-
Indian Journal of Pediatrics Mar 2015To estimate the association between serum bisphenol A and premature thelarche in female infants aged 4-mo to 2-y.
OBJECTIVES
To estimate the association between serum bisphenol A and premature thelarche in female infants aged 4-mo to 2-y.
METHODS
A total of 251 female infants (aged 4 mo to 2 y) with premature thelarche and 33 healthy age-matched control subjects were analyzed. All participants underwent physical examination and serum bisphenol A was measured by ultra-performance liquid chromatography tandem mass spectrometry.
RESULTS
Serum bisphenol A concentration in the premature thelarche group (3.48 ng/ml, 95%CI: 0.09-140.26) was significantly higher than that in the control group (1.70 ng/ml, 95%CI: 0.06-51.78) (p = 0.039). There was no correlation between age and serum bisphenol A (BPA) level. Univariate logistic regression analysis showed that serum BPA concentration positively associated with premature thelarche, and the effect of BPA fell down as the age grew.
CONCLUSIONS
This hospital-based study implied that there is an association between serum BPA concentrations and premature thelarche. Additionally, serum BPA levels were markedly higher in infants aged 4-mo to 2-y-old, raising a concern for public health authorities.
Topics: Benzhydryl Compounds; Breast; China; Chromatography, Liquid; Female; Humans; Infant; Phenols; Puberty, Precocious; Statistics as Topic
PubMed: 25120062
DOI: 10.1007/s12098-014-1548-7 -
International Journal of Environmental... Sep 2017Many scientific studies have revealed a trend towards an earlier onset of puberty and have disclosed an increasing number of children that display precocious puberty. As... (Review)
Review
Many scientific studies have revealed a trend towards an earlier onset of puberty and have disclosed an increasing number of children that display precocious puberty. As an explanation, some authors have considered the global socio-economic improvement across different populations, and other authors have considered the action of endocrine disrupting chemicals (EDCs). Among these, bisphenol A (BPA), an aromatic compound largely used worldwide as a precursor of some plastics and chemical additives, is well known for its molecular oestrogen-like and obesogenic actions. We reviewed the medical literature of the previous 20 years that examined associations between BPA exposure and the age of puberty in humans, considering only those referring to clinical or epidemiological data. Of 19 studies, only 7 showed a correlation between BPA and puberty. In particular, the possible disruptive role of BPA on puberty may be seen in those with central precocious puberty or isolated premature breast development aged 2 months to 4 years old, even if the mechanism is undefined. Some studies also found a close relationship between urinary BPA, body weight, and early puberty, which can be explained by the obesogenic effect of BPA itself. The currently available data do not allow establishment of a clear role for BPA in pubertal development because of the conflicting results among all clinical and epidemiological studies examined. Further research is needed to fully understand the potential role of exposure to EDCs and their adverse endocrine health outcomes.
Topics: Benzhydryl Compounds; Endocrine Disruptors; Environmental Pollutants; Female; Humans; Male; Phenols; Puberty; Puberty, Precocious
PubMed: 28891963
DOI: 10.3390/ijerph14091044 -
Frontiers in Endocrinology 2021The gonadotropin-releasing hormone (GnRH) stimulation test is the benchmark for diagnosing precocious puberty (PP). However, it is invasive, time-consuming, costly, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The gonadotropin-releasing hormone (GnRH) stimulation test is the benchmark for diagnosing precocious puberty (PP). However, it is invasive, time-consuming, costly, and may create an unpleasant experience for participants. Moreover, some overlaps may occur between PP and premature thelarche (PT) in the early stage of PP. Female pelvic ultrasonography may provide additional information to help differentiate PP from PT and subsequently initiate early treatment. In this study, we aimed to first directly compare pelvic ultrasonography parameters between PP and PT groups and secondly, investigate their diagnostic accuracy compared with the GnRH stimulation test.
METHODS
A systematic search of the PubMed/MEDLINE, EMBASE, Scopus, and Cochrane Library databases was performed up to March 31, 2021. All types of studies, except for case reports and review articles, were included. The GnRH stimulation test was used to confirm PP diagnosis. Those whose organic conditions might cause PP were excluded. The mean, standard deviation, sensitivity, and specificity of each parameter were documented. Forest plots were constructed to display the estimated standardized mean differences (SMDs) from each included study and the overall calculations. A bivariate model was used to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR).
