Cognitive performance in young adult women with a history of premature adrenarche.

BACKGROUND: Girls with premature adrenarche (PA) mature earlier than peers and have been found to have greater symptom accounts reflecting anxiety compared to peers. It is not known, however, whether PA effects cognitive development. This longitudinal case-control cohort study aimed: (1) To investigate whether a history of PA leads to measurable changes in adulthood cognitive performance, and (2) to assess whether findings characteristic of PA girls predict adulthood cognitive performance. METHODS: Twenty-seven girls with PA and 27 age-matched control girls were examined and followed from mid-childhood (mean age 7.2 years) until early adult age (18.5 years). Wechsler Adult Intelligence Scale, Fourth Edition scores were used as main outcome measure. RESULTS: Allostatic load (AL) scores, which compile multisystem variables to reflect the overall wear and tear of the body from increased and prolonged stress, were higher in the PA group in both prepuberty and adulthood, but there were no differences in WAIS-IV results between the groups (full-scale IQ 92.7 vs. 97.5, p 0.376; no differences in separate indexes). Childhood androgen levels, glucose metabolism biomarkers, and AL scores failed to predict adulthood cognitive performance outcomes. CONCLUSION: The study suggests that PA does not predispose to adverse adulthood outcomes of cognitive development. IMPACT: The study suggests that a history of premature adrenarche (PA) does not affect cognitive performance in adult age. Childhood androgen levels and biomarkers of glucose metabolism failed to predict adulthood cognitive outcomes in this study. Allostatic load scores were elevated in the PA group both in childhood and adulthood but did not predict adulthood cognitive outcomes.

Maternal caffeine intake during pregnancy and the risk of delivering a small for gestational age baby: Kuopio Birth Cohort.

PURPOSE: High caffeine intake during pregnancy is associated with restricted fetal growth. We aimed to evaluate the association between maternal caffeine intake during early and late pregnancy and the risk of delivering a small for gestational age (SGA) baby. METHODS: Kuopio Birth Cohort (KuBiCo) is a prospective cohort study including women whose pregnancies and deliveries were treated at the prenatal clinics in outpatient healthcare centers and in Kuopio University Hospital, Finland. Maternal diet and caffeine intake during the first (n = 2007) and third (n = 4362) trimester of pregnancy were assessed using a 160-item food frequency questionnaire (2013-2022). SGA was defined as birth weight corrected for gestational age below - 2 standard deviations from the mean, according to the sex-specific Finnish fetal growth curves. RESULTS: Altogether in 32 and 38% (1st and 3rd trimester) of all women and in 44 and 52% of coffee drinkers, caffeine intake exceeded the recommendation for caffeine intake ( ≤ 200 mg/day) during pregnancy. The women with moderate (51-200 mg/day) (aOR 1.87; 95% CI: 1.16-3.02) and high (> 200 mg/day) (aOR 1.51; 95% CI: 1.08-2.10) caffeine intake during the first trimester were in the highest risk of having an SGA newborn. Caffeine intake in the third trimester of pregnancy was not associated with SGA. CONCLUSIONS: Moderate and high caffeine intake during early pregnancy is associated with SGA. As the results suggest that even moderate caffeine intake during the first trimester may increase the risk of SGA, the intake within recommendation limits does not necessarily appear to be safe for pregnant women and their newborns.

Quantification of urinary gonadotropins by specific assays may improve the evaluation of sex-specific hormonal changes in early infancy.

