Objectives: We aimed to study the trend of referrals for precocious puberty during the COVID-19 pandemic compared to pre-COVID years, explore the differences in the demographic and clinical features, and evaluate the contributing factors. Methodology: The cases referred for assessment of PP from 2018-2021 to our endocrine centre were grouped into pre-COVID (2018-2019) and COVID (2020-2021) years. Cases fulfilling the diagnosis of PP included the onset of thelarche <8 years in females and 4 ml testicular volume <9 years in males. The PP was further differentiated as Isolated Thelarche (IST) and Central Precocious Puberty (CPP). Early menarche was defined as menarche <10 years old. Results: There were more referrals for PP and more diagnosed as CPP during the COVID-19 pandemic, predominantly among females. There were more endocrine tests done and more cases received treatment. None of the abnormal magnetic resonance imaging (MRI) pituitary findings required surgical intervention. The body mass index (BMI) was found to be positively associated with the risk of getting CPP with a crude-odd ratio (COR) of 1.8, P <0.001, and early menarche (COR 2.1, P <0.001). Conclusion We found a significant increase in the referrals of PP and diagnosis of CPP during the COVID-19 pandemic. Higher BMI was found to be associated with CPP and early menarche.
Puberty, Precocious ; COVID-19 ; Obesity

Peripheral precocious puberty(PPP),also known as puberty independent from hypothalamic-pituitary axis activation,is stimulated by hormones from other sources, with only partial sexual characteristics development but without mature sexual function. The secondary sexual characteristics development occurs before 7.5 years of age in girls and before 9 years of age in boys. Clinical manifestations are diverse, and PPP has varied etiology including congenital adrenal hyperplasia, McCune-Albright syndrome, ovarian cyst, adrenal tumor, ovarian tumor, testicular tumor, human chorionic gonadotropin producing tumor, familial male precocious puberty, aromatase excess syndrome, and environmental estrogen. Early identification of etiology, accurate differential diagnosis and prenatal gene screening play a significant role in the prevention, diagnosis and treatment of the disease.
Female ; Humans ; Male ; Child ; Puberty, Precocious/therapy* ; Fibrous Dysplasia, Polyostotic/complications* ; Aromatase

Humans ; Puberty, Precocious/therapy* ; Consensus ; Luteinizing Hormone ; Gonadotropin-Releasing Hormone

Puberty is a pivotal biological process that completes sexual maturation to achieve full reproductive capability. It is a major transformational period of life, whose timing is strongly affected by genetic makeup of the individual, along with various internal and external factors. Although the exact mechanism for initiation of the cascade of molecular events that culminate in puberty is not yet known, the process of pubertal onset involves interaction of numerous complex signaling pathways of hypothalamo-pituitary-testicular (HPT) axis. We developed a classification of the mechanisms involved in male puberty that allowed placing many genes into physiological context. These include (i) hypothalamic development during embryogenesis, (ii) synaptogenesis where gonadotropin releasing hormone (GnRH) neurons form neuronal connections with suprahypothalamic neurons, (iii) maintenance of neuron homeostasis, (iv) regulation of synthesis and secretion of GnRH, (v) appropriate receptors/proteins on neurons governing GnRH production and release, (vi) signaling molecules activated by the receptors, (vii) the synthesis and release of GnRH, (viii) the production and release of gonadotropins, (ix) testicular development, (x) synthesis and release of steroid hormones from testes, and (xi)the action of steroid hormones in downstream effector tissues. Defects in components of this system during embryonic development, childhood/adolescence, or adulthood may disrupt/nullify puberty, leading to long-term male infertility and/or hypogonadism. This review provides a list of 598 genes involved in the development of HPT axis and classified according to this schema. Furthermore, this review identifies a subset of 75 genes for which genetic mutations are reported to delay or disrupt male puberty.
Adolescent ; Male ; Humans ; Adult ; Child ; Gonadotropin-Releasing Hormone ; Gonadotropins/metabolism* ; Hypogonadism ; Testis/metabolism* ; Puberty/physiology* ; Sexual Maturation

