Pubertal Markers Research Articles

Size at birth, infant growth, and age at pubertal development in boys and girls.

PurposeThis study investigated whether size at birth and infant growth were associated with age of indicators of pubertal development in boys and girls. We hypothesized that restricted fetal growth and accelerated infant growth lead to earlier pubertal age.Patients and methodsIn total, 15,822 boys and girls answered questionnaires half-yearly with information on pubertal development: age at menarche, first ejaculation, voice break, Tanner stages, axillary hair, and acne. Birth weight and gestational age were used to calculate birth weight Z-scores. Changes in infant weight Z-score from 0 to 5, 5 to 12, and 0 to 12 months were estimated. We estimated the mean monthly difference in timing of puberty between children born small-for-gestational age (SGA) and large-for-gestational age (LGA) with children born appropriate-for-gestational age (AGA) as reference. We further investigated whether increasing infant weight Z-scores were associated with age at attaining indicators of pubertal development.ResultsGirls born SGA reached all pubertal markers at an earlier mean age than girls born AGA, as indicated by mean age differences below zero (eg, age at menarche: −2.3 months, 95% CI: −3.4, −1.2), except for breast development. Girls born LGA reached pubertal markers later than girls born AGA (eg, age at menarche: 1.7 months, 95% CI 0.5, 2.9). Boys born SGA and LGA achieved puberty earlier than boys born AGA, though with CIs crossing zero (eg, age at voice break for SGA: −0.7 months, 95% CI −2.1, 0.7 and for LGA: −0.7 months, 95% CI −2.1, 0.8). A 1-unit increase in weight Z-score from 0 to 12 months was associated with a mean age difference of −1.7 to −0.3 months for pubertal development in both sexes.ConclusionSmall size at birth and rapid infant growth were associated with early pubertal age, most consistent and pronounced in girls.

Timing of pubertal development in boys born with cryptorchidism and hypospadias: a nationwide cohort study.

Pubertal development may be altered in boys with cryptorchidism and hypospadias, but existing knowledge is inconsistent. Therefore, we investigated the association between cryptorchidism and hypospadias and pubertal development in a large cohort study. Boys in the Puberty Cohort, a cohort nested within the Danish National Birth Cohort, were included in this study. Information on cryptorchidism and hypospadias was retrieved from the Danish National Patient Register. From 11 years until 18 years or full pubertal development, information on physical markers of pubertal development was provided biannually, including Tanner stages, axillary hair, acne, voice break, and first ejaculation. In multivariate regression models for interval censored data, the mean (95% confidence intervals [CIs]) differences in months in obtaining the pubertal markers between boys with and without the anomalies were estimated. Among 7698 boys, 196 (2.5%) had cryptorchidism and 60 (0.8%) had hypospadias. Boys with hypospadias experienced first ejaculation and voice break 7.7 (95% CI: 2.5–13.0) months and 4.5 (95% CI: 0.3–8.7) months later than boys without hypospadias. The age at attaining the Tanner stages for gonadal and pubic hair growth was also higher, though not statistically significant. Pubertal development seemed unaffected in boys with mild as well as severe cryptorchidism. In conclusion, hypospadias may be associated with delayed pubertal development, but pubertal development seems unaffected by cryptorchidism. The relation between hypospadias and later pubertal development may be due to the underlying shared in utero risk or genetic factors.

Maternal age at menarche and pubertal development in sons and daughters: a Nationwide Cohort Study.

