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Communications Biology Jan 2024Age at menarche (AAM) and age at natural menopause (ANM) are highly heritable traits and have been linked to various health outcomes. We aimed to identify circulating...
Age at menarche (AAM) and age at natural menopause (ANM) are highly heritable traits and have been linked to various health outcomes. We aimed to identify circulating proteins associated with altered ANM and AAM using an unbiased two-sample Mendelian randomization (MR) and colocalization approach. By testing causal effects of 1,271 proteins on AAM, we identified 22 proteins causally associated with AAM in MR, among which 13 proteins (GCKR, FOXO3, SEMA3G, PATE4, AZGP1, NEGR1, LHB, DLK1, ANXA2, YWHAB, DNAJB12, RMDN1 and HPGDS) colocalized. Among 1,349 proteins tested for causal association with ANM using MR, we identified 19 causal proteins among which 7 proteins (CPNE1, TYMP, DNER, ADAMTS13, LCT, ARL and PLXNA1) colocalized. Follow-up pathway and gene enrichment analyses demonstrated links between AAM-related proteins and obesity and diabetes, and between AAM and ANM-related proteins and various types of cancer. In conclusion, we identified proteomic signatures of reproductive ageing in women, highlighting biological processes at both ends of the reproductive lifespan.
Topics: Humans; Female; Menarche; Mendelian Randomization Analysis; Proteomics; Biomarkers; Menopause; HSP40 Heat-Shock Proteins
PubMed: 38184718
DOI: 10.1038/s42003-023-05737-7 -
Journal of Pediatric and Adolescent... Aug 2023Menstrual dysfunction can impact both the physical and emotional health of young people. Multiple chronic diseases have been associated with menstrual dysfunction in... (Review)
Review
STUDY OBJECTIVE
Menstrual dysfunction can impact both the physical and emotional health of young people. Multiple chronic diseases have been associated with menstrual dysfunction in adults; however, there is little research in adolescents, despite nonadherence and suboptimal illness control in this group. We aimed to identify the impact of chronic illness on the age of menarche and the menstrual cycle in adolescents.
METHODS
Studies were extracted of female adolescents aged 10-19 who had a chronic physical illness. Data included outcomes on age of menarche and/or menstrual cycle quality. Exclusion criteria aimed to exclude diseases where menstrual dysfunction was a known part of the disease pathophysiology (ie, polycystic ovarian syndrome) or in which medications were used that directly impacted gonadal function. A literature search (to January 2022) was performed on the EMBASE, PubMed, and Cochrane library databases. Two widely used modified quality analysis tools were used.
RESULTS
Our initial search netted 1451 articles, of which 95 full texts were examined and 43 met the inclusion criteria. Twenty-seven papers focused on type 1 diabetes (T1D), with 8 papers examining adolescents with cystic fibrosis and the remaining studying inflammatory bowel disease, juvenile idiopathic arthritis, coeliac disease, and chronic renal disease. Metanalysis of 933 patients with T1D vs 5244 controls demonstrated a significantly later age of menarche in T1D (by 0.42 years; P ≤ .00001). There was also a significant association between higher HbA1c and insulin dose (IU/kg) and later age of menarche. Eighteen papers reviewed other aspects of menstruation, including dysmenorrhea, oligomenorrhoea, amenorrhea, and ovulatory function, with variable findings.
CONCLUSION
Most studies were small and in single populations. Despite this, there was evidence of delayed menarche and some evidence of irregular menses in those with cystic fibrosis and T1D. Further structured studies are needed to evaluate menstrual dysfunction in adolescents and how it relates to their chronic illness.
Topics: Adult; Female; Humans; Adolescent; Menstruation; Diabetes Mellitus, Type 1; Cystic Fibrosis; Menstruation Disturbances; Menarche; Menstrual Cycle; Chronic Disease
PubMed: 37192680
DOI: 10.1016/j.jpag.2023.05.005 -
Scientific Reports Aug 2023Among same-age adolescents, those who enter puberty relatively later and those who are relatively younger (e.g., born later in the year) might be at greater risk of...
