Early Pubertal Girls Research Articles

A Randomized School-Based Jumping Intervention Confers Site and Maturity-Specific Benefits on Bone Structural Properties in Girls: A Hip Structural Analysis Study

We compared 7-month changes in bone structural properties in pre- and early-pubertal girls randomized to exercise intervention (10-minute, 3 times per week, jumping program) or control groups. Girls were classified as prepubertal (PRE; Tanner breast stage 1; n = 43 for intervention [I] and n = 25 for control [C]) or early-pubertal (EARLY; Tanner stages 2 and 3; n = 43 for I and n = 63 for C). Mean +/- SD age was 10.0 +/- 0.6 and 10.5 +/- 0.6 for the PRE and EARLY groups, respectively. Proximal femur scans were analyzed using a hip structural analysis (HSA) program to assess bone mineral density (BMD), subperiosteal width, and cross-sectional area and to estimate cortical thickness, endosteal diameter, and section modulus at the femoral neck (FN), intertrochanter (IT), and femoral shaft (FS) regions. There were no differences between intervention and control groups for baseline height, weight, calcium intake, or physical activity or for change over 7 months (p > 0.05). We used analysis of covariance (ANCOVA) to examine group differences in changes of bone structure, adjusting for baseline weight, height change, Tanner breast stage, and physical activity. There were no differences in change for bone structure in the PRE girls. The more mature girls (EARLY) in the intervention group showed significantly greater gains in FN (+2.6%, p = 0.03) and IT (+1.7%, p = 0.02) BMD. Underpinning these changes were increased bone cross-sectional area and reduced endosteal expansion. Changes in subperiosteal dimensions did not differ. Structural changes improved section modulus (bending strength) at the FN (+4.0%, p = 0.04), but not at the IT region. There were no differences at the primarily cortical FS. These data provide insight into geometric changes that underpin exercise-associated gain in bone strength in early-pubertal girls.

Plasminogen activator inhibitor-1 in girls with precocious pubarche: a premenarcheal marker for polycystic ovary syndrome?

In both obese and nonobese women, polycystic ovary syndrome (PCOS) is essentially a disorder of hyperinsulinemic insulin resistance, and it may be heralded by precocious pubarche (PP; appearance of pubic hair in girls aged <8 y). The risk of progression from PP to PCOS is related to low birth weight, but there are no early biochemical markers of this risk. As increased plasminogen activator-inhibitor type 1 (PAI-1) activity (act) is an early marker of cardiovascular risk in PCOS, we have sought abnormalities in young girls with PP. In 33 young PP girls (age range 6-11 y), PAI-1-act was increased (mean + SEM: 15.6 +/- 1.5 IU/mL) compared with age-, sex-, and pubertal stage-matched controls (n = 13, 10.7 +/- 1.9, p < 0.05). PAI-1-act levels were inversely related to birth weight SD score (r = -0.33, p < 0.05), and PAI-1-act levels were therefore higher in PP girls with low birth weights (n = 14, 19.5 +/- 2.5 IU/mL) than normal birth weights (n = 19, 12.8 +/- 1.5, p < 0.01). During longitudinal observation in 10 PP girls (mean time interval 2.7 y), PAI-1-act levels in early puberty were positively related to postmenarcheal insulin levels (mean serum insulin SDS postoral glucose, r = 0.65, p < 0.05), and showed a similar relationship to postmenarcheal testosterone levels (r = 0.61, p = 0.06). Together with low birth weight, increased plasma PAI-1-act levels in early pubertal PP girls may indicate those girls with greater risk of developing hyperinsulinemic-hyperandrogenism features of PCOS.