Is maternal age at menarche associated with pubertal development in sons and daughters? Maternal age at menarche was associated with pubertal development in both sons and daughters. Studies have shown that age at menarche is greatly inherited from mother to daughter, but it remains largely unknown to what extent age at menarche in mothers is associated with timing of puberty in sons. In this population-based study we used data from the Puberty Cohort nested within the Danish National Birth Cohort. Live-born singletons aged 11 were followed from 2012 to 2016. In total, 15 822 children (7697 sons and 8125 daughters) gave half-yearly information on puberty from the age of 11 years until full sexual maturity or 18 years of age through self-administrated questionnaires (participation rate 71%). Information on maternal age at menarche was reported by the mothers during pregnancy. Maternal age at menarche was used both as a continuous and as a categorical variable (earlier, same time or later than peers). A multivariable regression model for interval-censored data was used. Maternal age at menarche was positively associated with timing of genital development, pubic hair development, first ejaculation of semen, voice break, axillary hair development and acne in sons, and with timing of breast development, pubic hair development, menarche, axillary hair development and acne in daughters. In sons, the associations were of similar strength for all pubertal markers, whereas in daughters, the associations were strongest for breast development and menarche. Age at menarche was recalled during pregnancy. However, studies indicate that age at menarche is recalled moderately in adulthood. Information on puberty was self-reported, but inaccuracy of data would probably cause non-differential misclassification. Early maternal age at menarche was associated with earlier pubertal development, and late maternal age at menarche was associated with later pubertal development in both sons and daughters. The largest effect-estimates were for the associations between maternal age at menarche and the daughters' age at menarche and age at breast development. The study was funded by the Danish Council for Independent Research (4183-00152). There are no competing interests. N/A.

Age at Pubertal Onset in Girls and Tobacco Smoke Exposure During Pre- and Postnatal Susceptibility Windows.

Tobacco smoke contains known hormonally active chemicals and reproductive toxicants. Several studies have examined prenatal maternal smoking and offspring age at menarche, but few examined earlier pubertal markers, nor accounted for exposure during childhood. Our objective was to examine pre- and postnatal smoke exposure in relation to timing of early pubertal events. An ethnically diverse cohort of 1239 girls was enrolled at age 6-8 years old for a longitudinal study of puberty at three US sites. Girls participated in annual or semi-annual exams to measure anthropometry and Tanner breast and pubic hair stages. Prenatal and current tobacco smoke exposures, as well as covariates, were obtained from parent questionnaire. Cotinine was measured in urine collected at enrollment. Using accelerated failure time models, we calculated adjusted time ratios for age at pubertal onset (maturation stages 2 or higher) and smoke exposure. Girls with higher prenatal (≥5 cigarettes per day) or secondhand smoke exposure had earlier pubic hair development than unexposed (adjusted time ratio: 0.92 [95% CI = 0.87, 0.97] and 0.94 [95% CI = 0.90, 0.97], respectively). Including both exposures in the same model yielded similar associations. Higher urinary cotinine quartiles were associated with younger age at breast and pubic hair onset in unadjusted models, but not after adjustment. Greater prenatal and childhood secondhand smoke exposure were associated with earlier onset of pubic hair, but not breast, development. These exposures represent modifiable risk factors for early pubertal development that should be considered for addition to the extensive list of adverse effects from tobacco smoke.

Associations between Repeated Measures of Agricultural Pesticide Exposures and Pubertal Markers in a Cohort of Girls

Tea is a widely consumed beverage in the world, and has become an important agricultural product. It has dozens of varieties, such as unfermented green tea, semifermented oolong tea, and fermented black tea. The major constituents in tea are polyphenols, alkaloids, volatile oils, polysaccharides, amino acids, lipids, vitamins, and inorganic elements, etc. Recently, water-soluble tea polysaccharides (TPSs) have attracted scientists’ attention. The polysaccharide from approximately 1.5% to nearly 13%. It has been demonstrated that TPSs have many bioactivities, such as reducing blood sugar levels, immunological, antiradiation, antiblood coagulation, anticancer, anti-HIV, and hypoglycemic activities. This chapter introduces the preparation of TPS, its structural features, chemical modifications, biological activities, and structure–bioactivity relationship.

Prenatal Alcohol Exposure and Pair Feeding Differentially Impact Puberty and Reproductive Development in Female Rats: Role of the Kisspeptin System.

