Possible role of melatonin in precocious and accelerated puberty in females during the COVID-19 pandemic

BackgroundPubertal development is a complex process influenced by a multitude of factors; among these, the role of melatonin has only been partially investigated. During the COVID-19 pandemic an unexpected increase in cases of precocious and fast puberty was observed.AimsTo evaluate the possible role of salivary melatonin in precocious and accelerated puberty during the COVID-19 lockdown.Patients and MethodsFifty-four females were evaluated from October 2020 to March 2021; of these, 39 children were diagnosed with central precocious puberty (CPP) and 15 with isolated premature thelarche (IPT). Thirty-three healthy children acted as controls. The enrolled patients were asked to take measures the day before the visit to avoid influencing readings of melatonin secretion. Salivary melatonin levels were analyzed using commercially available ELISA kit.ResultsThere was no difference in the time from B2 to diagnosis (months) between IPT and CPP patients. However, the anamnestic and clinical data of our CPP patients confirmed an acceleration in the stages of pubertal development. As expected, subjects with CPP showed a significantly greater stature SDS and height velocity SDS. There were no differences in BMI SDS and Delta BMI SDS. Interestingly, we discovered a significant difference regarding the use of electronic devices between children with CPP, IPT and controls (p < 0.05). Children with CPP showed significantly lower values of salivary melatonin than patients with TPT and controls (p < 0.0001).DiscussionOur results showed a marked reduction in salivary melatonin in children with CPP diagnosed during and after lockdown for COVID-19. Larger studies are needed to confirm and investigate these findings.

The effect of GnRH stimulation on AMH regulation in central precocious puberty and isolated premature thelarche

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.

Diagnostic Efficacy of Pelvic Ultrasound in Central Precocious Puberty in Girls: a Retrospective Cohort Study

Background: Differentiating central precocious puberty (CPP) patients from normal cases and CPP-like patients “isolated premature thelarche (IPA) and isolated premature thelarche (IPT)” is important for beginning of treatment. Although the GnRH stimulation test is considered the gold standard for diagnosis of CPP, Because of its wide limitations, our study targets to evaluate pelvic sonography parameters as a contributory tool for CPP diagnosis.Methods: We consecutively enrolled 183 cases (93 CPP, 16 IPT, 12 IPA and 62 of age-matched normal controls) in our study over four years. All cases are classified by clinical and laboratory findings and are followed up for at least 2 years. Pelvic sonography parameters included uterine fundus, body and cervix anteroposterior diameter, fundus/cervix ratio, uterine length and transverse diameter, uterine volume, endometrial thickness, ovarian volumes and diameter of the largest follicle are evaluated in all classified groups. One-way ANOVA, post hoc and receiver operating characteristic (ROC) analysis was used to compare the study groups.Results: Our study found that all sonography parameters differ significantly between CPP and normal control cases, also a significant difference is found between CPP compared to IPT or IPA cases in all parameters except in cervix anteroposterior diameter, ovarian volumes and diameter of the largest follicle. In order of best parameters for differentiating CPP compared to study groups, uterine volume (a cut-off of 1.40 ml had a sensitivity of 75.27% and a specificity of 75.56%), transverse diameter (a cut-off of 13.5 mm had a sensitivity of 72.04% and a specificity of 71.11%) and F/C ratio (a cut-off of 0.98 had a sensitivity of 78.49% and a specificity of 70%) was selected. Our study also classified sonography parameters as in equal diagnostic value to uterine volume (as the best diagnostic parameter with area under the curve of 0.826) and not equal diagnostic value to uterine volume.Conclusions: Pelvic Sonography parameters may improve the diagnosis of CPP patients and can have a contributory role in distinguishing treatment needed patients from other patients. The best diagnostic parameter and its cut-off value could change according to different ethnicities and studies.

Factors affecting bone maturation in Chinese girls aged 4-8 years with isolated premature thelarche

Background: In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age. However, some IPT girls confirmed by gonadotropin-releasing hormone (GnRH) stimulation test could show another trend. We analysed BA and possible potentiating factors in a selected group of girls aged 4-8 years with IPT. Methods: IPT girls confirmed by GnRH stimulation test aged 4-8 years hospitalized from January 2015 to April 2018 at Shenzhen Children's Hospital were included in this retrospective study. They were divided into two groups with advanced BA of 2 years as the cut-off. Body mass index (BMI) and hormone levels were the main outcome measures, and regression analysis was used to identify independent risk factors. IPT girls were divided into subgroups according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS for comparisons of advanced BA. Results: Overall, 423 subjects were included and classified into the advanced BA group (48.7%, n=206) and control group (51.3%, n=217). The advanced BA group had significantly higher BMI SDS, serum DHEAS SDS, IGF-1 SDS, androstenedione and fasting insulin and significantly lower sex hormone binding globulin (all p<0.001). Serum IGF-1 SDS (OR=1.926, p＜0.001), BMI SDS (OR=1.427, p=0.001) and DHEAS SDS (OR=1.131, p=0.005) were independent risk factors for significantly advanced BA. In the multiple linear regression model, serum IGF-1 SDS, BMI SDS and DHEAS SDS were the strongest predictors of advanced BA, accounting for 19.3% of the variance. According to BMI, 423 patients were classified into three groups: normal weight (56.03%, n=237), overweight (19.15%, n=81) and obesity (24.82%, n=105). The proportion of advanced BA in obesity group was significantly higher than those of normal weight and overweight groups (χ2=18.088, p＜0.001). In the subgroup with normal weight, higher serum IGF-1 SDS (p=0.009) and DHEAS SDS (p=0.003) affected BA advancement independent of BMI SDS. Conclusions: Girls with IPT confirmed by GnRH stimulation test aged 4-8 years might have significantly advanced BA. Obesity was highly associated with advanced BA. Age-specific serum IGF-1 SDS and DHEAS SDS were risk factors for BA advancement independent of BMI.