A school-based exercise intervention augments bone mineral accrual in early pubertal girls

Objective: To evaluate the effects of an elementary school-based physical education exercise intervention program on bone mineral accrual in prepubertal and early pubertal girls. Study design: A total of 14 schools were randomly assigned to control (C) and intervention (I) groups. Girls in the I group completed a 10-minute, 3 times per week circuit of varied jumping activities over 7 months. We measured total body, lumbar spine, proximal femur, femoral neck, and trochanteric bone mineral content and areal bone mineral density and estimated femoral neck volumetric bone mineral density at baseline and final measurement in 87 girls in the I group and 90 girls in the C group. Girls were between 8.7 and 11.7 years at baseline. Tanner stage 1 girls were considered prepubertal; Tanner stages 2 and 3 girls were considered early pubertal. We used analysis of covariance (adjusting for baseline bone values, change in size, age, and maturity) to compare 7-month change in bone mineral content, areal bone mineral density, and volumetric bone mineral density between C and I groups within prepubertal and early pubertal girls. Results: There was no difference in 7-month change in bone parameters between prepubertal I and C groups. Early pubertal girls in the I group gained 1.5% to 3.1% more bone at the femoral neck and lumbar spine than early pubertal girls in the C group (P < .05); gain at other sites did not differ. Conclusions: In girls, early puberty may be a particularly opportune time during growth for simple exercise interventions to have a positive effect on bone health. (J Pediatr 2001;139:501-8)

Muscle cross-sectional area is associated with specific site of bone in prepubertal girls: a quantitative magnetic resonance imaging study

It is well established that forces applied to bone are the result of muscle contraction. However, data regarding the contribution of muscle cross-sectional area (because muscle area is proportional to muscle strength) to cortical bone area before puberty are controversial. We tested the hypothesis that muscle cross-sectional area is associated with total cortical bone area, and whether there is a region-specific relationship between these parameters in prepubertal and early pubertal girls. Seventeen healthy (9–11 years, Tanner stages I–II) white girls participated in the study. We measured bone loading characteristics (maximal ground reaction forces; GRFs) for a drop jump (50 cm) and side-to-side jump (over a 20-cm-high fence) on a multicomponent force platform. Muscle cross-sectional area and bone cortical area (square centimeters) of the proximal third of the left and right lower leg was measured with a 1.5 T magnetic resonance system using a quadrature head coil. The sequence was T 1 weighted, with spin-echo in transverse (tibial) planes and 3 mm sections with no gap (ten slices). The tibial cross-sectional areas were subdivided into three anatomical sectors (SI–SIII), with the tibial centroid as origin. SI extended from the medial tibial border to the most anterior edge, SII extended from the anterior edge laterally to the interosseous border, and SIII extended posteromedially from the interosseous border to the medial tibial border. The nonparametric bone and muscle volume correlations demonstrated that the total muscle cross-sectional area correlated significantly with the total cortical area in both legs (left leg: r s = 0.59, p = 0.020; right leg: r s = 0.57, p = 0.016). Significant correlations were also found between left and right muscle area and cortical area in SII ( r s = 0.68, p = 0.003, 0.67, and 0.003, respectively). There was no significant association between the muscle area and cortical area in SI or SIII. In addition, there was a significant correlation between GRFs of the side-to-side jump and total cortical area (left leg: r = 0.75, p < 0.01; right leg: r = 0.78, p < 0.01). Thus, we found that muscle area was most highly associated with bone cortical area in SII, the anterolateral sector of the tibia, which emphasizes the specific interplay of muscles and bone in the lower limb. This relationship was present in a regional, site-specific fashion.