OBJECTIVES: To study the association between early-life factors (including birth weight, method of birth, gestational age, and history of gestational metabolic disorders) and pubertal timing in girls. METHODS: The stratified cluster sampling method was used to select the girls in grades 2-3 and 7-8 from three primary schools and three middle schools in Guangzhou, China from March to December, 2019, and breast development was examined for all girls. A questionnaire survey was performed to collect the information on early-life factors. The multivariate logistic regression model was used to evaluate the association of gestational metabolic disorders, birth weight, method of birth, and gestational age with pubertal timing in girls. The Bootstrap method was used to assess the mediation effect of body mass index (BMI) (Z score) between high birth weight (≥4 000 g) and pubertal timing. RESULTS: A total of 1 665 girls were enrolled, among whom 280 (16.82%) were judged to have early pubertal timing. The multivariate logistic regression analysis showed that high birth weight was associated with the increased risk of early pubertal timing (OR=2.12, 95%CI: 1.19-3.66, P=0.008). Nevertheless, no significant association was observed between other early-life factors and pubertal timing (P>0.05). The OR for the mediation effect of BMI (Z score) between high birth weight and early pubertal timing was 1.25 (95%CI: 1.09-1.47), accounting for 29.33% of the total effect of high birth weight on early pubertal timing. CONCLUSIONS High birth weight is associated with the increased risk of early pubertal timing in girls, and overweight/obesity may play a partial mediating role in the association between high birth weight and early pubertal timing in girls.
Female ; Humans ; Birth Weight ; Body Mass Index ; China ; Gestational Age ; Logistic Models ; Puberty, Precocious

OBJECTIVES: To study the value of basal luteinizing hormone (LH) level combined with uterine volume measurement in the early diagnosis of central precocious puberty (CPP) in girls with different Tanner stages. METHODS: A retrospective analysis was performed on the girls who presented with breast development before the age of 8 years and attended the Third Affiliated Hospital of Zhengzhou University from January 2017 to September 2022. According to the results of gonadotropin-releasing hormone (GnRH) agonist test, the girls with peak LH ≥5.0 IU/L and peak LH/follicle stimulating hormone ≥0.6 were enrolled as the positive group, and the other girls were enrolled as the negative group. The two groups were compared in terms of the basal LH level and uterine volume. The receiver operating characteristic (ROC) curve was used to analyze their value in the early diagnosis of CPP. RESULTS: For the girls with Tanner B2 and B3 stages, the positive group had significantly higher basal LH level and uterine volume than the negative group (P<0.05). The basal LH level had an optimal cut-off value of 0.325 IU/L and 0.505 IU/L respectively in the diagnosis of Tanner stage B2/B3 CPP, while uterine volume had an optimal cut-off value of 1.639 mL and 2.158 mL respectively. Basal LH level combined with uterine volume measurement had a significantly larger area under the ROC curve than uterine volume measurement alone (P<0.001), but with no significant difference compared with that of basal LH level measurement alone (P>0.05). CONCLUSIONS Basal LH level combined with uterine volume measurement is valuable in the early diagnosis of CPP in girls with different Tanner stages, which provides a basis and guiding significance for clinical diagnosis of CPP.
Child ; Female ; Humans ; Early Diagnosis ; Luteinizing Hormone/chemistry* ; Puberty, Precocious/diagnosis* ; Retrospective Studies ; Uterus/pathology*

