Search

Background: The association between 25(OH)D and pubertal timing has not been well studied. The aim of this study was to assess the relationship between 25(OH)D levels and pubertal timing in children., Methods: Participants aged 6-14 years who had available nutritional and serum sex hormone (total testosterone (TT) and estradiol (E2)) information (n =1318) were included. We conducted a cross-sectional analysis of the associations between 25(OH)D and sex steroid hormones among children in the National Health and Nutrition Examination Survey, 2015-2016. Puberty was indicated by high levels of steroid hormones (TT≥50 ng/dL in men, E2≥20 pg/ml in women) or menarche., Results: Serum 25(OH)D and pubertal status showed the same trend in both males and females. In the male population, the OR values of serum 25(OH)D between 50 and <75 and ≥75 nmol/L were 0.52 (0.25, 1.08) and 0.64 (0.23, 1.75), respectively, compared with serum 25(OH)D<50 nmol/L. The OR of serum 25(OH)D ≥50 nmol/L compared with <50 nmol/L was 0.54 (0.26, 1.10), and the P value was statistically significant (P=0.048). In the female population, when the serum 25(OH)D concentration was <50 nmol/L, the ORs corresponding to a serum 25(OH)D concentration between 50 and <75 and ≥75 nmol/L were 0.53 (0.29, 0.98) and 0.50 (0.19, 1.30), respectively. The OR of serum 25(OH)D≥50 nmol/L compared with <50 nmol/L was 0.52 (0.19, 0.96), and the P value was statistically significant (P=0.037)., Conclusions: A lower 25(OH)D level was associated with earlier puberty in both girls and boys. There was a negative association between 25(OH)D concentrations and pubertal timing., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu.)

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.

Migraine affects 959 million people worldwide,1 with the highest prevalence being in women of childbearing age. The interplay between female hormones and migraine can be a challenging area to navigate since issues relating to pregnancy, contraception and the menopause are often out of the neurology comfort zone. This review aims to help the neurologist to manage women with migraine, from menarche to menopause., Competing Interests: Competing interests: SKA received speaker’s fees and participated in advisory boards for Novartis, Teva and Eli-Lilly., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: The age of pubertal onset is influenced by many variables in young girls. Previous studies have not examined sex hormones longitudinally around the time of breast development and their relationship to pubertal onset., Objective: We sought to use an unbiased statistical approach to identify phenotypes of sex hormones in young girls and examine their relationship with pubertal milestones., Design and Setting: Longitudinal observational study., Participants and Main Outcome Measures: In 269 girls, serum concentrations of steroid sex hormones [estradiol (E2), estrone, testosterone, and dehydroepiandrosterone sulfate] were measured by HPLC-mass spectrometry at time points before, at, and after thelarche. Girls were classified into four hormone phenotypes using objective principal components and cluster analyses of longitudinal hormone data. The association between the identified phenotypes and age of pubertal milestones was estimated using Cox proportional hazards modeling., Results: Mean ages at thelarche, pubarche, and menarche were 9.02, 9.85, and 12.30 years, respectively. Girls with low levels of all four hormones, phenotype 3b, were youngest at thelarche (8.67 years); those in phenotype 2, with the highest E2 levels and E2 surge 6 months after thelarche, were youngest at menarche (11.87 years) with shortest pubertal tempo. When controlling for race, maternal age of menarche, caregiver education, and body mass, different phenotypes were associated with the age of pubertal events., Conclusions: Hormone phenotypic clustering can identify clinically relevant subgroups with differing ages of thelarche, pubarche, and menarche. These findings may enhance the understanding of timing of pubertal milestones and risk of adult disease., (Copyright © 2019 Endocrine Society.)

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.)

Ovarian cancer (OC) is the fourth most common cancer among Pakistani, Scottish and Chinese women. The aim of the present study was to determine the association of potential risk factors with OC and analysis of Cancer Antigen 125 (CA125) in its monitoring and diagnosis. A total of 200 patients diagnosed with OC were included in this study. All the patients were interviewed and 54 OC patients (case group) and 35 age-matched healthy subjects (control group) gave their blood for analysis of CA125. The blood of case and control groups was subjected to an ELISA test for the evaluation of CA125 levels. Majority of the patients were of 40-50 years of age and most of the patients were diagnosed at this period of life. The majority of the patients experienced their first menarche and menopause at the age of 13-14 and 40-50 years respectively. There is no significant association between early menarche and OC family history, nor between late menopause and OC family history. There is a significant association between family history of breast cancer (BC) and age of menarche (P = 0.005). An OC patient with an age of menarche of 13 years or younger has 2.8 times the odds of having a family history of BC than those whose age of menarche is more than 13 years. Eleven percent of patients diagnosed with OC received no intervention. All other patients underwent treatment options including hysterectomy (69.5%), radiotherapy (39%) and chemotherapy (95%). The profiles of the patients showed that those who had a family history of OC were more likely to provide blood samples (OR = 3.87, P = 0.025), and similarly for those with a history of breast cancer (OR = 2.83, P = 0.022) in comparison to those who were not willing to provide blood for testing of biomarker. The distribution of CA125 for OC patients and control group showed that CA125 values were significantly higher (P = 0.034) in the case patients compared with the control group. The decrease in CA125 levels indicated the positive response to treatment, whereas increase in CA125 values showed resistant and disease progression. 52% of the patients with OC were correctly diagnosed as having OC (based on the optimal cut-point of CA125), while 83% of those without OC were also correctly diagnosed (with 48% of OC patients and 17% of non-OC patients incorrectly diagnosed). We concluded that there is significant association between family history of breast cancer and OC history and use of CA125 as a biomarker is not an ideal diagnostic and monitoring test as it has low sensitivity and high specificity.

