Pubertal growth of the short normal girl

OBJECTIVES: To determine the timing, magnitude and duration of the pubertal spurt for short normal and average height girls, to compare these with Tanner's standard and to investigate predictors of pubertal growth. METHODS: The growth of 46 short normal and 55 control girls, identified at school entry, was monitored throughout puberty. Height and weight were measured at 6-month intervals from which body mass index (BMI) was derived. Annual velocities were calculated and used to estimate the age and magnitude of peak height velocity (PHV). Age of menarche was recorded to the nearest month. Parents provided information on the child's medical and social history. RESULTS: The mean age at PHV, the magnitude of PHV and age at menarche were similar for both groups and close to Tanner's 50th centile values. Pre-pubertal BMI predicted age at menarche for short and control girls, accounting for 17% of the variance. There was a tendency for early maturing girls of average stature to have greater PHV. However, this relationship was not observed in short girls, nor did any other variable, genetic or environmental, predict the timing or magnitude of their pubertal spurt. CONCLUSIONS: Delayed puberty in short normal girls is unlikely and their growth during puberty is comparable to girls of average height. The pubertal variables measured remain close to Tanner's original standards for both groups, suggesting the lack of a secular trend towards earlier puberty in girls. The onset of menstruation is influenced by pre-pubertal BMI. However, the clinician should be aware that short normal girls have normal pubertal growth and that no genetic or environmental variable can predict the timing or magnitude of their growth spurt.     

Puberty after prenatal growth restraint

There is increasing evidence for a link between prenatal growth and pubertal development. Here we highlight a selection of pubertal characteristics in children who were born small for gestational age (SGA). Boys born SGA are at risk of high levels of follicle-stimulating hormone (FSH) and low levels of inhibin B and a small testicular volume during adolescence. In girls born SGA, the age at pubertal onset and the age at menarche are advanced by about 5-10 months; prenatal growth restraint may also be associated with higher FSH levels and smaller internal genitalia in adolescence. The ovulation rate was found to be reduced in adolescent girls born SGA, and an insulin-sensitizing therapy was capable of raising this low ovulation rate. Menarche is definitely advanced in girls born SGA with precocious pubarche and in those with an early-normal onset of puberty. Current evidence suggests that insulin resistance is a key mechanism linking a post-SGA state to early menarche; hence, insulin sensitization may become a valid approach to prevent early menarche and early growth arrest in girls born SGA.     

Heritability of age at menarche in girls from the Fels Longitudinal Study

Menarche is the hallmark maturational event of female childhood. Many studies indicated a significant genetic contribution to the timing of the onset of menstruation, but most of these studies were limited by the use of retrospective data and by the use of data from only certain types of relatives (i.e., mothers and daughters, sisters, or twin sisters). The primary goal of this study was to use a modern maximum likelihood quantitative genetic method to estimate the heritability (h(2)) of age at menarche, using familial data collected over the course of the 74-year-old Fels Longitudinal Study. The secondary goal was to review earlier studies of the heritability of age at menarche. The study of the heritability of age at menarche presented here is unique for two reasons. First, because of the Fels Longitudinal Study's serial design, age-at-menarche data were collected prospectively from most participants. Second, because the Fels Longitudinal Study is a family study that has been conducted for decades, age-at-menarche data are available from many types of female relatives spanning multiple households and generations. The best-fitting and most parsimonious quantitative genetic model included provision for a secular decrease in age at menarche, and estimated the h(2) of age at menarche to be 0.49+/- 0.13 (95% confidence interval of h(2),=0.24-0.73). The results of this study are in general agreement with the findings of most previous studies of genetic influences on age at menarche, and suggest that it is reasonable to consider it well-established that approximately half the phenotypic variation among girls from developed nations in the timing of menarche is due to genetic factors.     