OBJECTIVE: To observe the efficacy and safety of acupuncture combined with auricular point sticking for girls aged 3-8 years with incomplete precocious puberty (IPP). METHODS: Sixty girls with IPP were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases were eliminated). The girls in the control group were treated with healthy diet and proper exercise for 12 weeks. On the basis of the treatment in the control group, the girls in the observation group were treated with acupuncture combined with auricular point sticking. The acupuncture was applied at Sanyinjiao (SP 6), Guanyuan (CV 4), Guilai (ST 29), etc., the needles were retained for 20 min, acupuncture was given twice a week (once every 3 days). The auricular point sticking was applied at Luanchao (TF₂), Neishengzhiqi (TF₂), Neifenmi (CO₁₈), Yuanzhong (AT_2,3,4i), etc., twice a week. The treatment was given for 12 weeks. Before treatment, after treatment and in follow-up after 12 weeks of treatment completion, the Tanner stage of breast, serum contents of sex hormone (luteinizing hormone [LH], follicle-stimulating hormone [FSH], estradiol [E₂]) were observed. The ovarian volume, the number of follicles with diameter>4 mm, and the uterine volume were measured by abdominal color Doppler ultrasound. In addition, the safety of the observation group was evaluated. RESULTS: Compared with before treatment, the Tanner stage of breast in the observation group was improved after treatment and in follow-up (P<0.05); after treatment and in follow-up, the Tanner stage of breast in the observation group was better than that in the control group (P<0.05). Compared with before treatment, the serum levels of LH and E₂ in the observation group were increased (P<0.05), and the volume of bilateral ovaries was larger (P<0.05) in follow-up. Compared with before treatment, the serum contents of LH, FSH and E₂ in the control group were increased (P<0.05), the volume of bilateral ovaries was larger (P<0.05), and the number of follicles was increased (P<0.05) after treatment and in follow-up. The serum levels of LH, FSH and E₂ in the observation group were lower than those in the control group (P<0.05), the volume of bilateral ovaries was smaller than that in the control group (P<0.05), and the number of follicles was lower than that in the control group (P<0.05). Compared with before treatment, the uterine volume in the two groups was larger in follow-up (P<0.05). There was no statistically significant difference between the two groups after treatment and in follow-up (P>0.05). During the treatment, 3 cases in the observation group had slight abdominal pain and subcutaneous blood stasis, without serious adverse reactions. CONCLUSION Acupuncture combined with auricular point sticking could improve the Tanner stage of breast, reduce the level of sex hormone, slow down the development and maturation of ovary and follicle, and control the degree and speed of sexual development in girls aged 3-8 years with IPP.
Female ; Humans ; Puberty, Precocious/therapy* ; Acupuncture Therapy ; Estradiol ; Luteinizing Hormone ; Ovary

Objective To explore the relationship of menarche age,menopause age,and reproductive period with cognitive function in the female patients with hypertension.Methods Hypertension screening was carried out in Wuyuan county of Jiangxi province from July to August in 2018.Data were collected through a face-to-face questionnaire survey,physical measurement,and biochemical tests.The cognitive function was scored according to the mini-mental state examination(MMSE)scale.Multiple linear regression and Logistic regression were employed to analyze the effects of menarche age,menopause age,and reproductive period on cognitive function,and the penalized spline regression to fit the curves.Results A total of 4595 postmenopausal women with hypertension were included in the analysis,with the mean age of(65.1±8.4)years,mean menarche age of(16.6±2.2)years,mean menopause age of(48.2±5.0)years,mean reproductive period of(31.7±5.5)years,mean MMSE score of(19.0±6.3)points,and total cognitive impairment detection rate of 40.4%(1859/4595).The detection rates of cognitive impairment were 28.4%,39.1%,and 45.8% in the females with the menarche ages of <15,15-16,and ≥17 years,47.9%,39.7%,and 38.3% in the females with the menopausal ages of <45,45-49,and ≥50 years,and 56.0%,44.4%,40.6%,and 32.6% in the females with the reproductive periods of <25,25-29,30-34,and ≥35 years,respectively.Moreover,the detection rates of cognitive impairment among different age groups were statistically significant(all P<0.05).Compared with the group with the menarche age <15 years,the groups with the menarche ages of 15-16 years and ≥17 years showed increased detection rates of cognitive impairment(OR=1.45,95%CI=1.19-1.75,P<0.001;OR=1.65,95%CI=1.37-1.98,P<0.001).Compared with the group with the menopausal age <45 years,the groups with the menopausal ages of 45-49 years and ≥50 years showed decreased detection rates of cognitive impairment(OR=0.80,95%CI=0.66-0.95,P=0.013;OR=0.78,95%CI=0.65-0.93,P<0.001).Compared with the group with the reproductive period <25 years,the groups with the reproductive periods of 25-29,30-34,and ≥35 years showed decreased detection rates of cognitive impairment(OR=0.66,95%CI=0.52-0.84,P<0.001;OR=0.62,95%CI=0.50-0.76,P<0.001;OR=0.51,95%CI=0.41-0.63,P<0.001).Conclusion The detection rate of cognitive impairment had a positive correlation with menarche age and negative correlations with menopause age and reproductive period in the female patients with hypertension.
Humans ; Female ; Middle Aged ; Aged ; Adolescent ; Menopause ; Menarche ; Reproduction ; Hypertension ; Cognition ; Age Factors ; Risk Factors

