Impact of sex steroids and their suppression on skeletal growth and maturation

1988 ◽  
Vol 255 (4) ◽  
pp. E559-E566 ◽  
Author(s):  
P. A. Boepple ◽  
M. J. Mansfield ◽  
K. Link ◽  
J. D. Crawford ◽  
J. F. Crigler ◽  
...  
Keyword(s):  
Sex Steroids ◽  
Adult Height ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Skeletal Growth ◽  
Skeletal Maturation ◽  
Gonadal Steroid ◽  
Steroid Secretion ◽  
Height Predictions ◽  
The Impact

Forty girls with central precocious puberty (CPP) were studied before and during 1-3 yr of luteinizing hormone-releasing factor (LHRH) agonist (LHRHa) administration to examine the impact of gonadal steroid secretion and its suppression on skeletal growth and maturation. Pubertal growth velocity (GV) was 10.1 +/- 0.7 (SE) cm/yr and, when normalized for chronological age (CA) and bone age (BA), demonstrated that the effects of sex steroids were most profound in patients with the youngest CA and BA. GV decreased significantly to 5.8 +/- 0.3 (n = 40), 4.6 +/- 0.3 (n = 30), and 3.2 +/- 0.6 cm/yr (n = 12) during 3 yr of gonadal suppression and correlated negatively with starting BA. Skeletal maturation was markedly accelerated by premature sex steroid secretion (BA/CA = 1.8 +/- 0.1), was slowed significantly with gonadal suppression (mean delta BA/delta CA less than 1), and also was negatively correlated with the starting BA. Cumulative increases in predicted adult height were observed regardless of starting BA and averaged +2.0 +/- 0.4, +5.2 +/- 0.5, and +6.7 +/- 1.2 cm after 1, 2, and 3 yr of gonadal suppression. The comparable changes in height predictions across all BAs despite highly variable GVs underscore the need for use of developmental (i.e., BA-based) rather than CA-based standards in the analysis of growth during gonadal steroid exposure and suppression in childhood.

Constitutional Delay of Growth: Expected versus Final Adult Height

PEDIATRICS ◽  
1991 ◽  
Vol 87 (1) ◽  
pp. 82-87 ◽  
Author(s):  
Stephen LaFranchi ◽  
Cheryl E. Hanna ◽  
Scott H. Mandel
Keyword(s):  
Adult Height ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Human Growth ◽  
Normal Growth ◽  
Bone Age ◽  
Final Adult Height ◽  
Constitutional Delay ◽  
Height Predictions

Constitutional delay of growth and puberty is believed to represent a variation of normal growth, and it is expected that children with this condition will grow for a longer duration than average and reach a height that is normal for their genetic potential. The records of children with constitutional delay of growth and puberty who were initially seen in the Pediatric Endocrine Clinic at the Oregon Health Sciences University between 1975 and 1983 were retrospectively reviewed. Criteria for study included a height more than 2 SD below the mean, a significantly delayed bone age, and a normal growth velocity on follow-up. Forty-two subjects were located and final adult height measurements were obtained. At contact, the 29 male subjects (mean age = 23.9 years) were 169.5 ± 4.5 cm tall (mean ± SD), and the 13 female subjects (mean age = 20.5 years) were 156 ± 3.8 cm tall. Adult height predictions during follow-up, using either the Bayley-Pinneau or Roche-Wainer-Thissen method, were close to final adult heights. The males were 1.2 SD and the females 1.3 SD below the 50th percentile as adults. This finding was not fully explained by genetic short stature; the males fell 5.1 cm and the females 5.3 cm below target heights based on midparental heights. It is concluded that this discrepancy is most likely explained by a selection bias of the shortest children referred to and observed in a subspecialty clinic, although a defect in human growth hormone secretion or function in children at the far end of the spectrum of constitutional delay of growth and puberty cannot be excluded.

