Association of Obesity with Onset of Puberty and Sex Hormones in Chinese Girls: A 4-Year Longitudinal Study

Objective

To examine the influence of childhood obesity on the early onset of puberty and sex hormones in girls.

Methods

Healthy girls with different percentages of body fat at baseline (40 obese, 40 normal, and 40 lean) were recruited from three elementary schools in Shenyang, China. These girls (mean age 8.5 years) were also matched by height, school grade, Tanner stage, and family economic status at baseline. Anthropometry, puberty characteristics, and sex hormone concentrations were measured at baseline and at each follow-up visit. The generalized estimating equation model and analysis of variance for repeated measures using a generalized linear model were used to determine the differences in puberty characteristics and sex hormones among three groups.

Results

Over 4 years, mean age of breast II onset was earlier among obese girls (8.8 years) than normal girls (9.2 years) and lean girls (9.3 years). The prevalence (%) of early-maturation in the obese, normal, and lean groups was 25.9%, 11.1%, and 7.4%, respectively. Obesity was associated with an increased risk for breast stage II (year 2: RR, 6.3; 95% CI, 1.9–21.1 and year 3: RR, 6.9; 95% CI, 0.8–60.1). None of the girls experienced menarche in the first year; however, by the fourth year 50.0% of obese girls had menarche onset, which was higher than normal weight (27.5%) and lean girls (8.1%). The mean estradiol level increased with age in the obese, normal, and lean groups. The mean estradiol concentration was higher in obese girls than in normal and lean girls throughout the 4-year period (P<0.05).

Conclusions

Childhood obesity contributes to early onset of puberty and elevated levels of estradiol in girls.     

Duration of ovarian hormone exposure and gynecological cancer risk in Korean women: the Korean Heart Study

BackgroundAlthough reproductive and hormonal factors – such as early menarche and late menopause – have been reported as independent risk factors for cancer, few studies have examined these factors in East Asian populations.MethodsWe performed a large prospective cohort study of 66,466 women. Ovarian hormone exposure was defined as length of time between menarche and menopause. Incidence rates for breast, ovarian, endometrial and cervical cancers were examined separately in relation to reproductive lifespan defined as age at menopause minus age at menarche. Multivariable adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated using the Cox proportional hazards model.ResultsWomen with early menarche were at increased risk for developing breast cancer (HR, 1.57, 95% CI, 1.17–2.10) for age at menarche ≤12 years compared to women with age at menarche ≥17 years. Women with late age at menopause (≥52 years) had increased risks for cancers of the breast (HR, 1.59, 95%CI, 1.11–2.28) and ovary (HR, 3.22, 95% CI, 1.09–9.55) compared to women with early menopause (≤45 years of age). Women with longer duration of ovarian hormone exposure (≥40 years) were at increased risk for developing breast cancer (HR, 2.23, 95% CI, 1.35–3.68) as well as endometrial cancer (p for trend, 0.0209).ConclusionsWe showed that longer reproductive spans are associated with an increased risk of breast and endometrial cancer in Korean women.     

Comment on "Female reproductive development: a hazards model analysis," by Andrew Foster, Jane Menken, Aladdin Chowdhury and James Trussell

This article summarizes the differences between 2 similar studies. Endocrinological studies of the time to the 1st ovulatory cycle in early and late maturing girls in Finland (Apter and Vihko, 1983) are contrary to the Bangladeshi results reported by Foster in 1986. Apter found that the frequency of ovulation depended significantly on both the time since menarche and the age at menarche. Early menarche was associated with early onset of ovulatory cycles. It would be interesting to know why the Bangladesh data differ. They are puzzling, and their use in fertility models is problematic. This article also makes 2 corrections in the use of the fatness index in the Foster paper.     

Age at menarche in Iceland

The purpose of this study was to elucidate the mean age at menarche in Icelandic girls and compare it with results from other Scandinavian populations as well as in other ethnic groups. The study was performed during the school year 1972-1973 on a cross-sectional sample of 682 girls (aged 8.5 to over 17 years), constituting 9.5% of the girls from the third to eleventh forms in all the primary and secondary schools of Reykjavik. The mean age at menarche in Iceland, elicited by the status quo method, proved to be 13.06 +/- 0.10 years (S.D. 1.17 years). According to the information given by the girls (recall method), the earliest time of menstruation was 9.83 years and the latest 15.17 years, at which age all but one of the girls were menstruating.     