Reproductive maturation is initiated with the onset of puberty, which activates the hypothalamic-pituitary-gonadal axis and coincidences with increased expression of the hormone kisspeptin within the hypothalamus. Maturational events are sensitive to environmental factors, including alcohol, which is known to delay reproductive development. We hypothesized that, similar to alcohol's adverse effects during reproductive maturation, prenatal alcohol exposure (PAE) would alter pubertal markers, sex hormone profiles, and kisspeptin expression in the hypothalamus. Female offspring from control (C), pair-fed (PF), and PAE groups were sacrificed prior to puberty onset (postnatal day [PND] 30), during puberty [PND 35], or in adulthood [PND 65]. Estradiol (E2 ), progesterone (P4 ), prolactin, and luteinizing hormone levels, and Kiss1 mRNA expression were measured in the arcuate (ARC) and anteroventral periventricular (AVPV) nuclei of the hypothalamus. Pubertal markers (vaginal opening [VO], uterus/body wt ratio) were assessed. Our findings indicate that (i) PAE inhibits the expected increases in E2 levels with age and delays maturational increases of P4 levels; (ii) PAE and pair feeding have similar adverse effects on VO and uterus/body wt ratio; (iii) differential relationships between PRL and P4 suggest that different mechanisms may underlie delayed maturation in PAE and PF; that is, PF females have low PRL levels and no increase in P4 with age, whereas PAE animals, despite low PRL, show the expected age-related increase in P4 ; and (iv) there is higher mean density of Kiss1 mRNA in the ARC of adult PAE females and altered Kiss1 expression in the AVPV of both PAE and PF females. PAE and pair feeding have some overlapping but important differential effects on hormonal profiles and Kiss1 mRNA expression during reproductive development. Preadolescent alterations in Kiss1 expression in the AVPV and ARC, which may change the balance of function in these 2 nuclei, may differentially contribute to delayed reproductive maturation in PAE and PF compared to C females.

Daily successive changes in reproductive gene expression and neuronal activation in the brains of pubertal female mice

Puberty is governed by the secretion of gonadotropin releasing hormone (GnRH), but the roles and identities of upstream neuropeptides that control and time puberty remain poorly understood. Indeed, how various reproductive neural gene systems change before and during puberty, and in relation to one another, is not well-characterized. We detailed the daily pubertal profile (from postnatal day [PND] 15 to PND 30) of neural Kiss1 (encoding kisspeptin), Kiss1r (kisspeptin receptor), Tac2 (neurokinin B), and Rfrp (RFRP-3, mammalian GnIH) gene expression and day-to-day c-fos induction in each of these cell types in developing female mice. Kiss1 expression in the AVPV/PeN increased substantially over the pubertal transition, reaching adult levels around vaginal opening (PND 27.5), a pubertal marker. However, AVPV/PeN Kiss1 neurons were not highly activated, as measured by c-fos co-expression, at any pubertal age. In the ARC, Kiss1 and Tac2 cell numbers showed moderate increases across the pubertal period, and neuronal activation of Tac2/Kiss1 cells was moderately elevated at all pubertal ages. Additionally, Kiss1r expression specifically in GnRH neurons was already maximal by PND 15 and did not change with puberty. Conversely, both Rfrp expression and Rfrp/c-fos co-expression in the DMN decreased markedly in the early pre-pubertal stage. This robust decrease of the inhibitory RFRP-3 population may diminish inhibition of GnRH neurons during early puberty. Collectively, our data identify the precise timing of important developmental changes – and in some cases, lack thereof – in gene expression and neuronal activation of key reproductive neuropeptides during puberty, with several changes occurring well before vaginal opening.

Child maltreatment and household dysfunction: associations with pubertal development in a British birth cohort

We aimed to establish the association between adverse childhood experiences (maltreatment and household dysfunction) and pubertal maturation, which is associated with later health outcome(s). The 1958 British birth cohort (n = 17 638) includes all born in one week, March 1958, followed up to mid adulthood. Pubertal stage was rated by medical personnel at 11 and 16 years of age (y). Childhood maltreatment (neglect or abuse) and household dysfunction scores were constructed from information ascertained in childhood and at 45 y. Childhood neglect, assessed at 7 y, was associated with late pubertal development on several markers after adjusting for early life circumstances: relative risk ratio (RRRadjusted) was 1.13 (95% CI: 1.06,1.21) and 1.06 (1.00,1.12) for late menarche and breast development (females) per unit increase in neglect score ranging 0-7, respectively; 1.14 (1.08,1.20) for late voice change and 1.07 (1.02,1.13) for pubic hair growth (males). The RRRadjusted for late pubic hair (females) and genitalia and facial hair (males) development was 1.04 (P = 0.052 to 0.085). Abuse score (0-3, for physical, sexual or psychological abuse) was associated in females with late menarche [RRRadjusted = 1.17 (1.01,1.36)] and in males with late pubic hair growth [RRRadjusted = 1.16 (1.01,1.34)] per unit increase, but not with other pubertal markers. Neither score (neglect or abuse) was associated with early puberty, but sexual abuse was associated with early [RRRadjusted = 1.86 (1.06,3.29)] as well as late menarche [RRRadjusted = 1.66 (1.02,2.71)] and witnessing abuse with early genitalia development [RRRadjusted = 1.57 (1.02,2.41)]. Household dysfunction score was not associated consistently with pubertal markers. Cumulative neglect by 7 y was associated with delayed development of several pubertal markers. The underlying role of pubertal development in linking childhood neglect with future adult health warrants further consideration.

