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Clinical Epigenetics Jun 2024Genetic and environmental factors are implicated in many developmental processes. Recent evidence, however, has suggested that epigenetic changes may also influence the...
BACKGROUND
Genetic and environmental factors are implicated in many developmental processes. Recent evidence, however, has suggested that epigenetic changes may also influence the onset of puberty or the susceptibility to a wide range of diseases later in life. The present study aims to investigate changes in genomic DNA methylation profiles associated with pubertal onset analyzing human peripheral blood leukocytes from three different groups of subjects: 19 girls with central precocious puberty (CPP), 14 healthy prepubertal girls matched by age and 13 healthy pubertal girls matched by pubertal stage. For this purpose, the comparisons were performed between pre- and pubertal controls to identify changes in normal pubertal transition and CPP versus pre- and pubertal controls.
RESULTS
Analysis of methylation changes associated with normal pubertal transition identified 1006 differentially methylated CpG sites, 86% of them were found to be hypermethylated in prepubertal controls. Some of these CpG sites reside in genes associated with the age of menarche or transcription factors involved in the process of pubertal development. Analysis of methylome profiles in CPP patients showed 65% and 55% hypomethylated CpG sites compared with prepubertal and pubertal controls, respectively. In addition, interestingly, our results revealed the presence of 43 differentially methylated genes coding for zinc finger (ZNF) proteins. Gene ontology and IPA analysis performed in the three groups studied revealed significant enrichment of them in some pathways related to neuronal communication (semaphorin and gustation pathways), estrogens action, some cancers (particularly breast and ovarian) or metabolism (particularly sirtuin).
CONCLUSIONS
The different methylation profiles of girls with normal and precocious puberty indicate that regulation of the pubertal process in humans is associated with specific epigenetic changes. Differentially methylated genes include ZNF genes that may play a role in developmental control. In addition, our data highlight changes in the methylation status of genes involved in signaling pathways that determine the migration and function of GnRH neurons and the onset of metabolic and neoplastic diseases that may be associated with CPP in later life.
Topics: Humans; Puberty, Precocious; Female; DNA Methylation; Child; CpG Islands; Epigenesis, Genetic; Epigenome; Case-Control Studies
PubMed: 38909248
DOI: 10.1186/s13148-024-01683-1 -
Journal of Pediatric Surgery May 2024Congenital adrenal hyperplasia (CAH) is the most common cause of genital atypia in females. A dedicated multidisciplinary team (MDT) should be included for an optimal...
Genito-urinary Reconstruction in Female Children With Congenital Adrenal Hyperplasia: Favorable Surgical Outcomes can be Achieved by Contemporary Techniques and a Dedicated Multidisciplinary Management.
INTRODUCTION
Congenital adrenal hyperplasia (CAH) is the most common cause of genital atypia in females. A dedicated multidisciplinary team (MDT) should be included for an optimal management. Here, we aimed to review our surgical experience and to assess long-term urinary, gynecological and endocrine outcomes after primary genitoplasty in this specific cohort.
METHODS
Patients born with CAH and who underwent feminizing genitoplasty in our institution were retrospectively identified (2001-2021). We analyzed patients' characteristics, intraoperative details, and postoperative urinary, gynecological, and endocrine outcomes.
RESULTS
Forty patients were included and followed-up for a median (IQR) time of 7 (1-19) years. Thirty-eight (95%) had 21-hydroxylase deficiency. After multidisciplinary decision and written consent from patient and/or family, a single-stage reconstructive surgery was performed at a median age of 10 (3-165) months. Median length of hospital stay was 5 (1-7) days. Procedures were: PUM (N = 35 (87.5%)), TUM (N = 3 (7.5%)), urogenital mobilization was unnecessary in 2 (5%). Reduction clitoroplasty was done in 33 (82.5%) patients. Only 3 (7.5%) experienced significant Clavien-Dindo complications requiring additional surgery during the follow-up period. Recurrent urinary tract infections (UTI) occurred in 6 (15%), one required ureteric reimplantation for symptomatic high-grade vesicoureteric reflux. All patients over 3 years were toilet-trained without incontinence. Severe vaginal stenosis occurred in 1 (2.5%) patient. In patients who achieved puberty, 6/9 had vaginal calibration at a median age of 17.3 (16-21) years without detected stenosis. One (2.5%) had major hypertrophy of the right labia minora requiring labiaplasty. Nine (22.5%) reached puberty. Two (5%) patients developed acne/hirsutism. Short stature was noted in 11 (27.5%) and obesity in 18 (45%).
CONCLUSION
Based on our contemporary series, genitourinary reconstructive surgery for female patients born with CAH is technically feasible and safe with a low complication rate. A regular follow-up with a MDT to assess long-term complications is necessary, and it is vital to inform patients and families about the different management options with all the risks and benefits of surgery.