Factors affecting bone maturation in Chinese girls aged 4-8 years with isolated premature thelarche

Background: In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age. However, IPT girls confirmed by gonadotropin-releasing hormone (GnRH) stimulation test could show another trend. We analysed BA and possible potentiating factors in girls aged 4-8 years with IPT.Methods: IPT girls aged 4-8 years hospitalized from January 2015 to April 2018 at Shenzhen Children's Hospital were divided into two groups with advanced BA of 2 years as the cut-off. Body mass index (BMI) and hormone levels were the main outcome measures, and regression analysis was used to identify independent risk factors. IPT girls were divided into subgroups separately according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS to compare BA.Results: Overall, 423 subjects were classified into the advanced BA (48.7%, n=206) and control groups (51.3%, n=217). The advanced BA group had significantly higher BMI SDS, DHEAS SDS, IGF-1 SDS, androstenedione and serum fasting insulin and significantly lower sex hormone binding globulin (all p<0.001). IGF-1 SDS (OR=1.926, p＜0.001), BMI SDS (OR=1.427, p=0.001) and DHEAS SDS (OR=1.131, p=0.005) were independent risk factors for advanced BA. In the multiple linear regression model, IGF-1 SDS, BMI SDS and DHEAS SDS were the strongest predictors of advanced BA, accounting for 19.3% of the variance. According to BMI, 423 patients were classified into three groups: normal weight (56.03%, n=237 ), overweight (19.15%, n=81) and obesity (24.82%, n=105). The proportion of advanced BA in obesity was significantly higher than that of normal weight and overweight (χ2=18.088, P＜0.001). In a subgroup with normal weight, higher IGF-1 SDS (p=0.009) and DHEAS SDS (p=0.003) affected BA advancement independent of BMI SDS. Conclusions: Girls with IPT confirmed by GnRH stimulation test aged 4-8 years might have significantly advanced BA. Obesity was highly associated with advanced BA. Age-specific serum IGF-1 SDS and DHEAS SDS were risk factors for BA advancement independent of BMI.

Factors affecting bone maturation in 423 Chinese girls aged 4-8 years with isolated premature thelarche

Background: In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age, but IPT girls requiring further investigations show another trend. We analysed BA and possible potentiating factors in girls aged 4-8 years with IPT. Methods: IPT girls aged 4-8 years hospitalized from January 2015 to April 2018 at Shenzhen Children's Hospital were divided into two groups with advanced BA of 2 years as the cutoff. Body mass index (BMI) and hormone levels were the main outcome measures, and regression analysis was used to identify independent risk factors. IPT girls were divided into subgroups seperately according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS to compare BA. Results: Overall, 423 subjects were classified into the advanced BA (48.7%, n=206) and control groups (51.3%, n=217). The advanced BA group had significantly higher BMI SDS, DHEAS SDS, IGF-1 SDS, androstenedione and serum fasting insulin and significantly lower sex hormone binding globulin (all p<0.001). IGF-1 SDS (OR=1.642, p＜0.001) and DHEAS SDS (OR=1.125, p=0.021) were independent risk factors for advanced BA. In the multiple linear regression model, IGF-1 SDS, BMI SDS and DHEAS SDS were the strongest predictors of advanced BA, accounting for 18.9% of the variance. According to BMI, 423 patients were classified into three groups: normal weight (56.03%, n=237 ), overweight (19.15%, n=81) and obesity (24.82%, n=105). The proportion of BA advancement in obesity was significantly higher than that of normal weight (χ2=18.088, P＜0.001). In a subgroup with normal weight, higher IGF-1 SDS (p=0.009) and DHEAS SDS (p=0.003) affect BA advancement independent of BMI SDS. Conclusions: Chinese girls aged 4-8 years with IPT requiring further investigations might have significantly advanced BA. Obesity was highly associated with advanced BA. Age-specific serum IGF-1 SDS and DHEAS SDS were risk factors for BA advancement independent of BMI.

Premature thelarche: clinical and laboratorial assessment by immunochemiluminescent assay

In order to establish cut-off limits and to distinguish isolated premature thelarche (IPT) from precocious puberty (PP), we evaluated data from 79 girls with premature thelarche, comparing basal and stimulated LH and FSH serum concentrations with those from 91 healthy girls. A GnRH stimulation test was performed in 10 normal girls and in 42 with premature thelarche. Comparison among groups was performed by Kruskal-Wallis and Dunn’s tests. LH values were significantly greater in girls with IPT than in control groups. Basal gonadotropin concentrations were higher in patients with PP than in controls, but not different from patients with IPT. Peak LH levels after GnRH stimulation distinguished those two groups, with a cut-off value of 4.0 IU/L, but still with minimal overlap. In conclusion, a girl with premature thelarche and LH peak value above 4.5 IU/L has, indeed, PP, but values between 3.5 and 4.5 IU/L point to careful follow-up.