Timing of menarche in girls adopted from China: a cohort study.

BACKGROUND: Girls adopted internationally from some states have been found to have high rates of early puberty, including early menarche. Explanations for the link between international adoption and early puberty include post-adoption catch-up growth triggering puberty, and under-recorded age. METHODS: We compared menarcheal age in a cohort of 814 girls adopted from China into North America against menarcheal ages in girls in China. Adoptive parents provided survey data on their daughters' weight in 2005 and on menarcheal status and age at menarche in 2011. RESULTS: Estimated median age at menarche for adopted Chinese girls is 12.37 years (95% CI: 11.84-13.00 years). Estimated prevalence of menarcheal age ≤10.00 years for adopted girls is 3%. These findings are similar to published findings on non-adopted Chinese girls. The distribution of menarche of adopted girls and non-adopted girls at the estimated incidence rates P3-P97 are also similar. Among the 609 girls whose parents reported on their weight shortly after adoption, 148 (24.3%) were -2SD or more below the median weight in the WHO weight-for-age tables. The proportion of these girls who had attained menarche was not statistically different from other girls. CONCLUSIONS: For girls adopted from China, the age of menarche, the percentage of girls attaining menarche <10 years and the distribution of menarcheal age are all similar to Chinese girls growing up in China.

The preventive effect of breast-feeding for longer than 6 months on early pubertal development among children aged 7-9 years in Korea.

OBJECTIVE: The present study was performed to investigate whether breast-feeding is associated with early pubertal development among children 7-9 years old in Korea. DESIGN: Children were divided into those who did and did not receive breast-feeding for 6 months or longer in accordance with the recommendations of the WHO. Pubertal status was determined by clinical examination using Tanner staging. SETTING: Prospective observational study. SUBJECTS: We conducted a follow-up study of children aged 7-9 years in 2011 who had taken part in the Ewha Birth & Growth Cohort study. RESULTS: Fifty (22.8%) of the total of 219 children were in early puberty, with the proportion being slightly higher for girls (24.1%) than boys (21.4%). Children who had entered early puberty were taller, weighed more and had a higher concentration of insulin-like growth factor 1. Moreover, the change in weight Z-score from birth to follow-up was significantly lower in children who were breast-fed than in those who were not (weight Z-score change: 0.32 (sd 1.59) v. 0.77 (sd 1.61), respectively, P=0.04). Comparison of breast-feeding by puberty status indicated a preventive association with early puberty in children who were breast-fed for 6 months or longer (OR=0.37; 95% CI 0.18, 0.74). This association remained significant after adjustment for relevant covariates. CONCLUSIONS: These results demonstrate a beneficial association between breast-feeding and early pubertal development, especially in those breast-fed for 6 months or longer. The study suggests that interventions would need to start early in life to prevent early pubertal development.

Does neighborhood environment influence girls' pubertal onset? findings from a cohort study.

BACKGROUND: Pubertal onset occurs earlier than in the past among U.S. girls. Early onset is associated with numerous deleterious outcomes across the life course, including overweight, breast cancer and cardiovascular health. Increases in childhood overweight have been implicated as a key reason for this secular trend. Scarce research, however, has examined how neighborhood environment may influence overweight and, in turn, pubertal timing. The current study prospectively examined associations between neighborhood environment and timing of pubertal onset in a multi-ethnic cohort of girls. Body mass index (BMI) was examined as a mediator of these associations. METHODS: Participants were 213 girls, 6-8 years old at baseline, in an on-going longitudinal study. The current report is based on 5 time points (baseline and 4 annual follow-up visits). Neighborhood environment, assessed at baseline, used direct observation. Tanner stage and anthropometry were assessed annually in clinic. Survival analysis was utilized to investigate the influence of neighborhood factors on breast and pubic hair onset, with BMI as a mediator. We also examined the modifying role of girls' ethnicity. RESULTS: When adjusting for income, one neighborhood factor (Recreation) predicted delayed onset of breast and pubic hair development, but only for African American girls. BMI did not mediate the association between Recreation and pubertal onset; however, these associations persisted when BMI was included in the models. CONCLUSIONS: For African American girls, but not girls from other ethnic groups, neighborhood availability of recreational outlets was associated with onset of breast and pubic hair. Given the documented risk for early puberty among African American girls, these findings have important potential implications for public health interventions related to timing of puberty and related health outcomes in adolescence and adulthood.