BONE MINERAL RESPONSE TO LOADING EXERCISE IS RELATED TO MATURITY

Several retrospective studies propose a pediatric “window of opportunity” when loading elicits an optimal osteogenic response. To test this hypothesis prospectively, we conducted an 8-month, randomized, controlled, school-based high impact intervention study in 174 pre-and early pubertal girls. Maturity was assessed by Tanner breast staging. Tanner 1 (at baseline) girls were rated as prepubertal (Pre; n = 43 Intervention (I), n = 25 Control (C)) while Tanner 2 and 3 girls were classified as early pubertal (Early; n = 43 I, n = 63 C). Mean (SD) age was 10(0.6) and 10.5(0.6) years for the Pre and Early girls, respectively. Girls attending intervention schools undertook a 10-minute, high impact, progressive circuit program 3 times per week. We measured total body (TB) bone mineral content and area density (aBMD), and aBMD at the total proximal femur (PF), femoral neck (FN) and trochanteric (TR) subregions (Hologic QDR 4500). Other measures were height, weight (standard techniques); lean mass (LM), fat mass (FM) (DXA); general physical activity and calcium intake (validated questionnaires). There were no differences in anthropometric or lifestyle variables between I and C within Pre and Early groups at baseline. Similar changes in height, weight, LM, and FM were observed for I and C within maturity groups over 8 months. We used ANCOVA to compare change in bone mineral from baseline and controlled for baseline bone and weight values, change in height and weight, and Tanner Stage (for Early only). The increase in TB BMC/aBMD, and PF, FN and TR aBMD were similar between Pre-I and Pre-C, and between Early-I and Early-C. However, FN aBMD increased more in the Early-I as compared to the Early-C (6.4 vs. 5.2%, p < 0.03). Thus, early as compared to pre-puberty may be an effective “window of opportunity” for femoral neck bone mineral to respond favourably to loading in growing girls.

The osteotrophic response to different mechanical loading regimes in pre and early pubertal girls

The osteotrophic response to different mechanical loading regimes in pre and early pubertal girls

Hormonal findings in African-American and Caribbean Hispanic girls with premature adrenarche: implications for polycystic ovarian syndrome.

Premature adrenarche refers to the early maturation of the adrenal zona reticularis such that the resultant modest hyperandrogenism causes the early appearance of pubic hair before the age of 8 years in girls and 9 years in boys. The precise etiology of premature adrenarche is not known. However, recent studies indicate that certain girls with premature adrenarche are at risk of developing functional ovarian hyperandrogenism, polycystic ovarian syndrome, and hyperinsulinism. Caribbean Hispanic women in general are at increased risk of developing polycystic ovarian syndrome, and African-Americans are at increased risk of developing the complications of hyperinsulinism. Previously, girls with premature adrenarche were reported to have androgens in the range found in normal children in the early stages of puberty. We noted that many of our African-American and Caribbean Hispanic patients with premature adrenarche had androgens that were much higher than what has been reported previously. This retrospective study was performed to characterize the adrenocorticotropin-stimulated androgen response in an African-American and Caribbean Hispanic population of girls with premature adrenarche. The androgen response to adrenocorticotropin stimulation in 72 African-American and Caribbean Hispanic girls with premature adrenarche was compared with those reported for normal girls in early puberty (Tanner stages II and III). The mean age was 6.8 +/- 0.8 years, bone age was 8 +/- 1.5 years, pubic hair was Tanner stages II and III, and body mass index was 18.6 +/- 4. Of the girls, 28% were found to have elevated stimulated 17OHPregnenolone (17OHPreg) levels that were >2 SD units above the mean for normal early pubertal children. The stimulated ratio of 17OHPreg/17OHProgesterone also was elevated in 18% of the girls and showed a modest correlation with body mass index. In contrast to previous studies of girls of mixed ethnic backgrounds with premature adrenarche, 28% of the 72 African-American and Caribbean Hispanic girls with premature adrenarche had adrenocorticotropin-stimulated 17OHPreg levels that were significantly higher than those seen in early pubertal girls. Because 17OHPreg hyperresponsiveness has been described previously in women with hirsutism or polycystic ovarian syndrome, the similar finding in many African-American and Caribbean Hispanic girls with premature adrenarche suggests that the two conditions may share a common mechanism for their hyperandrogenism. Therefore, the hyperandrogenism in certain African-American and Caribbean Hispanic girls with premature adrenarche may not be benign and may be the first presentation of polycystic ovarian syndrome.

