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Introduction: Objective: to analyze the relationship of age at menarche and leptin with the metabolically healthy (MH) and metabolically unhealthy (MUH) phenotypes in adolescent girls in different body mass index (BMI) categories. Method: an observational and cross-sectional study consisting of 139 female adolescents attended to at the Adolescent Reference Center in Macaé, Rio de Janeiro. Menarche was classified as early (EM) when the first menstruation occurred at or before 11 years of age; normal menarche (NM) was categorized at ages 12 to 14; menarche was considered late (LM) when it occurred at age 15 or older. The factors required to ascertain the subjects' phenotype, as well as their leptin levels, weight, and height, were measured and their BMIs were calculated. The girls were classified as MH or MUH based on the NCEP-ATP III criteria as adapted for children and adolescents. Results: 82 % (n = 114) of the girls were classified as MH and 18 % (n = 25) as MUH. Mean age at menarche was 11.79 ± 1.39 years. There was a higher prevalence of MUH amongst the girls who had EM (p = 0.04). A higher inadequacy of serum leptin concentrations was found in girls who had EM (p = 0.05) and in those classified as MUH (p = 0.01). The adolescents who were severely obese exhibited inadequate leptin levels (p < 0.01) and had gone through EM (p = 0.02). A total of 8.1 % (n = 7) of the normal-weight girls were classified as MUH, and 29.4 % (n = 5) of those who were severely obese were classified as MH (p < 0.01). Conclusion: early menarche and high serum leptin concentrations are related with the MUH phenotype in adolescent girls in different BMI categories.

The ratio between the length of second and fourth digits (2D:4D) is a putative biomarker for prenatal testosterone and estrogen exposure. The aim of the study was to examine the association between 2D:4D and women's general and reproductive health. This analysis was conducted within a prospective pregnancy cohort study. The study population included 187 women. 2D:4D was measured directly in both hands using a digital caliper. Multivariable linear and logistic models were used to study the associations between digit ratio and the studied health characteristics. Mean age of the participants was 30.7 ± 4.9 years. The mean age at menarche was 12.9 ± 1.4 years. Right hand 2D:4D mean ± SD was 0.965 ± 0.03. Left hand 2D:4D mean ± SD was 0.956 ± 0.03. An association was found between right 2D:4D and age at menarche, with older age in women with 2D:4D ≥ mean versus 2D:4D < mean (13.2 ± 1.5 and 12.8 ± 1.3 respectively, b = 0.48, 95%CI:0.06-0.91) while controlling for ethnicity. Higher 2D:4D was also associated with heavier menses bleeding and dysmenorrhea. There is an association between 2D:4D and sub optimal reproductive characteristics, including later age at menarche, heavier menses bleeding and dysmenorrhea. These findings support the association between the intrauterine period and reproductive characteristics. Further studies are required to support our findings.

Context: Increased testosterone (T) levels are a cardinal feature of polycystic ovary syndrome (PCOS). Female relatives of affected women, including premenarchal daughters, have elevated T levels supporting a genetic susceptibility to this phenotype. Girls with obesity (OB-g) also have increased T levels throughout puberty, which may indicate risk for PCOS., Objective: We tested the hypothesis that premenarchal daughters of women affected with PCOS (PCOS-d) have distinctive phenotypic features compared with OB-g., Design, Setting, and Participants: Forty-eight PCOS-d, 30 OB-g, and 22 normal weight (NW-g) premenarchal girls were studied. Mothers of OB-g and NW-g had no evidence for PCOS., Main Outcome Measures: Reproductive hormones were measured., Results: Body mass index differed by design, was highest in OB-g, followed by PCOS-d (P > 0.001). PCOS-d and OB-g had similar increases in free T levels compared with NW-g (PCOS-d vs NW-g, P = 0.01; OB-g vs NW-g, P = 0.0001). Sex hormone binding globulin levels were lowest in OB-g and lower in PCOS-d than in NW-g (PCOS-d vs NW-g, P = 0.005; OB-g vs NW-g, P < 0.0001; PCOS-d vs OB-g, P < 0.0001). Anti-Müllerian hormone (AMH) levels in PCOS-d were significantly increased compared with OB-g, who tended to have lower AMH levels than NW-g (PCOS-d vs OB-g, P < 0.0001; PCOS-d vs NW-g, P = 0.10)., Conclusions: Despite similarly elevated free T levels, PCOS-d had increased AMH levels compared with OB-g. This finding suggests that OB-g lack alterations in ovarian folliculogenesis, a key reproductive feature of PCOS. Causal mechanisms may differ in PCOS-d or OB-g, or elevated T in OB-g may not be an early marker for PCOS., (Copyright © 2019 Endocrine Society.)