Anthropometric, metabolic, and reproductive outcomes of patients with central precocious puberty treated with leuprorelin acetate 3-month depot (11.25 mg)

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Carolina O. Ramos ◽  
Ana P M Canton ◽  
Carlos Eduardo Seraphim ◽  
Aline Guimarães Faria ◽  
Flavia Rezende Tinano ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Adult Height ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Overweight And Obesity ◽  
Leuprorelin Acetate ◽  
The Mean ◽  
Hormone Analogs

Abstract Objectives Longer-acting gonadotropin-releasing hormone analogs (GnRHa) have been widely used for central precocious puberty (CPP) treatment. However, the follow-up of patients after this treatment are still scarce. Our aim was to describe anthropometric, metabolic, and reproductive follow-up of CPP patients after treatment with leuprorelin acetate 3-month depot (11.25 mg). Methods Twenty-two female patients with idiopathic CPP were treated with leuprorelin acetate 3-month depot (11.25 mg). Their medical records were retrospectively evaluated regarding clinical, hormonal, and imaging aspects before, during, and after GnRHa treatment until adult height (AH). Results At the diagnosis of CPP, the mean chronological age (CA) was 8.2 ± 1.13 year, and mean bone age (BA) was 10.4 ± 1.4 year. Mean height SDS at the start and the end of GnRHa treatment was 1.6 ± 0.8 and 1.3 ± 0.9, respectively. The mean duration of GnRHa treatment was 2.8 ± 0.8 year. Mean predicted adult heights (PAH) at the start and the end of GnRH treatment was 153.2 ± 8.6 and 164.4 ± 7.3 cm, respectively (p<0.05). The mean AH was 163.2 ± 6.2 cm (mean SDS: 0.1 ± 1). All patients were within their target height (TH) range. There was a decrease in the percentage of overweight and obesity from the diagnosis until AH (39–19% p>0.05). At the AH, the insulin resistance and high LDL levels were identified in 3/17 patients (17.6%) and 2/21 patients (9.5%), respectively. The mean CA of menarche was 12.2 ± 0.5 years. At the AH, PCOS was diagnosed in one patient (4.8%). Conclusions Long-term anthropometric, metabolic, and reproductive follow-up of patients with CPP treated with longer-acting GnRHa revealed effectivity, safety, and favorable outcomes.

scholarly journals Growth and Pubertal Development in Elite Female Rhythmic Gymnasts

1999 ◽  
Vol 84 (12) ◽  
pp. 4525-4530 ◽  
Author(s):  
N. Georgopoulos ◽  
K. Markou ◽  
A. Theodoropoulou ◽  
P. Paraskevopoulou ◽  
L. Varaki ◽  
...  
Keyword(s):  
Body Fat ◽  
Adult Height ◽  
Pubertal Development ◽  
Optimal Growth ◽  
Bone Age ◽  
Skeletal Maturation ◽  
Chronological Age ◽  
Average Height ◽  
Limited Information ◽  
Rhythmic Gymnasts

Optimal growth depends upon both environmental and genetic factors. Among environmental factors that could alter growth and sexual maturation are stress and intensive physical training. The influence of these factors has been documented in a variety of sports, but there is limited information on rhythmic gymnasts, who have entirely different training and performance requirements. The study was conducted during the 13th European Championships in Patras, Greece, and included 255 female rhythmic gymnasts, aged 11–23 yr. The study included measurement of height and weight, assessment of breast and pubic hair development, estimation of body fat and skeletal maturation, and registration of menarcheal age and parental height. Gymnasts were taller than average height for age, with mean height above and mean weight below the 50th percentile. Actual height sd score was positively correlated to weight sd score (P &lt; 0.001), number of competitions (P = 0.01), and body mass index (BMI; P &lt; 0.001). Predicted adult height sd score was positively correlated to weight sd score (P &lt; 0.001) and negatively to body fat (P = 0.004). There was a delay in skeletal maturation of 1.3 yr (P &lt; 0.001). Pubertal development was following bone age rather than chronological age. The mean age of menarche was significantly delayed from that of their mothers and sisters (P = 0.008 and P = 0.05, respectively), was positively correlated to the intensity of training and to the difference between chronological age and bone age (P &lt; 0.001 and P = 0.002, respectively), and was negatively correlated to body fat (P &lt; 0.001). In the elite female rhythmic gymnasts, psychological and somatic efforts have profound effects on growth and sexual development. Despite these aberrations, adult height is not expected to be affected.

scholarly journals Should Skeletal Maturation Be Manipulated for Extra Height Gain?

