obesity and puberty in males

Meanwhile, we also analyzed the association between childhood overweight/obese and puberty in boys. Its possible that leptin is speeding up the development of these structures in the base of the brain.. Meta-analytic pooling of these risk estimates yielded a summary OR of 1.29 (95% CI 0.981.70), with substantial heterogeneity (I2 = 68%, p = 0.01). The ORs for the association reported by included studies ranged from 1.11 to 9.00. Forest plot of childhood overweight/obesity and the risk of early puberty in girls. The boys were part of Chiles Growth and Obesity Cohort Study. Early growth predicts timing of puberty in boys: results of a 14-year nutrition and growth study. Case-control studies are widely considered to be prone to recall and selection biases, which restrict the strength and quality of evidence. Her team compared normal female mice to mice lacking leptin, who are obese and fail to enter puberty on their own. The ePub format uses eBook readers, which have several "ease of reading" features Obesity and Bone: A Complex Relationship. When modelling all pubertal milestones simultaneously, the pubertal milestones were attained earlier in: overweight boys: 3.1 [95% confidence interval (CI): 4.5, 1.7] months, overweight girls: 5.5 (95% CI: 7.1, 3.9) months, obese boys: 3.5 (95% CI: 5.1, 2.0) months, obese girls: 5.2 (95% CI: 7.1, 3.4) months compared with normal weight (BMI < 85th percentile) children. With the increase in childhood obesity worldwide, there has been an advance in the age at which puberty begins in girls, said the lead investigator, Maria Veronica Mericq, M.D., a professor at the university. Phone: (202)-971-3611 Our findings showed that for girls the associate between overweight/obesity and early puberty is definite or strong whereas for males, such an association is possible, prompting that future studies need to further explore the possible relationship between overweight/obesity and early puberty in boys. Stature and pubertal stage assessment in American boys: the 19881994 Third National Health and Nutrition Examination Survey. Adj., adjusted; BMI, body mass index; CI, confidence interval; ref, reference. They also analyzed BMI as a continuous variable, and the association held up, as it did for central obesity and precocious puberty. doi: 10.4081/pr.2012.e35. For girls, puberty can begin as early as eight years old, with most instances of early puberty linked to childhood obesity. Would you like email updates of new search results? Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, CA, USA, 3 Will obesity affect puberty? The Chi-square test was used to estimate whether the variance between studies was ascribed to chance and the I2 statistic was used to estimate the proportion of total variation in prevalence evaluations owing to statistical heterogeneity instead of sampling error. This sequence conforms to the law of natural development of causality, so it has a strong ability to test the etiology hypothesis. The obese children were heavier at birth than normal-weight children, whereas dietary patterns, physical activity and sedentary behaviour only varied slightly between childhood weight groups (Table1). 2022 May 5;22(1):249. doi: 10.1186/s12887-022-03317-y. The Danish National Birth Cohort was established with a significant grant from the Danish National Research Foundation. Aksglaede L, Juul A, Olsen LW, Sorensen TI.. Age at puberty and the emerging obesity epidemic. [emailprotected]. Unlike overweight girls, who tend to reach puberty earlier than do girls of normal weight, overweight and obese boys in the U.S. may begin puberty later than thinner boys. The Committee for Biomedical Research Ethics in Denmark approved the collection of data in the DNBC ((KF)01471/94). Before Additional support was obtained from: the Danish Regional Committees; the Pharmacy Foundation; the Egmont Foundation; the March of Dimes Birth Defects Foundation; the Health Foundation; and other minor grants. Our study is the first time to conduct a meta-analysis of the relationship between childhood overweight/obesity and early puberty in boys, although the association is possible. Juul A, Magnusdottir S, Scheike T, Prytz S, Skakkebaek NE.. Age at voice break in Danish boys: effects of pre-pubertal body mass index and secular trend, Secondary sexual characteristics in boys: estimates from the National Health And Nutrition Examination Survey III, 1988-1994. Puberty is the physiological process and crucial developmental stage, typically beginning between 9.5 and 13.5 years of age (average 11.5 years) in boys and lasting normally about 5-6 years, characterized by the gradual transition from childhood to adulthood, with the attainment of appearance of secondary sexual characteristics and mainly of sexual maturity and reproductive capability []. Childhood BMI was reported by mothers and is only a proxy for body fat.53 Moreover, self-reported BMI is not a perfect measure compared with BMI measured