Prenatal Lead Exposure and Puberty Timing in Girls

To the Editor: Findings from cross-sectional epidemiologic studies suggest that blood lead concentrations predict later development of secondary sexual characteristics and reproductive maturation in adolescent girls.1–6 Evidence on the role of prenatal lead exposure on puberty timing is lacking. We examined data from mother-daughter pairs enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) to determine this association. Whole blood samples were collected from pregnant mothers at enrollment (1991–1992) and analyzed for lead content using inductively coupled plasma mass spectrometry. The median gestational age of blood collection was 11 weeks. Repeated assessments of pubertal status were obtained from daughters, beginning at age 8 and continuing through age 17. Participants were asked to examine line drawings and descriptions of the five Tanner stages for breast size and pubic hair and to record which drawing most closely resembled their own stage of development. At each assessment, participants were asked whether their first menstrual period had occurred and when it had occurred.7 We restricted our analyses to singleton white daughters. The following covariates were selected a priori and included in all adjusted analyses: maternal smoking during pregnancy, maternal education, previous births, and daughters’ height at age 7. Data collection instruments and methods have been described elsewhere (www.bristol.ac.uk/alspac). We used parametric survival models to obtain the median age and cumulative probabilities of attainment of pubertal markers to describe unadjusted patterns in pubertal markers over time, assuming a Normal distribution. Hazards ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards models, using the group with prenatal lead concentrations <5 µg/dl as the reference. The proportional hazards assumption was assessed for all variables in the models. Time to menarche was based on the age of attainment given by participants or right-censored using the age of the last completed assessment. For Tanner stages, time to event was defined using the midpoint between two assessments. Alternatively, the data were left-censored if the participant reported a stage 2 or greater on their first returned assessment or right-censored if stage 2 was not attained. Human subject protection was assessed and approved by the ALSPAC Law and Ethics Committee, the Local Research Ethics Committees, and the Centers for Disease Control and Prevention Institutional Review Board. Menarche analyses (n = 918) comprised data for the full follow-up period, whereas Tanner stage analyses (n = 765) were based on status up to 14 years of age. The median age at menarche was 150 months (12.5 years), median age at breast stage ≥2 was 130 months (10.8 years), and median age at pubic hair stage ≥2 was 135 months (11.3 years). The median prenatal lead concentration was 3.4 µg/dl (range, 0.8–19.1 µg/dl). Fifteen percent of mothers had lead concentrations ≥5 µg/dl. The median age at menarche in daughters with prenatal concentrations ≥5 µg/dl did not vary from those with lead concentrations <5 µg/dl (both were 150 months). The two groups were also similar regarding breast stage ≥2 (129 vs. 131 months, respectively) and pubic hair stage ≥2 (133 vs. 135 months). Unadjusted survival distributions for age at menarche by exposure category did not vary over time (Figure). Curves for breast and pubic hair attainment showed similar patterns. The rate of attainment of pubertal markers in daughters with prenatal lead concentrations ≥5 µg/dl did not differ from those with lower lead concentrations. Attainment of menarche (adjusted HR = 1.00 [95% CI = 0.82–1.21]), breast stage ≥2 (1.08 [0.87–1.35]), and pubic hair stage ≥2 (1.02 [0.83–1.26]) were all unrelated to prenatal lead concentrations. Our findings are not consistent with those of cross-sectional studies, which have suggested an antiestrogenic effect of lead in adolescent girls.FIGURE: Unadjusted survival distribution for menarche attainment by categories of prenatal lead ≥5 µg/dl and <5 µg/dl.ACKNOWLEDGMENTS We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. Mildred Maisonet Jouni J. K. Jaakkola Center for Environmental and Respiratory Health Research, University of Oulu, Oulu, Finland, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland, [email protected] Caroline M. Taylor Centre for Child and Adolescent Health, University of Bristol, Bristol, United Kingdom Michele Marcus Kaiser Permanente Center for Health Research, Atlanta, GA Jean Golding Centre for Child and Adolescent Health, University of Bristol, Bristol, United Kingdoml