Developmental changes in the relationship between IGF-I and body composition during puberty

To examine the hypothesis that anthropometric measures and physical fitness influence circulating insulin-like growth factor-I (IGF-I) during puberty, we measured IGF-I, free IGF-I, IGFBP-1, and IGFBP-3 concentrations in 156 healthy girls (9-16 years old) characterized by aerobic capacity (VO2max), fat-free mass (FFM), percent fat mass and pubertal development. IGF-I, free IGF-I and IGFBP-3 increased with pubertal development while IGFBP-1 declined. Percent fat mass correlated inversely with IGFBP-1 (r = -0.57) and directly with insulin (r = 0.50), while VO2max correlated inversely with percent fat mass (r = -0.63), body mass index (BMI, r = -0.57), and FFM (r = -0.40). When subdivided by Tanner stage, IGF-I correlated directly with weight, height, BMI, and FFM in pre-pubertal girls, but these relationships all diminished or disappeared completely by late puberty. Inverse correlations between IGF-I and percent fat mass, and direct correlations between IGF-I and VO2max as observed previously in adults, were not seen until late puberty. These data suggest that in pre-pubertal and early pubertal girls, IGF-I concentrations in blood reflect overall somatic size. This relationship between IGF-I and body size diminishes with sexual maturation, while correlations between IGF-I and both fitness and fatness emerge.

Predictors of severity of acne vulgaris in young adolescent girls: Results of a five-year longitudinal study

Objectives: The objectives of this study were to determine which factors in early pubertal girls might be predictive of later, severe facial acne. Study design: The study was a 5-year longitudinal cohort study, with yearly visits from 1987 through 1991, in a volunteer sample of 439 black and 432 white fourth- and fifth-grade girls with consent from their legal guardians. The subjects were recruited from public and parochial schools in Cincinnati, Ohio. The degree of facial acne was classified annually as mild, moderate, or severe. Blood samples were obtained at the first, third, and fifth years of the study. Using the acne status during the fifth year of the study as the outcome variable, we determined the contributions from the prior acne status and the serum levels of dehydroepiandrosterone sulfate (DHEAS), testosterone, free testosterone (FT), estradiol (E 2 ), progesterone, and testosterone-estrogen binding globulin (TEBG) and compared the results at various ages and at times before and after menarche. Results: No racial differences in acne or hormone levels were found. There was a progressive increase in the number of acne lesions with age and maturation. The girls exhibited many more comedonal than inflammatory acne lesions, regardless of age. The girls in whom severe acne developed by the fifth year of the study had significantly more comedones and inflammatory lesions than girls with mild or moderate acne, as early as age 10 years, approximately 2½ years before menarche, a time when their degree of acne was mild. Girls with mild comedonal acne had significantly later onset of menarche (12.5 compared with 12.2 years) than girls with severe comedonal acne. Girls in whom severe comedonal acne developed had significantly higher levels of serum DHEAS and, in a longitudinal analysis, somewhat higher levels of testosterone and FT in comparison with girls who had mild or moderate comedonal acne. Serum E 2 , testosterone/E 2 , progesterone, and TEBG values were no different in girls with severe compared with mild or moderate comedonal acne. Conclusions: The early development of comedonal acne may be one of the best predictors of later, more severe disease. The adrenal hormone DHEAS appears to play an important role in the initiation of acne. DHEAS, testosterone, and FT are associated with the perpetuation of severe comedonal acne. Early recognition of young girls at risk of having severe comedonal acne may enable the clinician to intervene and thus prevent unwanted sequelae. J Pediatr 1997;130:30-9

Differences in the hypothalamic-pituitary-adrenal axis of black girls and white girls