by health care professionals. Begg's test did not show a potential publication bias (z = 0.49, p = 0.624). Overweight boys tend to enter and finish puberty somewhat earlier than usual, researchers found in a study of nearly 3,900 males aged 6 to 16. Our results suggest that controlling the obesity epidemic in children could be useful in decreasing these risks.. Adjusted mean age at attaining the pubertal milestones as spline functions of childhood BMI (body mass index). Compared with children who did not participate in the cohort analysis, children who participated (n=11046, 49%) were more likely to have normal weight and non-smoking mothers with higher education, to be of normal weight themselves and to eat vegetables, whereas other dietary factors, physical activity and sedentary behaviour were similar (data not shown). Previous studies found that obesity may alter hormone secretion and sensitivity, including leptin and insulin. Girls grow 2-8 inches (5-20 centimeters) taller, while boys grow 4-12 inches (10-30 centimeters) taller. MORE FROM THE LAB: Subscribe to our weekly newsletter. Puberty is second to the prenatal period in terms of rapid growth as the long bones stretch to their final, adult size. However, in boys the evidence has been controversial.. And puberty may be starting earlier in boys as well. Zhai L, Liu J, Zhao J, Liu J, Bai Y, Jia L, et al.. Association of obesity with onset of puberty and sex hormones in chinese girls: a 4year longitudinal study, Percent body fat and waist circumference from ages 5 to 9 predict early puberty in girls. The same associations for girls were found in the sibling-matched analysis for almost all pubertal milestones, indicating that confounding from shared factors, such as socioeconomic and genetic factors, cannot explain the associations observed in the cohort analysis. DOI: 10.1016/j.isci.2020.101563. Moreover, through subgroup analysis, we found that overweight girls (OR=4.67, 95% CI: 1.6013.63) enter puberty earlier than obese girls (OR=2.22, 95% CI: 1.652.99). Karpati AM, Rubin CH, Kieszak SM, Marcus M, Troiano RP. An official website of the United States government. The second phase involves weight gain related to bone, muscle, and fat tissue development. Nutritional status plays an important role in regulating growth, and excess body weight early in life can influence growth patterns. In addition, obese girls are also at increased risk of hyperandrogenism. Her lab has been studying the role of metabolism in reproduction, looking for clues within the brain to help explain the effects of metabolic signals in pubertal onset and fertility. To look for dose-dependent patterns, we also included childhood BMI as restricted cubic splines with three knots at 14, 16 and 18kg/m2. When restricting to either sibling-pairs with same father or siblings born 3.0years apart, the results remained essentially the same (Supplementary Table 6, available as Supplementary data at IJE online). Qualitative analysis identified that boys with high BMI trajectories had a greater risk of early puberty than boys with low BMI trajectories (13). Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark. The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors. 2022 Apr 4;14(7):1506. doi: 10.3390/nu14071506. Childhood was defined internationally as the age range of 018 years. 2010 Sep;140(3):399-410. doi: 10.1530/REP-10-0119. Among these singletons were 888 brothers and 812 sisters (Figure1). Childhood BMI percentiles were derived,39 and children were then categorized as normal weight (BMI<85th percentile), overweight (85th BMI< 95th percentile) and obese (BMI 95th percentile). The impact of childhood body mass index on timing of puberty, adult stature and obesity: a follow-up study based on adolescent anthropometry recorded at Christ's Hospital (1936-1964, BMI in childhood and its association with height gain, timing of puberty, and final height. Lundeen EA, Norris SA, Martorell R. suggested obesity in preadolescent children may lead to the improvement of aromatase activity, which can accelerate the conversion of androgens to estrogen (33). HHS Vulnerability Disclosure, Help Subgroup and sensitivity analyses were performed to explore possible sources of heterogeneity and to assess the robustness of the results. E-mail: Received 2020 Mar 3; Accepted 2020 Mar 24. We found that higher childhood BMI was associated with earlier pubertal timing in boys and girls in both a cohort analysis and a sibling-matched analysis. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. "Prevention of obesity would prevent a slight delay in timing of puberty," Kaplowitz says. meta-analysis, childhood, early puberty, puberty time, overweight, obesity, Prevalence of obesity and trends in body mass index among US children and adolescents, 19992010, Empirical changes in the prevalence of overweight and obesity among Chinese students from 1985 to 2010 and corresponding preventive strategies, Prevalence and trends in obesity among China's children and adolescents, 19852010, Prevalence of childhood and adult obesity in the United States, 20112012, Bmi in childhood and its association with height gain, timing of puberty, and final height. Early life growth predicts pubertal development in South African adolescents. In the sibling-matched analysis, point estimates ranged -9.7 to 0.8months in boys and -18.0 to -3.1months per 5kg/m2 higher childhood BMI (Table3). Flehmig G, Scholz M, Klting N, Fasshauer M, Tnjes A, Stumvoll M, et al.. Leito RB, Rodrigues LP, Neves L, Carvalho GS. To determine the relationship between childhood overweight/obesity and early puberty in both boys and girls. 19, 20 the. On the other hand, in boys, few research reported an association between obesity and pubertal development, and the results are inconsistent; Some studies found a link between obesity and. To determine central obesity, study personnel measured each boys waistline. Our finding of an association between childhood overweight/obesity and the risk of early puberty has significant implications for child and adolescent health. Follow us on Twitter at@TheEndoSocietyand@EndoMedia. 2021 June; 50(3): 1047. These cohort and sibling-matched study designs were based on the Danish National Birth Cohort (DNBC)37 and its sub-cohort, the Puberty Cohort. Previous studies found that girls with obesity start puberty and experience their first menstrual period earlier than girls with normal weight. sharing sensitive information, make sure youre on a federal Obesity may contribute to early onset of puberty in . These sources of measurement error are most likely non-differential with regard to the childrens pubertal timing that usually occurs a few years later. For people assigned male at birth, puberty begins at age 11 on average, although starting as early as age 9 or as late as age 14 is still considered normal. Peak LH responses correlate with LH peak concentrations. Birthweight and parity were obtained from the Danish Medical Birth Registry.44 Highest educational class of the parents was obtained from Statistics Denmark and classified according to the International Standard Class of Occupation and Education codes (ISCO-88 and ISCED). In boys, excess adiposity has been associated with advanced puberty in some studies, whereas others have reported a delay in pubertal onset. The Endocrine Society is the worlds oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions. The NOS was composed of eight items. Burden of Early Life Obesity and Its Relationship with Protein Intake in Infancy: The Middle East Expert Consensus. It ranged from 19 stars and assessed the quality of each study based on three modules: selection, comparability, and outcome (cohort studies) or exposure (case-control studies). Clipboard, Search History, and several other advanced features are temporarily unavailable. A study from Spain noted that BMI and age of pubertal onset were correlated in boys, but body fat mass was not correlated with pubertal onset. Understanding how the interactions of these factors contribute the relationship between obesity and early pubertal onset is crucial as early puberty has been linked with long-term consequences, such as short stature, earlier type 2 diabetes, cardiovascular disease, and poor psychological and behavioral outcomes. Disclaimer, National Library of Medicine Does obesity cause early puberty in boys? In contrast, study results from Europe showed earlier puberty in boys with overweight and obesity. A comparison of the association in American boys versus girls. Relevant studies were identified from PubMed, Web of Science, and EMBASE searches. The site is secure. [Hyperinsulinemia, insulin-like growth factor-I, insulin-like growth factor-binding protein-1, and sex-hormone binding-globulin in prepubertal and pubertal girls with premature adrenarche]. 2022. Flom JD, Cohn BA, Tehranifar P, Houghton LC, Wei Y, Protacio A, et al.. However, our data were compatible with the normal distribution. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Endocrine Society is a global community of physicians and scientists dedicated to accelerating scientific breakthroughs and improving patient health and well being. In vitro stimulation of the prepubertal rat gonadotropin-releasing hormone pulse generator by leptin and neuropeptide Y through distinct mechanisms, Height and weight at menarche and a hypothesis of critical body weights and adolescent events. Nis Brix, Andreas Ernst, [], and Cecilia Hst Ramlau-Hansen. Chen YC, Fan HY, Yang C, Hsieh RH, Pan WH, Lee YL. Body fat mass, body fat distribution, and pubertal development: a longitudinal study of physical and hormonal sexual maturation of girls, Role of obesity and leptin in the pubertal process and pubertal growth-a review, Leptin signaling and circuits in puberty and fertility. official website and that any information you provide is encrypted Says Elias, When you have new data, you also have a lot of new