval = 1.16-3.06; p for trend = 0.003). In rats, AceK consumption from in-utero to post-weaning stages accelerated puberty onset, accompanied by increased brain gonadotropin-releasing hormone (GnRH) expression. Intracerebroventricular AceK injection also induced early puberty onset in rats. In N44 hypothalamic neuron cells, AceK treatment increased reactive oxygen species production, which led to protein kinase A (PKA) activation and increased GnRH expression. These findings suggest that prepubertal girls should consume soft drinks or food products containing AceK more cautiously.
Topics: Humans; Female; Animals; Rats; Puberty, Precocious; Luteinizing Hormone; Follicle Stimulating Hormone; Longitudinal Studies; Sweetening Agents; Gonadotropin-Releasing Hormone
PubMed: 37738850
DOI: 10.1016/j.jhazmat.2023.132529 -
Toxins Aug 2023Fungi such as spp. and spp., which are commonly found in the environment, pose a serious global health problem. This study aims to present the results of... (Review)
Review
Fungi such as spp. and spp., which are commonly found in the environment, pose a serious global health problem. This study aims to present the results of epidemiological studies, including clinical cases, on the relationship between human exposure to some mycotoxins, especially zearalenone and aflatoxin, and the occurrence of reproductive disorders. In addition, examples of methods to reduce human exposure to mycotoxins are presented. In March 2023, various databases (PubMed, Google Scholar, EMBASE and Web of Science) were systematically searched using Google Chrome to identify studies evaluating the association between exposure to mycotoxins and the occurrence of complications related to impaired fertility or cancer incidence. The analysed data indicate that exposure to the evaluated mycotoxins is widespread and correlates strongly with precocious puberty, reduced fertility and increased cancer incidence in women and men worldwide. There is evidence to suggest that exposure to the Aspergillus mycotoxin aflatoxin (AF) during pregnancy can impair intrauterine foetal growth, promote neonatal jaundice and cause perinatal death and preterm birth. In contrast, exposure to the Fusarium mycotoxin zearalenone (ZEA) leads to precocious sexual development, infertility, the development of malformations and the development of breast cancer. Unfortunately, the development of methods (biological, chemical or physical) to completely eliminate exposure to mycotoxins has limited practical application. The threat to human health from mycotoxins is real and further research is needed to improve our knowledge and specific public health interventions.
Topics: Female; Humans; Infant, Newborn; Male; Pregnancy; Aflatoxins; Aspergillus; Food Contamination; Fusarium; Mycotoxins; Premature Birth; Zearalenone
PubMed: 37755941
DOI: 10.3390/toxins15090515 -
BMC Psychiatry Oct 2023Precocious puberty in girls has been associated with an increased risk of stress and anxiety in their mothers. This study aimed to investigate the effect of cognitive... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Precocious puberty in girls has been associated with an increased risk of stress and anxiety in their mothers. This study aimed to investigate the effect of cognitive behavioral therapy (CBT) on perceived stress and anxiety of mothers of girls with precocious puberty symptoms.
METHODS
This randomized controlled trial was conducted on 70 mothers of girls with precocious puberty symptoms in Tabriz-Iran, 2021. The participants were randomly assigned to CBT and control groups through blocked randomization. Group counseling was provided to the intervention group in eight sessions of 45-60 min weekly with 5 to 7 women. A booklet containing explanations about puberty was provided for the both groups. Data were collected using the questionnaires of socio-demographic characteristics, Spielberger State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS) and quality of life (SF-36). Independent t-test, ANCOVA, chi-square, and fisher's exact tests were used to compare the outcomes between the groups.
FINDINGS
After the intervention, based on ANCOVA test with adjusting the baseline values, mean scores of stress (mean difference (MD): -10.75; 95% confidence interval (95% CI): -11.77 to -9.72; P < 0.001), state anxiety (MD: -14.36; 95% CI: -15.7 to -12.7; P < 0.001) and trait anxiety (MD: -12.8; 95% CI: -14.4 to -11.1; P < 0.001) were significantly lower in CBT group compared to the control group. Also mean score of quality of life (MD: 9.82; 95% CI: -6.74 to -12.90; P < 0.001) was significantly higher in CBT group compared to the control group.
