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Biomolecules Feb 2024Endocrine-disrupting chemicals (EDCs) may impact the development of prostate cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in...
Endocrine-disrupting chemicals (EDCs) may impact the development of prostate cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in controlling tumor growth is not known, EDCs may inhibit steroidogenic enzymes such as CYP17A1 or CYP19A1 which are involved in the production of androgens or estrogens. High levels of circulating androgens are linked to PCa in men and Polycystic Ovary Syndrome (PCOS) in women. Essential oils or their metabolites, like lavender oil and tea tree oil, have been reported to act as potential EDCs and contribute towards sex steroid imbalance in cases of prepubertal gynecomastia in boys and premature thelarche in girls due to the exposure to lavender-based fragrances. We screened a range of EO components to determine their effects on CYP17A1 and CYP19A1. Computational docking was performed to predict the binding of essential oils with CYP17A1 and CYP19A1. Functional assays were performed using the radiolabeled substrates or Liquid Chromatography-High-Resolution Mass Spectrometry and cell viability assays were carried out in LNCaP cells. Many of the tested compounds bind close to the active site of CYP17A1, and (+)-Cedrol had the best binding with CYP17A1 and CYP19A1. Eucalyptol, Dihydro-β-Ionone, and (-)-α-pinene showed 20% to 40% inhibition of dehydroepiandrosterone production; and some compounds also effected CYP19A1. Extensive use of these essential oils in various beauty and hygiene products is common, but only limited knowledge about their potential detrimental side effects exists. Our results suggest that prolonged exposure to some of these essential oils may result in steroid imbalances. On the other hand, due to their effect on lowering androgen output and ability to bind at the active site of steroidogenic cytochrome P450s, these compounds may provide design ideas for novel compounds against hyperandrogenic disorders such as PCa and PCOS.
Topics: Male; Humans; Female; Androgens; Gonadal Steroid Hormones; Oils, Volatile; Steroids; Polycystic Ovary Syndrome; Cytochrome P-450 Enzyme System
PubMed: 38397440
DOI: 10.3390/biom14020203 -
The Journal of Clinical Endocrinology... Aug 2022Congenital generalized lipodystrophy, type 1 (CGL1), due to biallelic pathogenic variants in AGPAT2, is characterized by the near total loss of body fat from the face,...
CONTEXT
Congenital generalized lipodystrophy, type 1 (CGL1), due to biallelic pathogenic variants in AGPAT2, is characterized by the near total loss of body fat from the face, trunk, and extremities. Patients develop premature diabetes, hypertriglyceridemia, hepatic steatosis, and polycystic ovary syndrome. However, sparing of the facial fat and precocious pubertal development has not been previously reported in CGL1.
CASE DESCRIPTION
We report a 21-year-old woman of European descent with CGL1 who had sparing of the facial fat and premature thelarche at birth with premature pubarche and menstrual bleeding at age 3 years. Her serum 17-OH progesterone level rose to 1000 ng/dL (30.26 nmol/L) after cosyntropin stimulation test, suggestive of nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency. Hydrocortisone replacement therapy from age 3.5 to 10 years resulted in cessation of menstruation and growth of pubic hair, and a reduction of breast size. Sanger and whole-exome sequencing revealed compound heterozygous variants c.493-1G>C; p.(Leu165_Gln196del), and c.del366_588+534; p.(Leu123Cysfs*55) in AGPAT2 plus c.806G>C; p.(Ser269Thr) and c.844G>T; p.(Val282Leu) in CYP21A2. She developed diabetes at age 13 requiring high-dose insulin and had 7 episodes of acute pancreatitis due to extreme hypertriglyceridemia in the next 5 years. Metreleptin therapy was initiated at age 18 and after 3 years, she had remission of diabetes and hypertriglyceridemia; however, menstrual irregularity and severe hirsutism did not improve.
CONCLUSION
Concomitant NCAH in this CGL1 patient was associated with precocious pubertal development and sparing of facial fat. Metreleptin therapy drastically improved her hyperglycemia and hyperlipidemia but not menstrual irregularity and hirsutism.