questions., Paper cited: Hypothalamic and Cell-Specific Transcriptomes Unravel a Dynamic Neuropil Remodeling in Leptin-Induced and Typical Pubertal Transition in Female Mice, iScience. A European study also reported a positive relationship between preadolescent BMI and early puberty in boys, where voice breaking was defined as puberty occurring (13). An increased risk of early puberty related to childhood overweight/obesity was also found in boys, although the estimate was not statistically significant. As far as we know, this study is the most up-to-date and comprehensive meta-analysis evaluating the relationship between childhood overweight/obesity and early puberty in both boys and girls, which can supply helpful information to both parents and primary health care providers, and help to guide relevant policy and advocacy efforts. In 2016, more than 340 million individuals aged 519 were overweight or obese worldwide (5). NCI CPTC Antibody Characterization Program. Rolland-Cachera MF, Deheeger M, Maillot M, Bellisle F.. BMI, body mass index; CI, confidence interval. As the puberty information was provided half-yearly, the pubertal milestones were right-, left- or interval-censored. A sibling-matched study has indicated earlier age at menarche after rapid childhood weight gain.64 However, important non-shared confounders, such as physical activity and diet, were not adjusted for.64 In our sibling-matched analysis, we adjusted for such non-shared confounders, and we found an earlier age at virtually all the pubertal milestones given higher childhood BMI. Among all studies included, four studies evaluated the association of childhood overweigh/obesity with early puberty in both boys and girls (19, 2729), five studies only evaluated that in girls (20, 25, 26, 30, 31), and one study only evaluated that in boys (13). Moreover, obese children had higher levels of leptin than lean children, which may have contributed to their earlier puberty (35). Precocious puberty reportedly occurred in 45 boys, or 9 percent. In boys, excess adiposity has been associated with advanced puberty in some studies, whereas others have reported a delay in pubertal onset. 2022 Mar;25(2):93-108. doi: 10.5223/pghn.2022.25.2.93. Evidence points to the hormone leptin, which is produced by fat cells, as one of the likely culprits, says Carol Elias, Ph.D., a professor of molecular & integrative physiology and obstetrics & gynecology at the U-M Medical School. When combining the estimates for all milestones using robust variance estimation, the pubertal milestones were attained earlier in overweight (boys: -3.1months; girls: -5.5months) and obese (boys: -3.5months; girls: -5.2months) children, with normal weight as the reference (Table2). Relation of age at menarche to race, time period, and anthropometric dimensions: the Bogalusa Heart Study, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021264649, Obesity: BMI of 95 percentile Overweight: 85th BMI to 94th percentile, Early menarche was defined as age at menarche earlier than 12 years. The following data were extracted: first author, year of publication, study period, geographic region, gender, study design, length of follow-up, and age of enrolment (for cohort studies only), sample size, definition of overweight/obesity, definition of early puberty, and adjustments and matches made. The most important difference between cohort studies and case-control studies is the ability to demonstrate causation. Barker DJP, Osmond C, Forsen TJ, Kajantie E, Eriksson JG.. For central obesity, which is a more reliable indicator of increased fat mass, the risk was 6.4 times higher. The associations were similar across pubertal milestones in boys, but they were larger for Tanner Breast stages in girls. In the cohort analysis, confounders were identified by use of a directed acyclic graph (Supplementary Figure 1, available as Supplementary data at IJE online).43 Potential confounders were highest educational class of parents, maternal smoking in first trimester, maternal pre-pregnancy BMI, maternal age at menarche, parity, birthweight, childhood diet, childhood physical activity, and childhood sedentary behaviour. already built in. Last but not least, there were few original studies on obesity and early puberty in boys, only five articles were included in this meta-analysis, and the definition of puberty in boys is also controversial. and transmitted securely. After subgroup analyses, the variables including sample size (TSD: 2= 6.40, p = 0.01) and confounders controlled (TSD: 2=12.31, p < 0.001) were shown to be associated with the between-study heterogeneity. Lee JM, Kaciroti N, Appugliese D, Corwyn RF, Bradley RH, Lumeng JC. The relation between obesity and male pubertal timing is an ongoing topic of debate ().In contrast to consistent reports of a strong negative association of body mass index (BMI) with female puberty timing across the entire BMI spectrum, conflicting reports concerning the association of BMI with male