Mendelian randomization (MR) has emerged as a major tool for the investigation of causal relationship among traits, utilizing results from large-scale genome-wide association studies. Bias due to horizontal pleiotropy, however, remains a major concern. We propose a novel approach for robust and efficient MR analysis using large number of genetic instruments, based on a novel spike-detection algorithm under a normal-mixture model for underlying effect-size distributions. Simulations show that the new method, MRMix, provides nearly unbiased or/and less biased estimates of causal effects compared to alternative methods and can achieve higher efficiency than comparably robust estimators. Application of MRMix to publicly available datasets leads to notable observations, including identification of causal effects of BMI and age-at-menarche on the risk of breast cancer; no causal effect of HDL and triglycerides on the risk of coronary artery disease; a strong detrimental effect of BMI on the risk of major depressive disorder.

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.

Objective: To investigate whether menopausal factors are associated with the development of serologic rheumatoid arthritis (RA) phenotypes., Methods: Data were analyzed from the Nurses' Health Studies (NHS; 1976-2010 and NHSII 1989-2011). A total of 120,700 female nurses ages 30-55 years in the NHS, and a total of 116,430 female nurses ages 25-42 years in the NHSII, were followed via biennial questionnaires on lifestyle and disease outcomes. In total, 1,096 incident RA cases were confirmed by questionnaire and chart review. Seropositive RA was defined as rheumatoid factor positive (RF) or antibodies to citrullinated protein antigen (ACPA) positive, and seronegative RA was defined as RF negative and ACPA negative. We used Cox proportional hazards models to obtain multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) of seropositive/seronegative RA associated with menopausal status, age at menopause, type of menopause, ovulatory years, and postmenopausal hormone therapy (PMH) use., Results: Postmenopausal women had a 2-fold increased risk of seronegative RA, compared with premenopausal women (NHS: HR 1.8 [95% CI 1.1-3.0], NHSII: HR 2.4 [95% CI 1.4-3.9], and pooled HR 2.1 [95% CI 1.4-3.0]). Natural menopause at early age (≤44 years) was associated with an increased risk of seronegative RA (pooled HR 2.4 [95% CI 1.5-4.0]). None of the menopausal factors was significantly associated with seropositive RA. We observed no association between PMH use and the risk of seronegative or seropositive RA, except that PMH use of ≥8 years was associated with increased risk of seropositive RA (pooled HR 1.4 [95% CI 1.1-1.9])., Conclusion: Postmenopause and natural menopause at an early age were strongly associated with seronegative RA, but only marginally with seropositive RA, suggesting potential differences in the etiology of RA subtypes., (© 2017, American College of Rheumatology.)

Objective: To clarify the impact of body mass index (BMI) on luteinizing hormone (LH) secretion in response to gonadorelin (GnRH) stimulation testing in girls diagnosed with idiopathic central precocious puberty (ICPP)., Methods: Retrospective single-center cohort study was carried out in 865 confirmed ICPP girls who underwent GnRH stimulation tests. Pubertal development according to Tanner, sex hormone parameters, and LH secretion in response to GnRH-stimulation was compared., Results: Around 609 girls were of normal weight (70.4%), while 168 children (19.4%) were overweight, and 88 (10.2%) were obese. Peak LH levels after GnRH were much higher in the normal-weight group, with a median of 9.1 mIU ml(-1) (interquartile 5.2-13.1), compared with the median peak LH in the overweight and obese groups (8.5 mIU ml(-1), interquartile 5.3-11.6, and 6.2 mIU ml(-1), interquartile 5.3-11.0, respectively P < 0.001 for all comparisons). Peak LH/FSH ratio was also lower in the obese group (median 0.6, interquartile 0.68-0.90) compared with the normal-weight (median 0.8, interquartile 0.61-1.11) and overweight (median 0.8, interquartile 0.64-0.92) groups., Conclusions: Higher BMI is associated with lower LH response to GnRH-stimulation testing in girls with ICPP. It is recommended that BMI should be considered when interpreting GnRH-stimulation tests., (© 2015 The Obesity Society.)