RESULTS
A total of 13 studies were included for analysis. The SMDs (95% confidence interval - CI) in ovarian volume, fundal-cervical ratio, uterine length, uterine cross-sectional area, and uterine volume between PP and PT groups were 1.12 (0.78-1.45; p < 0.01), 0.90 (0.07-1.73; p = 0.03), 1.38 (0.99-1.78; p < 0.01), 1.06 (0.61-1.50; p < 0.01), and 1.21 (0.84-1.58; p <0.01), respectively. A uterine length of 3.20 cm yielded a pooled sensitivity of 81.8% (95% CI 78.3%-84.9%), specificity of 82.0% (95% CI 61.0%-93.0%), PLR of 4.56 (95% CI 2.15-9.69), NLR of 0.26 (95% CI 0.17-0.39), and DOR of 19.62 (95% CI 6.45-59.68). The area under the summary receiver operating characteristics curve was 0.82.
CONCLUSION
Female pelvic ultrasonography may serve as a complementary tool to the GnRH stimulation test in differentiating PP from PT.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021232427, ID: CRD42021232427.
Topics: Child; Diagnosis, Differential; Female; Humans; Puberty, Precocious; Sensitivity and Specificity; Ultrasonography; Uterus
PubMed: 34539579
DOI: 10.3389/fendo.2021.735875 -
Archives of Endocrinology and Metabolism Apr 2016Clinical and laboratory diagnosis and treatment of central precocious puberty (CPP) remain challenging due to lack of standardization. The aim of this revision was to... (Review)
Review
Clinical and laboratory diagnosis and treatment of central precocious puberty (CPP) remain challenging due to lack of standardization. The aim of this revision was to address the diagnostic and therapeutic features of CPP in Brazil based on relevant international literature and availability of the existing therapies in the country. The diagnosis of CPP is based mainly on clinical and biochemical parameters, and a period of follow-up is desirable to define the "progressive" form of sexual precocity. This occurs due to the broad spectrum of pubertal development, including isolated premature thelarche, constitutional growth and puberty acceleration, progressive and nonprogressive CPP, and early puberty. Measurement of basal and stimulated LH levels remains challenging, considering that the levels are not always in the pubertal range at baseline, short-acting GnRH is not readily available in Brazil, and the cutoff values differ according to the laboratory assay. When CPP is suspected but basal LH values are at prepubertal range, a stimulation test with short-acting or long-acting monthly GnRH is a diagnostic option. In Brazil, the treatment of choice for progressive CPP and early puberty is a long-acting GnRH analog (GnRHa) administered once a month or every 3 months. In Brazil, formulations of GnRHa (leuprorelin and triptorelin) are available and commonly administered, including 1-month depot leuprorelin 3.75 mg and 7.5 mg, 1-month depot triptorelin 3.75 mg, and 3-month depot leuprorelin 11.25 mg. Monthly or 3-month depot GnRHa are effective and safe to treat CPP. Arch Endocrinol Metab. 2016;60(2):163-72.
Topics: Age Factors; Anthropometry; Brazil; Female; Gonadotropin-Releasing Hormone; Hormone Replacement Therapy; Humans; Luteinizing Hormone; Male; Puberty, Precocious; Sex Factors
PubMed: 27191050
DOI: 10.1590/2359-3997000000144 -
Obstetrics and Gynecology Jun 2017Premature thelarche is a self-limited condition characterized by Tanner stage II-III breast development in girls younger than 8 years of age with no evidence of...
BACKGROUND
Premature thelarche is a self-limited condition characterized by Tanner stage II-III breast development in girls younger than 8 years of age with no evidence of advancing puberty. Evaluation concentrates on excluding central or peripheral causes of precocious puberty.
CASE
A girl aged 2 years 4 months with profound hypotonia and delayed developmental milestones presented with Tanner II breast development, elevated follicle-stimulating hormone levels, suppressed luteinizing hormone level, normal growth and skeletal development, and prepubertal uterine length and ovarian volume. Monitoring until 8 years of age revealed no pubertal progression. Whole exome sequencing at 8 years revealed an autosomal-dominant mutation in the purine-rich element-binding protein A (PURA) gene. Previous patients with PURA syndrome have had pituitary dysfunction and precocious puberty.
CONCLUSION
Purine-rich element-binding protein A syndrome can be associated with premature thelarche.
Topics: Breast; Child, Preschool; DNA-Binding Proteins; Diagnosis, Differential; Female; Gonadotropins, Pituitary; Humans; Puberty, Precocious; Syndrome; Transcription Factors
PubMed: 28486374
DOI: 10.1097/AOG.0000000000002047 -
Journal of the College of Physicians... Feb 2015To determine the etiology of precocious puberty in children and to compare the clinical and laboratory parameters of central and peripheral precocious puberty.
OBJECTIVE
To determine the etiology of precocious puberty in children and to compare the clinical and laboratory parameters of central and peripheral precocious puberty.
STUDY DESIGN
Cross-sectional study.