After intravenous administration of ovine corticotropin-releasing hormone (CRH), the plasma corticotropin (ACTH) concentrations of adult black women and men are approximately twice as high as those of adult white women and men; however, there are no corresponding differences in cortisol response. To determine whether these differences in ACTH secretion are also present in prepubertal and early pubertal girls, we studied the hypothalamic-pituitary-adrenal axis of 19 black and 19 white girls of normal weight (age 7 to 10 years) who were matched for body mass index, age, and socioeconomic status. Measures of cortisol's effects, including waist circumference, waist/hip ratio, and fasting insulin and glucose levels, were obtained and related to the ACTH and cortisol responses to 1 μg/kg CRH. There were no racial differences in waist circumference, waist/hip ratio, fasting glucose or insulin levels, baseline free or total plasma cortisol levels, baseline ACTH concentrations, or the plasma cortisol response to CRH. However, CRH-stimulated plasma ACTH concentrations, measured in a polyclonal radioimmunoassay, were significantly greater in prepubertal and early pubertal black girls than in white girls at all time points between 15 and 90 minutes after administration of CRH (area under curve [AUC] 1754 ± 121 pmol/L • min in black girls vs 1304 ± 124 pmol/L • min in white girls, p <0.001). This difference was confirmed by an immunoradiometric assay believed to be specific for intact ACTH (AUC 1634 ± 139 pmol/L • min in black girls vs 1224 ± 104 pmol/L • min in white girls, p <0.001). Neither ACTH AUC nor cortisol AUC was significantly correlated with body mass index in either black or white girls. We conclude that there are differences in the hypothalamic-pituitary-adrenal axis of prepubertal and early pubertal black and white girls similar to those found previously in adult women. The cause of these differences remains to be elucidated. (J P EDIATR 1996;129:130-5)

Calcium metabolism in girls: current dietary intakes lead to low rates of calcium absorption and retention during puberty

We evaluated the effects of self-selected diets on calcium absorption and calculated retention in girls during pre-, early, and late puberty. Dietary calcium absorption was measured in 51 girls aged 4.9-16.7 y by using a dual-tracer stable-isotope technique. We found that calcium intake was similar among girls of all ages and all degrees of pubertal development and was below the recommended dietary allowance (1200 mg/d) for 21 of 25 girls aged > or = 11 y. The early pubertal period was associated with a higher percent of dietary calcium absorption (34.4 +/- 11.9%) than was the prepubertal (27.7 +/- 8.2%) or late pubertal periods (25.9 +/- 7.8%). Calculated calcium retention averaged 132 +/- 83 mg/d in prepubertal girls, 161 +/- 88 mg/d in early pubertal girls, and 44 +/- 91 mg/d in late pubertal girls. Peak calcium retention during early puberty was far below that previously reported after higher calcium intakes. We conclude that peak periods for calcium retention for girls are in the pre- and early pubertal periods. The current calcium intake of American girls during the pubertal growth period may not enable maximal mineral retention; therefore, increased calcium intakes should be considered.

Effects of development on techniques for calcium stable isotope studies in children.

We evaluated the effects of age and pubertal status on the tracer excess measured in urine samples collected during the 120 h after the oral and intravenous administration of calcium stable isotopes to 90 children (16 preterm infants and 74 females aged 4.9-16.8 years). Analysis of subjects shows differences in distribution volume and fractional absorption of calcium based on developmental status, with four separate groups being identified. These are: (i) premature infants; (ii) prepubertal girls (Tanner stage 1); (iii) early pubertal girls (Tanner states 2-3); and (iv) late pubertal girls (Tanner stages 4-5). Identification of groups in this fashion allows for adequate dosing in calcium stable isotope studies, with the minimum dose being given to achieve an increase in urinary isotopic content consistent with the precision of the analytical equipment.

Twenty-four-hour concentration profiles of gonadotropin and estradiol (E2) in prepubertal and early pubertal girls: the diurnal rise of E2 is opposite the nocturnal rise of gonadotropin.