Early influences on the tempo of puberty

Fetal growth retardation appears to be associated with an increased risk of premature adrenarche, early puberty, polycystic ovary syndrome and associated fertility problems. In a rat model of intrauterine growth retardation, based on ligation of the uterine arteries, the onset of puberty was delayed in female pups, with anovulation during the first cycle. The ovaries showed a lower number of follicles. The onset of puberty was also delayed in male pups. Testosterone production was lower in these growth-retarded rats compared with controls. The relationship between birth weight and the onset of puberty and pubertal progression in different cohorts of healthy children has been examined. In girls, no differences were observed in timing and progression of puberty, including age of menarche, between groups of different birth weights. In boys, a relatively delayed onset of puberty was observed in those with low birth weight, with a normally timed progression. In children with low birth weight, particularly boys, higher dehydroepiandrosterone levels were found compared with children with a normal birth weight, indicating an overactive adrenal gland in children with low birth weight. These data indicate that impaired fetal growth may have long-lasting effects on pubertal development. The fact that results of human studies on the relationship between fetal growth and the onset of puberty are often controversial may be explained by the heterogeneity of children born small for gestational age with respect to the intrauterine insult that they experience. From rat studies, it is clear that a serious intrauterine insult associated with growth failure can lead to dysregulation of puberty and gonadal function.     

Age at menarche,socio‐sexual behavior,and fertility

Abstract

This paper examines the relationship between age at menarche and fertility from two perspectives. Age at menarche is regarded as a crude indicator of the timing of fecundity that may affect the timing of conception among those sexually active; and age at menarche is regarded as a crude indicator of the timing of sexual maturation that may influence the timing of socio‐sexual behavior, namely dating and sexual intercourse. The data are drawn from a survey of New York City women who recently had their first child. The findings suggest that age at menarche as an indicator of fecundity is not a good predictor of the timing of the first birth, when controlling for age at first sexual intercourse. Looking only at initial noncontraceptors, however, we find the relationship is stronger. Age at menarche, viewed as an indicator of the timing of sexual maturation, does seem to have some influence on the timing of dating, but only for Blacks. For both races, age at first date is related to age at first sexual intercourse.     

Single versus serial assessment of skeletal age: Either,both or neither?

Assessments of skeletal age are a valuable adjunct to the clinical evaluation of physical maturity but are more meaningful when considered in relation to chronological age, especially over time, than as separate entities. Data on 51 girls from the Child Research Council study series gave a correlation coefficient of 0.51 between skeletal age (SA) at menarche and chronological age (CA) at menarche — a value in close agreement with data reported from other studies. With a range in SA of 11.58 to 14.89 years, these data were examined further for changes in SA related to timing of adolescence. SA was greater than CA in each of the nine girls whose menarche occurred between 10.5 and 12 years of age. SA was equal to CA in one girl, greater than CA in eight girls and less than CA in 11 girls with menarche between 12.15 and 13.4 years. Of the 22 girls with menarche after 13.5 years, one had SA = CA at 14.89 years and the other 21 all had SA less than CA. An r of 0.84 was calculated between the values of CA minus SA at menarche and CA at menarche. Similar relationships were found between SA and CA at age of maximum increment in growth in height for these girls and for 53 boys in the study series. Longitudinal data for height, weight and SA for four boys and five girls demonstrate the problems of prediction of the timing of adolescence and of adult size from skeletal ages in the childhood years.     

Blunted pubertal growth after leukemia: a new pattern of growth hormone insufficiency

Growth, age at menarche and spontaneous GH secretion were studied in girls after treatment for acute lymphoblastic leukemia (ALL). These girls had normal prepubertal growth but subnormal pubertal growth. Mean final height was 1 SD less than expected before puberty. The average age at menarche was significantly lower than the normal mean for Swedish girls. The mean 24-hour GH secretion was severely blunted and there was no increase during puberty. We suggest that girls treated for ALL, including CNS irradiation, have a relative GH insufficiency which becomes clinically obvious only when the girls cannot respond to the increased demands for GH in puberty.     