OBJECTIVE: The aim of this study was to investigate the feasibility of different gonadotropin assays for determining total and intact luteinizing hormone (LH), and follicle-stimulating hormone (FSH) immunoreactivity in urine (U-LH-ir and U-FSH-ir, respectively) during early infancy. DESIGN, PATIENTS AND MEASUREMENTS: Morning urine samples were obtained from 31 infants, aged between 0 and 6 months, to study the age-related course of urinary gonadotropins. Additionally, we investigated bi-hourly urine samples of a 5-day-old male neonate for 24 h to observe the course of urinary gonadotropins during a daily cycle. We employed different immunofluorometric assays for measuring total and intact U-LH-ir, and U-FSH-ir. RESULTS: In neonates up to 21 days of age, the U-LH-ir levels measured by the regular LH assay (also detecting hCG) were significantly higher than those determined by the total (specific) LH assays (p = .004). U-FSH-ir was higher in girls than boys during both the first and the next 5 months (p = .02 and p < .001, respectively), whereas total U-LH-ir was higher in boys until 6 months of age (p < .001). Total U-LH-ir/U-FSH-ir ratio was significantly higher in boys than girls across the first half-year (p < .001). CONCLUSIONS: The assessment of total U-LH-ir and U-FSH-ir, and their respective ratio constitutes a noninvasive, practical and scalable tool to investigate sex-specific changes during early infancy, with the ratio being significantly higher in boys than girls. Only highly specific LH assays detecting beta-subunit and its core fragment in addition to intact LH should be used for determining U-LH-ir in the neonatal period to avoid potential cross-reactivity with hCG of placental origin.

Health-related quality of life of young adult women with a history of premature adrenarche.

INTRODUCTION: Children with premature adrenarche (PA) have increased adrenal androgen concentrations and earlier pubertal development than their peers. Early sexual maturation and exposure to androgens have both been associated with an increased risk for neuropsychological adversities in adulthood. Such adversities would presumably influence the experienced health-related quality of life (HRQoL) of those affected. METHODS: A longitudinal case-control cohort study, in which 30 PA girls and 40 age-matched controls were followed from childhood to young adult age. The main outcome measure was the total 15D HRQoL score. In addition, we assessed specific dimensions of the questionnaire, the subjects' relationship statuses and living arrangements. RESULTS: There were no differences between the groups in the overall 15D scores (PA, 0.956 (0.052); control, 0.947 (0.055); p 0.482), or on any dimension of this instrument. CONCLUSION: The study suggests that a history of PA does not lead to impaired HRQoL in adult age.

Accelerated Early Childhood Growth Is Associated With the Development of Earlier Adrenarche and Puberty.

Context: Small birth size and increased postnatal growth have been associated with earlier timing of adrenarche and puberty, but it is not well known whether these factors alone or together lead to earlier maturation. Objective: This work aimed to search for different growth trajectories using a clustering approach to analyze the effects of birth size and postnatal growth on adrenarchal and pubertal development. Methods: Altogether 351 children (48% girls) were examined prospectively at ages 6 to 9 and 9 to 11 years. Birth and early-growth data were collected retrospectively. Main outcome measures included clinical signs of adrenarche and puberty, and serum androgen concentrations (dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, testosterone). Results: We detected 4 clusters with different birth sizes and postnatal growth trajectories: 1) children with average birth size and increased postnatal growth (AI), 2) children with small birth size and increased postnatal growth (SI), 3) children with average birth size and postnatal growth (AA), and 4) children with small birth size and average postnatal growth (SA). Thelarche at age 9 to 11 was most common and serum androgens at ages 6 to 9 and 9 to 11 years were highest in girls belonging to the AI and SI groups. Similar patterns in the onset of puberty and in androgen levels were not seen in the SA group. Conclusion: Increased early growth and weight gain predict higher serum androgen concentrations and earlier onset of puberty in girls. Adrenarche and puberty do not appear to be shifted earlier in children with small birth size who do not have catch-up growth.

Maternal caffeine, coffee and cola drink intake and the risk of gestational diabetes - Kuopio Birth Cohort.