Purpose: To determine whether there is a relationship between the age of seizure onset and the age of menarche., Methods: 1144 women with epilepsy (WWE) in the community, ages 18-47 years, provided web-based survey data. We compared the frequencies of the individual differences between their ages of seizure onset and menarche to each other and chance. We determined whether the age of menarche is a predictor of the age of seizure onset and the percentage of the variance that menarche explains. We used two-step cluster analysis to auto-identify a cluster of years relative to the age of menarche that showed the greatest predilection for seizure onset., Results: Average age of menarche was 12.55 [95% CI: 12.45-12.65]. It was greater in WWE who developed seizures before versus after menarche (12.70 [12.54-12.86] v 12.42 [12.30-12.54], p = 0.006). More WWE had seizure onset during the year of menarche than during any other year (8.3% v expected 2.1%; p < 0.0001). Menarche, however, explained only 1% of the variance. Seizure onset frequencies were greatest for an auto-identified cluster that spanned 2 years before to 6 years after menarche and subsumed 49.3% of seizure onset., Conclusion: Although the results indicate a significant relationship between the age of seizure onset and the age of menarche, the broader auto-identified perimenarchal cluster that subsumes 49.3% of seizure onset suggests that research target the potential role of the great increase in adrenarchal, as well as gonadarchal, neuroactive steroids that modulate neuronal excitability and seizures during that span., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Early menarche has been associated with increased risk of metabolic syndrome. Therefore, investigating the association of each component of metabolic syndrome with age at menarche, and interactions between them, might lead to a better understanding of metabolic syndrome pathogenesis. In this study, we evaluated age at menarche for risk of metabolic syndrome and associations with its components. As a result, the risk of MetS incidence was significantly increased only at ≤12 years of age at menarche (OR = 1.91, P < 0.05). Women with early menarche (≤12 years) had significantly higher levels of triglycerides ( β coefficient = 37.83, P = 0.02). In addition, hypertriglyceridemia was significantly increased at early menarche with 1.99 (95% CI: 1.16-3.41, P < 0.01). With GWAS-based pathway analysis, we found the type 2 diabetes mellitus, stress-activated protein kinase signaling, and Jun amino-terminal kinase cascade pathways (all nominal P < 0.001, all FDR < 0.05) to be significantly involved with early menarche on triglyceride levels. These findings may help us understand the role of early menarche on triglyceride and interaction between gene and early menarche on triglyceride for the development of metabolic syndrome.