Study Objective: To investigate an association between pubertal development and timing of menarche with glycemic control, disease duration, and body mass index (BMI) in patients diagnosed with diabetes mellitus type 1 (DM1) before puberty., Design: Retrospective study., Setting: The study was performed at the diabetes outpatient clinic of Instituto de Puericultura e Pediatria Martagão Gesteira--IPPMG of the Federal University of Rio de Janeiro--UFRJ., Participants: A total of 131 children, 61 girls and 70 boys, diagnosed with DM1 before puberty participated in the study., Main Outcome Measures: The study investigated how age at puberty onset relates to mean glycated hemoglobin (HbA1c) before puberty, BMI percentile, and disease duration; how puberty duration relates to mean HbA1c before and during puberty and to disease duration; and how timing of menarche relates to mean HbA1c before puberty, BMI percentile, and disease duration., Results: Age at puberty onset was positively correlated with mean HbA1c before puberty (r = 0.204, R(2) = 0.042; P = .019) and disease duration (r = 0.451, R(2) = 0.203; P < .0001), and negatively correlated with BMI percentile (r = -0.289, R(2) = 0.084; P = .001). Timing of menarche was negatively correlated with BMI percentile (r = -0.556, R(2) = 0.310; P < .001)., Conclusions: Children with longer disease duration began puberty later than those diagnosed more recently. Girls in higher BMI percentiles reached menarche sooner.

Context: Puberty is marked by sleep-associated changes in LH pulse frequency and amplitude. Early pubertal girls with obesity exhibit blunted day-to-night changes in LH secretion; whether this occurs in late pubertal obese girls is unknown., Objective: The objective of the study was to test two hypotheses: 1) blunted day-to-night changes in LH secretion occur in both early and late pubertal obese girls, and 2) such alterations are specifically associated with hyperandrogenemia., Design: This was a cross-sectional analysis., Setting: The study was conducted at a clinical research center., Patients or Other Participants: Twenty-seven early pubertal, premenarcheal girls (12 of whom were obese) and 63 late pubertal (postmenarcheal) girls (27 of whom were obese) participated in the study., Intervention: Blood samples were taken every 10 minutes from 7:00 pm to 7:00 am., Main Outcome Measure: Change in LH pulse frequency [LH interpulse interval (IPI)] from daytime hours (7:00 pm-11:00 pm, while awake) to nighttime hours (11:00 pm to 7:00 am, while generally asleep)., Results: Both nonobese and obese postmenarcheal girls demonstrated significant day-to-night decreases in LH pulse frequency (IPI increases of 33% and 16%, respectively), but day-to-night changes were blunted in obese girls (P = .004, obese vs nonobese). Day-to-night LH pulse frequency decreased significantly in postmenarcheal obese subjects with normal T concentrations (26% IPI increase) but not in those with hyperandrogenemia. Similar differences were evident for LH pulse amplitude. Nonobese and obese early pubertal girls exhibited nonsignificant differences in day-night LH pulse frequency (day to night IPI increase of 26% vs decrease of 1%, respectively)., Conclusions: Day-to-night changes in LH pulse secretion are blunted in postmenarcheal obese adolescent girls. This phenomenon may in part reflect hyperandrogenemia.

Objective: To study the association between endocrine disturbances and metabolic complications in women seeking gynecologic care., Design: Retrospective study, cluster analysis., Setting: Outpatient clinic, university medical center., Patient(s): 573 women, including 384 at low risk and 189 at high risk of cardiometabolic disease., Intervention(s): None., Main Outcome Measure(s): Cardiovascular and metabolic parameters and clinical and biochemical characteristics., Result(s): Risk factors for metabolic disease are associated with a low age of menarche, high levels of high-sensitivity C-reactive protein and liver enzymes, and low levels of sex hormone-binding globulin. Overweight/obese status, polycystic ovary syndrome, oligo/amenorrhea, and hyperandrogenism were found to increase the risk of cardiometabolic disease. However, hyperprolactinemia and premature ovarian failure were not associated with the risk of cardiometabolic disease. In terms of androgens, the serum total testosterone level and free androgen index but not androstenedione or dehydroepiandrosterone sulfate (DHEAS) were associated with cardiometabolic risk., Conclusion(s): Although polycystic ovary syndrome is associated with metabolic risk, obesity was the major determinant of cardiometabolic disturbances in reproductive-aged women. Hyperprolactinemia and premature ovarian failure were not associated with the risk of cardiovascular and metabolic diseases., Clinical Trial Registration Number: NCT01826357., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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.