Among same-age adolescents, those who enter puberty relatively later and those who are relatively younger (e.g., born later in the year) might be at greater risk of physical activity discontinuation. This study aimed to (1) describe gender-specific discontinuation, re-engagement, and uptake rates in various types of physical activities from the age of 11 to 17 years, and (2) assess puberty timing and relative age as predictors of discontinuation from organized, unorganized, individual, and group-based physical activities. Longitudinal data from 781 (56% girls, age 10-13 years at study baseline) Canadian participants who self-reported puberty status, birthdate, and involvement in 36 physical activities every four months from 2011 to 2018 was analyzed. The incidence of discontinuation, re-engagement, and uptake in organized/unorganized and individual/group activities from grade 6 until grade 12 was described and Cox proportional hazard models were used to estimate associations of puberty timing and relative age with organized/unorganized and individual/group activity discontinuation. Results demonstrate that individual and unorganized activities are maintained longer than group-based and organized activities. Girls who started puberty earlier were more likely to discontinue organized activities than girls with average-puberty timing [Hazard ratio (HR) (95% confidence interval (CI)) 1.68 (1.05-2.69)]. Compared to boys born in the 4th quarter of the year, boys born in the 2nd quarter of the year were less likely to discontinue organized [HR (95% CI) 0.41 (0.23-0.74)], unorganized [HR (95% CI) 0.33 (0.16-0.70)], group [HR (95% CI) 0.58 (0.34-0.98)], and individual activities[HR (95% CI) 0.46 (0.23-0.91)], and boys born in the 3rd quarter were less likely to discontinue unorganized activities[HR (95% CI) 0.41 (0.19-0.88)]. This study illustrates the patterns of physical activity participation throughout adolescence. However, the generalizability of findings may be limited due to participant representation.
Topics: Humans; Female; Adolescent; Exercise; Puberty; Longitudinal Studies; Sex Factors; Male; Students; Youth Sports; Canada
PubMed: 37612356
DOI: 10.1038/s41598-023-40882-3 -
Differential methylation pattern in pubertal girls associated with biochemical premature adrenarche.Epigenetics Dec 2023Biochemical premature adrenarche is defined by elevated serum DHEAS [≥40 μg/dL] before age 8 y in girls. This condition is receiving more attention due to its...
Biochemical premature adrenarche is defined by elevated serum DHEAS [≥40 μg/dL] before age 8 y in girls. This condition is receiving more attention due to its association with obesity, hyperinsulinemia, dyslipidemia, and polycystic ovary syndrome. Nevertheless, the link between early androgen excess and these risk factors remains unknown. Epigenetic modifications, and specifically DNA methylation, have been associated with the initiation and progression of numerous disorders, including obesity and insulin resistance. The aim of this study was to determine if prepubertal androgen exposure is associated with a different methylation profile in pubertal girls. Eighty-six healthy girls were studied. At age 7 y, anthropometric measurements were begun and DHEAS levels were determined. Girls were classified into Low DHEAS (LD) [<42 μg/dL] and High DHEAS (HD) [≥42 μg/dL] groups. At Tanner stages 2 and 4 a DNA methylation microarray was performed to identify differentially methylated CpG positions (DMPs) between HD and LD groups. We observed a differential methylation pattern between pubertal girls with and without biochemical PA. Moreover, a set of DNA methylation markers, selected by the LASSO method, successfully distinguished between HD and LD girls regardless of Tanner stage. Additionally, a subset of these markers were significantly associated with glucose-related measures such as insulin level, HOMA-IR, and glycaemia. This pilot study provides evidence consistent with the hypothesis that high DHEAS concentration, or its hormonally active metabolites, may induce a unique blood methylation signature in pubertal girls, and that this methylation pattern is associated with altered glucose metabolism.
Topics: Female; Humans; Child; Adrenarche; Androgens; Pilot Projects; DNA Methylation; Dehydroepiandrosterone Sulfate; Obesity
PubMed: 37053179
DOI: 10.1080/15592294.2023.2200366 -
Children (Basel, Switzerland) Oct 2023Puberty identifies the transition from childhood to adulthood. Precocious puberty is the onset of signs of pubertal development before age eight in girls and before age... (Review)
Review
Puberty identifies the transition from childhood to adulthood. Precocious puberty is the onset of signs of pubertal development before age eight in girls and before age nine in boys, it has an incidence of 1/5000-1/10,000 with an F:M ratio ranging from 3:1 to 20:1. Precocious puberty can be divided into central, also known as gonadotropin-dependent precocious puberty or true precocious puberty, and peripheral, also recognized as gonadotropin-independent precocious puberty or precocious pseudopuberty. Thus, the main aim of this narrative report is to describe the standard clinical management and therapy of precocious puberty according to the experience and expertise of pediatricians and pediatric endocrinologists at Policlinico Umberto I, Sapienza University of Rome, Italy. In the suspicion of early sexual maturation, it is important to collect information regarding the age of onset, the speed of maturation of secondary sexual features, exposure to exogenous sex steroids and the presence of neurological symptoms. The objective examination, in addition to the evaluation of secondary sexual characteristics, must also include the evaluation of auxological parameters. Initial laboratory investigations should include serum gonadotropin levels (LH and FSH) and serum levels of the sex steroids. Brain MRI should be performed as indicated by the 2009 Consensus Statement in all boys regardless of chronological age and in all girls with onset of pubertal signs before 6 years of age. The gold standard in the treatment of central precocious puberty is represented by GnRH analogs, whereas, as far as peripheral forms are concerned, the triggering cause must be identified and treated. At the moment there are no reliable data establishing the criteria for discontinuation of GnRH analog therapy. However, numerous pieces of evidence suggest that the therapy should be suspended at the physiological age at which puberty occurs.