AIMS: Coffee intake is associated with a decreased risk of type 2 diabetes among non-pregnant people. We aimed to investigate the association between caffeine, coffee and cola drink intake in early pregnancy and the risk of gestational diabetes (GDM). METHODS: Kuopio Birth Cohort (KuBiCo) is a prospective cohort study including pregnant women who were followed at the prenatal clinics in outpatient healthcare centers and gave birth in Kuopio University Hospital, Finland (n=2214). Maternal diet during the first trimester of pregnancy was assessed using a 160-item food frequency questionnaire. GDM was diagnosed by oral glucose tolerance test according to the Finnish national guidelines mainly between 24 and 28 gestational weeks. RESULTS: Women with moderate coffee intake in the first trimester were less likely diagnosed with GDM than women without coffee intake in an age-adjusted model (OR 0.87; 95% CI 0.76-0.99; p = 0.03), but the association was attenuated in multi-adjusted models (p = 0.11). No association was found between caffeine intake and GDM. One third (32.4%) of pregnant women consumed caffeine over the recommendation (> 200 mg/d). Women who consumed cola drinks more than the median (33.3 mL/d) had an increased risk of GDM (OR 1.29; 95% CI 1.02-1.63, p = 0.037) in multi-adjusted model compared to those who consumed less. CONCLUSIONS: Caffeine intake during the first trimester of pregnancy was not associated with the risk of GDM but a minor non-significant decrease was seen with moderate coffee intake. Although the average consumption of cola drinks was low in the KuBiCo cohort, higher consumption was associated with an increased risk of GDM. Further studies are needed to evaluate the safe amount of coffee during pregnancy, since the recommended caffeine intake was exceeded in almost half of the coffee drinkers.

Effects of 2-Year Physical Activity and Dietary Intervention on Adrenarchal and Pubertal Development: The PANIC Study.

CONTEXT: Childhood overweight has been linked to earlier development of adrenarche and puberty, but it remains unknown if lifestyle interventions influence sexual maturation in general populations. OBJECTIVE: To investigate if a 2-year lifestyle intervention influences circulating androgen concentrations and sexual maturation in a general population of children. METHODS: We conducted a 2-year physical activity and dietary intervention study in which 421 prepubertal and mostly normal-weight 6- to 9-year-old children were allocated either to a lifestyle intervention group (119 girls, 132 boys) or a control group (84 girls, 86 boys). The main outcome measures were serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), and testosterone concentrations, and clinical adrenarchal and pubertal signs. RESULTS: The intervention and control groups had no differences in body size and composition, clinical signs of androgen action, and serum androgens at baseline. The intervention attenuated the increase of DHEA (P = .032), DHEAS (P = .001), A4 (P = .003), and testosterone (P = .007) and delayed pubarche (P = .038) in boys but it only attenuated the increase of DHEA (P = .013) and DHEAS (P = .003) in girls. These effects of lifestyle intervention on androgens and the development of pubarche were independent of changes in body size and composition, but the effects of intervention on androgens were partly explained by changes in fasting serum insulin. CONCLUSION: A combined physical activity and dietary intervention attenuates the increase of serum androgen concentrations and sexual maturation in a general population of prepubertal and mostly normal-weight children, independently of changes in body size and composition.

Comparative steroid profiling of newborn hair and umbilical cord serum highlights the role of fetal adrenals, placenta, and pregnancy outcomes in fetal steroid metabolism.

Previous steroid hormone studies concerning pregnancy and newborns have mainly focused on glucocorticoids; wider steroid profiles have been less commonly investigated. Here, we performed a comparative analysis of 17 steroids from newborn hair and umbilical cord serum at the time of delivery. The study participants (n = 42, 50% girls) were a part of the Kuopio Birth Cohort and represent usual Finnish pregnancies. The hair and cord serum samples were analyzed with liquid chromatography high resolution mass spectrometry and triple quadrupole tandem mass spectrometry, respectively. We detected high individual variations in steroid hormone concentrations in both sample matrices. The concentrations of cortisol (F), corticosterone (B), estrone (E1), estradiol (E2), dehydroepiandrosterone (DHEA), 11ß-hydroxyandostenedione (11bOHA4), 5α-androstanedione (DHA4), and 17α-hydroxypregnenolone (17OHP5) correlated positively between cord serum and newborn hair samples. In addition, F and 11bOHA4 concentrations correlated positively with each other in both newborn hair and cord serum samples. The cortisone-to-cortisol ratio (E/F) was significantly higher in cord serum than in newborn hair samples reflecting high placental 11ßHSD2 enzyme activity. Only minor sex differences in steroid concentrations were observed; higher testosterone (T) and 11-deoxycortisol (S) with lower 11bOHA4 in male cord serum, and higher DHEA, androstenedione (A4) and 11bOHA4 in female newborn hair samples. Parity and delivery mode were the most significant pregnancy- and birth-related parameters associating with F and some other adrenocortical steroid concentrations. This study provides novel information about intrauterine steroid metabolism in late pregnancy and typical concentration ranges for several newborn hair steroids, including also 11-oxygenated androgens.