OBJECTIVE: To investigate the clinical features and genetic etiology of a case of Turner syndrome (TS) with rapidly progressive puberty. METHODS: A child who had presented at the Pediatric Endocrinology Clinic of the Shenzhen People's Hospital on January 19, 2022 was selected as the study subject. Clinical data of the child were collected. Peripheral blood sample of the child was subjected to chromosomal microarray analysis (CMA) and multiple ligation-dependent probe amplification (MLPA). Previous studies related to TS with rapidly progressive puberty were retrieved from the CNKI, Wanfang Data Knowledge Service Platform, Boku, CBMdisc and PubMed databases with Turner syndrome and rapidly progressive puberty as the keywords. The duration for literature retrieval was set from November 9, 2021 to May 31, 2022. The clinical characteristics and karyotypes of the children were summarized. RESULTS: The child was a 13-year-and-2-month-old female. She was found to have breast development at 9, short stature at 10, and menarche at 11. At 13, she was found to have a 46,X,i(X)(q10) karyotype. At the time of admission, she had a height of 143.5 cm (< P3), with 6 ~ 8 nevi over her face and right clavicle. She also had bilateral simian creases but no saddle nasal bridge, neck webbing, cubitus valgus, shield chest or widened breast distance. She had menstruated for over 2 years, and her bone age has reached 15.6 years. CMA revealed that she had a 58.06 Mb deletion in the Xp22.33p11.1 region and a 94.49 Mb duplication in the Xp11.1q28 region. MLPA has confirmed monosomy Xp and trisomy Xq. A total of 13 reports were retrieved from the CNKI, Wanfang Data Knowledge Service Platform, Boku, CBMdisc and PubMed databases, which had included 14 similar cases. Analysis of the 15 children suggested that their main clinical manifestations have included short stature and growth retardation, and their chromosomal karyotypes were mainly mosaicisms. CONCLUSION The main clinical manifestations of TS with rapidly progressive puberty are short stature and growth retardation. Deletion in the Xp22.33p11.1 and duplication in the Xp11.1q28 probably underlay the TS with rapid progression in this child, which has provided a reference for clinical diagnosis and genetic counselling for her.
Humans ; Female ; Adolescent ; Puberty ; Turner Syndrome/genetics* ; Chromosomes, Human, X ; Karyotyping

OBJECTIVE: To describe the secular trends of age at menarche and age at natural menopause of women from a county of Shandong Province. METHODS: Based on the data of the Premarital Medical Examination and the Cervical Cancer and Breast Cancer Screening of the county, the secular trends of age at menarche in women born in 1951 to 1998 and age at menopause in women born in 1951 to 1975 were studied. Joinpoint regression was used to identify potential inflection points regarding the trend of age at menarche. Average hazard ratios (AHR) of early menopause among women born in different generations were estimated by performing multivariate weighted Cox regression. RESULTS: The average age at menarche was (16.43±1.89) years for women born in 1951 and (13.99±1.22) years for women born in 1998. The average age at menarche was lower for urban women than that for rural women, and the higher the education level, the lower the average age at menarche. Joinpoint regression analysis identified three inflection points: 1959, 1973 and 1993. The average age at menarche decreased annually by 0.03 (P < 0.001), 0.08 (P < 0.001), and 0.03 (P < 0.001) years respectively for women born during 1951-1959, 1960-1973, and 1974-1993, while it remained stable for those born during 1994-1998 (P=0.968). As for age at menopause, compared with women born during 1951-1960, those born during 1961-1965, 1966-1970 and 1971-1975 showed a gradual decrease in the risk of early menopause and a tendency to delay the age at menopause. The stratified analysis presented that the risk of early menopause gradually decreased and the age of menopause showed a significant delay among those with education level of junior high school and below, but this trend was not obvious among those with education level of senior high school and above, where the risk of early menopause decreased and then increased among those with education level of college and above, and the corresponding AHRs were 0.90 (0.66-1.22), 1.07 (0.79-1.44) and 1.14 (0.79-1.66). CONCLUSION The age at menarche for women born since 1951 gradually declined until 1994 and leveled off, with a decrease of nearly 2.5 years in these years. The age at menopause for women born between 1951 and 1975 was generally delayed over time, but the trend of first increase and then decrease was observed among those with relatively higher education levels. In the context of the increasing delay in age at marriage and childbearing and the decline of fertility, this study highlights the necessity of the assessment and monitoring of women' s basic reproductive health status, especially the risk of early menopause.
Female ; Humans ; Aged ; Menarche ; Menopause ; Regression Analysis ; Fertility ; China/epidemiology* ; Age Factors