High serum isoflavone concentrations are associated with the risk of precocious puberty in Korean girls.

OBJECTIVE: The gradual decrease in the age of onset of puberty raises concerns about the contribution of phytoestrogen intake on sexual maturation. However, no data are available on the association between serum isoflavone (genistein, daidzein) concentration and central precocious puberty (CPP). The aim of the study was to test the association between serum isoflavone concentrations and the risk of CPP in Korean girls. STUDY DESIGN: A case-control study was conducted at Inje University Hospital in Korea. One-hundred and eight girls with CPP (aged 8·6 ± 0·8 year) and 91 age-matched controls (aged 8·5 ± 0·8 year) were examined. RESULTS: Serum concentrations of daidzein (P = 0·0202), genistein (P = 0·0021) and total isoflavones (P = 0·0009) were higher in children with CPP than in normal children. When the children were categorized into three groups according to total serum isoflavone as follows: <30, 30-70 and ≥70 nmol/l, serum concentrations of daidzein, genistein and total isoflavones significantly increased across three categories of serum isoflavone (P < 0·0001). The prevalence of CPP was significantly higher in children with serum isoflavone level of ≥30 nmol/l than those with serum level of <30 nmol/l (P = 0·0008). The adjusted OR for precocious puberty increased significantly across a range of total serum isoflavone (OR = 4·39; 95% CI: 1·83-10·51 vs OR = 5·22; 95% CI: 2·07-13·20; P = 0·001). CONCLUSION: These results suggest that elevated serum isoflavones may be associated with the risk of CPP in Korean girls.

Menstruation in adolescents: what's normal, what's not.

The conventional wisdom about menstruation in adolescents, perpetuated in textbooks, requires updating. Recently published national surveys and reviews of large historical databases provide information about menstruation in adolescents, including the following: (1) Girls are experiencing earlier pubertal development than previously noted, suggesting that guidelines for the evaluation of potentially pathologic precocious puberty be reassessed. (2) There are racial differences in pubertal development, with African American girls experiencing earlier signs than Caucasian girls, and Mexican American girls intermediate in pace. (3) The absence of pubertal development by age 14 is associated with a high probability of conditions with impaired reproductive potential. (4) Absence of menarche by age 15 is statistically uncommon and should be evaluated. (5) Parameters for normal menstrual cyclicity indicate that most menstrual cycles for adolescents are between approximately 20 and 45 days. (6) Because menstrual cycles outside of this range are statistically uncommon, consideration should be give to evaluating adolescents with bleeding that is either too frequent or too infrequent. (7) A number of conditions with the potential for significant sequelae in adulthood can present as abnormal menses in adolescence, and thus merit early diagnosis and management.

Early Puberty, School Context, and Delinquency Among South Korean Girls.

Compared with chronological age, criminologists have paid less attention to the biological sense of age typically expressed by pubertal development. Studies that have examined pubertal timing's effects on delinquency have almost exclusively been conducted in Western countries using mostly White samples. To our knowledge, no study has ever examined this issue in the Asian context. The current study is the first attempt to bridge this research gap by examining the association among menarcheal timing, the sex composition of schools, and delinquency in a representative sample of 1,108 ninth-grade girls in South Korea. The results show that significant association between early menarche and delinquency exists only in mixed-sex schools but not in all-girls schools. In addition, the significant linkage between early menarche and delinquency in mixed-sex schools is mediated by delinquent peer associations.