Cardiorespiratory Fitness in Young Adult Women With a History of Premature Adrenarche.

Context: Premature adrenarche (PA) may predispose to some adverse long-term health outcomes. Cardiorespiratory fitness (CRF) is one of the strongest factors known to predict overall health, but no data exist on the CRF of women with a history of PA. Objective: To study if hyperandrogenism in childhood resulting from PA leads to a measurable difference in CRF between young adult PA and control women. Methods: A total of 25 women with PA and 36 age-matched controls were followed from prepubertal age until adulthood. Anthropometric measurements, body composition, biochemical, and lifestyle factors were assessed. The main outcome measure was maximal cycle ergometer test result at the mean age of 18.5 years. We also assessed prepubertal predicting factors for CRF with different linear regression models. Results: Though prepubertal children with PA were taller and heavier than their non-PA peers, there were no significant differences in height, body mass index, body composition, or physical activity in young adulthood. We observed no significant differences in any of the parameters of the maximal cycle ergometer test, including maximal load (P = .194) or peak oxygen consumption (P = .340). Hemodynamic responses of the groups were similar. None of the examined models or prepubertal factors significantly predicted CRF at adult age. Conclusion: This study suggests that hyperandrogenism in childhood/adolescence resulting from PA does not have a significant impact on adulthood CRF.

Health-related quality of life in boys with constitutional delay of growth and puberty.

Introduction: Constitutional delay of growth and puberty (CDGP) is the most common reason for delayed puberty in healthy male adolescents. The main indication for medical treatment for this condition is psychosocial burden. However, to the best of our knowledge, no previous study has addressed the impact of puberty-promoting treatment on health-related quality of life (HRQoL) among boys with CDGP. Methods: We investigated HRQoL in 22 boys with CDGP, who participated in a randomized controlled trial in four Finnish pediatric endocrinology outpatient clinics between 2013 and 2017. The boys were randomized to receive either aromatase inhibitor letrozole (2.5mg/day; n=11) or intramuscular testosterone (1mg/kg/every 4 weeks; n=11) for 6 months and followed up to 12 months. HRQoL was assessed with a generic self-assessment 16D© instrument developed and validated for adolescents aged 12 to 15 years. The 16D includes 16 dimensions (vitality, sight, breathing, distress, hearing, sleeping, eating, discomfort and symptoms, speech, physical appearance, school and hobbies, mobility, friends, mental function, excretion and depression). The results were compared with an age-matched reference population that included 163 boys from the Finnish capital-city area. The study protocol is registered to ClinicalTrials.gov (registration number: NCT01797718). Results: At baseline, the mean 16D score of the CDGP boys was similar to the age-matched reference population (0.95 vs 0.96, p=0.838). However, the physical appearance score (satisfaction with general appearance, height and weight) was significantly lower in the CDGP boys (0.75 vs 0.92, p=0.004) than their peers. Twelve months after treatment, Appearance had improved significantly (0.75 vs 0.87, p=0.004) and no HRQoL dimension was inferior compared to the age-matched reference population. Discussion: In terms of HRQoL, the main impact of delayed puberty was dissatisfaction with physical appearance. Puberty promoting therapy was associated with a positive change in perceived appearance, with no clear difference between low-dose testosterone and letrozole treatments.