Animal studies suggest that perfluorocarbons (PFCs) may alter sexual maturation. Relationships of human PFC exposure with puberty are not clear. We conducted a cross-sectional study to investigate whether perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were associated with indicators of sexual maturation in a 2005-2006 survey of residents with PFOA water contamination from the Mid-Ohio Valley. Participants were 3076 boys and 2931 girls aged 8-18 years. They were classified as having reached puberty based on either hormone levels (total >50 ng/dL and free >5 pg/mL testosterone in boys and estradiol >20 pg/mL in girls) or onset of menarche. We estimated the odds of having reached puberty classified by these criteria and the fitted median age of reaching puberty in relation to serum PFOA and PFOS concentrations measured when puberty status was assigned. For boys, there was a relationship of reduced odds of reached puberty (raised testosterone) with increasing PFOS (delay of 190 days between the highest and lowest quartile). For girls, higher concentrations of PFOA or PFOS were associated with reduced odds of postmenarche (130 and 138 days of delay, respectively). In conclusion, our study showed a later age of puberty in this population correlated with PFC concentrations.

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.)

Background: Birth characteristics and adult hormone concentrations influence breast cancer risk, but little is known about the influence of birth characteristics on hormone concentrations, particularly during adolescence., Methods: We evaluated the association of birth characteristics (birth weight, birth length, and gestational age) with serum sex hormone concentrations during late childhood and adolescence in 278 female participants of the Dietary Intervention Study in Children. Repeated measures analysis of variance models were used to assess the relationships of birth characteristics and serum estrogens and androgens at five different time points over a mean period of 7 years., Results: In analyses that did not take into account time from blood draw until menarche, birth weight was inversely associated with pre-menarche concentrations of estradiol, estrone sulfate, androstenedione, testosterone, and dehydroepiandrosterone sulfate (DHEAS). In the post-menarche analyses, birth weight was not significantly associated with concentration of any of the hormones under investigation. Birth length and gestational age were not associated with hormone concentrations before or after menarche., Conclusion: Birth weight is inversely associated with sex hormone concentrations before menarche in the model unadjusted for time from blood draw until menarche., Impact: The in utero environment has long-term influences on the hormonal milieu, which could potentially contribute to breast cancer risk.

Background: Analysis of metabolic alterations and body composition in adolescents., Objectives: To study the correlation of serum levels of lipids, glycemia, insulin, homocysteine, HOMA-IR and blood pressure among themselves and with body variables., Methods: Data concerning glycemia, total cholesterol and fractions (LDL, HDL and VLDL), triacylglycerols, insulin, homocysteine and blood pressure were measured in 100 adolescents at the age range of 14 to 17 years, who had already had menarche and attended the public schools in Vicosa, state of Minas Gerais, Brazil. The percentage of body fat (%BF) was evaluated by horizontal bioimpedance., Results: In relation to nutritional status, 83%, 11% and 6%, respectively were eutrophic (EU), presented overweight/overweight risk (OW/OR) or low weight (LW) (CDC/NCHS, 2000) and 61% presented high percentage of BF. Total cholesterol presented the highest percentage of inadequacy (57%), followed by HDL (50%), LDL (47%) and triacylglycerols (22%). Inadequacy in 11%, 9%, 5% and 4% were observed in relation to insulin resistance, insulin, blood pressure and glycemia, respectively. For total cholesterol, insulin, HOMA-IR and nutritional state, OW/OR>LW (p<0.05). For body composition and nutritional status, OW/OR>EU>LW (p <0.001). Some positive and strong correlations were found between BMI and the anthropometrical measures estimating the % of total BF, as well as central distribution, except for the waist/hip ratio. The %BF was correlated with insulin levels (r=0.303; p <0.001) and HOMA-IR (r=0.281; p<0.001)., Conclusions: Some metabolic alterations, most often related with excess weight and body fat as well as insulin resistance were found, reinforcing the importance of specific programs directed at the adolescent health.

The objective of this study is to investigate the effect of menstrual and reproductive variables, breastfeeding, exogenous hormones, and gynecological conditions on endometrial cancer risk. We conducted a case-control study in Italy, including 454 women with endometrial cancer and 908 hospital controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate logistic regression models. Endometrial cancer risk was inversely associated with age at menarche (OR = 0.7, 95% CI = 0.5-1.0, for > or =14 vs. <12 years), and directly associated with age at menopause (OR = 1.8, 95% CI = 1.1-2.7, for > or =55 vs. <50 years) and years of menstruation (OR = 2.4, 95% CI = 1.7-3.4, for highest vs. lowest tertile). Multiparity strongly reduced the risk among women under 60 years of age (OR = 0.3, 95% CI = 0.2-0.6, for > or =3 deliveries vs. <2). Oral contraceptive use conferred a 40% reduced risk (95% CI = 0.4-1.0), irrespective of time since cessation. Although based on small numbers, women with a history of treated infertility (OR = 2.7, 95% CI = 1.1-6.4) or endometriosis (OR = 4.0, 95% CI = 1.0-15.5) were at increased risks. No significant associations with endometrial cancer risk emerged for age at first/last birth, breastfeeding, menopausal status, hormone replacement therapy, and history of uterine fibromyomas or polycystic ovary. In conclusion, this study confirms the importance of multiparity, years of menstruation, and oral contraceptive use in endometrial cancer etiology, thus contributing to identify women at elevated risk of such neoplasm.