PubMed: 37892335
DOI: 10.3390/children10101672 -
Journal of Personalized Medicine Jun 2024Limited knowledge is available about the association between autistic spectrum disorder (ASD) and precocious puberty. Our study examined the association between the two...
Limited knowledge is available about the association between autistic spectrum disorder (ASD) and precocious puberty. Our study examined the association between the two medical conditions and effect modification by sex and neuropsychiatric comorbidities in a nationwide population. To compare the risk of precocious puberty between ASD and non-ASD cases, we conducted a Cox regression analysis using ASD as the exposure and time to precocious puberty as the outcome. We adjusted for sex, attention-deficit/hyperactivity disorder (ADHD), tic disorder, obsessive-compulsive disorder (OCD), anxiety disorder, intellectual disability, and epilepsy. We performed a moderation analysis to examine the potential moderating effects of sex and comorbidities. Patients with ASD were prone to have precocious puberty, with an adjusted hazard ratio (aHR) of 1.80 (95% CI: 1.61-2.01). For effect modification, sex, specifically females, moderated the association between ASD and precocious puberty, with a relative excess risk due to interaction (RERI) of 7.35 (95% CI 4.90-9.80). No significant effect modification was found for any of the comorbidities within the scope of additive effect modification. We found that patients with ASD were prone to precocious puberty, regardless of sex or comorbid neuropsychiatric disorders. Girls with ASD are at a particularly higher risk of developing precocious puberty.
PubMed: 38929853
DOI: 10.3390/jpm14060632 -
Annals of Epidemiology Nov 2023To quantitatively estimate the association of age at menarche with the risk of childhood- and adult-onset asthma separately.
PURPOSE
To quantitatively estimate the association of age at menarche with the risk of childhood- and adult-onset asthma separately.
METHODS
A retrospective cohort study of 24,282 US girls and women was conducted using continuous National Health and Nutrition Examination Survey (NHANES) data from 2001 to 2018, and Cox proportional hazards regression models with censoring ages of 19 and 79 years were employed to separately estimate hazard ratios of childhood- and adult-onset asthma associated with age at menarche.
RESULTS
Each one-year increase in age at menarche was significantly associated with a 16% (hazard ratio [HR] = 0.84; 95% confidence interval [CI]: 0.77-0.91) decrease in the risk of childhood-onset asthma. Compared with age at menarche of 12-14 years, we observed a 56% (HR = 1.56; 95% CI: 1.19-2.04) increased risk of childhood-onset asthma for early menarche (age at menarche < 12 years) and a 40% (HR = 0.60; 95% CI: 0.32-1.10) decreased risk for late menarche (age at menarche ≥ 15 years). No significant association was noted between age at menarche and adult-onset asthma.
CONCLUSIONS
Early menarche may represent a risk factor for childhood-onset asthma, which indicates the need for timely and effective management of individuals with early menarche to prevent asthma.
Topics: Adult; Humans; Female; Child; Adolescent; Menarche; Nutrition Surveys; Retrospective Studies; Risk Factors; Asthma; Age Factors
PubMed: 37598789
DOI: 10.1016/j.annepidem.2023.08.003 -
Journal of Pediatric Endocrinology &... Nov 2023Disorders of pubertal development are enlisted as associated conditions in children and adolescents with type-1 diabetes (T1D). We conducted this study with objective...
OBJECTIVES
Disorders of pubertal development are enlisted as associated conditions in children and adolescents with type-1 diabetes (T1D). We conducted this study with objective (1) To estimate the median age at onset of puberty and luteinizing hormone (LH) and sex-steroid concentrations in Indian adolescents with T1D and (2) To assess the impact of puberty on glycemic control and insulin resistance (IR).
METHODS
This cross-sectional study included 399 children and youth aged 6-23 years with T1D. Demographic, anthropometric, biochemical and pelvic ultrasound data were collected using standard protocols. IR was calculated using estimated glucose disposal rate and puberty was assessed using Tanner staging.
RESULTS
Median age at onset of thelarche, pubarche and menarche were 11.3, 11.4 and 12.8 years in girls and that of gonadarche and pubarche were 10.6 and 12.7 years for boys. The mean LH and sex-steroid concentrations of subjects with T1D were similar to healthy subjects at each stage of puberty. The cut-offs of LH and sex-steroids derived from healthy Indian children yielded high sensitivity and specificity in determining pubertal onset. The prevalence of precocity, delayed puberty, ovarian cysts and polycystic ovaries was 0.9 , 5.1, 5.1 and 8.6 %, respectively. Glycaemic control and insulin sensitivity was poor in pubertal subjects.