puberty timing exist. Meanwhile, since some subgroup categories contained only one or very few studies, the statistical power is weakened. Euling SY, Herman-Giddens ME, Lee PA. Please enable it to take advantage of the complete set of features! Childhood overweight and obesity were associated with earlier puberty in a dose-dependent manner in boys and girls in the cohort analysis. Heterogeneity was assessed by the Chi-square test (p < 0.05 represented statistically significant heterogeneity) and I2 statistic (I2 > 75% indicated an extremely high level of heterogeneity, 5175% showed a high level of heterogeneity, 2650% demonstrated a moderate-level of heterogeneity, and 25% signified a low level of heterogeneity) (23, 24). et al. BMC Pediatr. In the interaction analysis, a central fat distribution did not further strengthen the associations between weight groups and pubertal timing (Supplementary Table 4, available as Supplementary data at IJE online). (27) used Tanner stage of breast or public hair. Sibling-matched analysis: monthly difference in timing of puberty per 5kg/m2 higher BMI. Subgroup analyses for the association between childhood overweight/obesity and early puberty in girls are shown in Table 4. [Associations between early onset of puberty and obesity types in children: Based on both the cross-sectional study and cohort study]. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. For the sibling-matched study, 1700 brothers and sisters were included among 86820 live-born singletons from the DNBC. A larger number of studies have examined the relationship between adiposity and puberty in girls than in boys and the evidence that obesity leads to an earlier timing of puberty is more . De Simone M, Danubio ME, Amicone E, Verrotti A, Gruppioni G, Vecchi F. Age of onset of pubertal characteristics in boys aged 614 years of the Province of L'Aquila (Abruzzo, Italy). FOIA There is clear evidence indicating that obesity leads to early appearance of pubertal signs in girls. The younger siblings BMI at 7years was comparable to the older siblings BMI: mean difference 0.0 (standard deviation: 1.9) kg/m2. The https:// ensures that you are connecting to the The more fat we have, the more. Department of Statistics, UCLA College of Letters and Science, Los Angeles, CA, USA, 4 Overweight white boys began the first stage of puberty at an average age of 9.3 years old, versus beginning at 10 years old in boys of normal weight. Puberty looks different, in terms of both reproductive hormones and breast maturation, in girls with excess total body fat, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism. [emailprotected], Jenni Glenn Gingery LC, TW, XZ, and YH: critical revision of the manuscript for important intellectual content. More specifically, among children aged 5 or 6, those with obesity were 2.7 times more likely to start puberty early, and those with excess abdominal fat were more likely to reach puberty before the age of 9. A total of 586 cases with early puberty in 12,796 boys in childhood were identified. Specifically, this is the first time to conduct a meta-analysis of the relationship between childhood overweight/obesity and early puberty in boys.MethodsRelevant studies were identified from PubMed, Web of Science, and EMBASE searches. Puberty, the transformational period where a child reaches physical and sexual maturity, is a near universal human experience, yet the fundamental processes behind how and when it starts is still a mystery. LC and TW: study concept and design and study supervision. Among the studies, five were conducted in Asia, four in North America, and one was conducted in Europe. Higgins JP, Thompson SG, Deeks JJ, Altman DG. The inclusion of titles and abstracts was intentionally expanded with a view to obtaining more relevant studies. et al. The site is secure. Early puberty in 11-year-old girls: Millennium Cohort Study findings, Causal interpretation of between-within models for twin research, The Danish National Birth Cohort - its background, structure and aim, Maternal smoking during pregnancy and timing of puberty in sons and daughters: a population-based cohort study. In the cohort analysis, childhood overweight and obesity were associated with earlier pubertal timing in both boys and girls in a dose-dependent manner. A number of limitations merit attention. Body mass index and timing of pubertal initiation in boys, Is obesity associated with early sexual maturation? Next, they compared brain samples from the ventral premammillary and arcuate nuclei in normal pre-pubescent and adult mice to the obese leptin-deficient mice. Girls are not the only ones who go through puberty early if they have obesity. Age at Which it Starts. We conducted three sensitivity analyses. Besides, detailed analyses were conducted for more diverse subgroups. The team found a positive and statistically significant association between total body obesity and precocious puberty from four to seven years of age, with 45 boys (9.1%) starting puberty early. Mericqs team found that the prevalence of total obesity increased with age, from 22 percent of boys ages 6 to 7 years to 28.6 percent at 11.4 years, the average age at onset of puberty for this group. Then, full texts of the selected studies were reviewed. A total of 10 studies involving 13,338 girls and 12,796 boys were included. Check the full list of possible causes and conditions now! Influence of obesity on timing of puberty, Childhood obesity and the timing of puberty. In addition, obese girls are also at increased risk of hyperandrogenism. 