Early puberty in 11-year-old girls: Millennium Cohort Study findings.

OBJECTIVE: Early puberty in girls is linked to some adverse outcomes in adolescence and mid-life. We address two research questions: (1) Are socioeconomic circumstances and ethnicity associated with early onset puberty? (2) Are adiposity and/or psychosocial stress associated with observed associations? DESIGN: Longitudinal data on 5839 girls from the UK Millennium Cohort Study were used to estimate associations between ethnicity, family income, adiposity and psychosocial stress with a marker of puberty. MAIN OUTCOME MEASURE: Reported menstruation at age 11 years. RESULTS: All quoted ORs are statistically significant. Girls in the poorest income quintile were twice as likely (OR=2.1), and the second poorest quintile nearly twice as likely (OR=1.9) to have begun menstruation compared with girls in the richest income quintile. Estimates were roughly halved on adjustment for Body Mass Index and markers of psychosocial stress (poorest, OR=1.5; second poorest, OR=1.5). Indian girls were over 3 times as likely compared with whites to have started menstruation (OR=3.5) and statistical adjustments did not attenuate estimates. The raised odds of menstruation for Pakistani (OR=1.9), Bangladeshi (OR=3.3) and black African (OR=3.0) girls were attenuated to varying extents, from about a third to a half, on adjustment for income and adiposity. CONCLUSIONS: In contemporary UK, excess adiposity and psychosocial stress were associated with social inequalities in early puberty, while material disadvantage and adiposity were linked to ethnic inequalities in early puberty among girls.

Near-final height in 82 Chinese patients with congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency: a single-center study from China.

BACKGROUND: The objective of this study was to identify variables that might interfere with reaching the near final height (NFH) in Congenital adrenal hyperplasia (CAH) due to classic 21-hydroxylase deficiency (21-OHD). METHODS: A cross-sectional study of 82 (24 males and 58 females) classic (23 salt-wasting form [SW] and 59 simple-virilizing form [SV]) CAH 21-OHD patients seen in our institution between 1989 and 2015 with 10.6 (0.5~25.5) years of follow-up who reached their NFH was conducted. The variables related to NFH were explored. RESULTS: NFH (153.35±8.31) cm, (-1.9±1.1) SD was significantly lower than the normal population (p<0.001). The treated patients reached a significantly higher NFH (-1.7±1.1) SD than those untreated (-2.6±1.0) SD (p<0.05). Both of early treatment and late treatment group were taller than untreated group (p<0.001, p=0.013, respectively), and early treatment group had a taller height trend than late treatment group (p=0.089). A better height outcome was observed in patients with advantage in target height, good compliance, and low hydrocortisone dose by multivariate Cox regression analysis in 62 treatment patients. NFH and hydrocortisone dose was negatively correlated (r=-0.23, p=0.078) in treated group. Patients complicated by central precocious puberty (CPP) received gonadotropin-releasing hormone analogue (GnRHa) plus letrozole had increased NFH with height SD for bone age and Ht SD improved after treatment compare to no intervention group (p=0.001, p=0.035). CONCLUSIONS: Patients with classic 21-OHD have blunted final height, as compared with their target height and the population norm, not-treated even worse. Careful treatment adjustments have a favorable influence on growth. Alternative treatments, such as the use of puberty inhibitors GnRHa in addition to anti-estrogen therapy letrozole can somewhat improve NFH in children with 21-OHD complicated by CPP.

Gamma knife surgery for hypothalamic hamartomas accompanied by medically intractable epilepsy and precocious puberty: experience in Mexico.