A quantitative ultra-performance liquid chromatography high-resolution mass spectrometry analysis of steroids from human scalp hair.

Hair steroid analysis offers the possibility to evaluate long-term steroid metabolism. It is especially beneficial when studying the steroid milieu in newborns and children, for example it can provide new insights into steroid metabolism over months and is unaffected by diurnal fluctuations in steroid concentrations. This study describes a quantitative and highly selective high-resolution mass spectrometry method for the simultaneous analysis of multiple steroids from human scalp hair. The developed method utilizes parallel reaction monitoring in the analysis of hydroxylamine derivatized steroids from hair samples first washed with isopropanol, extracted with methanol, and further purified with solid-phase extraction and liquid-liquid extraction. The method was proven suitable for the quantitative analysis of endogenous glucocorticoids (cortisol [1.5-364 pg/mg]; cortisone [3.6-355 pg/mg]; corticosterone [0.7-347 pg/mg]; 11-deoxycortisol [0.1-343 pg/mg]), androgens (testosterone [0.1-288 pg/mg]; dehydroepiandrosterone [0.3-288 pg/mg]; androstenedione [0.1-285 pg/mg]; 11ß-hydroxyandrostenedione [0.3-304 pg/mg]), progestogens (pregnenolone [0.1-313 pg/mg]; progesterone [0.1-313 pg/mg]; 17α-hydroxypregnenolone [0.3-315 pg/mg]; 17α-hydroxyprogesterone [0.7-330 pg/mg]; 21-hydroxyprogesterone [0.6-320 pg/mg]), and estrogens (estrone [0.1-267 pg/mg]; estradiol [0.5-274 pg/mg]). In addition, 11-ketoandrostenedione [0.6-60 pg/mg]; dihydrotestosterone [0.3-290 pg/mg]; 11-ketotestosterone [0.1-12 pg/mg]; and 5α-androstanedione [0.6-281 pg/mg] could be analyzed semi-quantitatively. Aldosterone [3.5-346 pg/mg]; 11ß-hydroxytestosterone [0.3-300 pg/mg]; and 11-ketodihydrotestosterone [0.3-300 pg/mg] were also included in the method, but their concentrations were below the lower limit of quantification in all tested hair samples. The method was applied for the analysis of authentic hair samples from different age groups ranging from newborns to adults, including mothers within 48 h after delivery. The newborn hair samples displayed the widest variety and had also the highest amounts of steroids in comparison to the samples of the other groups.

The Mediating Role of Endocrine Factors in the Positive Relationship Between Fat Mass and Bone Mineral Content in Children Aged 9-11 Years: The Physical Activity and Nutrition in Children Study.

Introduction: We aimed to investigate whether the relationship between fat mass and bone mineral content (BMC) is mediated by insulin, leptin, adiponectin, dehydroepiandrosterone sulphate, testosterone and estradiol in children aged 9-11 years. Materials and Methods: We utilised cross-sectional data from the Physical Activity and Nutrition in Children study (n = 230 to 396; 112 to 203 girls). Fat mass and BMC were assessed with dual-energy X-ray absorptiometry. Endocrine factors were assessed from fasted blood samples. We applied the novel 4-way decomposition method to analyse associations between fat mass, endocrine factors, and BMC. Results: Fat mass was positively associated with BMC in girls (ß = 0.007 to 0.015, 95% confidence interval (CI) 0.005 to 0.020) and boys (ß = 0.009 to 0.015, 95% CI 0.005 to 0.019). The relationship between fat mass and BMC was mediated by free leptin index in girls (ß = -0.025, 95% CI -0.039 to -0.010) and boys (ß = -0.014, 95% CI -0.027 to -0.001). The relationship between fat mass and BMC was partially explained by mediated interaction between fat mass and free leptin index in boys (ß = -0.009, 95% CI -0.013 to -0.004) and by interaction between fat mass and adiponectin in girls (ß = -0.003, 95% CI -0.006 to -0.000). Conclusion: At greater levels of adiponectin and free leptin index, the fat mass and BMC relationship becomes less positive in girls and boys respectively. The positive association between fat mass with BMC was largely not explained by the endocrine factors we assessed. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT01803776], identifier NCT01803776.