2021 ◽  
Vol 12 ◽  
Author(s):  
Jan M. Wit
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
Precocious Puberty ◽  
Adult Height ◽  
Central Precocious Puberty ◽  
Idiopathic Short Stature ◽  
Hormone Deficiency ◽  
Skeletal Maturation ◽  
Gnrh Analogue

Skeletal maturation can be delayed by reducing the exposure to estrogens, either by halting pubertal development through administering a GnRH analogue (GnRHa), or by blocking the conversion of androgens to estrogens through an aromatase inhibitor (AI). These agents have been investigated in children with growth disorders (off-label), either alone or in combination with recombinant human growth hormone (rhGH). GnRHa is effective in attaining a normal adult height (AH) in the treatment of children with central precocious puberty, but its effect in short children with normal timing of puberty is equivocal. If rhGH-treated children with growth hormone deficiency or those who were born small-for-gestational age are still short at pubertal onset, co-treatment with a GnRHa for 2-3 years increases AH. A similar effect was seen by adding rhGH to GnRHa treatment of children with central precocious puberty with a poor AH prediction and by adding rhGH plus GnRHa to children with congenital adrenal hyperplasia with a poor predicted adult height on conventional treatment with gluco- and mineralocorticoids. In girls with idiopathic short stature and relatively early puberty, rhGH plus GnRHa increases AH. Administration of letrozole to boys with constitutional delay of growth puberty may increase AH, and rhGH plus anastrozole may increase AH in boys with growth hormone deficiency or idiopathic short stature, but the lack of data on attained AH and potential selective loss-of-follow-up in several studies precludes firm conclusions. GnRHas appear to have a good overall safety profile, while for aromatase inhibitors conflicting data have been reported.

scholarly journals Long-Term Observation of 87 Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogs: Impact on Adult Height, Body Mass Index, Bone Mineral Content, and Reproductive Function

2008 ◽  
Vol 93 (1) ◽  
pp. 190-195 ◽  
Author(s):  
Anna Maria Pasquino ◽  
Ida Pucarelli ◽  
Fabiana Accardo ◽  
Vitan Demiraj ◽  
Maria Segni ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Bone Mineral ◽  
Precocious Puberty ◽  
Adult Height ◽  
Reproductive Function ◽  
Central Precocious Puberty ◽  
Idiopathic Central Precocious Puberty ◽  
Discontinuation Of Treatment ◽  
The Impact

Abstract Objective: We assessed in a retrospective unicenter study the impact of treatment with GnRH analogs (GnRHa) on adult height (AH), body mass index (BMI), bone mineral density (BMD), and reproductive function in girls with idiopathic central precocious puberty (ICPP). Patients: Eighty-seven ICPP patients were treated with GnRHa for 4.2 ± 1.6 yr (range 3–7.9) and observed for 9.9 ± 2.0 yr (range 4–10.6 yr) after discontinuation of treatment; to estimate the efficacy better, 32 comparable ICPP untreated girls were analyzed. Results: AH was 159.8 ± 5.3 cm, significantly higher than pretreatment predicted AH (PAH) either for accelerated or for average tables of Bayley and Pinneau. The gain in centimeters between pretreatment PAH and AH was 5.1 ± 4.5 and 9.5 ± 4.6 cm, respectively. Hormonal values and ovarian and uterine dimensions, reduced during treatment, increased to normal after 1 yr without therapy. Age of menarche was 13.6 ± 1.1 yr with an interval of 0.9 ± 0.4 yr after therapy. Menstrual pattern was normal. Six girls became pregnant and delivered normal offspring. BMI sd score for chronological age increased, but not significantly, before, during, and after therapy. BMD at discontinuation of treatment was significantly lower and increased to control values after gonadal activity resumption. Conclusions: GnRHa treatment in ICPP is safe for the reproductive system, BMD, and BMI and helpful in reaching AH close to target height; however, the variability of individual responses suggests that one choose more parameters than increment in height, especially in girls with pubertal onset over 8 yr of age.

scholarly journals Long-Term Growth Hormone Therapy Does Not Advance Skeletal Maturation in Children and Adolescents