Objective: To study the reproductive and metabolic differences between daughters of women with polycystic ovary syndrome (PCOSd) and control women (Cd) after menarche., Design: Case-control study., Setting: Clinical endocrinology unit., Patient(s): We studied 43 PCOSd and 28 Cd 1.5-6 years after menarche., Intervention(s): Determination of anthropometry, pubertal development, hirsutism, oral glucose tolerance test, and GnRH analogue test., Main Outcome Measure(s): Ferriman score, sex steroids, gonadotropins, antimüllerian hormone (AMH), ovarian volumes, and glucose and insulin levels., Result(s): The groups were similar in chronologic, gynecologic, and menarchal ages and anthropometric variables. Ferriman score, ovarian volumes, and AMH were higher in PCOSd. Propensity score analysis showed that there were significant differences in LH, LH-FSH ratio, T and free androgen index, post-stimulated LH and LH-FSH ratio, and 2-hour insulin that could be attributed only to the fact of being a PCOS daughter. The generalized linear model showed that higher LH levels were positively associated with AMH and T levels., Conclusion(s): We found that higher LH, androgen, and insulin levels are present in PCOSd during the postmenarchal period, which may establish the basis for the development of PCOS during adulthood. Moreover, LH levels were associated with AMH levels, which supports that the neuroendocrine feedback proposed for AMH and LH is present in humans and that this feature is probably programed in utero, as recently shown in mice., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Adolescence is an important developmental period of childhood. Good health and adequate nutrition consisting major food constituents and trace elements like zinc are fundamental for optimal sexual maturation. To determine the relationship between zinc levels and pattern of breast and pubic hair development, as well as menarcheal age of female SCA children aged 6-18 years and their matched controls with hemoglobin genotype AA. Cross sectional, case-control study. Information on biodata, age at menarche, medical and drug history as well as 24-hour dietary recall was documented using interviewer administered questionnaire. Sexual maturation was assessed using Tanner staging and zinc levels determined using Atomic absorption spectrophotometer. Eighty-one subjects were compared with 81 controls. There was significant delay in the mean age of attainment of various Tanner stages of breast and pubic hair in the subjects. Mean age of 14.81 ± 1.07 years at menarche in subjects was significantly higher than 12.62 ± 1.18 years in controls (p = 0.001). Serum zinc of 58.01 ± 10.58 µg/dl in subjects was significantly lower than 68.37 ± 8.67 µg/dl in controls (p = 0.001). Serum zinc levels were found to have a significant positive relationship with stages of sexual maturation and mean age at menarche. Reduced serum zinc in children with SCA was associated with delayed sexual maturation.

Childhood intake of animal foods is associated with age at first menstrual period (menarche). It is unknown whether the micronutrients present in these foods could explain this association. Our objective was to investigate the associations of micronutrient status biomarkers in middle childhood with age at menarche. We quantified circulating Hb, ferritin, mean corpuscular volume, Zn, vitamin B12, erythrocyte folate and retinol in 1464 pre-menarcheal girls aged 5-12 years in Bogotá, Colombia, and followed them for a median 5·7 years for the occurrence and date of menarche. We estimated median age at menarche and hazard ratios (HR) with 95 % CI by levels of each biomarker with use of Kaplan-Meier survival probabilities and Cox regression, respectively. Median age at menarche was 12·4 years. Middle childhood Hb was inversely related to age at menarche whereas plasma ferritin was positively associated with this outcome in a linear manner. HR of menarche for every 1 sd of Hb (11 g/l) and ferritin (23·2 µg/l) were 1·11 (95 % CI 1·04, 1·18; P=0·001) and 0·94 (95 % CI 0·88, 0·99; P=0·02), respectively, after adjustment for baseline age, C-reactive protein concentration, maternal age at menarche and parity and socioeconomic status. The association with ferritin was stronger in girls aged 9-10 years at baseline. Additional adjustment for baseline height- and BMI-for-age did not change the results. We conclude that higher Fe status in middle childhood is related to later age at menarche whereas Hb concentrations are inversely associated with age at onset of menses.

Objectives: Early menarche has been linked to higher risk of type 2 diabetes in Western and Asian societies, yet whether age at menarche is associated with diabetes in Latin America, where puberty and diabetes may have different life courses, is unknown. We tested the hypothesis that earlier menarche is associated with higher diabetes risk in Brazilian adults., Methods: We used data from 8,075 women aged 35-74 years in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) who had complete information on age at menarche, diabetes status, and covariates. Diabetes was defined based on self-reported physician diagnosis, medication use, and laboratory variables (fasting glucose, 2-hour glucose, and glycated hemoglobin). Poisson regression was used to generate risk ratios (RR) and 95% confidence intervals (CI)., Results: Menarche onset < 11 years [vs. 13-14 years (referent)] was associated with higher risk of diabetes (RR = 1.34; 95% CI: 1.14-1.57) after adjusting for sociodemographic factors, maternal education, maternal and paternal diabetes, and birth weight. This persisted after further control for BMI at age 20 years and relative leg length. Additionally, among those not taking diabetes medications, earlier menarche [<11 years vs. 13-14 years (referent)] was associated with higher % glycated hemoglobin (p < 0.001), alanine aminotransferase (p < 0.001), triglycerides (p < 0.001), C-reactive protein (p = 0.003), waist circumference (p < 0.001), and BMI measured at baseline exam (p < 0.001)., Conclusion: These findings support the hypothesis that earlier menarche is associated with greater risk for adult diabetes and cardiometabolic disease in the Brazilian context.