CONCLUSION
Based on the results, group CBT is effective in reducing stress and anxiety and improving the quality of life of mothers of girls with precocious puberty symptoms. However, more studies are required to make a definite conclusion in this field.
TRIAL REGISTRATION
Iranian Registry of Clinical Trials (IRCT): IRCT20110826007418N6. Date of registration: 11/10/2021. URL: https://en.irct.ir/trial/57346 ; Date of first registration: 11/10/2021.
Topics: Female; Humans; Quality of Life; Puberty, Precocious; Iran; Anxiety; Cognitive Behavioral Therapy; Surveys and Questionnaires
PubMed: 37817169
DOI: 10.1186/s12888-023-05216-7 -
Journal of Pediatric Endocrinology &... Aug 2023Case reports show hypertension in children treated with GnRH analogues for central precocious puberty (CPP). However, relevant data on blood pressure are scarce. We...
OBJECTIVES
Case reports show hypertension in children treated with GnRH analogues for central precocious puberty (CPP). However, relevant data on blood pressure are scarce. We aimed to evaluate blood pressure (BP) among girls with idiopathic CPP and early-onset puberty before and during GnRH analogue therapy; and to examine associations of blood pressure with clinical parameters.
METHODS
For this retrospective longitudinal cohort study, demographic, anthropometric, clinical, and laboratory data were collected from electronic files. The study group included 112 girls with idiopathic CPP or early-onset puberty followed in a tertiary pediatric endocrinology institute, and a control group of 37 healthy pre-pubertal girls. The main outcome measures were BP percentile, before, and during treatment with GnRH analogue.
RESULTS
At baseline, similar proportions of the study and control groups had BP values>90th percentile: 64 (53 %) and 17 (46 %), respectively (p=0.57). The mean systolic and diastolic BP percentiles measured under treatment remained unchanged. In the study group, baseline BP>90th percentile compared to normal baseline BP was associated with lower birthweight and a higher body mass index-standard deviation score: 2,821 ± 622 vs. 3,108 ± 485 g and 1.0 ± 0.7 vs. 0.70 ± 0.8, respectively, p=0.01 for both.
CONCLUSIONS
GnRH analogue therapy for precocious or early puberty was not associated with increased blood pressure. The stability of mean blood pressure percentile during treatment is reassuring.
Topics: Child; Female; Humans; Puberty, Precocious; Gonadotropin-Releasing Hormone; Longitudinal Studies; Retrospective Studies; Blood Pressure; Immunologic Factors
PubMed: 37392130
DOI: 10.1515/jpem-2023-0118 -
Pediatric Research Mar 2024Precocious puberty is an endocrine disease that is diagnosed by sex, age, and Tanner stage of puberty. This study aimed to investigate the association between various...
BACKGROUND
Precocious puberty is an endocrine disease that is diagnosed by sex, age, and Tanner stage of puberty. This study aimed to investigate the association between various dietary patterns and early or precocious puberty, especially Traditional dietary patterns, which have been rarely investigated.
METHODS
A total of 4085 primary school students in grades 1-3 (6-9 years) completed individual characteristic surveys, health examinations, and food frequency questionnaires (FFQs). Physical examinations were also conducted to assess obesity and pubertal onset. Traditional, Westernized, and Protein dietary patterns were determined by factor analysis, and their associations with pubertal onset were analyzed by multiple logistic regression analysis.
RESULTS
Compared to the other two patterns, children who predominant the Traditional dietary pattern were protectively associated with precocious puberty (OR = 0.72, 95% CI = 0.55, 0.94), even after adjusting the confounders (OR = 0.66, 95% CI = 0.48, 0.89). Neither the Westernized nor Protein dietary pattern demonstrated an association with pubertal onset. The Traditional dietary pattern was negatively associated with children's weight status, classified by body mass index (BMI), and was positively associated with parental education. The maternal education and the Protein dietary pattern were negatively related.
CONCLUSIONS
Traditional dietary patterns were protective associated with early and precocious puberty among Chinese children.