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A679-A679
Author(s):  
Benjamin Udoka Nwosu ◽  
Sadichchha Parajuli ◽  
Gabrielle Jasmin ◽  
Austin F Lee
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Adult Height ◽  
Recombinant Human Growth Hormone ◽  
Bone Age ◽  
Skeletal Maturation ◽  
Z Score ◽  
Rhgh Therapy ◽  
Catch Up

Abstract Context: There is no consensus on the effect of recombinant human growth hormone (rhGH) therapy on skeletal maturation in children despite the current practice of annual monitoring of skeletal maturation with bone age in children on rhGH therapy. Aims: To investigate the effects of long-term rhGH therapy on skeletal age in children and explore the accuracy of bone age predicted adult height (BAPAH) at different ages based on 13 years of longitudinal data. Methods: A retrospective longitudinal study of 71 subjects aged 2-18 years, mean 9.9 ± 3.8y, treated with rhGH for non-syndromic short stature for a duration of 2-14y, mean, 5.5 ± 2.6y. Subjects with syndromic short stature and systemic illnesses such as renal failure were excluded. Results: Bone age minus chronological age (BA-CA) did not differ significantly between baseline and the end of rhGH therapy (-1.05 ± 1.42 vs -0.69 ± 1.63, p=0.09). Piece-wise regression however showed a quantifiable catch-up phenomenon in BA of 1.6 months per year of rhGH therapy in the first 6.5y, 95%CI 0.023 - 0.229, p=0.017, that plateaued thereafter, β=0.015, 95% CI -0.191-0.221, p=0.88. There was no relationship between BAPAH z score – height z score and the duration of rhGH therapy, p=0.68. BAPAH overestimated final adult height in younger subjects but became more precise in older subjects (p&lt;0.0001). Conclusion: Long-term rhGH therapy demonstrated an initial catch-up phenomenon in skeletal maturation in the first 6.5y that plateaued thereafter with no overall significant advancement in bone age. These findings are reassuring and do not support the practice of yearly monitoring of skeletal maturation with bone age in children on rhGH therapy, especially in younger subjects where BAPAH is imprecise.

scholarly journals Gonadotropin-dependent pubertal disorders are common in patients with virilizing adrenocortical tumors in childhood

2019 ◽  
Vol 8 (5) ◽  
pp. 579-589 ◽  
Author(s):  
Monica F Stecchini ◽  
Zilda Braid ◽  
Candy B More ◽  
Davi C Aragon ◽  
Margaret Castro ◽  
...  
Keyword(s):  
Final Height ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Tall Stature ◽  
Early Exposure ◽  
Single Institution ◽  
Androgen Excess ◽  
Adrenocortical Tumors ◽  
The Impact

Objective To investigate the impact of early exposure to androgen excess on gonadotropin-dependent puberty (GDP) and final height (FH) of patients with androgen-secreting adrenocortical tumors (ACT) in childhood. Methods Retrospective cohort study. Occurrence of GDP and achievement of FH were evaluated. Central precocious puberty (CPP) and early fast puberty (EFP) were considered pubertal disorders. Patients with normal puberty and pubertal disorders were compared. Results The study included 63 patients (44F), followed in a single institution from 1975 until 2017. At diagnosis of ACT, median age was 25.8 months; duration of signs, 6 months; stature SDS, 0.5 (−3.6 to 3.9) and bone age advancement, 14.7 months (−27.9 to 85.4). To date, 37 patients developed GDP: 26 had normal puberty; one, precocious thelarche; seven, CPP and three, EFP. GnRHa effectively treated CPP/EFP. Tall stature and older age at diagnosis of ACT were associated with risk of CPP alone (RR 4.17 (95% CI 1.17–14.80)) and CPP/EFP (RR 3.0 (95% CI 1.04–8.65)). Recurrence/metastasis during follow-up were associated with risk of CPP alone (RR 4.17 (95% CI 1.17–14.80)) and CPP/EFP (RR 3.0 (95% CI 1.12–8.02)). Among the 19 patients that reached FH, stature SDS dropped from 1.4 to −0.02 since diagnosis of ACT (P = 0.01). Seventeen achieved normal FH. There was no difference in FH SDS between patients with normal puberty and pubertal disorders (P = 0.75). Conclusions Gonadotropin-dependent pubertal disorders are common in patients with androgen-secreting ACT in childhood. FH is usually not impaired. The study reinforces the importance of close follow-up after surgery to identify and treat consequences of early exposure to androgen excess.