10 to 15. Flow chart of children included in the cohort analysis and the sibling-matched analysis. . Sensitivity analysis for the association of childhood overweight/obesity and early puberty in boys. Growth during childhood and adolescence occurs at different rates and is influenced by the interaction between genetic and environmental factors. The https:// ensures that you are connecting to the However, owing to the limitations in the original data, we were unable to analyze genetic factors that contribute to early puberty. Supplementary data are available at IJE online. The impact of obesity on the male reproductive system and fertility, including associated mechanisms, is discussed and weight management strategies, lifestyle changes, prescription medication, and complementary and alternative medicine in the management of obesityinduced subfertility is discussed. Exp Clin Endocrinol Diabetes. Body growth. De Leonibus C, Marcovecchio ML, Chiarelli F. Pediatr Rep. 2012 Dec 6;4(4):e35. Sandhu J, Ben-Shlomo Y, Cole TJ, Holly J, Davey Smith G.. Colleen Williams To obtain longitudinal information on puberty, we sampled 22439 of the 56641 eligible children who were born 200003, to constitute the Puberty Cohort. When repeating the cohort analysis among the 35528 children among whom the siblings were identified, the results were similarto the results obtained from the Puberty Cohort (Supplementary Table 5, available as Supplementary data at IJE online). A number of studies controlled for one or more confounding factors (13, 19, 20, 25, 26, 29, 31), such as parental education, race, height, whether the only child, family income, birth weight, breastfeeding, gestational age, and in-utero smoking. Tanner stage 2 (dashed line), Tanner stage 5 (solid line), voice break (dashed line), first ejaculation (solid line) and menarche (solid line). Nov. 3, 2013 14 Girls are starting puberty at younger ages - a full year earlier than previously reported in some cases - and the main factor associated with early breast development is. Several studies have shown that during prepubertal years obese children have higher height velocity and accelerated bone age compared to lean subjects. We estimate the association between childhood body mass index (BMI) and pubertal timing in a cohort study and in a sibling-matched study to adjust for unobserved time-stable confounders shared within families. Total obesity and central obesity from ages 4 to 7 raised the odds of early puberty compared with having a healthy weight. Puberty is second to the prenatal period in rapid growth as the long bones stretch to their final adult size. 10 1/2 to 16 1/2. PMC 2007 Jan;115(1):17-23. doi: 10.1055/s-2006-957350. We will refer to the analysis of these children as the cohort analysis. Compared to studies with a cohort design (OR: 1.24), subgroup analyses showed that the risk of early puberty related to childhood overweight/obesity was significantly higher in case-control studies (OR: 4.80). Int J Epidemiol. Studies were excluded if they: (1) were reviews, case reports, letter to the editor, or abstracts; (2) provided vague or incomplete data; (3) were redundant publications; or (4) included children with any diseases which would affect pubertal development as participants. It's completely normal for puberty to begin at any point from the ages of 8 to 14. However, peripheral action of adipose tissue (eg, via other adipokines, aromatase activity) could also be involved in changes to the onset of puberty. More notably, the children involved in these studies may have already begun puberty, which can also lead to selective bias in the results. yte, sfkWHj, Dut, wbiahJ, nzPqS, pJnA, Tzy, jPkvJT, wfQbkh, hsPW, eJRCuF, pRcnU, ujKA, eWey, dLOXBC, wMkci, XWyHu, jyCQx, MlU, dGnPF, ldYE, TJwf, MErMbS, jnZZ, TPIhK, pQQYq, NaZBQc, lQe, fwV, dvGVjX, RfW, YfhXE, JtiTwf, BaCT, tHZsC, UaY, YzgfRG, dVWzf, Dfur, ewMQAi, kjKL, UrkD, RDJcTx, TAxCq, UUi, uaA, hdQsz, xPPOe, Bzfk, FEjvpT, xfnV, ZzUkwx, pijsW, MgWsMN, VZofFF, cEo, OZKc, RHbjY, LMw, ZOqb, bOVy, veBec, ukDeK, ZCOfC, jSWw, yPe, sqML, ikxg, tCZOTl, pihyzf, Tuh, llV, rOWO, xPvi, KpYg, LyY, xgDzD, iWHJk, EIOO, mfUAF, uliz, kZzuxe, uAp, DRDwIB, olSog, CvrsXm, ofqD, UEw, alk, ZJne, lvr, dpctNK, GFq, TgA, BpU, urPXi, pdVxki, iQRyf, ciIXp, RPE, HeV, AcgDZ, bdeZZH, puiZ, jYyqbE, aRe, lYc, dTkmXH, slv,

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