Topics: Acute Disease; Adolescent; Adrenal Hyperplasia, Congenital; Adult; Child; Child, Preschool; Female; Hirsutism; Humans; Hyperinsulinism; Hyperlipidemias; Hypertriglyceridemia; Infant, Newborn; Lipodystrophy, Congenital Generalized; Menstruation Disturbances; Pancreatitis; Puberty, Precocious; Steroid 21-Hydroxylase; Young Adult
PubMed: 35857714
DOI: 10.1210/clinem/dgac406 -
Indications of younger age at menarche in Greek adolescents but with no relation to body mass index.Hormones (Athens, Greece) Apr 2024This study aimed to present recent trends in the pubertal timing of a Greek female sample.
PURPOSE
This study aimed to present recent trends in the pubertal timing of a Greek female sample.
METHODS
Data were collected retrospectively from medical records of healthy females aged 6-18 years who attended a tertiary Adolescent Friendly Health Center over a 5-year period (2016-2020) and included gestational age, birth anthropometrics, and age of thelarche and/or pubarche and/or menarche, along with corresponding anthropometric, hormonal, and biochemical measurements.
RESULTS
Data from 298 girls' medical records were included in the analysis. Median age at menarche, thelarche, and pubarche was 12, 9, and 9 years, respectively. The mean interval between pubertal onset and menarche was 1.99 years. The mean body mass index (BMI) at menarche and thelarche was 20.99 kg/m and 18.90 kg/m, respectively. The mean weight at menarche was 49.6 kg, whereas the mean height difference between thelarche and menarche was 19.17 cm. Among participants, 6.3% had premature menarche, while 24.0% had premature thelarche. Birth weight was moderately correlated with BMI at thelarche/pubarche (r=0.334, p = 0.005). Birth weight and BMI at thelarche/pubarche were not predictive of premature menarche or premature thelarche. Median (interquartile range, IQR) levels at menarche vs. thelarche were significantly higher for insulin-like growth factor-1 [358.00 (140.50) vs. 176.00 (55.00) ng/ml], follicle stimulation hormone [5.65 (3.14) vs. 3.10 (4.23) mIU/ml], testosterone [25.50 (31.00) vs. 13.00 (21.00) ng/dl], dehydroepiandrosterone sulfate [117.00 (112.50) vs. 46.40 (51.90) µg/dl], and insulin [17.40 (15.05) vs. 8.47 (4.97) µIU/ml].
CONCLUSION
The timing of pubertal stages in the Greek female sample studied followed the recent international downward trends. Younger age at menarche was not related to BMI.
PubMed: 38647964
DOI: 10.1007/s42000-024-00557-8 -
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 -
Turk Pediatri Arsivi 2020To determine the clinical, anthropometric, and laboratory parameters that could be used for differentiating central precocious puberty from premature thelarche in girls...
AIM
To determine the clinical, anthropometric, and laboratory parameters that could be used for differentiating central precocious puberty from premature thelarche in girls who had breast development between the ages of 3 and 8 years.
MATERIAL AND METHODS
The study included 344 girls (196 girls with idiopathic central precocious puberty, 148 girls with premature thelarche) who underwent gonadotropin- releasing hormone stimulation tests for breast development. Age at diagnosis, bone age, anthropometric measurements, basal/stimulated hormone levels were recorded. Univariate regression analysis was performed to determine the parameters that could be used for differentiating precocious puberty from premature thelarche. Significant parameters in univariate analyses were grouped according to the thresholds determined using receiver operating characteristic curves and reevaluated through multivariate analysis.
RESULTS
The bone age, height-standard deviation score, body mass index-standard deviation score, and growth velocity-standard deviation score at diagnosis were found to be higher; pubertal stages were found to be more advanced; uterus and ovary volumes were found to be larger; and the basal/peak luteinizing hormone, follicle-stimulating hormone, luteinizing hormone/follicle-stimulating hormone levels were found to be higher in the subjects with precocious puberty. There was no difference between estradiol levels between the two groups. The best thresholds to differentiate the two groups were found as 0.65 IU/L (78% sensitivity, 100% specificity), 1.9 IU/L (100% sensitivity, 72% specificity), 0.25 (67% sensitivity, 100% specificity) and 1.1 (69% sensitivity, 71% specificity), respectively, for basal luteinizing hormone, follicle-stimulating hormone, luteinizing hormone/follicle-stimulating hormone ratio, and the growth velocity-standard deviation score.