Forty years trends in timing of pubertal growth spurt in 157,000 Danish school children

Background

Entering puberty is an important milestone in reproductive life and secular changes in the timing of puberty may be an important indicator of the general reproductive health in a population. Too early puberty is associated with several psychosocial and health problems. The aim of our study was to determine if the age at onset of pubertal growth spurt (OGS) and at peak height velocity (PHV) during puberty show secular trends during four decades in a large cohort of school children.

Methods and Findings

Annual measurements of height were available in all children born from 1930 to 1969 who attended primary school in the Copenhagen Municipality. 135,223 girls and 21,612 boys fulfilled the criteria for determining age at OGS and age at PHV. These physiological events were used as markers of pubertal development in our computerized method in order to evaluate any secular trends in pubertal maturation during the study period (year of birth 1930 to 1969). In this period, age at OGS declined statistically significantly by 0.2 and 0.4 years in girls and boys, respectively, whereas age at PHV declined statistically significantly by 0.5 and 0.3 years in girls and boys, respectively. The decline was non-linear with a levelling off in the children born between 1940 and 1955. The duration of puberty, as defined by the difference between age at OGS and age at PHV, increased slightly in boys, whereas it decreased in girls.

Conclusion

Our finding of declining age at OGS and at PHV indicates a secular trend towards earlier sexual maturation of Danish children born between 1930 and 1969. Only minor changes were observed in duration of puberty assessed by the difference in ages at OGS and PHV.     

Factors regulating the timing of puberty onset in female rhesus monkeys (Macaca mulatta): role of prenatal androgens, social rank, and adolescent body weight

This study investigated whether prenatal androgen exposure, social rank, and body weight are factors regulating pubertal development in outdoor-housed female rhesus monkeys. Subjects' mothers received injections of testosterone enanthate (20 mg/ wk), flutamide (an androgen receptor blocker, 30 mg/kg twice daily), or vehicle during Gestational Days 35/40-70 (early) or Days 105/110-140 (late). Monitoring of pubertal development began around 28 mo of age during the fall breeding season, with frequent assessment of menstruation, circulating steroids, and weight. Menarche occurred 1.5 mo later in females treated late in gestation than in females treated early in gestation. This short menarche delay occurred in females treated with androgen, flutamide, or vehicle. No effect of prenatal manipulations on first ovulation were found. Social rank was related to first ovulation but not menarche, with low-ranked females less likely than high- or middle-ranked females to ovulate at 2.5 yr than at 3.5 yr of age. Females ovulating early, around 2.5 yr, had higher pubertal body weights and body mass indexes (BMI) than did females ovulating later, suggesting that better nutritional reserves or positive energy balance affect pubertal development. Thus, social rank and likely nutritional status influenced pubertal development in this study. Hormonal manipulations had no detectable effect; instead, handling late in gestation, which may have increased maternal adrenal activity, delayed menarche. This finding contrasts with earlier studies that showed that prenatal androgens delay menarche by 4-6 mo on average. This study supports late gestation as a period of increased sensitivity to environmental insult and demonstrates that multiple factors, including prenatal programming, modulate the specific timing of pubertal events.     

Physical and psychological changes in relation to the period before and after onset of the menarche

This cross-sectional study on 452 girls between 11 and 16 years of age examines the physical and psychological changes in the period 30 months before and 60 months after onset of menarche. Indicators of maturity showed the strongest alterations around menarche. In the majority of the physical characters (e. g. thickness of skinfold) adult values are achieved only a longer period after menarche, whereas others (e. g. dimensions of the head) terminate growth already largely by onset of menarche. We found out a minimum in development of thickness of skinfold at the time of menarche indicating a "second loss of body fat" in girls. In four different dimensions of personality (health, anxiety, neuroticism, power of concentration) menarche causes an interruption of the psychic development, and that in an adverse sense.     