Correlation of the probability of occurrence of breast neoplasms with solar activity]

A contingent with high incidence of precancerous breast diseases (1080 persons) was studied to assess the relationship between solar activity and 1) alterations in the relationship between women with early menarche and women with middle and late menarche (high and low risk of breast cancer respectively) and 2) incidence of benign breast diseases. It was established that population content alterations were wave-like and had statistically significant periods 3,5; 7 and 12 years, and correlate with Wolf number changes. Incidence of benign breast diseases in the group aged 20-50 years also changed periodically (T = 11 years) depending on the birth-year and correlated conversely with Wolf numbers at the birth-years. Incidence of benign breast diseases changes periodically in the population of women with early menarche with the period of 3.6 years, and in those with middle and late menarche--with the periods of 10.5, 3.2 and 4 years. There is a statistically significant correlation between the incidence of benign breast diseases and Wolf numbers in population of women with middle and late menarche.     

Reproductive events and family history as risk factors for breast cancer in northern Alberta.

Reproductive events and family history as risk factors for breast cancer in northern Alberta were investigated with the use of data from a computerized population-based registry. Women aged 30 to 79 years attending diagnostic breast clinics at the Cross Cancer Institute from 1971 through 1975 constituted the two study groups; 1232 women had diagnosed breast cancer (malignant disease group) and 602 women were clinically free of all types of breast disease (control group). An increased relative risk of breast cancer was found in women with a family history of breast cancer, those who gave birth to their first term infant at age 30 years or older, those in whom more than 15 years elapsed between menarche and that birth, and those with a late natural menopause. There was a decreased risk, relative to nulliparity, in the postmenopausal women who first gave birth to a term infant 5 years or less after menarche. Artificial menopause (bilateral oophorectomy), parity and age at menarche had no apparent effect on the risk. The pattern of risk factors in northern Alberta differed from that reported for other geographic areas, including other provinces of Canada, thus emphasizing the need for local studies in the planning of screening programs.     

Formula feeding in infancy is associated with adolescent body fat and earlier menarche.

The tempo, level of growth and maturation during adolescence may have important implications to future adult health. The purpose of the study was to examine factors associated with menarche. Three hundred and forty girls, 9 to 14 years old, were selected from all age eligible girls at Kaiser Permanente Oahu (Honolulu). Girls' age, ethnicity, menstrual status and feeding pattern during infancy were obtained by questionnaire. The mean age of girls was 11.5 +/- 1.4 yr and the mean age at menarche among 112 (33%) girls who had reached menarche was 11.6 +/- 1.1 yr. In logistic regression, achievement of menarche was positively explained by age, Asian ethnicity and formula feeding during infancy. In simple linear regression, higher body mass index (BMI) and subcutaneous fat were also positively associated with formula feeding during infancy. The study suggests that girls who were formula fed deposit more body fat than girls who were breast-fed, resulting in early attainment of menarche.     

Changes and Tracking of Fat Mass in Pubertal Girls

Puberty is a critical period in body composition development. The influence of puberty on the development of fat mass asks for further investigation. We investigated the development of fat mass during puberty in a longitudinal prospective study in 152 healthy nonobese white girls, initial ages between 9 to 12 years. The influence of menarcheal age and the existing of tracking of fat mass have been analyzed. In 10 years time, participants were measured on eight time points. Various anthropometric data were collected, breast development was staged according to Tanner and body composition was determined with the dual‐energy X‐ray absorptiometry (DXA) scan. Calculations were made with the use of a linear mixed model. Fat mass increases from 7.9 kg (23.6%) at B1 to 18.5 kg (29.3%) at B5. Fat mass is higher in girls with an early menarche than in girls with a late menarche from B2. Girls in the quartile with initially the lowest fat mass have a chance of being in the same quartile after 10 years of 77% (P < 0.001). Girls in the quartile with initially the highest fat mass, have a risk of staying in the highest quartile of 55% (P < 0.001). Menarcheal age is of great influence on the development of fat mass. Girls with an early menarche, will have a bigger fat mass, especially at the end of puberty. Tracking of fat mass exists: a high amount of fat mass in early puberty will continue to exist at young adulthood.     