Context: Earlier age at menarche is associated with rapid infancy weight gain and childhood obesity. The role of hormone levels in mediating these associations is unclear., Objective: The aim of this study was to identify childhood hormone levels at age 8 yr that are associated with early menarche, independent of body size., Design, Settings, and Subjects: A total of 329 girls from a prospective United Kingdom birth cohort study provided blood samples at mean age 8.1 yr (range, 8.0-8.5) for hormone measurements and were followed longitudinally to establish age at menarche., Main Outcome Measures: Fasting plasma levels of IGF-I, androstenedione, dehydroepiandrosterone sulfate (DHEAS), leptin, insulin, IGF binding protein-1, and SHBG were measured. Age at menarche was reported by questionnaire and categorized as before 12.0, 12.0-13.0, or later than 13 yr., Results: Earlier menarche was associated with greater body weight, height, and body mass index at age 8 yr (all P-trend <0.001). Before adjustment for body size, earlier menarche was associated with higher levels of IGF-I, androstenedione, DHEAS, leptin, and fasting insulin, and with lower levels of IGF binding protein-1 and SHBG at age 8 yr (all P < 0.01). After adjustment for body mass index and height at age 8 yr, only IGF-I (P = 0.004), androstenedione (P = 0.01), and DHEAS (P = 0.01) remained associated with earlier menarche., Conclusions: Associations between higher levels of IGF-I and adrenal androgens at age 8 yr with earlier menarche, independent of body size, support functional roles of these hormones in regulating puberty timing in girls. Higher levels of these hormones reported in children who exhibited rapid weight gain during infancy may indicate their role in developmental pathways leading to earlier sexual maturation.

Background: Polybrominated diphenyl ethers (PBDEs), widely used as flame retardants since the 1970s, have exhibited endocrine disruption in experimental studies. Tetra- to hexa-BDE congeners are estrogenic, while hepta-BDE and 6-OH-BDE-47 are antiestrogenic. Most PBDEs also have antiandrogenic activity. It is not clear, however, whether PBDEs affect human reproduction., Objectives: The analysis was designed to investigate the potential endocrine disruption of PBDEs on the age at menarche in adolescent girls., Methods: We analyzed the data from a sample of 271 adolescent girls (age 12-19 years) in the National Health and Nutrition Examination Survey (NHANES), 2003-2004. We estimated the associations between individual and total serum BDEs (BDE-28, -47, -99, -100, -153, and -154, lipid adjusted) and mean age at menarche. We also calculated the risk ratios (RRs) and 95% confidence intervals (CI) for menarche prior to age 12 years in relation to PBDE exposure., Results: The median total serum BDE concentration was 44.7ng/g lipid. Higher serum PBDE concentrations were associated with slightly earlier ages at menarche. Each natural log unit of total BDEs was related to a change of -0.10 (95% CI: -0.33, 0.13) years of age at menarche and a RR of 1.60 (95% CI: 1.12, 2.28) for experiencing menarche before 12 years of age, after adjustment for potential confounders., Conclusion: These data suggest high concentrations of serum PBDEs during adolescence are associated with a younger age of menarche., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Context: There has been a resurgence of vitamin D deficiency among infants, toddlers, and adolescents in the United Kingdom. Myopathy is an important clinical symptom of vitamin D deficiency, yet it has not been widely studied., Objective: Our objective was to investigate the relationship of baseline serum 25 hydroxyvitamin D [25(OH)D] concentration and PTH with muscle power and force., Design: This was a cross-sectional study., Setting: The study was community based in a secondary school., Participants: A total of 99 post-menarchal 12- to 14-yr-old females was included in the study., Main Outcome Measures: Jumping mechanography to measure muscle power, velocity, jump height, and Esslinger Fitness Index from a two-legged counter movement jump and force from multiple one-legged hops was performed. Body height, weight, and serum concentrations of 25(OH)D, PTH, and calcium were measured., Results: Median serum 25(OH)D concentration was 21.3 nmol/liter (range 2.5-88.5) and PTH 3.7 pmol/liter (range 0.47-26.2). After correction for weight using a quadratic function, there was a positive relationship between 25(OH)D and jump velocity (P = 0.002), jump height (P = 0.005), power (P = 0.003), Esslinger Fitness Index (P = 0.003), and force (P = 0.05). There was a negative effect of PTH upon jump velocity (P = 0.04)., Conclusion: From these data we conclude that vitamin D was significantly associated with muscle power and force in adolescent girls.