OBJECT: Hypothalamic hamartoma is a nonneoplastic malformative mass of neurons and glia in the region of the hypothalamus. Because of its location, open surgery is associated with high morbidity and mortality rates. Gamma knife surgery (GKS) may be an efficient and safe treatment approach, which produces little morbidity. The authors describe the results of GKS in three patients with hypothalamic hamartomas. METHODS: All patients were male, aged 3, 12, and 15 years. The lesions were classified according to the Valdueza scale: one was Type IIb and two were Type IIa. The patients presented with gelastic seizures (15-20 per day), generalized epilepsy, behavioral abnormalities, and alterations of the sleep cycle. Precocious puberty was present in one patient. The Type IIb tumor had a volume of 1.8 cm3, and the Type IIa tumors were 597 mm3 and 530.1 mm3. The lesions received 12.5 Gy, 14 Gy, and 15 Gy, respectively, to the 50% isodose line. The patients were followed for 30 to 50 months. After 3 months, all patients showed improvement of their sleep, behavior, and epilepsy. At the present time, these patients are receiving low-dose antiepileptic agents and have achieved adequate social development and school integration. CONCLUSIONS: Gamma knife surgery appears to be a good, safe, and effective option for the treatment of selected hypothalamic hamartomas. No morbidity or mortality was associated with these three cases.

Pre- and postpuberal findings in premature adrenarche.

The complications of hyperinsulinism and insulin resistance are becoming more common in pediatrics (including type 2 diabetes mellitus, dyslipidemia and polycystic ovary syndrome) because of the increased occurrence of obesity in children. We report the occurrence of insulin resistance and marked hyperandrogenism in prepubertal minority group girls (African-American and Caribbean Hispanic) with premature adrenarche. Approximately one-third of our prepubertal patients with premature adrenarche evaluated have been noted to have marked hyperandrogenism with ACTH stimulated levels of 17-hydroxypregnenolone and the ratio of 17-hydroxypregnenolone/17-hydroxyprogesterone more than two standard deviations above the mean of normal early pubertal girls (Tanner II-III). Furthermore, those girls with the more marked hyperandrogenism have been noted to have insulin resistance as assessed by the frequently sampled intravenous glucose tolerance test. A preliminary evaluation of adolescent girls previously evaluated for premature adrenarche has revealed that those girls with hyperandrogenism and insulin resistance when evaluated in the prepubertal period continue to have obesity, insulin resistance, hyperandrogenism and symptoms of hyperandrogenism (irregular menses, hirsutism and acne). Hence, the early identification of children at risk for insulin resistance should permit early intervention in order to avoid complications.

Premature adrenarche: findings in prepubertal African-American and Caribbean-Hispanic girls.

Premature adrenarche was previously thought to be a benign condition. However, the authors and several other research groups have noted hyperinsulinism and insulin resistance in many girls with premature adrenarche. African-American and Caribbean-Hispanic girls with premature adrenarche are frequently obese with marked hyperandrogenism, signs which correlate with the degree of insulin resistance (i.e., those girls who are obese and insulin resistant tend to have higher levels of adrenocorticotropic hormone-stimulated androgens). Also, girls with premature adrenarche and reduced insulin sensitivity can have subtle decreases in their high-density lipoprotein (HDL) profile. Many of these girls have a strong family history of type 2 diabetes mellitus. Preliminary data regarding long-term follow-up of girls with premature adrenarche indicate that those girls who remain obese are at risk of developing polycystic ovary syndrome (PCOS). The term 'syndrome X' refers to the constellation of laboratory and clinical findings associated with hyperinsulinism stemming from insulin resistance. These findings include obesity, acanthosis nigricans, glucose intolerance, type 2 diabetes mellitus, dyslipidaemia with reduced HDL and elevated low-density lipoprotein, cardiovascular disease and PCOS. Hence, for certain girls, premature adrenarche may be a part of the clinical spectrum of syndrome X.

Early puberty, negative peer influence, and problem behaviors in adolescent girls.