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.

Background: Fluctuating hormone levels are known to influence a woman's mood and well-being. This study aimed to determine whether lifetime hormonal markers are associated with late-life depression symptoms among elderly community-dwelling women., Method: Detailed reproductive histories of 1013 women aged 65 years and over were obtained using questionnaires, and depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale. Multivariate logistic regression models were generated to determine whether any lifetime endogenous or exogenous hormonal factors were associated with late-life depression., Results: The prevalence of depressive symptoms was 17%. Age at menopause was associated with depressive symptoms, but only among women with a lower education level. For these women, an earlier age at menopause increased their risk of late-life depression (linear effect, OR = 0.95, 95%CI: 0.91-0.99). The odds of late-life depression were also increased for women who were past (OR = 1.6, 95%CI: 1.1-2.5), but were not current users. On the other hand, long-term oral contraceptive use (> or =10 years) was protective against depression (OR = 0.3, 95%CI: 0.1-0.9). These associations remained significant even after extensive adjustment for a range of potential confounding factors, including sociodemographic factors, mental and physical incapacities, antidepressant use and past depression. The other factors examined - including age at first menses, parity, age at childbirth and surgical menopause - were not associated with late-life depressive symptoms., Conclusions: Lifetime hormonal factors that are significantly associated with depression symptoms in later life have been identified. Further work is needed to determine how potential hormonal interventions could be used in the treatment of late-life depression in certain subgroups of women.

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

Objective: To investigate the effect of type 1 diabetes on pubertal onset and development, and to identify factors potentially affecting puberty, including glycemic control, relative diabetes duration, body mass index standard delta score (BMI SDS), insulin dose, and intensity of insulin therapy., Research Design and Methods: Initiated in 1990, the Diabetes-Patienten-Verlaufsdaten (DPV) is an ongoing, prospective longitudinal follow-up program to benchmark the quality of diabetes care provided to, predominantly, pediatric patients. Data collection for this non-interventional audit was carried out at 202 German diabetes treatment centers. Patient recruitment was done by referral, clinic/hospital ascertainment, or self-report. Data were analyzed for subcohorts of 1218-2409 boys and 579-2640 girls from a cohort of 24 385 pediatric type 1 diabetic patients. Selection was based on ethnicity and availability of data on Tanner stage 2, or higher, of genital and pubic hair development (boys) or breast and pubic hair development, and menarche (girls)., Results: Boys showed significant (P<0.05) delay (years) in mean ages at onset of genital development (12.0 (+/-0.9) years) and pubarche (12.2 (+/-0.4) years). In girls, mean ages at thelarche (11.4 (+/-0.5) years), pubarche (11.5 (+/-0.1) years), and menarche (13.2 (+/-0.5) years) were significantly delayed compared with the general population. Sexual maturity (Tanner stage 5) was not delayed in either sex. Elevated glycohemoglobin and decreased BMI SDS were associated with significantly delayed pubertal onset, whereas relative diabetes duration and insulin dose were not., Conclusions: Pubertal onset, but not sexual maturity, is delayed in children with type 1 diabetes. Delay increases with higher glycohemoglobin and lower BMI SDS.

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.

Objective: To relate endocrine and nutritional correlates of fitness in postpubertal physically active females across the normal weight spectrum to identify markers and how these might serve as associations of exercise-related endocrine disruption., Design: Cross-sectional study analyzed by repeated-measures analysis of variance for frequent blood sampling., Setting: A general clinical research center., Subjects: Twenty-two healthy postpubertal female subjects recruited 2 years or more after menarche., Main Outcome Measures: Maximum oxygen consumption was determined as an index of fitness and daily caloric intake was calculated from a 3-day food diary. During the follicular phase of the cycle, luteinizing hormone was sampled every 10 minutes during a 24-hour period, while follicle-stimulating hormone and cortisol were sampled hourly., Results: For every 1-unit increase in maximum oxygen consumption, cortisol concentration increased by 2% (P =.005; 95% confidence interval, 1%-3%). However, there was no association between mean gonadotropin concentrations and fitness. Hormone concentrations were not significantly associated with body mass index or percentage of body fat. Higher mean caloric intake from a 3-day summary was inversely related to mean luteinizing hormone concentration, which decreased by 5.5% for every 100-kcal increase (P =.03; 95% confidence interval, 1%-10%). With every 1-year increase in age at menarche, follicle-stimulating hormone concentration decreased by 12% (P =.01; 95% confidence interval, 4%-19%) and cortisol concentration increased by 7% (P =.03; 95% confidence interval, 1%-12%)., Conclusions: In active adolescents, increased cortisol concentration may represent an adaptive change to exercise that may precede gonadotropin changes seen with higher levels of fitness.