A New Model of Adult Height Prediction Validated in Boys with Constitutional Delay of Growth and Puberty

2019 ◽  
Vol 91 (3) ◽  
pp. 186-194 ◽  
Author(s):  
Thomas Reinehr ◽  
Elisa Hoffmann ◽  
Juliane Rothermel ◽  
Theresa Johanna Lehrian ◽  
Jürgen Brämswig ◽  
...  
Keyword(s):  
Prediction Model ◽  
Adult Height ◽  
Bone Age ◽  
New Model ◽  
Significant Difference ◽  
Constitutional Delay ◽  
Height Prediction ◽  
Height Predictions ◽  
Bp Model ◽  
Independent Cohort

Background: For children with retarded bone ages such as in constitutional delay of growth and puberty (CDGP) there are no specific methods to predict adult height based on bone age. Widely used methods such as Bayley-Pinneau (BP) tend to overestimate adult height in CDGP. Objective: We aimed to develop a specific adult height prediction model for teenage boys with retarded bone ages >1 year. Methods: Based on the adult heights of 68 males (median age 22.5 years) a new height prediction model was calculated based on 105 height measurements and bone age determinations at a median age of 14.0 years. The new model was adapted for the degree of bone age retardation and validated in an independent cohort of 32 boys with CDGP. Results: The BP method overestimated adult height (median +1.2 cm; p = 0.282), especially in boys with a bone age retardation ≥2 years (median +1.6 cm; p = 0.027). In the validation study, there was no significant difference between adult height and predicted adult height based on the new model (p = 0.196), while the BP model led to a significant overestimation of predicted adult height (median +4.1 cm; p = 0.009). Conclusions: The new model to predict adult height in boys with CDGP provides novel indices for height predictions in bone ages >13 years and is adapted to different degrees of bone age retardation. The new prediction model has a good predictive capability and overcomes some of the shortcomings of the BP model.

scholarly journals The Impact of Reversible Gonadal Sex Steroid Suppression on Serum Leptin Concentrations in Children with Central Precocious Puberty1

1998 ◽  
Vol 83 (4) ◽  
pp. 1091-1096
Author(s):  
Mark R. Palmert ◽  
Sally Radovick ◽  
Paul A. Boepple
Keyword(s):  
Body Composition ◽  
Longitudinal Study ◽  
Sex Steroids ◽  
Central Precocious Puberty ◽  
Sex Steroid ◽  
Serum Leptin ◽  
Reproductive Axis ◽  
Discernible Effect ◽  
The Impact ◽  
The Relationship

Serum leptin concentrations increase during childhood in both sexes. During sexual maturation, levels rise further in girls, but decrease in boys. These data suggest that testosterone either directly suppresses leptin levels or induces changes in body composition that result in lower leptin concentrations. To examine further the relationship between sex steroids and leptin, we performed a longitudinal study in children with central precocious puberty (28 girls and 12 boys) before, during, and after discontinuation of GnRH agonist-induced pituitary-gonadal suppression. Nighttime and daytime leptin levels were measured to determine whether the activity of the pituitary-gonadal axis affects their diurnal variation. In the boys, suppression of testosterone increased leptin levels, whereas resumption of puberty was associated with decreased leptin levels [3.5 ± 0.8 vs. 9.5 ± 3.1 ng/dL (P = 0.005) and 12.2 ± 4.5 vs. 7.0 ± 2.6 ng/dL (P = 0.012), respectively]. Serum leptin levels did not change in the girls with alteration of the pituitary-ovarian axis and consistently exceeded those in boys. Nighttime levels were consistently greater than daytime values by an average of 38.3% in the girls and 29.4% in the boys. These serial observations during reversible pituitary-gonadal suppression suggest that testosterone decreases leptin concentrations, but that estrogen, at least in this childhood model, has no discernible effect. In addition, our data indicate that the presence of the diurnal rhythm in leptin concentrations is independent of the state of the reproductive axis.

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