PLACE AND DURATION OF STUDY
Endocrine Clinic at National Institute of Child Health, Karachi, from January 2009 to December 2011.
METHODOLOGY
Children presenting with precocious puberty were included. The age of onset of puberty was documented. Clinical evaluation, Tanner staging, height, height SDS, weight, weight SDS, body mass index, bone age, pelvic USG, plasma estradiol level and GnRH stimulation were done. Ultrasound of adrenal glands, serum level of 17 hydroxyprogesterone, ACTH, Renin, aldosterone and testosterone were performed in children with peripheral precocious puberty. MRI of adrenal glands and gonads was done in patients with suspected tumor of that organ and MRI of brain was done in patients with central precocious puberty. Skeletal survey was done in patients with Mc Cune-Albright syndrome.
RESULTS
CAH (81.8%) indentified as a main cause in peripheral percocious puberty and idiopathic (67.74%) in central precocious puberty. Eighty five patients were registered during this period. The conditions causing precocious puberty were central precocious puberty (36.47%), peripheral precocious puberty (38.82%), premature pubarche (10.58%) and premature thelarche (14.11%). There was a difference in the age of onset of puberty in case of central precocious puberty (mean=3, 2-6 years) versus peripheral precocious puberty (mean=5.25; 3.62 - 7.0 years). Children with central precocious puberty showed higher height SDS, weight SDS, FSH, LH than those with peripheral precocious puberty.
CONCLUSION
Etiology in majority of cases with peripheral precocious puberty was congenital adrenal hyperplasia and idiopathic in central precocious puberty. Central precocious puberty children showed higher height SDS, weight SDS, FSH, LH than peripheral precocious puberty.
Topics: 17-alpha-Hydroxyprogesterone; Adrenocorticotropic Hormone; Body Mass Index; Body Weight; Child; Child, Preschool; Cross-Sectional Studies; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infant; Male; Pakistan; Puberty, Precocious; Sex Distribution; Testosterone
PubMed: 25703757
DOI: No ID Found -
Gynecological Endocrinology : the... Oct 2017Premature thelarche (PT) is a benign, nonprogressive condition defined as isolated breast development. While the pathophysiology of PT remains unclear, increased...
OBJECTIVE
Premature thelarche (PT) is a benign, nonprogressive condition defined as isolated breast development. While the pathophysiology of PT remains unclear, increased sensitivity to estrogen may cause PT. The aim of this study was to investigate the association between polymorphisms in the estrogen receptor alpha (ERα) gene and PT in girls.
METHODS
In this case-control study, we examined 96 girls referred for early breast development (before the age of 8 years). The control group included healthy Korean females with normal pubertal progression. Anthropometric and hormonal parameters were measured and PvuII and XbaI ERα gene polymorphisms were evaluated by PCR. Out of the 96 girls, all coding exon and exon-intron boundaries of ERα were sequenced from the DNA of 46 girls.
RESULTS
There was no significant difference in the distribution of PvuII and XbaI polymorphisms between patients and controls. However, the carriers of XbaI polymorphisms had more advanced Tanner stage than did the non-carriers. Also, four ERα gene polymorphisms were previously identified, but these polymorphisms had no clinical significance.
CONCLUSION
No association was found between the ERα gene polymorphisms and PT in girls. However, XbaI polymorphisms may contribute to early breast budding.
Topics: Breast; Case-Control Studies; Child; DNA-Cytosine Methylases; Deoxyribonucleases, Type II Site-Specific; Estrogen Receptor alpha; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Polymorphism, Restriction Fragment Length; Puberty, Precocious
PubMed: 28440677
DOI: 10.1080/09513590.2017.1318374 -
Acta Bio-medica : Atenei Parmensis Dec 2023The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to...
BACKGROUND
The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to comprehensively analyze and summarize research articles to elucidate the potential link between precocious or early pubertal onset (CPP) and crucial health factors.
METHODS
We conducted a systematic review of studies published from -January 2000 to March 2023, sourced from databases of Medline, PubMed, Google Scholar and Web of Science. We assessed the relationship between CPP and final adult height (FHt), bone health, reproductive function, body mass index, metabolic and cardiovascular abnormalities, and increased cancer risk.
RESULTS
Upon reviewing and analyzing selected studies, the following key findings emerged: (a) treating CPP in girls before age 6-7 and in boys before age 9 improves FHt; (b) bone mineral density (BMD) decreases during GnRHa treatment but normalizes afterward, with no lasting effects on peak bone mass during puberty; (c) GnRH treatment does not negatively affect menstrual cycles; however, untreated CPP increases the risk of premature or early-onset menopause; (d) the incidence of PCOS/hyperandrogenemia may be slightly elevated in women with a history of CPP, but overall reproductive function remains largely unaffected; (e) earlier thelarche and menarche may enhance susceptibility to breast carcinogenesis; (f) CPP contributes to an increased risk of obesity and type 2 diabetes in both genders; (g) early menarche may slightly increase the risk of coronary heart disease and ischemic strokes and (h) early pubertal timing increases the risk of depression and anxiety disorders.