To investigate the detailed pattern of circulating gonadotropin and estradiol (E2) concentrations around the onset of puberty, plasma gonadotropin and E2 were measured at 20-min intervals for 24 h in seven prepubertal and six early pubertal normal short girls. The hormone concentrations obtained were analyzed by Cluster pulse detection algorithm, cosinor analysis, and cross-correlation analysis. All subjects showed spontaneous LH and FSH pulses, and six early pubertal girls showed spontaneous E2 pulses. Cosinor analysis revealed 24-h LH rhythms in all subjects except two early pubertal girls and 24-h FSH rhythms in all subjects except one early pubertal girl. The acrophases (clocktime for maximal value) in the 24-h rhythm of LH and FSH were both found in the late hours of sleep. All subjects except three prepubertal girls showed significant 24-h E2 rhythms. In contrast to the 24-h LH and FSH rhythms, the acrophase of the 24-h E2 rhythm was found in the daytime waking period. Cross-correlation analysis demonstrated significant positive cross-correlations between LH and E2 that were maximum at an E2 lag of 5.7-9.3 h in three of the six early pubertal girls. In conclusion, the E2 concentration profiles in girls around the onset of puberty show marked 24-h rhythm, with acrophase during the daytime waking period. There exists a 5.7- to 9.3-h time lag between LH and E2 time series, and this long time lag might correspond to the time required for aromatization for E2 synthesis.

Twenty-four-hour concentration profiles of gonadotropin and estradiol (E2) in prepubertal and early pubertal girls: the diurnal rise of E2 is opposite the nocturnal rise of gonadotropin

Twenty-four-hour concentration profiles of gonadotropin and estradiol (E2) in prepubertal and early pubertal girls: the diurnal rise of E2 is opposite the nocturnal rise of gonadotropin

Univariate Genetic Analysis of Oxygen Transport Regulation in Children: The Medical College of Virginia Twin Study

We investigated the relative contributions of genetic, individual environmental, and shared environmental effects on 2,3-diphosphoglycerate (DPG) regulation in preadolescent children. In a population of 165 early pubescent boy and girl twin pairs (11.4 y old), of whom 63 were passive smokers, we asked: 1) Are there differences in the control of DPG levels between early pubertal boys and girls? 2) If present, are these differences influenced by exposure to passive cigarette smoke? Non-passive-smoking boys and girls had similar DPG levels. With exposure to passive smoke, DPG levels increased in boys (p = 0.02) but not in girls. Analysis of variance on DPG demonstrated a parental smoking effect (p = 0.008) and suggested an interactive effect between parental smoking and sex of the child (p = 0.08). Univariate genetic analyses suggested that genes operated at different magnitudes in boys (9%) and girls (39%) in explaining a significant portion of the variance in DPG. The magnitude of shared environmental influences was greater in boys (62%) than in girls (34%), whereas individual environmental effects were similar in boys (29%) and girls (26%). Early pubertal boys differ from girls in their regulation of DPG. Environmental stressors such as passive cigarette smoke may elicit different responses in males and females, even at an early age. The use of path analysis may provide important insights into the mechanisms and interactions of genetic and environmental effects that underly the childhood antecedents of atherosclerotic heart disease.

MONTHLY URINARY GONADOTROPIN AND OVARIAN HORMONE SECRETORY PATTERNS IN NORMAL CHILDREN AND PATIENTS WITH IDIOPATHIC PRECOCIOUS PUBERTY

We have already reported a simple and improved method for the quantification of urinary gonadotropins needed in amounts of urine smaller than those previously reported. Good correlation was observed between urinary gon-adotropin and ovarian steroid/creatinine ratios in first morning voided(FMV) urine and 24-h urine collections in children. Using consecutive 30-d FMV urine specimens from 29 normal children and from 9 patients with idiopathic precocious puberty, we have studied the monthly patterns of nighttime gonadotropin and ovarian steroid excretions. Urinary LH levels in normal prepubertal girls were low with few fluctuations. FSH levels were higher and showed remarkable, episodic fluctuations. In early pubertal girls, urinary LH and FSH excreted with alternate every other day variations at the same time. Their urinary total estrogen excretions remained low levels. In mid-pubertal girls, urinary LH excretion increased to near the levels of urinary FSH and they fluctuated with alternate every other day variations. Urinary total estrogen also increased and fluctuated with an opposite way to these variations in urine LH and FSH. With progressive sexual maturation, urine LH excretion increased. The cycle of a normal postmenarcheal girl aged 14 years showed a pattern similar to those of normal adults. In patients with idiopathic precocious puberty, those hormonal patterns showed similar to those of normal subjects matched for sexual stage. Measuring monthly urinary gonadotropins and ovarian steroids seems to be useful to investigate the process of sexual maturation and the endocrine requirements for ovulation.