TYPE OF THE STUDY
original research, clinical research.
LEVEL OF EVIDENCE
Level 3 retrospective study.
PubMed: 38902168
DOI: 10.1016/j.jpedsurg.2024.05.009 -
Frontiers in Endocrinology 2024The age at menarche has decreased worldwide. Previous studies on Korean adolescents have reported a downward trend in age at menarche. This study aimed to investigate...
BACKGROUNDS
The age at menarche has decreased worldwide. Previous studies on Korean adolescents have reported a downward trend in age at menarche. This study aimed to investigate the current trends in age at menarche among Korean adolescents using nationally representative data.
MATERIALS AND METHODS
The study used data from the Korea National Health and Nutrition Examination Survey 2007-2021. A total of 50,730 females born between 1927 and 2004 with information on age at menarche were included. The trend in age at menarche was analyzed according to 15 birth-year groups (with 5-year intervals) using quantile regression analysis.
RESULTS
The mean age at menarche decreased from 16.92 ± 0.06 years for females born before 1935 to 12.45 ± 0.04 years for females born between 2000 and 2004 ( <.001). According to the percentile group of age at menarche, mean menarche age decreased by -0.071 years per year (95% confidence interval [CI], -0.072 to -0.070) in total, -0.050 years per year (95% CI, -0.052 to -0.048) in the 3rd percentile group, -0.088 years per year (95% CI, -0.091 to -0.085) in the 97th percentile group ( <.001 for all). A decreasing trend of age at menarche was more prominent in the obesity group (-0.080 years per year, 95% CI, -0.082 to -0.078) compared to the non-obesity group (-0.069 years per year, 95% CI, -0.071 to -0.068) ( <.001 for both).
CONCLUSION
Ongoing downward trend in age at menarche was observed in Korean females born until 2004, decreasing by 0.71 years per decade. The downward trend was faster in individuals with a higher percentile of age at menarche and in those with obesity.
Topics: Humans; Menarche; Female; Republic of Korea; Adolescent; Age Factors; Nutrition Surveys; Child
PubMed: 38894747
DOI: 10.3389/fendo.2024.1399984 -
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 -
Nutrients May 2024Children with a history of extrauterine growth restriction (EUGR), later at prepubertal age, exhibit an increased metabolic risk including risen insulin resistance and...
Children with a history of extrauterine growth restriction (EUGR), later at prepubertal age, exhibit an increased metabolic risk including risen insulin resistance and low-grade inflammation. However, the progression of such metabolic changes after puberty and the lasting health implications have not yet been investigated. The objective of this study was to ascertain whether young adults with a history of EUGR faced increased vulnerability to metabolic disorders. A study was conducted comparing a group of adults with a history of EUGR with a healthy reference group. A total of 110 young adults (36 from the EUGR group and 74 from the control group) were included. Anthropometric variables, blood pressure (BP), general biochemical parameters, plasma inflammatory biomarkers, and adipokines were assessed. Compared to the reference group, the EUGR group had a shorter height and body weight with higher lean mass and waist circumference, as well as a greater percentage of individuals with high BP. In addition, EUGR patients had higher values of insulin, HOMA-IR, nerve growth factor, and leptin, and lower levels of adiponectin and resistin. The present study suggests that young adults with a history of EUGR present increased metabolic risk factors therefore, clinical follow-up should be considered.
Topics: Humans; Male; Female; Young Adult; Inflammation; Biomarkers; Insulin Resistance; Adult; Risk Factors; Growth Disorders; Adipokines; Blood Pressure
PubMed: 38892541
DOI: 10.3390/nu16111608 -
Healthcare (Basel, Switzerland) May 2024People with intellectual disability want friendships and meaningful relationships, and some want intimacy. However, the expression of sexuality is an area where...
The Experiences of Young People with Intellectual Disability, Parents and Professionals in Relationships and Sexuality Education Programmes: Findings from a Qualitative Study.
People with intellectual disability want friendships and meaningful relationships, and some want intimacy. However, the expression of sexuality is an area where potential freedoms are often limited and restricted compared to their peers. While some relationships and sexuality education programmes do exist for this population, most focus on knowledge acquisition regarding sexuality and sex but lack in their focus on relationships, informed choices and decision-making. The aim of this study was to identify good practices and methods of delivery in relationships and sexuality education for children and young people with intellectual disability. A qualitative design was undertaken. Information about our study was distributed to eight special schools in the UK. Semi-structured interviews and focus groups were employed for data collection. Data from 37 pupils with intellectual disability, 11 parents and 16 healthcare and other professionals were thematically analysed. Following data analysis, three themes emerged: (i) seeking and sharing information; (ii) protecting and keeping safe; and (iii) learning for the future. The findings highlight that pupils are keen to learn about life changes and societal influences and want reliable information. Parents and professionals recognise that children and young people with intellectual disability will develop into adults and may be vulnerable when they leave the security of the school setting. They recognise that children and young people need to know about socialising, puberty, consent and contraception. Evidence-based programmes should be designed with these stakeholders to ensure children and young people with intellectual disability receive developmentally appropriate information to make happy and safe decisions about their relationships.