Circulating Liver-enriched Antimicrobial Peptide-2 Decreases During Male Puberty.

CONTEXT: Circulating levels of liver-enriched antimicrobial peptide 2 (LEAP2), a ghrelin receptor antagonist, decrease under caloric restriction and increase in obesity. The role of LEAP2 in male puberty, a phase with accelerated energy demand, is unclear. OBJECTIVE: This work aimed to investigate whether circulating LEAP2 levels are downregulated in boys following the onset of puberty to respond to the energy need required for growth. METHODS: We determined circulating LEAP2 levels in 28 boys with constitutional delay of growth and puberty (CDGP) who participated in a randomized controlled trial (NCT01797718), and were treated with letrozole (n = 15) or intramuscular low-dose testosterone (T) (n = 13) for 6 months. Blood sampling and dual-energy x-ray absorptiometry-measured body composition were performed at 0-, 6-, and 12-month visits. RESULTS: Serum LEAP2 levels decreased statistically significantly during pubertal progression (0-6 months: mean decrease -4.3 [10.3] ng/mL, P = .036 and 0-12 months: -3.9 [9.3] ng/mL, P = .033). Between 0 and 6 months, the changes in serum LEAP2 levels correlated positively with changes in percentage of body fat (rs = 0.48, P = .011), and negatively with growth velocity and estradiol levels (rs = -0.43, P = .022, rs = -0.55, P = .003, respectively). In the T group only, the changes in serum LEAP2 correlated negatively with changes in T and estradiol levels. Between 0 and 12 months, the change in LEAP2 levels correlated negatively with the change in high-density lipoprotein levels (rs = -0.44, P = .022) and positively with the change in insulin (rs = 0.50, P = .009) and HOMA-IR (rs = 0.51, P = .007) levels. CONCLUSION: Circulating LEAP2 levels decreased after induction of puberty reciprocally with increased growth rate and energy demand, reflecting the metabolic state of the adolescent. Further, the results suggest that estradiol levels may have a permissive role in downregulating circulating LEAP2 levels.

Serum testosterone and oestradiol predict the growth response during puberty promoting treatment.

OBJECTIVE: The influence of androgens and oestrogens on growth is complex, and understanding their relative roles is important for optimising the treatment of children with various disorders of growth and puberty. DESIGN: We examined the proportional roles of androgens and oestrogens in the regulation of pubertal growth in boys with constitutional delay of growth and puberty (CDGP). The study compared 6-month low-dose intramuscular testosterone treatment (1 mg/kg/month; n = 14) with per oral letrozole treatment (2.5 mg/day; n = 14) which inhibits conversion of androgens to oestrogen. PATIENTS: Boys with CDGP were recruited to a randomized, controlled, open-label trial between 2013 and 2017 (NCT01797718). MEASUREMENTS: The patients were evaluated at 0-, 3- and 6-month visits, and morning blood samples were drawn. Linear regression models were used for data analyses. RESULTS: In the testosterone group (T-group), serum testosterone concentration correlated with serum oestradiol concentration at the beginning of the study and at 3 months, whereas in the letrozole group (Lz-group) these sex steroids correlated only at baseline. Association between serum testosterone level and growth velocity differed between the T and Lz groups, as each nmol/L increase in serum testosterone increased growth velocity 2.7 times more in the former group. Serum testosterone was the best predictor of growth velocity in both treatment groups. In the Lz-group, adding serum oestradiol to the model significantly improved the growth estimate. Only the boys with serum oestradiol above 10 pmol/L had a growth velocity above 8 cm/year. CONCLUSIONS: During puberty promoting treatment with testosterone or aromatase inhibitor letrozole, growth response is tightly correlated with serum testosterone level. A threshold level of oestrogen appears to be needed for an optimal growth rate that corresponds to normal male peak height velocity of puberty. Serum testosterone 1 week after the injection and serum testosterone and oestradiol 3 months after the onset of aromatase inhibitor treatment can be used as biomarkers for treatment response in terms of growth.