Pattern of secretion of bioactive and immunoreactive gonadotrophins in normal pubertal children

The aim was to investigate the relationship between the nocturnal pulsatile secretory patterns of immunoreactive and bioactive luteinizing hormone in normal children at various stages of puberty. Blood samples were taken at 15-minute intervals from 2000 hours to 0800 hours. Pubertal stage was assessed by the method of Tanner (1962). Thirty-four healthy siblings (17 males, 17 females) of diabetic children were recruited (median age 13.1, range 9.1-20.9 years). They were of normal height, non-obese, and covered the range of puberty. Follicle stimulating and luteinizing hormone levels were measured by radioimmunoassay in all 34 subjects; bioactive LH (B-LH) was assayed in a subgroup of 13 subjects selected to encompass the range of normal puberty. Oestradiol (girls) and testosterone (boys) were also measured at hourly intervals. Immunoreactive luteinizing and follicle stimulating hormone concentrations showed a progressive rise during puberty in both sexes. FSH concentrations were significantly higher in females than in males at all stages of puberty. Overnight mean bioactive luteinizing hormone concentrations were higher than immunoreactive luteinizing hormone levels in all the girls studied (n = 7). Although the number of bioactive luteinizing hormone pulses (31) was greater than immunoreactive pulses (27), the profiles were generally very similar. In the early pubertal girls an increase in the bioactive: immunoreactive ratio was observed during the middle of the night with the onset of pulsatility. Oestrogen was detected in the girls in breast stage 4-5 but not in two of the early pubertal girls, despite pulses of immunoreactive and bioactive luteinizing hormone. The boys had higher mean bioactive than immunoreactive luteinizing hormone levels and overall bioactive and immunoreactive luteinizing hormone and testosterone concentrations increased with puberty stage. Concordance between bioactive and immunoreactive hormone pulses was good although more immunoreactive pulses (16) were seen than bioactive pulses (14). As in the girls, an increase in the bioactive: immunoreactive ratio was observed in the middle of the night with the onset of pulsatility at genital stage 2 but, in contrast to the oestrogen data in the girls, testosterone secretion always followed luteinizing hormone pulsatility overnight. We conclude that mean overnight immunoreactive luteinizing and follicle stimulating hormone concentrations increase during puberty in both sexes. Bioactive luteinizing hormone levels are two to three times higher than immunoreactive luteinizing hormone in both sexes, but there is very little discordance between immunoreactive and bioactive luteinizing hormone pulsatility. The bioactive: immunoreactive ratio increases with the occurrence of pulsatility overnight in early pubertal children. The relationship between these changes in bioactive and immunoreactive luteinizing hormone and sex steroids is clearest in boys where the nocturnal testosterone rise always follows pulsatile LH secretion.

Monthly Urinary LH and FSH Secretory Patterns in Normal Children and Patients with Sexual Disorders

Urinary gonadotropin concentrations were determined by polyclonal double antibody RIA after ammonium sulfate extraction. Good correlation was observed between urinary gonadotropin/creatinine ratios in first morning voided and full 24-h urine collections. Using consecutive 30-d first morning voided urine specimens from normal children and from patients with sexual disorders, we have studied the monthly patterns of nighttime gonadotropin secretion. In normal prepubertal girls, the levels of urinary LH were low with few variations and those of urinary FSH were higher with episodic fluctuations. In early pubertal girls, the levels of urinary LH increased with striking, rhythmic fluctuations. The same changes were seen in urinary FSH. A single big surge of urinary gonadotropins was observed in postmenarcheal girls. In normal boys, the secretory patterns of urinary gonadotropins were similar to those of normal girls, but varied less. In patients with idiopathic precocious puberty, the patterns of urinary gonadotropins were similar to those of normal subjects matched for sexual stage. The measurement of 30-d first morning voided urinary gonadotropins can provide a simple and physiologic test of gonadotropin function in children.