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.

Girls with premature adrenarche (PA) (the onset of pubic hair before the age of 8 yr associated with elevated levels of adrenal androgens and no evidence of true puberty or adrenal dysfunction) may be at increased risk for development of polycystic ovarian syndrome (PCOS). Alterations in the IGF system, including elevated free IGF-I, have been demonstrated in PCOS and may be involved in its pathogenesis. Hyperinsulinemia, elevated total IGF-I, and decreased IGF-binding protein-1 (IGFBP-1) have also been reported in PA. Dysregulation of the IGF system may be involved in the pathogenesis of PA and its progression to PCOS. We compared the insulin/IGF system in 17 prepubertal girls with PA and nine prepubertal controls. Both groups were predominantly obese. Total and free IGF-I were elevated in the premature adrenarche group. No differences in basal insulin, insulin area under the curve in response to an oral glucose tolerance test, or IGFBP-1 were noted. These effects persisted when adjusted for adiposity using body mass index-Z score. Total and free IGF-I were positively correlated, and IGFBP-1 was negatively correlated with Delta4-androstenedione, but not with dehydroepiandrosterone sulfate. Free IGF-I trended toward higher levels in the insulin-resistant subgroup, compared with the insulin-sensitive subgroup. These results suggest altered regulation of the insulin/IGF system in prepubertal girls with PA and a possible role for free IGF-I in the pathogenesis of the hyperandrogenism of PA as well as its progression to PCOS.

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.

Objective: Young girls with precocious pubarche (PP) are at increased risk of developing polycystic ovary syndrome (PCOS), including hyperinsulinism, dyslipidaemia and ovarian hyperandrogenism, particularly if PP itself was preceded by a low birthweight. Resistance to insulin is thought to be a key factor in the pathogenesis of this sequence. We aimed to elucidate the peripubertal ontogeny of the low birthweight effect on hyperinsulinism, dyslipidaemia and ovarian dysfunction after PP., Patients and Design: We obtained fully longitudinal data from 51 girls with a history of PP and compared normal-birthweight (n = 26) with low-birthweight (n = 25) girls (birthweight SD score 0.0 +/- 0-2 vs. - 2.4 +/- 0.2) for measurements obtained at diagnosis of PP (mean age 7.0 years), in early puberty (10.4 years) and after menarche (14.3 years)., Measurements: Fasting serum lipids and lipoproteins, together with insulin responses to an oral glucose load, were assessed at diagnosis of PP, in early puberty and after menarche; serum gonadotropins were measured in early puberty and after menarche; ovarian function was examined postmenarche., Results: Comparisons of endocrine-metabolic results between normal- and low-birthweight PP girls showed no detectable differences before puberty. The hypertriglyceridaemia and elevated LDL-cholesterol levels characterizing low-birthweight PP girls became detectable by early puberty; reduced insulin sensitivity was not evident until postmenarche, when the tendency to ovarian dysfunction also became obvious. Body mass indices of normal- and low-birthweight subgroups were identical in early puberty and postmenarche., Conclusions: These longitudinal data show that, in PP girls, the endocrine-metabolic risk conferred by prenatal growth restraint is not readily detectable until puberty or postmenarche, and is not attributable to a higher body mass index.

The objective was to determine whether serum creatine kinase (CK) and serum CK MB activity following exercise-induced muscle damage activity differs among females of varying menarchial status and to determine whether there is a relationship between serum estradiol (E2) concentration, CK, and CK MB activity. Fifteen menarchial (M), 15 premenarchial (P), and 10 postmenopausal (PM) females participated in the study. Exercise consisted of eccentric hamstring contractions. Estradiol concentrations were significantly higher in M women (p =.0001; M, 125.0 +/- 20.8 pg/mL, P, 54.6 +/- 38.6 pg/mL, PM, 46.2 +/- 34.6 pg/mL). Menarchial women had lower resting CK and CK MB activity and responded with a higher efflux of CK and CK MB post exercise (p =.0001). An inverse relationship was found between E2 concentration and baseline CK (p =.02) and CK MB activity (p =. 006). No relationship existed between post exercise efflux of CK and CK MB and E2 concentration. At rest, E2 influenced CK and CK MB activity across menarchial levels. However, E2 did not significantly reduce the level of CK and CK MB activity following this intense bout of eccentric exercise.