OBJECTIVE: To determine how early puberty and peer deviance relate to trajectories of aggressive and delinquent behavior in early adolescence and whether these relationships differ by race/ethnicity. METHODS: In this longitudinal study, 2607 girls from 3 metropolitan areas and their parents were interviewed at ages 11, 13, and 16 years. Girls reported on their age of onset of menarche, best friend's deviant behavior, delinquency, and physical, relational, and nonphysical aggression. Parents provided information on family sociodemographic characteristics and girls' race/ethnicity. RESULTS: Sixteen percent of girls were classified as early maturers (defined by onset of menarche before age 11 years). Overall, relational and nonphysical aggression increased from age 11 to age 16, whereas delinquency and physical aggression remained stable. Early puberty was associated with elevated delinquency and physical aggression at age 11. The relationship with early puberty diminished over time for physical aggression but not for delinquency. Best friend's deviant behavior was linked with higher levels of all problem behaviors, but the effect lessened over time for most outcomes. Early puberty was associated with a stronger link between best friend's deviance and delinquency, suggesting increased vulnerability to negative peer influences among early-maturing girls. A similar vulnerability was observed for relational and nonphysical aggression among girls in the "other" racial/ethnic minority group only. CONCLUSIONS: Early puberty and friends' deviance may increase the risk of problem behavior in young adolescent girls. Although many of these associations dissipate over time, early-maturing girls are at risk of persistently higher delinquency and stronger negative peer influences.

Premature thelarche in infants and toddlers: prevalence, natural history and environmental determinants.

STUDY OBJECTIVE: The aim of this study was to measure the prevalence of premature thelarche in infant and toddler girls and to determine if environmental sources of estrogen were associated with early breast development. DESIGN: Observational with mixed methods: Retrospective chart review, cross-sectional component involving an interview survey, along with longitudinal follow-up of girls with thelarche up to six months. SETTING: A general pediatric clinic within a teaching hospital located in a large Midwestern city. PARTICIPANTS: Girls, between the ages of 12 and 48 months, and their mothers, presenting for well-child care. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Prevalence of premature thelarche; association of premature thelarche with selected environmental exposures. RESULTS: Among the 318 subjects, the overall prevalence of premature thelarche was measured at 4.7% (n = 15). The prevalence by race/ethnicity was 4.2% among White Non-Hispanics, 4.6% among Blacks and 6.5% among White Hispanics. The peak prevalence occurred between 12-17 months of age. All thelarche cases were Tanner stage 2. No statistically significant relationship was found between premature thelarche and environmental exposures. Upon follow-up, 44% of the cases of premature thelarche had persistent breast development. CONCLUSIONS: Our study demonstrated a higher prevalence of premature thelarche than has been previously reported. This study lacked power because of the small number of premature thelarche cases, the ubiquitous presence of environmental exposure as well as the potentially small effect of each environmental factor. Future studies need to employ a very large sample in order to accurately analyze the relationship between environmental toxicants and premature thelarche.

An association study between the genetic polymorphisms within GnRHI, LHß and FSHß genes and central precocious puberty in Chinese girls.

OBJECTIVES: Gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are three hypothalamic-pituitary-gonadal axis expressing hormones. They play critical roles in the onset of puberty. Here we report the relationship between the three hormones and Central Precocious Puberty (CPP) in Chinese Han girls. METHODS: We analyzed the single nucleotide polymorphisms (SNPs) of 5'-flanking regions of these genes by DNA sequencing in 27 CPP samples. Then the SNPs sites were genotyped by ligase detection reaction in a total of 283 Chinese Han CPP cases and 284 matched controls. Distributions of the polymorphisms and haplotypes were calculated for statistical evaluation. RESULTS: Nine SNPs (One in GnRHI gene: -2003 C/T; Five in LHß gene: -1456 C/G, -1424 C/G, -238 G/A, -164 G/A and -34 T/A; Three in FSHß gene: -1825 T/C, -261 G/T and -132 T/A.) were found. A quantitative genetic association study was made. -1825 T/C in FSHß gene was related with CPP with a weak effect (P=0.025). A haplotype in the 5'-flanking region of LHß gene was significantly associated with CPP in Chinese Han girls (P=8.25×10(-09)). However, analysis software showed that none of SNP was found in the regulating control element of these genes. CONCLUSIONS: Our finding implies that the polymorphisms in the 5'-flanking regions of FSHß gene and LHß gene probably were related to the puberty onset time of these girls. Further studies on the polymorphisms are needed for the exact mechanism.