CONCLUSION
Monitoring and early diagnosis of these conditions are of paramount importance for successful management.
Topics: Female; Humans; Male; Child; Diabetes Mellitus, Type 2; Gonadotropin-Releasing Hormone; Puberty, Precocious; Obesity; Puberty
PubMed: 38054666
DOI: 10.23750/abm.v94i6.15316 -
Endocrine Mar 2022Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). However, intravenous GnRH is not always...
PURPOSE
Gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). However, intravenous GnRH is not always readily available. The aim of the present study was to evaluate the diagnostic accuracy of triptorelin-stimulated luteinizing hormone (LH) concentrations in the diagnosis of CPP among girls presenting with premature thelarche compared to the gold standard GnRH test.
METHODS
A prospective, case-control (CPP vs isolated premature thelarche), clinical study evaluating the diagnostic accuracy of triptorelin-stimulated LH concentrations in 60 girls with premature thelarche was performed. All girls underwent stimulation with subcutaneous triptorelin injection and intravenous GnRH in a randomized order. During the stimulation test with triptorelin, LH and FSH were measured at time 0, 30, 60, 90, 120, and 180 min after the injection. Estradiol was sampled 24 h after the injection. During the GnRH test, LH and FSH were measured at time 0, 30, 45, and 60 min. Girls with peak GnRH-stimulated LH concentrations ≥5.0 IU/L were classified as having CPP. Area under the curve (AUC) for triptorelin-stimulated LH concentrations was assessed using the receiver operating characteristic (ROC) analysis.
RESULTS
Triptorelin-stimulated LH concentrations were significantly higher in girls who had CPP according to the GnRH test (53.3%). LH peaked at 180 min after the triptorelin injection. The highest diagnostic accuracy for CPP (AUC = 0.973, sensitivity 96.9%, specificity 89.3%) at 180 min was at a LH concentration ≥3.4 IU/L. The 24 h estradiol concentration did not improve the predictive model.
CONCLUSIONS
Measuring LH concentrations 180 min after triptorelin injection with a cut-off value of ≥3.4 IU/L demonstrated a high diagnostic accuracy compared to the GnRH test. Thus, stimulation with triptorelin can be used as a reliable alternative for diagnosing CPP in girls with premature thelarche.
Topics: Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Prospective Studies; Puberty, Precocious; Triptorelin Pamoate
PubMed: 34826116
DOI: 10.1007/s12020-021-02947-z -
Endocrine Connections Sep 2021To evaluate the characteristics and significance of serum kisspeptin and makorin ring finger protein 3 (MKRN3) levels for the diagnosis of central precocious puberty...
OBJECTIVE
To evaluate the characteristics and significance of serum kisspeptin and makorin ring finger protein 3 (MKRN3) levels for the diagnosis of central precocious puberty (CPP) in girls.
METHOD
Thirty four individuals with CPP, 17 individuals with premature thelarche (PT), and 28 age-matched prepubertal girls as normal control (NC) were recruited in this case-control study. Physical measurements included BMI and tests for breast, bone, and sexual characteristics. Biochemical measurements included serum LH, FSH, estradiol, insulin-like growth factor-1, MKRN3, and kisspeptin. Blood samples were taken from individuals with CPP and PT before the gonadotrophin-releasing hormone stimulation test and at 30, 60, 90, and 120 min after injection with triptorelin.
RESULTS
Serum kisspeptin levels were higher in the CPP group when compared to the NC group (P = 0.020), while serum MKRN3 levels were lower in the two groups (P = 0.028). There were no significant differences between the CPP and PT groups as well as the PT and NC groups (all, P > 0.05). The cut-off value of serum kisspeptin differentiating patients with CPP from those without CPP was 0.40 nmol/L, with 82.4% sensitivity and 57.1% specificity, while the cut-off value of serum MKRN3 was 0.33 pmol/L, with 79.4% sensitivity and 53.6% specificity. The area under the curves (AUCs) of both kisspeptin and MKRN3 for differentiating those girls with CPP from PT were less than 0.5.
CONCLUSIONS
Serum levels of kisspeptin and MKRN3 may play an auxiliary role in predicting CPP. However, the two measurements were not able to differentiate girls with CPP from PT and prepubertal control. This study emphasizes the need to search for markers to simplify the accurate diagnosis of CPP in girls.
PubMed: 34414898
DOI: 10.1530/EC-21-0182