Context: We have previously observed increased anti-Müllerian hormone (AMH) levels in prepubertal daughters of polycystic ovary syndrome (PCOS) women, suggesting that these girls may have an altered follicular development. However, it is not known whether AMH levels remain increased during puberty., Objective: The aim was to establish whether the increased AMH levels observed in prepubertal daughters of PCOS women persist during the peripubertal period, a stage during which the gonadal axis is activated and PCOS may become clinically manifested., Design: We studied 28 daughters (8-16 yr old) of PCOS women (PCOSd) and 33 daughters (8-16 yr old) of control women (Cd). In both groups, an oral glucose tolerance test was performed. Gonadotropins, sex hormones, and AMH were determined in a fasting sample., Results: Both groups were comparable in age, body mass index, and breast Tanner stage. Free androgen index, testosterone, AMH (Cd 14.4 +/- 8.0 pM vs. PCOSd 24.0 +/- 19.0 pM; P = 0.012), and 2-h insulin levels were significantly higher in the PCOSd group compared with the control group. The average ovarian volume was significantly higher in the PCOSd group. In both groups a positive correlation between 2-h insulin and AMH concentrations was observed (PCOSd: r = 0.530, P = 0.007; Cd: r =0.561, P = 0.008)., Conclusions: AMH concentrations are increased in peripubertal PCOSd. These findings, along with the results of our previous study, suggest that PCOSd appear to show an increased follicular mass that is established during early development, and persists during puberty.

Background: Although dichlorodiphenyl trichloroethane (DDT) exposure is known to affect human endocrine function, few previous studies have investigated the effects of DDT exposure on age at menarche or menstrual cycle length., Methods: A cross sectional study was conducted to study the effects of DDT exposure on age at menarche and menstrual cycle length among 466 newly married, nulliparous female Chinese textile workers aged 20-34 years enrolled between 1996 and 1998. Serum was analysed for DDT and its major metabolites. Multivariate linear regression was used to estimate DDT exposure effects on age at menarche and multivariate logistic regression was used to estimate DDT exposure effects on odds of experiencing short or long cycles., Results: Relative to those in the lowest DDT quartile, the adjusted mean age at menarche was younger in those in the fourth quartile (-1.11 years). Modeled as a continuous variable, a 10 ng/g increase in serum DDT concentration was associated with an adjusted reduction in age at menarche of 0.20 years. Relative to those in the lowest DDT quartile, odds of any short cycle (<21 days) in the previous year were higher for those in the fourth quartile (odds ratio = 2.78; 95% CI 1.07 to 7.14). There were no associations between serum DDT concentrations and odds of experiencing a long cycle (>40 days)., Conclusion: Results suggest that DDT exposure was associated with earlier age at menarche and increased risk of experiencing a shortened menstrual cycle.