[Thelarche and nutritional status: an epidemiological study of two ethnic groups]. / Telarquia y estado nutricional: Estudio epidemiológico en dos grupos étnicos.

BACKGROUND: Improvements in environmental conditions may result in an earlier onset of thelarche. However, its onset is not homogeneous among different population groups. AIM: To assess the relationship between nutritional status, ethnicity and age of thelarche. MATERIAL AND METHODS: Cross-sectional study of girls in second through sixth grade, attending 165 schools located in Chile's Araucania region. Of these, 231 girls who presented thelarche (breast button) were selected. The girls' surnames were used to identify their ethnicity: indigenous had three or four last names of Mapuche indigenous origin (n =113), while non-indigenous were those who only had Chilean-Spanish last names (n =118). Weight, height, waist circumference and skinfold thicknesses were measured and socio-economic background information was collected through a home interview. RESULTS: The median age of thelarche was 10 years and 4 months, regardless of ethnic group. Multivariant models showed that an increase of one z score unit of body mass index (BMI) decreased the median age of thelarche by 5.6 months (CI: -7.24 to -3.90), controlling for the effect of different covariables. A decrease in one z score of height retards the median age of thelarche by 5.5 months (CI: 4.02 to 6.98). Ethnicity did not influence the age of thelarche. CONCLUSIONS: The age of thelarche found by us is similar to that reported in international studies, it comes earlier as weight increases, is delayed as height decreases and is not related to ethnicity.

Insulin resistance after precocious pubarche: relation to PAI-1-675 4G/5G polymorphism, and opposing influences of prenatal and postnatal weight gain.

OBJECTIVE: The common promoter -675 4G/5G insertion/deletion polymorphism (indel) in the plasminogen activator inhibitor-1 (PAI-1) gene has been associated with quantitative components of the metabolic syndrome. We hypothesized that this polymorphism is associated with precocious pubarche (PP), a population known to be at risk for hyperinsulinaemic hyperandrogenism. DESIGN: A cross-sectional, hospital-based study. PATIENTS: A total of 115 control and 182 PP Catalan girls and young women. MEASUREMENTS: Subjects were genotyped for the -675 4G/5G indel in the PAI-1 gene. Insulin resistance and insulin secretion were estimated by the homeostasis model assessment. RESULTS: Genotype frequencies for the PAI-1-675 4G/5G indel (4G4G, 4G5G and 5G5G) were similar in control and PP subjects (24%vs. 27%, 50%vs. 47%, and 26%vs. 26%, respectively; P = 0.85) and these frequencies were in Hardy-Weinberg equilibrium. The 5G allele, however, was associated with insulin resistance in both postmenarcheal control and PP subjects (P < 0.01 for pooled postmenarcheal subjects, N = 122). The coexistence with the at-risk genotype of both a low birthweight (standard deviation score, SDS < -1.0) and a high body mass index (BMI) at time of the study (SDS > +1.0) resulted in a noteworthy increase (P < 0.001) in insulin resistance. CONCLUSION: The common promoter -675 4G/5G indel of the PAI-1 gene is not associated with PP but, in Catalan young women, the 5G allele enhances the risk for insulin resistance imposed by the sequence of a low birth weight (LBW) and a high BMI.

Increased risk of precocious puberty in internationally adopted children in Denmark.