Circulating kisspeptin levels exhibit sexual dimorphism in adults, are increased in obese prepubertal girls and do not suffer modifications in girls with idiopathic central precocious puberty

The system KISS1–KISS1R is one of the main regulators of the hypothalamic-pituitary-gonadal axis and constitutes a link between metabolism and reproduction through its interaction with leptin. The aim of this study was to clarify the possible utility of kisspeptin as a pubertal marker and/or the possible influence of nutritional status in kisspeptin levels. To this end, we have studied kisspeptin plasma levels throughout sexual development and in prepubertal obese girls and girls affected by idiopathic central precocious puberty (CPP). Plasma kisspeptin concentrations were analyzed by RIA. An increase in kisspeptin levels was observed in adult females compared to healthy prepubertal and pubertal girls (p<0.001) and to adult males (p<0.001). Additionally, kisspeptin was increased in prepubertal obese girls compared to healthy prepubertal girls (p<0.01) and girls with idiopathic CPP (p<0.05). As revealed by the regression analysis, in prepubertal healthy and obese girls and girls with idiopathic CCP, the parameters that influenced kisspeptin levels were BMI (R2=0.10, p<0.05) and leptin levels (R2=0.14, p<0.01). In conclusion, kisspeptin levels do not seem to be a good pubertal marker. The results obtained in prepubertal and idiopathic CCP girls point to a relationship between leptin, BMI and kisspeptin at least in this group, and suggest a possible role for adipose tissue in the modulation kisspeptin synthesis.

Prepubertal Glucocorticoid Status and Pubertal Timing

Whether prepubertal glucocorticoid status impacts on the timing of puberty is not clear. The objective of the study was to examine the relationship between prepubertal glucocorticoid status and early or late pubertal markers, independent of adrenarchal and nutritional status. Prospective cohort study of healthy Caucasian children (n = 111, 56 boys) who provided both 24-h urine samples and weighed dietary records 1 and 2 yr before the start of pubertal growth spurt [age at take-off (ATO)]. Major urinary glucocorticoid and androgen metabolites determined by gas chromatography-mass spectrometry analysis were summed to assess daily overall cortisol (ΣC21) and adrenal androgen secretion; urinary free cortisol and cortisone measured by RIA were summed (UFF+UFE) as an indicator of potentially bioactive free glucocorticoids. The main outcomes included ATO, age at peak height velocity, age at menarche/voice break, ages at Tanner stage 2 for breast (girls) and genital (boys) development, and pubic hair. In girls ΣC21, but not UFF+UFE, was associated with pubertal markers after adjusting for overall adrenal androgen, urinary nitrogen, and body fat. Girls with higher ΣC21 (fourth quartile) reached ATO 0.7 yr (P = 0.01) and menarche 0.9 yr later (P = 0.006) than girls with lower ΣC21 (first quartile). The ΣC21 tended to be also positively associated with age at Tanner stage 2 for breast (P = 0.1), Tanner stage 2 for pubic hair (P = 0.1), and age at peak height velocity (P = 0.06). In boys, neither the ΣC21 nor UFF+UFE was related to pubertal timing. An individually higher prepubertal glucocorticoid secretion level, even in physiological range, appears to delay early and late pubertal timing of healthy girls, particularly their onset of pubertal growth spurt and menarche.