Unlabelled: There is strong evidence that the initiation of adrenarche and gonadarche during puberty in girls depends on body mass in general and body fat in particular. The aim of this study was to analyze changes in body composition, i.e. body fat (BF), fat percentage (BF%), and lean tissue mass (LM) in girls during pre-menarcheal stages of development, including the earliest stage lacking clinical manifestations of changes in primary, secondary, and tertiary sexual characteristics. Puberty was assessed according to clinical and ultrasonographic staging of sex features developed by us. Concentrations of leptin and DHEA-S were compared and related to changes in body composition., Subjects and Methods: The study was carried out on 65 healthy girls aged 8 years and older who were followed every 3 months over a 5-year period. Age, height, weight, and BMI were recorded. Body composition (BF, BF%, LM) was determined with an infrared method. Tertiary sexual features were staged according to Tanner. Vaginal secretion was assessed according to Peter et al. Transabdominal ultrasound of the uterus and ovaries was performed with the bladder unvoided. Groups were formed according to developmental stage: E0A = pre-estrogenization (no ultrasonographic or clinical evidence of estrogenization); E0B pre-estrogenization with 'luminosity' of mucus in cervical canal; E1 = onset of estrogenization; E = full estrogenization; M = menarche +/- 3 months. Concentrations of DHEA-S and leptin were determined by radioimmunoassay., Results: BF in prepubertal girls averaged 16%. At menarche, BF was 23.9%. Body weight at menarche was 50.6 kg and the LM/BF ratio was 3.0. High leptin concentrations were found in E0B and M groups. Leptin concentrations were lowest during full estrogenization (E). Positive correlations of leptin with BF and LM were found in girls during developmental stages preceding menarche. Mean concentration of DHEA-S started at 1,091.6 microg/l during E0A stage, dropped significantly on passing to E0B (p <0.05), and increased by menarche. DHEA-S levels were found to correlate with BF, LM, and leptin in E0A, E0B, and E1 groups. Correlation coefficients were highest (DHEA-S/BF r = 0.61; DHEA-S/LM r = 0.54; DHEA-S/LEP r = 0.57) in the E0A group, i.e. about 5 months before the appearance of 'luminosity' of cervical mucus, considered to be the first ultrasonographic sign of puberty. Apparently, leptin stimulates somatic maturation during this stage of gonadarche which terminates with menarche. The action of DHEA-S is exerted during the early stages of female puberty.

Objective: Constitutional delay of puberty (CDP) is the absence of secondary sexual features in otherwise healthy girls past the 13th year of life. The aim of the present work was to follow the development of estrogen-dependent sexual features, determine the concentrations of gonadotropins, estradiol and sex hormone-binding globulin (SHBG) in girls with CDP at menarche and compare the findings with normal controls., Methods: We enrolled 11 girls with CDP and 40 controls. Primary, secondary and tertiary sexual features were studied at menarche +/- 3 months. The size of the ovaries and uterus was measured using transabdominal ultrasound. Maturation of breasts and pubic hair was staged according to Tanner. Concentrations of gonadotropins (follicle-stimulating hormone (FSH), luteinizing hormone) and estradiol were measured with immunoenzymatic methods. For measurement of SHBG, a radioimmunoassay was applied., Results: Menarche in CDP girls usually appeared with Stage IV or V of breast development and Stage IV of pubic hair development according to Tanner. CDP girls demonstrated a significantly smaller volume of the uterine body at menarche compared with controls (p = 0.0004). Significantly lower levels of FSH (p = 0.0363) and estradiol (p = 0.0332), as well as a tendency towards lower levels of SHBG, were revealed in CDP girls at menarche., Conclusion: In CDP girls, menarche is accompanied by more mature tertiary sexual features, apparently resulting from longer exposure of estrogen-dependent tissues to the action of bioactive endogenous estrogens. The smaller volume of the uterine body in CDP girls at menarche may be attributed to decreased concentrations of FSH and estradiol, as well as to the possibility of decreased insulin-like growth factor-1 and increased neuropeptide Y levels.

Temperature regulation during exercise in the cold was examined in 13 adolescent female individuals, aged 13-18 yr. Six girls with established menstrual cycles comprised the eumenorrheic menarcheal (EM) group, and seven nonmenstruating girls comprised the premenarcheal (PM) group. During the first visit, maximal oxygen consumption (Vo(2 max)), height, weight, and percent body fat were measured. The second visit included a determination of metabolic rate in thermoneutrality (21 degrees C), consisting of a 10-min rest period and 20 min of cycling (30% of Vo(2 max)), and a cold test (5 degrees C, 40% humidity, <0.3 m/s air velocity) involving a 20-min rest period and 40 min of cycling (30% of Vo(2 max)). Subjects in the EM group were tested twice in the chamber: once during the follicular and once during the luteal phase. Heat production per kilogram in thermoneutrality and in the cold was significantly (P < 0.05) higher in the PM compared with the EM girls. However, the PM girls had a significantly (P < 0.05) lower core temperature in the cold than the EM group. PM girls also had a significantly higher body surface area-to-mass ratio compared with the EM girls. Although percent body fat between groups was not significantly different, within the PM group percent body fat explained 79% (P < 0.01) of the variance in the decrease of core temperature. There were no menstrual phase-related differences in temperature regulation in either the thermoneutral or cold environment. In conclusion, menstrual phase does not influence temperature regulation in female individuals during adolescence. EM girls had lower metabolic heat production but maintained their core temperature more effectively in the cold than did the PM girls. This thermoregulatory difference between PM and EM girls is mainly a function of geometric differences with maturation-related peripheral vasoconstrictive differences maybe limiting the effectiveness of the mechanism of increased heat storage in younger female individuals.