PubMed: 38891180
DOI: 10.3390/healthcare12111105 -
European Journal of Medical Research Jun 2024Nowadays, there has been limited Mendelian randomization (MR) research focusing on the causal relationship between estradiol and vaginitis. Therefore, this study...
OBJECTIVE
Nowadays, there has been limited Mendelian randomization (MR) research focusing on the causal relationship between estradiol and vaginitis. Therefore, this study conducted a two-way MR study to clarify the causal effect and related influencing factors between them.
METHODS
All genetic datasets were obtained using publicly available summary statistics based on individuals of European ancestry from the IEU GWAS database. MR analysis was performed using MR-Egger, weighted median (WM) and inverse variance weighted (IVW) methods to assess the causal relationship between exposure and outcome and to validate the findings by comprehensively evaluating the effects of pleiotropic effects and outliers.
RESULTS
MR analysis revealed no significant causal relationship between estradiol and vaginitis risk. There was a negative correlation between estradiol and age at menarche (IVW, OR: 0.9996, 95% CI: 0.9992-1.0000, P = 0.0295; WM, OR: 0.9995, 95% CI: 0.9993-0.9998, P = 0.0003), and there was a positive correlation between age at menarche and vaginitis (IVW, OR: 1.5108, 95% CI: 1.1474-2.0930, P = 0.0043; MR-Egger, OR: 2.5575, 95% CI: 1.7664-9.6580, P = 0.0013). Estradiol was negatively correlated with age at menopause (IVW, OR: 0.9872, 95% CI: 0.9786-0.9959, P = 0.0041). However, there was no causal relationship between age at menopause and vaginitis (P > 0.05). In addition, HPV E7 Type 16, HPV E7 Type 18, and Lactobacillus had no direct causal effects on estradiol and vaginitis (P > 0.05). Sensitivity analyses revealed no heterogeneity and horizontal pleiotropy.
CONCLUSION
When estrogen levels drop, it will lead to a later age of menarche, and a later age of menarche may increase the risk of vaginitis, highlighting that the longer the female reproductive tract receives estrogen stimulation, the stronger the defense ability is formed, and the prevalence of vaginitis is reduced. In conclusion, this study indirectly supports an association between reduced level of estrogen or short time of estrogen stimulation and increased risk of vaginitis.
Topics: Humans; Female; Mendelian Randomization Analysis; Estradiol; Vaginitis; Menarche; Inflammation
PubMed: 38890725
DOI: 10.1186/s40001-024-01914-4 -
Cureus Jun 2024This narrative review comprehensively examines the intricate relationship between period poverty and the Sustainable Development Goals (SDGs), positioning it as a... (Review)
Review
This narrative review comprehensively examines the intricate relationship between period poverty and the Sustainable Development Goals (SDGs), positioning it as a critical public health challenge with far-reaching implications. Through an in-depth analysis of the multifaceted impact of period poverty on public health, including its effects on reproductive health, mental well-being, and economic participation, the paper underscores the urgent need to address this issue within the framework of the SDGs. An overview of existing literature on period poverty, its impact on health and well-being, and its relation to the SDGs was carried out. Different perspectives, interventions, and policy approaches to addressing period poverty were also explored. By illuminating the interplay between period poverty and various SDGs, particularly those related to gender equality, health, education, and economic empowerment, the study emphasizes the imperative of integrating menstrual health and hygiene into global development efforts. Advocating for targeted policies, funding, and advocacy, the manuscript calls for a holistic and inclusive approach to breaking the cycle of period poverty, ultimately contributing to advancing the SDGs and fostering a more equitable and healthier global society. Efforts to eradicate period poverty - providing affordable menstrual products, improving sanitation infrastructure, enhancing education, and implementing supportive policies - lead to significant progress in public health and gender equity. By prioritizing menstrual health management in public health policies, educational programs, and economic strategies, we can ensure that everyone who menstruates can do so with dignity and without limits on their potential.
PubMed: 38887745
DOI: 10.7759/cureus.62499 -
Reproductive Health Jun 2024Adolescents in Ghana are vulnerable to unequal power relations at the personal, community and structural levels which in turn limits their opportunities in access to...
BACKGROUND
Adolescents in Ghana are vulnerable to unequal power relations at the personal, community and structural levels which in turn limits their opportunities in access to critical sexual and reproductive health information and services. There is therefore high unmet need for sexual and reproductive health (SRH) information and services and the Bono East region typifies this situation, recording some of the poorest SRHR outcomes among adolescents. We, therefore, aimed to investigate the SRH needs (unmet), behaviors and utilization of SRH services among adolescents in the Bono East region.