Prepubertal urinary estrogen excretion and its relationship with pubertal timing

Whether prepubertal estrogen production impacts on the timing of puberty is not clear. We aimed to investigate prepubertal 24-h estrogen excretion levels and their association with early and late pubertal markers. Daily urinary excretion rates of estrogens of 132 healthy children, who provided 24-h urine samples 1 and 2 yr before the start of the pubertal growth spurt [age at takeoff (ATO)], were quantified by stable isotope dilution/GC-MS. E-sum3 (estrone + estradiol + estriol) was used as a marker for potentially bioactive estrogen metabolites and E-sum5 (E-sum3 + 16-epiestriol + 16-ketoestradiol) for total estrogen production. Pubertal outcomes were ATO, age at peak height velocity (APHV), duration of pubertal growth acceleration (APHV-ATO), age at Tanner stage 2 for pubic hair (PH2), genital (G2, boys) and breast (B2, girls) development, and age at menarche. Prepubertal urinary estrogen excretions (E-sum3 and E-sum5) were not associated with ATO, APHV, and age at PH2 but with duration of pubertal growth acceleration (P < 0.01) in both sexes. Girls with higher E-sum3 reached B2 0.9 yr (P = 0.04) and menarche 0.3 yr earlier (P = 0.04) than girls with lower E-sum3. E-sum3 was not associated with age at G2 in boys (P = 0.6). For most pubertal variables, the associations with E-sum3 were stronger than with E-sum5. In conclusion, prepubertal estrogens may not be critical for the onset of the pubertal growth spurt but are correlated with its duration in both boys and girls. Prepubertal estrogen levels may already predict the timing of girls' menstruation and breast development but do not appear to affect sexual maturation in boys.

Relation of isoflavones and fiber intake in childhood to the timing of puberty

It has been suggested that phytoestrogens and dietary fiber can affect puberty timing. We examined whether intake of isoflavone and fiber in healthy white children before their pubertal growth spurt [age at take-off (ATO)] was associated with puberty timing. Multivariate regression analyses were performed in 227 DONALD (DOrtmund Nutritional and Anthropometric Longitudinally Designed) Study participants with 3-d weighed dietary records and information on potential confounders at baseline (1 and 2 y before ATO). In a subsample (n = 111), urinary isoflavones were determined in 24-h urine samples by gas chromatography-mass spectrometry analysis. Puberty timing was examined by using ATO and chronologic ages at pubertal stage 2 for breast development (B2) or gonadal development, peak height velocity (PHV), and menarche or voice break. Girls whose diet was in the highest dietary isoflavone tertile experienced Tanner stage 2 for breast development ap 0.7 y later and reached PHV ap 0.6 y later than did girls whose diet was in the lowest isoflavone tertile [age (95% CI) at B2: 10.7 y (10.4, 10.9 y) compared with 10.0 y ( 9.7, 10.3 y), respectively; P for trend = 0.04; age at PHV: 11.9 y (11.6, 12.2 y) compared with 11.3 y (11.0, 11.6 y), respectively; P for trend = 0.04; adjusted for body mass index z score and fiber intake]. In boys, dietary isoflavones were not associated with pubertal markers. Urinary isoflavone and dietary fiber intakes were not associated with pubertal markers. Girls, but not boys, with higher prepubertal isoflavone intakes appear to enter puberty at a later age. Fiber intake in this sample of healthy white girls and boys was not relevant for puberty timing.

Prepubertal Adrenarchal Androgens and Animal Protein Intake Independently and Differentially Influence Pubertal Timing