Predictors of age at menarche in the newcastle thousand families study

Several studies have found relationships between early life factors (birth weight, length of gestation, height, weight, duration of breast-feeding, maternal age, social class, periods of infection, presence of adverse life events, and quality of housing conditions in childhood) and age at menarche but none has considered all of these factors in the same study. The follow-up study of the Newcastle Thousand Families birth cohort, established in 1947, provided age at menarche data collected retrospectively at age 50 from 276 women who returned self-completion questionnaires in 1997. Three main independent associations were observed: girls who experienced a shorter gestation, girls whose mothers were younger when they were born, and girls who were heavier at age 9 had earlier menarche. Birth weight, standardized for gestational age, was found to have different relationships with age at menarche depending upon how heavy or light a girl was at age 9. The results of this study support the hypotheses that conditions in fetal and early life are associated with the timing of menarche and that greater childhood growth is associated with earlier menarche. It is suggested that future work should focus on illuminating the mechanisms underlying these statistical relationships.     

Age at Puberty and the Emerging Obesity Epidemic

Background

Recent studies have shown that puberty starts at younger ages than previously. It has been hypothesized that the increasing prevalence of childhood obesity is contributing to this trend. The purpose of this study was to analyze the association between prepubertal body mass index (BMI) and pubertal timing, as assessed by age at onset of pubertal growth spurt (OGS) and at peak height velocity (PHV), and the secular trend of pubertal timing given the prepubertal BMI.

Methodology/Principal Findings

Annual measurements of height and weight were available in all children born from 1930 to 1969 who attended primary school in the Copenhagen municipality; 156,835 children fulfilled the criteria for determining age at OGS and PHV. The effect of prepubertal BMI at age seven on these markers of pubertal development within and between birth cohorts was analyzed. BMI at seven years was significantly inversely associated with age at OGS and PHV. Dividing the children into five levels of prepubertal BMI, we found a similar secular trend toward earlier maturation in all BMI groups.

Conclusion/Significance

The heavier both boys and girls were at age seven, the earlier they entered puberty. Irrespective of level of BMI at age seven, there was a downward trend in the age at attaining puberty in both boys and girls, which suggests that the obesity epidemic is not solely responsible for the trend.     

Body composition characteristics during puberty in girls and boys from Eastern Austria

Puberty represents the final stage of sexual differentiation during which time the individual acquires reproductive capacity. Puberty is not only characterized by maturation of sexual organs and the formation of oocytes and mature spermatozoa, but also by the development of secondary sexual dimorphism. In industrialized countries the age of puberty has decreased steadily over the last 150 years in association with improved socio-economic conditions. However, the decreased onset of puberty is, especially in the female sex, associated with problematic changes in behaviour such as early onset of sexual activity and resulting in high risk teenage pregnancies. First of all, the improved nutritional status during childhood is discussed as a major cause for the decrease of puberty onset, whereas the impact of nutritional status especially on female sexual maturity is discussed controversially. In our study we analysed the association between body composition (fat tissue and fat free body mass, estimated by BIA analyses), height, Body Mass Index and fat distribution, and signs of puberty such as the timing of menarche in 228 girls and voice breaking and facial hair growth in 191 boys ageing between 10 and 15 years. In both sexes signs of puberty were highly significantly associated with body composition parameters. Nevertheless, marked differences between the two sexes were observed: Female puberty was positively associated first of all with weight status and the absolute and relative amount of body fat, while in signs of male puberty were related positively with a higher amount of fat free body mass and a decreased fat mass. Male voice breaking was significantly associated with increased stature, body weight, waist and hip circumference, lean body mass and total body water, in contrast voice breaking was significantly negatively associated with the fat percentage, the total fat mass and the waist to hip ratio. Female menarche was significantly positively associated with increased body weight, weight status, waist and hip circumference but also with increased absolute and relative fat mass, relative hip circumference, lean body mass and total body water. Only the waist to hip ratio was significantly negatively associated with the onset of menarche.     