Correlates and predictors of the age of menarche

In a cross-sectional study of 452 girls between 10 and 16 years of age 36 indices of physical and 50 of mental development were tested for their correlation with age at menarche and chronological age, as well as for their predictive power for estimating menarche by multiple regression analysis. Indices of physical maturity and body weight when adjusted for chronological age showed the highest partial correlation coefficients with age at menarche. Among mental characters which show lower intercorrelations with menarche occurred the highest correlation coefficients for a handmotor factor "Spurennachzeichnen" and a factor "Gruppenabh?ngigkeit" (which indicates a type of social motivation). In general physical and mental factors correlate higher with chronological age than with age at menarche. By multiple regression analysis we determined 14 physical and 25 mental predictors explaining 21% and 17% respectively of the variance of age at menarche. The error of the estimate predicting menarche on body weight without knowledge of onset of menarche is +/- 1 year. Using chronological age in a sample of girls before menarche the error of the estimate only is +/- 6 months. To compare the predictive power of chronological age combined with body weight or with skeletal age the time interval is calculated within which 95% of girls attain menarche. The range of prediction extends from 4.3 to 1 year on chronological age (11-16 years); using mean body weight it can be improved by 1.8 to 6 months, while using mean skeletal age an improvement of 0.2 to 3.9 months is possible compared with body weight. The correlations between age at menarche and physical and mental variables are attributed to a common hormonal influence on rate of development.     

Equol producer status, salivary estradiol profile and urinary excretion of isoflavones in Irish Caucasian women, following ingestion of soymilk

Equol production, isoflavone excretion, and the salivary estradiol profile among 36 females, native Irish Caucasian volunteers following ingestion of 200mL soymilk is reported. The soymilk contained daidzein (73+/-6.7mg) and genistein (86+/-10.2mg). Volunteers provided personal and family medical history. Dietary analysis revealed that all volunteers regularly consumed soy-based or soy-supplemented food products. The mean age, mean age at menarche, and body mass index of volunteers were 46.6+/-12.3 years, 13.1 years and 26.1, respectively. The average number of children per volunteer was 2.13. Twelve (34%) of the volunteers were found to be first-degree relatives of breast cancer patients. Following consumption of the soymilk, equol was detected in the urine of 18 (51%) of the volunteers. Mean urinary daidzein and genistein concentrations during the hours following soymilk ingestion were 13.5 and 16.7microg/mg creatinine, respectively, however, some volunteers excreted little (less than 4.0microg/mg) or no isoflavone. Salivary estradiol in most (24) volunteers had decreased from 51.5+/-28.67pmol/L pre-ingestion to 29.75+/-16.13pmol/L 5h after drinking the soymilk. However, the salivary estradiol in 12 subjects (34%) increased from 33.76+/-13.4pmol/L to 137.4+/-65.64pmol/L over the same period. Individuals whose salivary estradiol increased had significantly less children (1.58 (P<0.05)), were more likely to (a) return urine samples with low isoflavone content (50.3% compared to 25%), (b) to be equol producers (67% compared to 41.7%), and (c) to be first-degree relatives of breast cancer patients (41.7% compared to 25%). Volunteers who reported a first-degree link to breast cancer were more likely to have a higher body mass index (29.0 compared to 26.1 (P<0.05)), to be equol producers (75% compared to 51%), and to excrete isoflavones in low quantities only (60% compared to 50%). First-degree relatives also had fewer children (1.75 (P<0.05)). The results indicate a significant, distinctive variation in equol production, isoflavone excretion and salivary estradiol profile among individual volunteers following ingestion of soymilk.     

Cervical patency during non-ovulatory and ovulatory estrus cycles in domestic cats