Whether adrenarche impacts on pubertal development is controversial. The objective of the study was to examine the associations of adrenal androgen (AA) secretion with early and late pubertal markers, independent of potential influences of dietary animal protein intake. This was a prospective cohort study of healthy free-living Caucasian children (n = 109) who provided both 24-h urine samples and 3-d weighed dietary records 1 and 2 yr before the biological age at take-off of the pubertal growth spurt (ATO). Twenty-four-hour excretion rates of androgen (C19) metabolites quantified by gas chromatography-mass spectrometry were measured. ATO, age at peak height velocity (APHV), age at menarche/voice break, duration of pubertal growth acceleration, and ages at Tanner stage 2 for breast (girls) and genital (boys) development (B2-G2) and pubic hair (PH2). Higher adrenarchal C19 steroids predicted earlier ages at Tanner stage 2 for pubic hair (P < 0.0001) and B2-G2 (P = 0.009) as well as a shorter pubertal growth acceleration period (P = 0.001), independently of animal protein intake. Children with a higher AA secretion had a 1.5-yr earlier beginning of pubarche and a 0.8-yr earlier beginning of B2-G2 than those with a lower AA excretion. Furthermore, animal protein intake was independently negatively associated with ATO and APHV (P < 0.05 each) and tended to be negatively associated with age at menarche/voice break (P = 0.07). A higher animal protein intake may be involved in an earlier attainment of ATO and APHV, whereas a more intensive adrenarchal process may precipitate a shorter pubertal growth spurt and a notably earlier onset of breast and genital development in girls and boys, respectively.

Assessing Inter-Rater Reliability (IRR) of Tanner Staging and Orchidometer Use with Boys: A Study from PROS

Few studies have systematically assessed the reliability of pubertal markers; most are flawed by limited numbers of markers and ages studied. To conduct a comprehensive examination of inter-rater reliability in the assessment of boys' sexual maturity. Eight pairs of practitioners independently rated 79 consecutive boys aged 8-14 years. Two raters in each of eight practices independently rated boys aged 8-14 years, presenting for physical examinations, on key pubertal markers: pubic hair and genitalia (both on 5-point Tanner scales), testicular size (via palpation and comparison with a four-bead Prader orchidometer), and axillary hair (via a three-point scale). Intraclass correlations assessing degree of inter-rater reliability for pubertal markers ranged from 0.61 to 0.94 (all significant at p < 0.001). Rater Kappas for signs of pubertal initiation ranged from 0.49 to 0.79. Practitioners are able to reliably stage key markers of male puberty and identify signs of pubertal initiation.

Association of prepubertal body composition in healthy girls and boys with the timing of early and late pubertal markers

BackgroundIt is controversial whether prepubertal body composition is implicated in the timing of puberty onset. ObjectiveThe objective was to investigate whether body composition in the 2 y preceding the start of the pubertal growth spurt—a marker of puberty onset—is associated with the attainment of early and late pubertal markers in healthy German boys and girls. DesignMultivariate-adjusted regression analyses were performed in 215 participants of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study for whom body mass index (BMI) and its components fat mass/height2 (FM/m2) and fat-free mass/height2 (FFM/m2) 1 and 2 y before the onset of the pubertal growth spurt (age at takeoff; ATO) and information on early life exposures were available. In addition, age at peak height velocity (APHV) and menarche were examined. ResultsHigher BMIs and FM/m2z scores 1 and 2 y before ATO showed modest associations with chronological age at ATO among girls only (girls: P for = trend 0.05–0.1, adjusted for early life factors; boys: P = 0.2–0.6). FFM/m2z scores were not related to age at ATO (P for trend = 0.5–0.8). Conversely, prepubertal BMI and FM/m2 more clearly predicted APHV and puberty duration (APHV minus ATO) in both sexes and age at menarche in girls (girls: adjusted P for trend <0.0001–0.03; boys: P = 0.01–0.046). ConclusionThis longitudinal study suggests that prepubertal body composition in healthy boys and girls may not be critical for the initiation of the pubertal growth spurt but instead affects the progression of pubertal development, which results in earlier attainment of later pubertal stages.

Examination of US Puberty-Timing Data from 1940 to 1994 for Secular Trends: Panel Findings

Whether children, especially girls, are entering and progressing through puberty earlier today than in the mid-1900s has been debated. Secular trend analysis, based on available data, is limited by data comparability among studies in different populations, in different periods of time, and using different methods. As a result, conclusions from data comparisons have not been consistent. An expert panel was asked to evaluate the weight of evidence for whether the data, collected from 1940 to 1994, are sufficient to suggest or establish a secular trend in the timing of puberty markers in US boys or girls. A majority of the panelists agreed that data are sufficient to suggest a trend toward an earlier breast development onset and menarche in girls but not for other female pubertal markers. A minority of panelists concluded that the current data on girls' puberty timing for any marker are insufficient. Almost all panelists concluded, on the basis of few studies and reliability issues of some male puberty markers, that current data for boys are insufficient to evaluate secular trends in male pubertal development. The panel agreed that altered puberty timing should be considered an adverse effect, although the magnitude of change considered adverse was not assessed. The panel recommended (1) additional analyses of existing puberty-timing data to examine secular trends and trends in the temporal sequence of pubertal events; (2) the development of biomarkers for pubertal timing and methods to discriminate fat versus breast tissue, and (3) establishment of cohorts to examine pubertal markers longitudinally within the same individuals.