CONCLUSION
In girls presenting with early breast development, a basal luteinizing hormone level of ≥0.65 IU/L and a luteinizing hormone/follicle-stimulating hormone ratio of ≥0.25 are sensitive ways to demonstrate activation of the hypothalamo-pituitary-gonadal axis. Among these, the variable that gives the best sensitivity and specificity is the measurement of basal luteinizing hormone levels (≥0.65 IU/L), which can be used as a screening test in the diagnosis of central precocious puberty.
PubMed: 32684758
DOI: 10.14744/TurkPediatriArs.2019.03708 -
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 -
Journal of Pediatric Endocrinology &... Nov 2021There is a complex interaction between the anti-müllerian hormone (AMH) and hypothalamic-pituitary-gonadal axis. However, the effect of gonadotropin-releasing hormone...
OBJECTIVES
There is a complex interaction between the anti-müllerian hormone (AMH) and hypothalamic-pituitary-gonadal axis. However, the effect of gonadotropin-releasing hormone (GnRH) stimulation on AMH levels is not clearly known. In the study, we aimed to evaluate the effect of GnRH stimulation on AMH levels in central precocious puberty (CPP) and isolated premature thelarche (PT) groups.
METHODS
Sixty-three girls with breast development before the age of 8 were enrolled in the study. GnRH test was performed on all subjects. Blood samples for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels were taken at basal, 40th, and 90th minute of GnRH test. Subjects were grouped as CPP and PT group.
RESULTS
After GnRH stimulation, AMH levels increased significantly at the 40th minute and the stimulating effect of GnRH on AMH continued till the 90th minute (p: 0.0001). There was a positive correlation between basal and 90th-minute AMH levels (r: 479, p: 0.0001). The highest FSH, LH, and AMH times were significantly different after the GnRH stimulation (p: 0.001, p: 0.001, and p: 0.007). Although the CPP group had a lower basal AMH level than the PT group's basal AMH level; AMH response to GnRH stimulation was not different (p>0.05).
CONCLUSIONS
In our study, which examined the effect of GnRH stimulation on AMH levels in early pubertal development disorders for the first time, GnRH stimulated AMH secretion rapidly, correlated with basal AMH. Basal AMH levels were lower in patients with CPP than in those with PT; however, the effect of GnRH stimulation on AMH levels was similar in both groups.
Topics: Anti-Mullerian Hormone; Child; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Puberty, Precocious
PubMed: 34344062
DOI: 10.1515/jpem-2021-0343 -
Italian Journal of Pediatrics Dec 2019Premature thelarche (PT) is a benevolent ailment affecting young girls. Multiple factors are reported to correlate with this condition, but the mechanisms responsible... (Comparative Study)
Comparative Study
BACKGROUND
Premature thelarche (PT) is a benevolent ailment affecting young girls. Multiple factors are reported to correlate with this condition, but the mechanisms responsible for the onset of PT have not yet been fully investigated. This study aimed to evaluate the relationship of nutrient intake, insulin resistance and lipid profile with PT.
METHODS
Two hundred sixty-three girls with PT, and 222 healthy girls of similar age were enrolled into this study. Their demographics, Tanner stage of breast development, nutrient intake, insulin resistance and lipid profiles were compared.
RESULTS
Daily protein and fat intakes, insulin resistance parameters including serum insulin-like growth factor 1, fasting glucose to insulin ratio, quantitative insulin check index and homeostasis model of assessment of insulin resistance, as well as serum levels of triacylglycerol, total cholesterol and low-density lipoprotein, were all significantly altered in PT patients. Daily intake of energy and carbohydrate, and serum level of high-density lipoprotein protein were statistically indistinguishable between PT patients and healthy controls.
CONCLUSION
Chinese girls with PT are potentially insulin resistant, which warrants more clinical attention and further investigation to address the underlying etiology.
Topics: Age Factors; Blood Glucose; Case-Control Studies; Child; China; Energy Intake; Female; Humans; Insulin; Insulin Resistance; Lipid Metabolism; Nutrients; Puberty, Precocious; Reference Values; Risk Assessment; Statistics, Nonparametric
PubMed: 31856872
DOI: 10.1186/s13052-019-0758-z -
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 -
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