Boys but Not Girls Exposed to Maternal Gestational Diabetes Mellitus Have Unfavorable Fat Distribution.

BACKGROUND: Maternal gestational diabetes mellitus (GDM) and overweight are associated with an increased risk of obesity and the metabolic syndrome in the adult offspring. We studied the influence of maternal GDM on prepubertal children's body composition and bone mineral biochemistry. METHODS: A total of 134 prepubertal Caucasian children (age range 4.4-9.7 years) were studied in a controlled cross-sectional study. Seventy-six children had been exposed to maternal GDM and 58 children born after a normal pregnancy served as controls. The outcome variables were body fat %, android fat %, gynoid fat %, android/gynoid fat ratio, bone mineral density (BMD), bone mineral content (BMC), muscle mass, lean mass (LM) and serum 25-hydroxyvitamin D, ionized calcium, phosphate, and alkaline phosphatase concentrations. RESULTS: There were no differences in body fat %, android fat %, BMD, BMC, muscle mass, or LM between the study groups. Gynoid fat % was higher in the GDM than control children (p = 0.03). Android fat %, gynoid fat %, and android/gynoid fat ratio were higher in the GDM boys than control boys (p = 0.046, 0.037, and 0.038) respectively, but no differences were found between the GDM and control girls. CONCLUSIONS: Boys exposed to maternal GDM presented with more unfavorable fat distribution than their controls, whereas no difference was found between the girls. Otherwise, the differences in body composition were minimal between prepubertal GDM and control children.

PCOS Features and Steroid Profiles Among Young Adult Women with a History of Premature Adrenarche.

CONTEXT: Premature adrenarche (PA) may increase the risk for polycystic ovary syndrome (PCOS). OBJECTIVE: To study features of PCOS in young adult women with a history of PA. METHODS: Thirty PA and 42 control females were followed from prepuberty to young adulthood (median age 18.1 years). The main outcome measures were ovarian function, the use of contraceptives, and clinical and biochemical indicators of hyperandrogenism. RESULTS: We found no differences in the use of hormonal contraceptives (50 vs 50%, PA vs controls, respectively; P > .999), indication for using contraceptives (P = .193), or in the history of oligo- (17 vs 26%, P = .392) and amenorrhea (0 vs 0%, P > .999). Among women not using hormonal contraceptives, those with a history of PA had a higher prevalence of hirsutism (27 vs 0%, P = .023) but not acne (87 vs 67%, P = .252). Steroid profiles were broadly comparable between the groups, but PA women had lower sex hormone-binding globulin (SHBG) concentrations (30.1 vs 62.4 nmol/L, P < .001) resulting in higher free androgen index (3.94 vs 2.14, P < .001). The difference in SHBG levels persisted through body mass index adjustment. SHBG correlated negatively with the homeostasis model assessment for insulin resistance (r -0.498, P = .003). Anti-Müllerian hormone concentrations were comparable between the groups (39.3 vs 32.1 pmol/L, P = .619). CONCLUSION: PA was not associated with evident ovarian dysfunction in young adult women. However, women with a history of PA had decreased SHBG levels and thus, increased bioavailability of circulating androgens.

MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of primary amenorrhea and female delayed puberty.