BACKGROUND: Studies have indicated that internationally adopted children have an increased risk of developing precocious puberty, but no epidemiologic risk estimates have previously been calculated. We aimed to assess the risk of developing precocious puberty in intercountry adoptees, children immigrating with their family, and descendants of immigrants living in Denmark. METHODS: Patients who were registered with the diagnosis of precocious puberty during the period 1993-2001 were identified through the national patient registry. The background population of children born from 1983 to 2001 were identified through the unique Danish Civil Registration System and subsequently categorized as being Danish (N = 1,062,333), adopted (N = 10,997), immigrating with their family (N = 72,181), or being descendants of immigrants (N = 128,152). The incidence rate ratio of precocious puberty was estimated by log-linear Poisson regression. All rate ratios were adjusted for age and its interaction with gender and calendar year. P values were based on likelihood ratio tests, and 95% confidence intervals were calculated by Wald's test. RESULTS: In the study period, 655 children developed precocious puberty during 5,627,763 person-years at risk. Adopted children were followed during 39,978 person-years at risk, during which 45 girls and 6 boys developed precocious puberty. The risk of developing precocious puberty was significantly increased 10 to 20 times in adopted girls compared with girls with Danish background. The risk of developing precocious puberty depended on the country of origin. In children immigrating with their family, the risk of developing precocious puberty was only marginally increased. Older age at adoption significantly increased the risk of precocious puberty in adoptees independent of region of origin. The incidence rate ratio was significantly higher in children adopted after the age of 2. In children immigrating with their family, we found no effect of age at migration. DISCUSSION: In this large, nationwide, register-based study including 655 cases of precocious puberty, we found that intercountry boys and girls were 10 to 20 times more likely to develop precocious puberty compared with the Danish reference group. Older age at adoption significantly increased the risk of precocious puberty. Uncertainty of the exact age is a well-known problem in adopted children, and systematic underestimation of age might bias the result. However, using the worst-case scenario that all children who according to the Danish Civil Registration System were adopted after 2 years of age were in fact 1 year older, we still observed a highly increased risk of precocious puberty associated with adoption and especially with adoption after 2 years of age. Surprisingly, the risk of precocious puberty was not increased in the large group of children adopted from Korea. One case of precocious puberty was identified among Korean children, whereas > 20 cases of precocious puberty would have been expected if the risk for a Korean child was at the same level as observed among adopted children from India and South America. In the study population, 99% of Korean children were adopted before 2 years of age, which may contribute to explaining our finding. In Korea, children appointed for adoption are often living in foster care settings from birth to adoption, whereas most other countries are reported to take care of the children in orphanages before adoption. It can only be speculated whether a relation between preadoption living conditions and later risk of precocious puberty exists. Genetic factors play a key role in the timing of puberty, and large variations in age at menarche are observed worldwide. Age at menarche is reported to be in the same age range in South Korea as in well-off populations in other parts of the world, indicating that the different risk of precocious puberty observed between Korean and other adoptees probably cannot be explained by genetic factors alone. The finding that the risk of precocious puberty was significantly increased among adoptees in contrast to what was seen in children immigrating with their families contradicts a direct effect of migration. An increasing number of studies have shown long-term effects of certain prenatal and postnatal growth patterns, including advancement in pubertal maturation after poor intrauterine growth and catch-up growth during childhood. Different growth patterns and dietary habits between adoptees and children immigrating with their families might contribute to explain our findings. It has been hypothesized that stressful psychosocial factors in infancy and childhood may lead to earlier pubertal maturation. In general, adoptees have experienced several traumatic life events, and it may be speculated that these events alter the susceptibility for developing precocious puberty. CONCLUSIONS: Foreign-adopted children originating from regions other than Korea had a 15- to 20-fold increased risk of precocious puberty compared with Danish-born children, whereas adoptees originating from Korea had no increased risk of precocious puberty. In addition, children immigrating with their families had no increased risk of precocious puberty. The effect of country of origin might be explained by genetic factors or by different environmental exposures and living conditions in the different countries. Older age at adoption increased the risk for premature onset of puberty, which may suggest that environmental factors influence the risk of precocious pubertal development in adopted children.