Association of the Q223R polymorphism with age at menarche in the leptin receptor gene in humans

Although genetics clearly influences the onset of menarche, the association of age at menarche (AAM) with variants in genes related to energy homeostasis remains unexplored. Our aim was to analyze the relationship of the Q223R polymorphism in the leptin receptor gene (LEPR(Q223R)) with AAM in a population-based sample of healthy pubertal girls. The study included 338 Spanish girls aged between 11 and 17 yr. Data were collected on AAM. The Q223R polymorphism in LEPR was detected by TaqMan allelic discrimination assays. Girls carrying the RR genotype had a significantly younger AAM (11.5 yr) than those carrying the QR (11.9 yr) or QQ (12.0 yr) genotype (P < 0.05). Furthermore, we found a significantly higher frequency of the RR genotype in girls with an AAM of 11 yr or younger than in girls with an AAM older than 12 yr (23.9% vs. 7.8%, χ(2) = 11.17, P = 0.0008). Also, the RR genotype frequency in girls with an AAM between 11 and 12 yr was significantly higher than in girls with an AAM older than 12 yr (16.8% vs. 7.8%, χ(2) = 3.97, P = 0.0046). The Q223R polymorphism in the LEPR gene is associated with variations in AAM among Spanish girls, with the RR genotype being related to earlier onset.     

Body Composition Characteristics During Puberty in Girls and Boys from Eastern Austria

Puberty represents the final stage of sexual differentiation when the individual acquires reproductive capacity. Puberty is not only characterized by maturation of sexual organs and the formation of oocytes and mature spermatozoa, but also by the development of secondary sexual dimorphism. In industrialized countries, the age of puberty has decreased steadily over the last 150 years in association with improved socio-economic conditions. However, the decreased onset of puberty, especially in females, is associated with problematic changes in behaviour such as early onset of sexual activity resulting in high-risk teenage pregnancies. In our study, we analysed the association between body composition (fat tissue and fat-free body mass, estimated by BIA analyses), height, body mass index and fat distribution and signs of puberty such as the timing of menarche in 228 girls and voice breaking and facial hair growth in 191 boys ageing between 10 and 15 years. In both sexes, signs of puberty were associated, highly significantly, with body composition parameters. Nevertheless, marked differences between the two sexes were observed: Female puberty was positively associated with weight status and the absolute and relative amount of body fat, while in males, puberty was positively related with a higher amount of fat-free body mass and a decreased fat mass. Male voice breaking was significantly associated with increased stature, body weight, waist and hip circumference, lean body mass and total body water. In contrast, voice breaking was significantly negatively associated with the fat percentage, the total fat mass and the waist-to-hip ratio. Female menarche was significantly positively associated with increased body weight, weight status, waist and hip circumference and also with increased absolute and relative fat mass, relative hip circumference, lean body mass and total body water. Only the waist-to-hip ratio was significantly negatively associated with the onset of menarche.     

The Cannabinoid Receptor 2 Q63R Variant Modulates the Relationship between Childhood Obesity and Age at Menarche

Background

The ovary is an important site where gene variants modulate pubertal timing. The cannabinoid receptor 2 (CB2) is expressed in the ovary, plays a role in folliculogenesis and ovulation, and can be modulated by estrogens. Obesity is strictly associated with early menarche and is characterized by sex hormone and endocannabinoid derangement.

Aim

In this study, we investigated the role of the CB2 receptor in determining the age at menarche in obese girls.

Methods

We studied a cohort of 240 obese girls (age 11.9±3 years; BMI z-score 2.8±0.8). The age at menarche (if it had already occurred) was recorded at the time of the visit or via phonecall. The CNR2 rs35761398 polymorphism, which leads to the CB2 Q63R variant, was detected by the TaqMan assay.