The cervix functions as a barrier to spermatozoa. Vaginal artificial insemination in cats is, therefore, likely to be successful only at the period of estrus when the cervix is open. This study aimed to define the period of cervical patency in cats in both non-ovulatory and ovulatory estrus cycles. A total of 15 reproductive cycles were studied in six cats during the estrous stage. Cervical patency was monitored with the cats under sedation, by infusing 2 mL of Iohexol contrast medium via a 3.5 French tomcat catheter into the cranial vagina during estrus. Day one of estrus was defined as the first day the cats showed estrous behavior. Non-ovulatory cycles were characterized by a serum progesterone concentration on days 11-15 that was below 5 nmol/L and a normal interestrus interval of 7-14 days. Ovulatory cycles were characterized by a serum progesterone concentration on days 11-15 that was above 5 nmol/L and an interestrus interval that exceeded 30 days. The cervix was considered to be open when the contrast medium was seen to enter the uterus, and to be closed when the contrast medium remained in the vagina. Blood samples were collected at each examination and were assayed for estradiol-17beta and progesterone concentrations. The cervix was open on the first day of standing estrus at a mean estradiol-17beta serum concentration of 87.4+/-21.8 pmol/L (range 14 to >or=180 pmol/L) and closed at an estradiol concentration of 47.1+/-12.4 pmol/L (range 4 to >or=180 pmol/L). In the ovulatory cycles the cervix was closed at a progesterone concentration of 9.8+/-4.4 nmol/L (range 0.6-28.4 nmol/L). There was no difference in the duration of cervical patency in non-ovulatory and ovulatory cycles (5.5+/-1.2 days and 5.2+/-0.5 days, respectively) (p>0.05). The higher overall mean concentrations of estradiol-17beta seen in the ovulatory cycles than in the non-ovulatory cycles, indicate that a high level of estradiol is necessary for induction of ovulation. Ovulation in 60% of unmated females in this study indicates that the techniques used for evaluation of cyclus stage and cervical opening have the potential to induce ovulation in the cat. This study demonstrates that cervical patency is not influenced by the occurrence of ovulation, but is due to individual variations between cats.     

Intake of Dairy Products,Calcium, Magnesium,and Phosphorus in Childhood and Age at Menarche in the Tehran Lipid and Glucose Study

Purpose

Studies indicate that milk intake is associated with insulin-like growth factor 1 (IGF-1) concentrations and height in childhood, whether milk and other dairy products promote puberty remains unclear. This study aimed to investigate influences of pre-pubertal intakes of milk, yogurt and cheese on menarcheal age in Tehranian girls. The associations of total dietary calcium (Ca), magnesium (Mg), and phosphorus (P) with menarcheal age were also examined.

Methods

This prospective study was conducted on 134 pre-pubertal girls, aged 4-12 years at baseline, who participated in the Tehran Lipid and Glucose Study (TLGS), and were followed for a median of 6.5 years. Dietary intakes were determined at initiation of the study using two non-consecutive 24-h dietary recalls and the age of menarche was documented during the follow-up. Logistic regression was used to calculate the risk of reaching menarche ≤ 12 years according to pre-pubertal levels of dairy or mineral intakes.

Results

The risk of earlier menarche was higher in girls with higher intakes of milk [OR: 2.28 (95% CI: 1.03–5.05)], Ca [OR: 3.20 (95%CI: 1.39–7.42)], Mg [OR: 2.43 (95% CI: 1.12–5.27)] and P [OR: 3.37 (95 % CI: 1.44–7.87) after controlling for energy and protein intake, interval between the age at study initiation and the age of menarche, and maternal age at menarche (Model 1). Girls in the middle tertile of cheese intakes had a lower risk of reaching menarche ≤ 12 years than those in the lowest tertile after controlling for covariates in model 1. These associations remained significant after further adjustment of BMI Z-score at baseline. The relationship of Ca, Mg, and P with menarche remained after further adjustment for height Z-score at baseline, whereas the association between milk and cheese intakes became non-significant.

Conclusions

Pre-pubertal intake of milk, but not cheese and yogurt, may hasten age at menarche.     

Use of the oral contraceptive pill by Austrian adolescents with emphasis on the age of onset,side effects,compliance and lifestyle

The present study investigated the use of the oral contraceptive pill in 880 Austrian high school girls. All participants filled in a questionnaire on lifestyle and menarche. Furthermore, subjects on the pill were asked about their preparation, age at first use, reasons why they take it, side effects and oral contraceptive compliance. All 139 subjects on the pill used low dose monophasic preparations. The girls started the pill at a mean age of 16.0 +/- 0.9 years for contraceptive and therapeutic reasons. The most commonly noted side effects were weight gain, an increase in breast size, fatigue and depression. The results also indicate that most users comply sufficiently. Regarding lifestyle, it can be stated that there is a correlation between the use of the pill and smoking, the frequency of consuming alcoholic drinks and being physically active.     