IMPACT
The Traditional dietary pattern was protective associated with early puberty or precocious puberty in children, as found in large-scale population-based public health research. Current research primarily focuses on Westernized dietary patterns, and we studied Traditional dietary patterns to further explore the influence of food on children's puberty development. We discovered that children's preference for Traditional dietary patterns is protective of pubertal development, which implies that society and parents can benefit from diet guidance to protect children's natural development during adolescence.
PubMed: 38431666
DOI: 10.1038/s41390-024-03110-w -
Nutrients May 2024The onset of puberty, which is under the control of the hypothalamic-pituitary-gonadal (HPG) axis, is influenced by various factors, including obesity, which has been... (Review)
Review
The onset of puberty, which is under the control of the hypothalamic-pituitary-gonadal (HPG) axis, is influenced by various factors, including obesity, which has been associated with the earlier onset of puberty. Obesity-induced hypothalamic inflammation may cause premature activation of gonadotropin-releasing hormone (GnRH) neurons, resulting in the development of precocious or early puberty. Mechanisms involving phoenixin action and hypothalamic microglial cells are implicated. Furthermore, obesity induces structural and cellular brain alterations, disrupting metabolic regulation. Imaging studies reveal neuroinflammatory changes in obese individuals, impacting pubertal timing. Magnetic resonance spectroscopy enables the assessment of the brain's neurochemical composition by measuring key metabolites, highlighting potential pathways involved in neurological changes associated with obesity. In this article, we present evidence indicating a potential association among obesity, hypothalamic inflammation, and precocious puberty.
Topics: Humans; Pediatric Obesity; Hypothalamus; Child; Puberty, Precocious; Puberty; Inflammation; Female; Gonadotropin-Releasing Hormone; Male; Hypothalamo-Hypophyseal System
PubMed: 38892653
DOI: 10.3390/nu16111720 -
The Journal of Clinical Endocrinology... Jan 2024Children with congenital adrenal hyperplasia (CAH) are at risk for early puberty. Gonadotropin-releasing hormone analog (GnRHa) is frequently used and can decrease bone...
CONTEXT
Children with congenital adrenal hyperplasia (CAH) are at risk for early puberty. Gonadotropin-releasing hormone analog (GnRHa) is frequently used and can decrease bone mineral density (BMD).
OBJECTIVE
Our aim was to investigate the effect of GnRHa therapy on BMD in a longitudinal study of patients with CAH spanning both childhood and adulthood.
DESIGN AND SETTING
Sixty-one patients with classic CAH due to 21-hydroxylase deficiency (20 treated with GnRHa) were followed with dual-energy X-ray absorptiometry (DXA) scans at puberty onset, attainment of adult height, and during early adulthood.
MAIN OUTCOME MEASURES
Whole body, lumbar spine, femoral neck, total hip, and distal radius BMD z-score at adult height. Longitudinal BMD and adult height were also assessed.
RESULTS
Twenty patients received GnRHa for an average of 4.5 ± 2 years. There were no differences in BMD between GnRHa-treated and -untreated groups at adult height for all sites. Overall, the follow-up DXA during early adulthood showed decreases in BMD z-scores for whole body (P = .01), lumbar spine (P < .0001), femoral neck (P = .06), total hip (P = .009), and distal radius (P = .05). GnRHa treatment correlated with improved height outcomes compared to predicted height at puberty onset after adjusting for midparental height (P = .02). Patients in both groups achieved similar adult height.
CONCLUSION
In children with CAH, GnRHa does not compromise BMD. However, BMD decreases with time and during the second and third decades of life is a possible effect of chronic supraphysiologic glucocorticoids. Children with CAH who experience early puberty benefit from GnRHa treatment as evidenced by the positive effect on height.
Topics: Child; Adult; Humans; Adrenal Hyperplasia, Congenital; Bone Density; Longitudinal Studies; Gonadotropins; Puberty, Precocious; Lumbar Vertebrae; Gonadotropin-Releasing Hormone; Body Height
PubMed: 37643900
DOI: 10.1210/clinem/dgad514