Dietary Ca and osteocalcin (OC), parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH-D), insulin-like growth factor (IGF)-I and sex hormone binding globulin (SHBG) were assessed simultaneously to bone mineral density (BMD) in 200 adolescent girls (aged 11-15 years) and 100 young women (aged 20-23 years), selected from the lowest and highest end of the Ca intake distribution of a larger population sample. Ca intake was evaluated by food frequency questionnaires, BMD was measured by dual energy x-ray absorptiometry at ultradistal and proximal radius of non-dominant arm, bone age was estimated from x-rays of left hand and wrist according to Tanner et al. (1983). Surprisingly, mean Ca intakes were below the dietary reference intakes in the subgroups of girls and women with the highest measured Ca consumption. Postmenarcheal, but not premenarcheal girls showed radial densities as high as the women and in no group was BMD associated with Ca intake. In all adolescents serum PTH was negatively related to dietary Ca. In girls before menarche IGF-I was positively associated with bone age, while in the same subjects the negative relationship between SHBG and BMD pointed to the crucial role of bioavailable sex steroids on bone mass apposition in early puberty. OC levels decreased progressively with age, while serum 25-OH-D significantly increased after menarche. In conclusion, although in adolescents low Ca intake has not been shown to induce any immediate deleterious effect on radial density, the compensatory hypersecretion of PTH supports the need for an adequate Ca intake to achieve peak bone mass.

The regulation of androgen synthesis during puberty in females is complicated, with changes in steroidogenic and peripheral interconversion capacity. In the present study we have investigated the diurnal rhythm of testosterone secretion in 56 healthy girls before and during puberty, up to 2 yr postmenarche. The girls' ages ranged between 4.6-16.5 yr, and their height SD scores ranged between -3.6 and +3.7. One to 5 serum profiles (seven samples per 24 h) were taken from each girl for steroid measurements, and a total of 84 serum profiles were obtained. Serum testosterone concentrations were determined using a RIA with a detection limit of 30 pmol/L. The results demonstrate that there is a diurnal rhythm of testosterone secretion during both prepuberty and puberty in girls. The pattern has its nadir in the late evening or just after midnight, with the highest levels in the morning (0600-1000 h). Serum testosterone concentrations in prepubertal girls were significantly lower than those in pubertal girls and were significantly lower in early puberty than in girls in mid- or late puberty. No differences were found in levels between girls in midpuberty or late puberty. Before puberty, serum testosterone concentrations correlated with serum dehydroepiandrosterone sulfate, consistent with the adrenals being the major source of testosterone. After the onset of puberty, a correlation between testosterone and 17beta-estradiol was seen, consistent with the ovaries being the major source of testosterone during puberty. Furthermore, the present study showed that there is a relative hyperandrogenicity in early puberty, with high levels of androgens relative to estrogens.

Objective: To assess the prevalence of anemia among urban school children of Punjab., Design: Cross sectional study., Setting: Urban schools of Ludhiana, Punjab., Subjects: Two thousand school children of 5-15 years age., Methods: Relevant history was taken and a complete physical examination done in all the children. Hemoglobin was estimated using cynmethemoglobin method and peripheral blood smears were also examined. Anemia was diagnosed when hemoglobin was less than 11 g/dl for children of 5-6 years age and 12 g/dl for more than 6 years age., Results: Overall prevalence of anemia was 51.5%. Girls had a significantly higher prevalence of anemia except at 5 years and 10-12 years age. More menarcheal girls were anemic as compared to non-menarcheal ones. The prevalence of anemia was high (38%) even in higher socioeconomic groups. Nearly half (47.6%) of well nourished children were anemic. The mean Hb also was lower than expected normal values in both nutritional groups. Compared to non-vegetarians (38%), more vegetarians (65.9%) were anemic. The commonest blood picture seen was microcytic hypochromic (55.4%)., Conclusions: The present study revealed a high prevalence of anemia among healthy urban school children of higher socio-economic classes. Vegetarians and girls, especially after menarche were more at risk to develop anemia.

Objectives: The amount of adipose tissue influences pubertal development and fertility in girls. A candidate for mediating this is the hormone leptin, derived from adipocytes. This work was carried out to determine whether the leptin concentration in serum is regulated during pubertal development., Subjects and Methods: Serum concentrations of leptin were determined by radioimmunoassay in a sample of 252 healthy children representing all pubertal stages., Results: Serum leptin concentrations correlated directly with age (r = 0.53), body mass index (BMI) (r = 0.71), and weight for height SD score (r = 0.44) in girls and with BMI (r = 0.33) and weight for height SD score in boys (r = 0.36). Leptin concentrations increased with pubertal development in girls, resulting in significantly higher concentrations at pubertal stages 4 and 5 than at the prepubertal stage, whereas there was no change in the boys., Conclusions: Serum leptin concentrations increased during pubertal development in the girls, but remained constant in the boys. Whether the increase in serum leptin concentrations in girls is of importance for, or a consequence of, pubertal development is still to be determined.