CONCLUSIONS
The age at onset of puberty, LH, and sex-steroid concentrations in subjects with T1D were like otherwise healthy Indian children with poor glycemic control and IR in pubertal subjects. Although most complications of T1D are associated with poor glycemic control, pubertal disorders were significantly low despite the less-than-optimal glycemic control.
Topics: Male; Female; Humans; Child; Adolescent; Diabetes Mellitus, Type 1; Cross-Sectional Studies; Puberty; Menarche; Luteinizing Hormone; Insulin Resistance; Steroids
PubMed: 37743516
DOI: 10.1515/jpem-2023-0153 -
Journal of Clinical Research in... Nov 2023This study was designed to examine the effect of blue light exposure and exposure time on puberty in an animal model.
OBJECTIVE
This study was designed to examine the effect of blue light exposure and exposure time on puberty in an animal model.
METHODS
Eighteen 21-day-old female Sprague Dawley rats were divided into three equal groups which were: control group (CG); blue light-6 hours (BL-6); and blue light-12 hours (BL-12). CG rats were maintained with 12/12-hour light-dark cycles. The animals in BL-6 and BL-12 were exposed to blue light of wavelength 450-470 nm and intensity of 0.03 uW/cm for 6 and 12 hours, respectively. Exposure to blue light continued until the first signs of puberty. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, dehydroepiandrosterone sulfate (DHEA-S), leptin and melatonin were measured. Subsequently the ovaries and uterus were examined histomorphologically.
RESULTS
The median day of puberty start was 38, 32 and 30 for the CG, BL-6, and BL-12 groups, respectively (p=0.001). FSH, testosterone, DHEA-S, and leptin concentrations of all groups were similar. However, LH and estradiol concentrations in BL-6 were higher compared to CG (p=0.02). There was a negative correlation between blue light exposure, exposure time, and melatonin concentrations (r=-0.537, p=0.048). Ovarian tissue was compatible with puberty in all groups. As blue light exposure time increased, capillary dilatation and edema in the ovarian tissue increased. Prolonged exposure was associated with polycystic ovary-like (PCO) morphological changes and apoptosis in granulosa cells.
CONCLUSION
These results suggest that exposure to blue light and the duration of exposure induced earlier puberty in female rats. As the duration of blue light exposure increased, PCO-like inflammation, and apoptosis were detected in the ovaries.
Topics: Rats; Female; Humans; Animals; Leptin; Melatonin; Rats, Sprague-Dawley; Luteinizing Hormone; Follicle Stimulating Hormone; Estradiol; Puberty; Polycystic Ovary Syndrome; Testosterone; Dehydroepiandrosterone
PubMed: 37212628
DOI: 10.4274/jcrpe.galenos.2023.2022-12-1 -
The Journal of Clinical Endocrinology... Jun 2024The assessment and treatment of children with growth retardation is increasingly complex, and due to availability of targeted genetic sequencing, an ever-expanding... (Review)
Review
CONTEXT
The assessment and treatment of children with growth retardation is increasingly complex, and due to availability of targeted genetic sequencing, an ever-expanding number of conditions impeding growth are being identified. Among endocrine-related etiologies of short stature amenable to hormonal treatment, defects in the growth hormone (GH)-insulin-like growth factor I axis remain pre-eminent, with a multiplicity of disorders causing decreased secretion or insensitivity to GH action. Sex steroids in puberty increase epiphyseal senescence and eventual growth plate closure. This is mediated mostly via estrogen receptor (ER)α in males and females, effects that can greatly limit time available for growth.
EVIDENCE ACQUISITION
Extensive literature review through PubMed and other search engines.
EVIDENCE SYNTHESIS
Therapeutic strategies to be considered in peripubertal and pubertal children with disordered growth are here discussed, including daily and weekly GH, low-dose sex steroids, gonadotropin hormone releasing hormone (GnRH) analogues in combination with GH, aromatase inhibitors (AIs) alone and in combination with GH in boys. When used for at least 2 to 3 years, GnRH analogues combined with GH can result in meaningful increases in height. AIs used with GH permit puberty to progress in boys without hindrance, selectively decreasing estrogen, and resulting in taller height. With more than 20 years of cumulative experience in clinical use of these medications, we discuss the safety profile of these treatments.
CONCLUSION
The approach of growth retardation in the peripubertal and pubertal years must consider the sex steroid milieu and the tempo of bone acceleration. Treatment of affected children in this period must be individualized.
Topics: Humans; Child; Growth Disorders; Human Growth Hormone; Puberty; Body Height; Male; Female; Aromatase Inhibitors; Gonadotropin-Releasing Hormone; Insulin-Like Growth Factor I; Adolescent
PubMed: 38181434
DOI: 10.1210/clinem/dgae011