The timing of pubertal changes depends on the concerted function of the hypothalamic - pituitary - ovarian and other endocrine systems. The somatotropin system and insulin play important roles during the growth and maturation of girls. Our clinical observations have enabled us to determine and implement criteria that split the pre-menarcheal period into three phases with distinct features associated with rising levels of estrogens (pre-estrogenization, onset of estrogenization and full estrogenization). The aim of this work was to determine levels of growth hormone, insulin - like growth factor 1 (IGF-1), sex hormone binding globulins (SHBG), insulin, and estradiol in relation to somatic features in girls during subsequent phases of estrogenization. This prospective study was done in 45 healthy girls. Every three months, we recorded weight, height, BMI, maturation of tertiary sex features, estrogen-related changes in hymen, sonographic dimensions of ovaries and uterus and serum levels of growth hormone, IGF-1, SHBG, insulin, and estradiol. Onset of estrogenization was accompanied by reduction of body mass and slowing down of growth associated with declining levels of growth hormone. These changes were followed by weight gain, pubertal acceleration of growth, rising levels of growth hormone, IGF-1, insulin, and estradiol, and falling levels of SHBG.

Introduction: The growth hormone (GH) is the main activator of growth, exerting its biological effects through IGF-1 and IGF-2 growth factors. Secretion of GH is partly controlled by steroid sex hormones., Material and Methods: Body mass, height, BMI, and body composition were recorded every three months in 45 healthy girls 8 years of age. Tertiary sex features according to Tanner were determined. Transabdominal ultrasound of the uterus and ovaries was done. GH, insulin, and IGF-1 levels in serum were measured radioimmunologically with commercial test kits. E2 levels were determined with an immunoenzymatic method., Results: GH levels increased until stage M3 of breast maturation and gradually decreased during stage M4 (12 girls with menarche). IGF-1 and insulin levels continued to increase until stage M4. Uterine and ovarian dimensions correlated with levels of hormones studied., Conclusion: High levels of GH and IGF-1 during the early and central stages of puberty seem to affect the maturation of internal sex organs.

The fasting insulin resistance index, mean blood glucose, mean serum insulin (MSI), early insulin response to glucose, glucose uptake rate in peripheral tissues, and insulin sensitivity indexes in response to a standard oral glucose tolerance test; serum insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGFBP-3, and sex hormone binding-globulin (SHBG) levels; and the free androgen indexes were evaluated in 98 girls with premature pubarche [PP; prepubertal (B1; n = 32), early pubertal (B2; n = 27), midpubertal (B3; n = 23), and postmenarcheal (B5; n = 16)] and in 86 Tanner stage- and bone age-matched controls. We ascertained whether hyperinsulinemia is already present in PP girls before or during pubertal development and whether these patients show a similar pattern of growth factor secretion as normal girls. Body mass indexes did not differ significantly between patients and controls within the same pubertal stage. MSI levels showed a significant increase with pubertal onset in all subjects, as expected. Patients showed significantly higher MSI values than controls at all Tanner stages (P < 0.03, P = 0.03, P = 0.03, and P < 0.05 for B1, B2, B3, and B5, respectively); higher insulin response to glucose at B1, B2, and B3 (P < 0.03, P = 0.03, and P < 0.05, respectively); higher glucose uptake rate in peripheral tissues at B1 and B2 (P < 0.04 and P = 0.02, respectively); and a later rise in insulin sensitivity compared to controls. PP girls also showed lower IGFBP-1 levels at B1 and B5 (P < 0.01 and P = 0.02, respectively), lower SHBG concentrations at B5 (P < 0.0005), and higher free androgen indexes at B1, B3, and B5 (P < 0.01, P < 0.05, and P < 0.001, respectively) compared to controls. Among others, significant correlations between SHBG and MSI levels (r = -0.49; P < 0.0001) and between SHBG and IGFBP-1 levels (r = 0.41; P < 0.0001) were found in all subjects. Hyperinsulinemia, increased early insulin responses to glucose, increased glucose uptake rate in peripheral tissues, elevated free androgen indexes, and decreased SHBG and IGFBP-1 levels are present in most girls with PP from childhood. These findings lend strong support to the concept that PP is not a benign condition, and long term follow-up of these patients into adulthood is recommended. The possible causal role of hyperinsulinemia in adrenal and/or ovarian androgen hypersecretion remains to be established.