Menarche age,fatness, and fat distribution in Hawaiian adolescents

Menarche age was assessed in 93 adolescent females in a sample of public schools in East Hawaii. Native Hawaiian girls had significantly lower reported age at menarche than non-Hawaiian classmates. Age at menarche was significantly correlated with total fatness as measured by the sum of six skinfolds in girls who had reached menarche at least 2 years previous to measurement. When fatness was controlled in comparisons, the ethnic differences were not significant. Fat distribution, independent of fatness, was also significantly related to age at menarche. Socioeconomic, cultural, and admixture variables were not significantly related to age at menarche. Adiposity appears to be both a cause and a consequence of early age at menarche, with the relationship dependent on the elapsed time between menarche and measurement. This suggests that studies relating body composition to age at menarche must carefully control for the time interval between measurement and the date of menarche. © 1996 Wiley-Liss, Inc.     

Menarcheal age of Turkish girls in Bremen

Several studies have shown that there is a Northwest-Southeast gradient in menarcheal age of European girls, with menarche occurring on the average about one year earlier in girls living in the Southern parts of Europe as compared with those from the Northern and Northwestern European countries. Eveleth & Tanner (1976) as well as Danker-Hopfe (1986a) suggested that this gradient is due primarily to genetic differences rather than climatic or nutritional variation. To substantiate this hypothesis menarcheal age of Turkish girls who lived in Bremen for several years has been investigated. The mean age at menarche estimated by probit analysis based on status quo data from n = 494 girls aged from 9.0 to 16.5 years was 12.90 +/- 1.21 years. These results correspond very well to those reported by Neyzi et al. (1975) for girls from Istanbul. On the other hand mean menarcheal age of Turkish girls living in Bremen is distinctly lower than mean age at menarche of urban German girls, living in the same district. In summary the results of the present study support the hypothesis of a predominantly genetic cause for the observed Northwest-Southeast gradient in age at menarche in Europe.     

Association between age at menarche and early-life nutritional status in rural Bangladesh

Age at menarche is associated with anthropometry in adolescence. Recently, there has been growing support for the hypothesis that timing of menarche may be set early in life but modified by changes in body size and composition in childhood. To evaluate this, a cohort of 255 girls aged <5 years recruited in 1988 were followed up in 2001 in Matlab, Bangladesh. The analysis was based on nutritional status as assessed by anthropometry and recalled age at menarche. Data were examined using lifetable techniques and the Cox regression model. The association between nutritional status indicators and age at menarche was examined in a multivariate model adjusting for potential confounding variables. Censored cases were accounted for. The median age at menarche was 15.1 years. After controlling for early-life predictors (birth size, childhood underweight, childhood stunting) it appeared that adolescent stunting stood out as the most important determinant of age at menarche. Adolescent stunting still resonates from the effect of stunting in early childhood (OR respectively 2.63 (p<0.01 CI: 1.32-5.24) and 8.47 (p<0.001 CI: 3.79-18.93) for moderately and severely stunted under-fives as compared with the reference category). Birth size was not a significant predictor of age at menarche. It is concluded that age at menarche is strongly influenced by nutritional status in adolescence, notably the level of stunting, which is in turn highly dependent on the level of stunting in early childhood. A 'late' menarche due to stunting may be detrimental for reproductive health in case of early childbearing because of the association between height and pelvic size.     

Menarcheals age and socio-economical factors in Marrakech (Morocco)

Data on the menarcheal age was collected from a sample of 749 girls, aged between 11 and 17 years of age, drawn from the population of Marrakech (Morocco). The mean age at menarche calculated for the entire sample was of 14.26 year of age (SD=1.20). Once having grouped the girls according to the different environmental factors, we calculated the mean menarcheal age for earch group. Comparisons of these means show that only the family size and the number of sibling have an effect on the age at menarche.     

Geographic and social factors that affect the age of puberty

1866 girls aged 11-15 1/2 years in Northwest Slovakia were interviewed at their schools concerning the age at menarche, number of siblings, and altitude of their residence. 518 of the girls had undergone menarche. An angular transformation of the data was carried out, and an analysis of the variance of percentages of young girls who had attained puberty was performed. An increase in the number of girls attaining puberty with age was observed as expected, but decreases in the proportion attaining puberty at a given age corresponding with an increase in the number of siblings or of altitude were also observed. The age f pubety for those with 0-1 siblings was 14.32 years; for each additional 2 siblings, it increased by about .105 years, or about 5 weeks. The average age of puberty for girls whose homes were located at 450 m above sea level or less was 14.19 years, with each additional 100 meters of altitude adding about .253 years, or 3 months, to the age at menarche. The effects of both altitude and number of siblings were statistically significant.     

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.     

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.