METHODS
Using a maximum variation sampling approach, this qualitative study conducted in-depth interviews and focused group discussions with adolescent boys and girls, parents, community leaders, and healthcare providers.
RESULTS
Our findings are presented under two broad categories: major SRHR concerns of adolescents, and perspectives about that influences adolescents' utilization of SRHR services. Under the major SRHR need of adolescents, the following themes emerged: information and services on pregnancy prevention, menstrual hygiene management, availability of comprehensive abortion care services, and attitudes towards adolescent pregnancy. The perspectives about the factors that influence adolescent children were discussed at multiple levels: individual/personal. interpersonal and community/societal. At the individual level, limited understanding of adolescence/puberty, desire of adolescents to belong and misperceptions about contraceptives. At the interpersonal level, issues relating to technical capacity needs of service providers, disrespect exhibited by service providers, and parental failure were identified as influential factors. Then at the community/societal level, we identified structural constraints and compromised social safety concerns in accessing contraceptives and services.
CONCLUSION
In conclusion, the findings from this study offer valuable insights into the complex landscape of adolescent sexual and reproductive health in the Bono East region. The implications for policy and practice are manifold, ranging from comprehensive education to addressing menstrual hygiene, involving parents, training healthcare providers, and promoting respectful care.
Topics: Humans; Adolescent; Female; Ghana; Male; Reproductive Health Services; Reproductive Health; Sexual Health; Health Services Needs and Demand; Qualitative Research; Pregnancy; Health Services Accessibility; Patient Acceptance of Health Care; Sexual Behavior; Pregnancy in Adolescence; Health Knowledge, Attitudes, Practice; Adolescent Health Services; Adolescent Behavior
PubMed: 38886821
DOI: 10.1186/s12978-024-01822-0 -
Breast Cancer Research : BCR Jun 2024Early menarche is an established risk factor for breast cancer but its molecular contribution to tumor biology and prognosis remains unclear.
BACKGROUND
Early menarche is an established risk factor for breast cancer but its molecular contribution to tumor biology and prognosis remains unclear.
METHODS
We profiled transcriptome-wide gene expression in breast tumors (N = 846) and tumor-adjacent normal tissues (N = 666) from women in the Nurses' Health Studies (NHS) to investigate whether early menarche (age < 12) is associated with tumor molecular and prognostic features in women with breast cancer. Multivariable linear regression and pathway analyses using competitive gene set enrichment analysis were conducted in both tumor and adjacent-normal tissue and externally validated in TCGA (N = 116). Subgroup analyses stratified on ER-status based on the tumor were also performed. PAM50 signatures were used for tumor molecular subtyping and to generate proliferation and risk of recurrence scores. We created a gene expression score using LASSO regression to capture early menarche based on 28 genes from FDR-significant pathways in breast tumor tissue in NHS and tested its association with 10-year disease-free survival in both NHS (N = 836) and METABRIC (N = 952).
RESULTS
Early menarche was significantly associated with 369 individual genes in adjacent-normal tissues implicated in extracellular matrix, cell adhesion, and invasion (FDR ≤ 0.1). Early menarche was associated with upregulation of cancer hallmark pathways (18 significant pathways in tumor, 23 in tumor-adjacent normal, FDR ≤ 0.1) related to proliferation (e.g. Myc, PI3K/AKT/mTOR, cell cycle), oxidative stress (e.g. oxidative phosphorylation, unfolded protein response), and inflammation (e.g. pro-inflammatory cytokines IFN and IFN ). Replication in TCGA confirmed these trends. Early menarche was associated with significantly higher PAM50 proliferation scores (β = 0.082 [0.02-0.14]), odds of aggressive molecular tumor subtypes (basal-like, OR = 1.84 [1.18-2.85] and HER2-enriched, OR = 2.32 [1.46-3.69]), and PAM50 risk of recurrence score (β = 4.81 [1.71-7.92]). Our NHS-derived early menarche gene expression signature was significantly associated with worse 10-year disease-free survival in METABRIC (N = 952, HR = 1.58 [1.10-2.25]).
CONCLUSIONS
Early menarche is associated with more aggressive molecular tumor characteristics and its gene expression signature within tumors is associated with worse 10-year disease-free survival among women with breast cancer. As the age of onset of menarche continues to decline, understanding its relationship to breast tumor characteristics and prognosis may lead to novel secondary prevention strategies.
Topics: Humans; Female; Breast Neoplasms; Menarche; Neoplasm Recurrence, Local; Middle Aged; Prognosis; Transcriptome; Gene Expression Profiling; Adult; Biomarkers, Tumor; Risk Factors; Gene Expression Regulation, Neoplastic; Age Factors
PubMed: 38886818
DOI: 10.1186/s13058-024-01839-0