Environmental Factors and Puberty Timing: Expert Panel Research Needs

Serono Symposia International convened an expert panel to review the impact of environmental influences on the regulation of pubertal onset and progression while identifying critical data gaps and future research priorities. An expert panel reviewed the literature on endocrine-disrupting chemicals, body size, and puberty. The panel concluded that available experimental animal and human data support a possible role of endocrine-disrupting chemicals and body size in relation to alterations in pubertal onset and progression in boys and girls. Critical data gaps prioritized for future research initiatives include (1) etiologic research that focus on environmentally relevant levels of endocrine-disrupting chemicals and body size in relation to normal puberty as well as its variants, (2) exposure assessment of relevant endocrine-disrupting chemicals during critical windows of human development, and (3) basic research to identify the primary signal(s) for the onset of gonadotropin-releasing hormone-dependent/central puberty and gonadotropin-releasing hormone-independent/peripheral puberty. Prospective studies of couples who are planning pregnancies or pregnant women are needed to capture the continuum of exposures at critical windows while assessing a spectrum of pubertal markers as outcomes. Coupled with comparative species studies, such research may provide insight regarding the causal ordering of events that underlie pubertal onset and progression and their role in the pathway of adult-onset disease.

Body composition and bone measurements in intra-uterine growth retarded and early postnatally undernourished male and female rats at the age of 6 months: comparison with puberty

Undernutrition in early life may permanently change body structure, physiology and metabolism and leads to chronic diseases in later life. To test whether malnutrition during different critical time periods around birth in the rat has long-lasting effects on body composition and skeletal growth, we examined body weight and body composition in pubertal rats and adult rats of 6 months after pre- and postnatal malnutrition. Prenatal malnutrition or intra-uterine growth retardation (IUGR) was induced by ligation of the uterine arteries on day 17 of gestation and postnatal food restriction (FR) by litter enlargement to 20 pups per mother from day 2 after birth until weaning (day 24). Pubertal markers were balanopreputial separation (BPS) in the male and vaginal opening (VO) in the female. IUGR as well as FR resulted in a persistent growth retardation. From birth in IUGR rats and from day 4 after birth in FR rats until 6 months of age body weight in male and female rats was significantly lower compared with controls ( P < 0.01 and P < 0.05). Although total body bone mineral content (TBBMC) did not differ between male IUGR rats and controls at BPS, at the age of 6 months TBBMC was significantly lower ( P < 0.01) compared with controls. At BPS as well as at 6 months of age, TBBMC was significantly lower in male FR rats compared with controls ( P < 0.05 and P < 0.01). In the female IUGR rats TBBMC was significantly lower compared with controls at VO ( P < 0.01) and 6 months ( P < 0.05). TBBMC in the female FR rats was significantly lower at VO ( P < 0.01), but did not differ from controls at the age of 6 months. For both IUGR and FR male and female rats these differences disappeared after adjusting for body weight. Body composition in terms of total fat mass, percentage fat and percentage lean did not differ from controls in male and female IUGR rats at 6 months and the same results were observed in the female FR rats. However, in the male FR rats, total fat mass and percentage fat were significantly lower compared with controls ( P < 0.01 and P < 0.05), while the percentage lean mass was significantly higher ( P < 0.05). We conclude that different critical time periods of malnutrition around birth have different effects later in life on growth, which do not disappear at least after 6 months of life. With respect to body composition, only in the FR male rats, differences are found in total fat mass and the balance of percentage fat mass and lean mass. At time of puberty and at the age of 6 months bone mass adjusted for body weight does not seem to be affected by perinatal undernutrition.