LUTEINIZING HORMONE AND FOLLICLE STIMULATING HORMONE SECRETION PATTERNS IN GIRLS THROUGHOUT PUBERTY MEASURED USING HIGHLY SENSITIVE IMMUNORADIOMETRIC ASSAYS

Pulsatile gonadotrophin secretion patterns were studied in 36 healthy girls by measuring every 10 min and applying immunoradiometric assays (IRMA). Different stages of puberty were associated with significant changes in the plasma LH and FSH levels, pulse numbers (Pno) and pulse amplitudes (pA). Plasma LH was not detectable by day or night in young prepubertal girls (B1), neither was plasma oestradiol (E2); however, plasma FSH was detectable in a pulsatile pattern. In the older prepubertal girls (B1-onset) a discrete pulsatile LH pattern became detectable only during the night; plasma FSH tended to rise, while E2 became just detectable. In the early pubertal girls (B2) most daytime LH values were above the detection limit, in some with low-amplitude pulses. At night, pulses with a wide range of pulse amplitudes were detected. Plasma FSH increased further, plasma E2 only slightly. With the progression of puberty the plasma LH and FSH levels, Pno and pA increased significantly from stage B2 to B3 during the day (P less than or equal to 0.05) and close to significance during the night (0.05 less than or equal to P less than or equal to 0.1). However, in stage B4 the secretory characteristics tended to decline, while from stage B3 onwards plasma E2 started to rise rapidly (P less than or equal to 0.05, during the night from stage B2 to B3, during the day from B3 to B4m-). Simultaneous LH and FSH pulses were observed throughout puberty, usually during the night. Using these IRMA methods nocturnal LH in older prepubertal girls and both diurnal and nocturnal FSH pulsatility could be demonstrated in young prepubertal girls. From this study we conclude that (1) puberty in girls, as in boys, may be brought about by an increasing GnRH secretion both in frequency and amplitude, first appearing during the night. This increased GnRH stimulation results in LH secretion only during the night; (2) a cyclical pulsatile LH pattern including an LH surge can be established before the menarche; the capacity for positive feedback activity is not the final maturation characteristic to achieve an ovulatory menstrual cycle.

Body Fat Mass, Body Fat Distribution, and Plasma Hormones in Early Puberty in Females

We examined whether there is a relationship between body fat mass or body fat distribution and hormonal profiles in the plasma of early pubertal girls. Thirty-five apparently healthy caucasian schoolgirls were selected for Tanner's breast development stage M2; they had all been classified as being stage M1 6 months earlier. Body fat mass had no relationship with the total plasma sex steroid concentration or gonadotropins. However, body fat mass was correlated with the fraction of testosterone that was not bound to sex hormone-binding globulin and considered the fraction available for biological activity. Body fat distribution, rather than body fat mass, was different in relation to the total concentrations of estrone, estradiol (E2), and testosterone as well as the percentage of available E2 or testosterone. Girls with fat localized predominantly on the hips had the highest levels of sex steroids and gonadotropins. It seems likely that this type of fat distribution is a result of ovarian activity. Girls with predominantly abdominal fat were also more obese and showed increased plasma levels of total E2 and a lower androgen/estrogen ratio in plasma, possibly due to increased aromatization, especially in abdominal adipose tissue. The findings suggest a reciprocal relationship among body fat distribution, plasma sex hormone levels, and availability of sex steroids in early female puberty.