Results

In total, 105 patients were homozygous for the R63-coding allele (RR), 113 were QR and 22 were QQ. Variance analysis revealed a significantly earlier age of menarche in subjects carrying the Q63 allele, which was also found after adjusting for BMI z-score (11±1.2 vs. 11.6±1.2 years, p = 0.0003). Logistic regression analysis demonstrated that patients homozygous for the Q allele had a 2.2-fold higher risk (odds ratio = 2.2; CI1.1–3.4; p = 0.02) of presenting with an early menarche (age at menarche <12 years).

Conclusion

We demonstrated for the first time the association between the CB2 Q63R functional variant and the age at menarche in a cohort of Italian obese girls.     

Critical period for menarche derived by the wavelet interpolation method from changes in BMI with age in South Korean girls

Recently, few studies regarding the changes in BMI with age have been reported. In the present study, the wavelet interpolation method (WIM) was applied to the changes in BMI with age from the first grade of elementary school until the second year of high school in Korean girls, and the relationship between age at the maximum peak velocity (MPV) of BMI and age at menarche was confirmed by determining the age at MPV of BMI. Age at menarche and activity status were obtained from questionnaires given to 263 second grade high school girls in the Pusan area of South Korea. Moreover, longitudinal growth data on height and weight from the first grade of elementary school until the second year of high school (from 1997 to 2008) were obtained from health examination records. BMI was calculated from height and weight values from the first grade of elementary school until the second year of high school, and wavelet interpolation was applied to the distances of BMI in each grade. The change curve of BMI with age was determined by wavelet interpolation, and the age at MPV of BMI was determined from the changes in the velocity curve with age as the differentiation curve. Age at MPV of BMI was found to be 12.76 +/- 1.6 years, and age at menarche to be 12.34 +/- 1.1 years. The interval in age at the two times was -0.42 +/- 1.6 years, and a significant difference was seen between age at menarche and age at MPV of BMI. The reason that the age at menarche was a little earlier than the age at MPV of BMI is hypothesized to be abnormal melatonin levels influenced by lack of sleep in Korean school girls. However, it is proposed that the age at MPV of BMI is valid as the critical period for the age at menarche.     

Pakistan's new national family planning experiment

Abstract

A survey of 1, 155 girls aged 10 through 20 was conducted in a rural area of Bangladesh in March, 1976, to assess the impact of nutritional status on the onset of menarche and the association between age at menarche and age at marriage. In recent years there has been an increased age at onset of menarche which appears to have been associated with malnutrition caused by war, postwar inflation, floods, and famine in the period 1971–76. Body weight was highly correlated with the age of onset of menarche. A seasonal trend in onset of menarche was noted with the peak occurring in the winter months corresponding to the largest annual rice harvest. An increased age of marriage was also noted, which may be correlated with the increased age of menarche.     

Malnutrition, menarche, and marriage in rural Bangladesh

In order to assess the impact of nutritional status on the onset of menarche and the association between age at menarche and age at marriage, a survey of 1155 girls, ages 10 through 20, was conducted in a rural area of Bangladesh in March 1976. In order to obtain an estimated mean of age of menarche, probit analysis was used. The mean age of menarche using this technique is estimated at 15.65 for Muslims and 15.91 for Hindus. It was learned that in recent years the age of menarche has increased in a rural area. This increase seems to be associated with malnutrition caused by the war, postwar inflation, floods and famines during the 1971-75 period. When age is controlled for, the prominent effect of weight on menstrual status is evident. 98% of the girls whose weights were 88 pounds or greater had reached menarche compared to only 1% of those weighing less than 66 pounds. Body weight appears to be 1 of the most important factors for the determination of onset of menarche. There exists a seasonality of onset of menarche with a peak in winter. Age of marriage among this rural population has increased and may be associated with the increasing age of menarche. Since both age of menarche and age of marriage have increased, fertility among females age 15-19 may be expected to decrease in the future if this pattern continues.