Reproductive maturation, the menstrual cycle, and the transition to postreproductive life are complex processes. Detailed understanding of reproduction underlies logical patient management. Greater understanding of physiology has brought about better control of ovulatory problems and the beginnings of a logical approach to other problems such as androgen excess, where two complex systems overlap.

Five prepubertal girls (2.3-8.1 years old) were studied for isolated or recurrent vaginal bleeding in the absence of other signs of precocious puberty (premature menarche). Four of these girls with recurrent vaginal bleeding were studied for pulsatile gonadotropin secretory patterns. During sleep 3 girls showed luteinizing hormone (LH) pulses with low amplitude and a pubertal pattern of frequency whereas follicle-stimulating hormone (FSH) increased without demonstrable episodic secretion. Luteinizing hormone-releasing hormone (LHRH) tests demonstrated that FSH responses are greater than the LH responses, as in prepuberty. In 3 cases estradiol levels had augmented above normal prepubertal range. The menses spontaneously stopped during the follow-up. A reevaluation of the gonadotropin pattern, having the menses stopped for 6 months, in one of the girls with pulsatile LH secretion showed an apulsatile prepubertal LH pattern. Also estradiol levels returned to prepubertal range. A follow-up of 10-66 months of these patients did not show any growth and bone acceleration or signs of precocious puberty. Our data suggest that in premature menarche a partial and transient activation of hypothalamo-pituitary axis could be present. Premature menarche seems to be a benign and self-limiting condition and one of the girls had a normal onset of puberty during follow-up.

Our study group consisted of 43 healthy preadolescence and adolescence of which 17 were boys and 13 premenarcheal and 13 postmenarcheal girls. Haematocrit, haemoglobin, serum iron, transferrin saturation, total iron-binding capacity, latent iron-binding capacity and serum ferritin were analyzed. Authors found that post-menarcheal girls are at lower levels than boys and that menstrual blood loss is a significant factor in determining iron status.

The purpose of this study was to evaluate the increases in plasma levels of E1, E1S and E2 during constant infusion of dehydroepiandrosterone (D) in premenarchal girls (PG) and in normal menstruating women (AW). Unlabelled D was infused for 48 h in 10 premenarchal girls and in 10 normal menstruating women. Plasma levels of D, estrone (E1), estrone sulfate (E1S) and estradiol (E2) were measured before and during 48 h infusion. Metabolic clearance rates of D (MCRD), production rates of D (PRD), and increases in plasma concentration of E1, E1S and E2, relative to the corresponding increase in plasma concentration of D, were determined. The baseline plasma levels of D were found significantly lower in premenarchal girls than in normal menstruating women. MCRD was found significantly higher in premenarchal girls than in normal menstruating women (2565 +/- 467 L/day versus 1317 +/- 242 L/day, p less than 0.01). Administration of D increased the plasma levels of E1 and E1S in the group of normal menstruating women but not in the premenarchal girls. Considering all subjects studied, the increases in plasma levels of E1 and E1S during the infusion of D were significantly correlated with body weight (p less than 0.01 and p less than 0.001, respectively). From these results, we conclude that in premenarchal+ girls there is: a reduced peripheral contribution of D to E1 and E1S, and/or a higher MCRE1 and MCRE1S than in normal menstruating women.