Puberty is the period of transition from childhood to adulthood characterized by the attainment of adult height and body composition, accrual of bone strength and the acquisition of secondary sexual characteristics, psychosocial maturation and reproductive capacity. In girls, menarche is a late marker of puberty. Primary amenorrhea is defined as the absence of menarche in ≥ 15-year-old females with developed secondary sexual characteristics and normal growth or in ≥13-year-old females without signs of pubertal development. Furthermore, evaluation for primary amenorrhea should be considered in the absence of menarche 3 years after thelarche (start of breast development) or 5 years after thelarche, if that occurred before the age of 10 years. A variety of disorders in the hypothalamus-pituitary-ovarian axis can lead to primary amenorrhea with delayed, arrested or normal pubertal development. Etiologies can be categorized as hypothalamic or pituitary disorders causing hypogonadotropic hypogonadism, gonadal disorders causing hypergonadotropic hypogonadism, disorders of other endocrine glands, and congenital utero-vaginal anomalies. This article gives a comprehensive review of the etiologies, diagnostics and management of primary amenorrhea from the perspective of pediatric endocrinologists and gynecologists. The goals of treatment vary depending on both the etiology and the patient; with timely etiological diagnostics fertility may be attained even in those situations where no curable treatment exists.

Bone structure assessed with pQCT in prepubertal males with delayed puberty or congenital hypogonadotropic hypogonadism.

OBJECTIVE: Congenital hypogonadotropic hypogonadism (CHH) is associated with impaired bone mineral density in adulthood, whereas the estimates on bone structure in adolescents with CHH has not been previously evaluated. This study describes bone structure in CHH patients and compares it to that in boys with constitutional delay of growth and puberty (CDGP). DESIGN: A cross-sectional study. METHODS: Peripheral quantitative computed tomography (pQCT) of non-dominant arm and left leg were performed. Volumetric bone mineral density (BMD), bone mineral content, and area in trabecular and cortical bone compartments were evaluated, and bone age-adjusted Z-scores for the bone parameters were determined. RESULTS: The participants with CHH had more advanced bone age and were older, taller and heavier than the CDGP boys, yet they had lower trabecular BMD in distal radius (147.7 mg/mm3 [95% CI, 128-168 mg/mm3 ] vs. 181.2 mg/mm3 [172-192 mg/mm3 ], p = .002) and distal tibia (167.6 mg/mm3 [145-190 mg/mm3 ] vs. 207.2 mg/mm3 [187-227 mg/mm3 ], p = .012), respectively. CHH males had lower cortical thickness at diaphyseal tibia than the participants with CDGP (p = .001). These between-group differences remained significant in corresponding Z-scores adjusted for bone age and height (p = .001). In CDGP group, serum testosterone correlated positively with trabecular BMD (r = 0.51, p = .013) at distal radius, and estradiol levels correlated positively with trabecular BMD at the distal site of tibia (r = 0.58, p = .004). CONCLUSIONS: Five treatment-naïve male patients with CHH exhibited poorer trabecular BMD than untreated males with CDGP. We speculate that timely low-dose sex steroid replacement in CHH males may benefit skeletal health in adulthood.

The impact of postpartum depressive symptoms on self-reported infant health and analgesic consumption at the age of 12 months: A prospective cohort study.

The infants of mothers with elevated depressive symptoms (EDS) postpartum appear to be at increased risk of somatic health problems during their first 12 months of life in low- and lower-middle-income countries. However, in higher-income countries, knowledge of this association is scarce. We sought to examine whether maternal reports of infant health problems, adherence to vaccination schedules and analgesic supply to the infant during the first 12 months of life differ between mothers with and without postpartum EDS. Altogether, 969 women who were enrolled in the Kuopio Birth Cohort study (www.kubico.fi) during 2012-2017 were included in this investigation. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale during pregnancy (1st and/or 3rd trimester) and at eight weeks postpartum. Infant health data were collected as a part of a 12-month online follow-up questionnaire for mothers and were based on self-reports of either maternal observations or physician-determined diagnoses. Postpartum EDS were associated with a 2- to 5-fold increased likelihood of abnormal crying and paroxysmal wheezing (based on parental observations), as well as gastroesophageal reflux and food allergy (based on physician-determined diagnoses). Mothers with postpartum EDS also supplied their infants with analgesic medication for longer periods. Adherence to vaccination schedules was similar between the examined groups. In conclusion, infants of mothers with postpartum EDS may be more likely to experience health problems or to be perceived by their mother as having health problems, and thus receive more medications.