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.

Puberty is initiated by a nocturnal rise in gonadotropin secretion, which, in boys, results in an increased nocturnal secretion of testosterone. To characterize any similar diurnal rhythm of 17 beta-estradiol in healthy girls, we determined the secretion of 17 beta-estradiol before and during puberty. The study group consisted of 45 healthy girls whose height SD scores ranged from -3.7 to +4.9 compared with Swedish growth reference values. One to 6 profiles of 17 beta-estradiol (7 samples/24 h) were obtained from each girl during puberty and from 21 of the girls before clinical signs of puberty (a total of 76 serum profiles). Serum 17 beta-estradiol concentrations were determined using a modified RIA. The detection limit for the RIA was 1.8 fmol/tube, which corresponded to a serum level of 7.8 pmol/L in extracted serum. It was considered that levels above 50 pmol/L could be determined accurately without extraction. The serum levels of 17 beta-estradiol in prepubertal girls were, in most cases, below the detection limit, except in the morning, when in 17 of the 21 prepubertal girls, serum 17 beta-estradiol levels were just above the detection limit. All girls in early puberty (Tanner breast stage 2) had measurable serum levels of 17 beta-estradiol in the morning, whereas 10 of these 15 girls had levels below the detection limit around midnight. Later in puberty (Tanner breast stages 3 and 4), but before menarche, the diurnal rhythm was more obvious, with high levels of 17 beta-estradiol during the latter part of the night and in the morning. This diurnal rhythm was lost by 1 yr after menarche. There was a high degree of correlation between serum concentrations of 17 beta-estradiol and bone age, whereas there was much less, if any, correlation between 17 beta-estradiol and levels of sex hormone-binding globulin or dehydroepiandrosterone sulfate during puberty. We conclude that the nocturnal rise in gonadotropin secretion during puberty in girls is accompanied by an increased secretion of 17 beta-estradiol in the morning. This diurnal rhythm is lost 1 yr after menarche. Determination of 17 beta-estradiol levels in the morning could be useful in determining the initiation of puberty, whereas determinations in the late evening could provide information on the tempo of puberty.

Low bone mass is known to be associated with an increased risk of fractures. Osteoporosis prevention by maximizing bone mass will be crucial and requires a better knowledge of bone mass acquisition during adolescence. Bone mass was assessed in 574 healthy volunteer females aged 10-24 years. Spine bone mineral density (BMD) in anteroposterior (AP L2-4) and lateral (LAT L3) views was measured using dual-energy X-ray absorptiometry (DXA) and AP bone mineral content (BMC) was calculated. At the same time, spine AP-BMD (L2-4) was evaluated in 333 normal menstruating women, aged 27-47 years. Bone values, osteocalcin and IGF-1 serum concentrations were correlated with chronological age, skeletal age, pubertal stages and time after menarche. In this cross-sectional study, AP- and LAT-BMD and BMC increased dramatically between skeletal ages 10 and 14 or until the first year after menarche. Between 14 and 17 skeletal years of age, AP-BMD and BMC increased moderately, whereas LAT-BMD remained unchanged. After skeletal age 17, or the fourth year after menarche, there was no significant increase in BMD or BMC, and their values did not differ from those of menstruating women. A serum osteocalcin peak was observed at skeletal ages 11-12 or at stage P3, whereas IGF-1 peaked at 13-14 skeletal years of age or at P4 and the first year after menarche. Eighty-six per cent of the adult bone mass of the spine is acquired before skeletal age 14 or the second year after menarche; therefore osteoporosis prevention programs will be particularly effective before that age.

Ornithine transcarbamylase deficiency (OTCD) is caused by an alteration of urea synthesis, linked with partial modification of the X-chromosome, whose clinical manifestations are: lethargy, nausea, vomiting and cerebral edema. While in newborn males OTCD presents with hyperammoniemia leading to cerebral palsy with profound neurological impairment and eventually death, in women who are healthy carriers, it is possible to detect the disorder only through specific tests, since heterozygote women are rarely symptomatic. We describe the case of a young woman admitted to the hospital after an episode of mental confusion with vomiting and psychomotor restlessness, which had previously occurred several times during the premenstruum and lasted a few hours. A 2 day history of stupor made admission mandatory. Tests carried out during the hospital stay showed marked hyperammoniemia and unconjugated hyperbilirubinemia, marked cerebral edema documented by a CT scan. Liver biopsy and CSF test were normal. Screening of plasma and urinary aminoacids, level of orotic acid in the urine and OTC activity in the liver, confirmed the diagnosis of OTCD. The possibility of early diagnosis and therapy of a disease which otherwise leads to death, emphasizes the importance of precise evaluation of a possible organic cause of anorexia and behaviour disorders in young women.

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.