THE FUNCTIONAL STATE OF THE HYPOTHALAMO-PITUITARY AXIS AFTER HIGH-DOSE OESTROGEN THERAPY IN EXCESSIVELY TALL GIRLS

1979 ◽  
Vol 91 (1) ◽  
pp. 19-29 ◽  
Author(s):  
J. P. Hanker ◽  
G. Schellong ◽  
H. P. G. Schneider
Keyword(s):  
Functional State ◽  
Adult Height ◽  
Bone Age ◽  
Steroid Treatment ◽  
High Dose ◽  
Functional Disturbance ◽  
Final Adult Height ◽  
Tall Girls ◽  
Lh Rh

ABSTRACT Sixteen excessively tall girls were treated with 0.3 mg of ethinyloestradiol daily and 10 mg of norethisterone for 5 days every 3 weeks for 7–26 months. The reduction of adult height varied from 0–12.3 cm, depending on the bone age (115/12–148/12) before treatment. The more advanced the bone age was the less final adult height was reduced. The functional state of the hypothalamo-pituitary axis was assessed by standardized LH-RH testing immediately after termination of therapy as well as 1, 4, 8 and 12 weeks thereafter. Basal levels of oestradiol and prolactin were recorded before each test. Absent LH-responses to LH-RH were observed in all girls when therapy was stopped. Four to eight weeks later the LH responses had normalized in 13 girls and 12 weeks after therapy normal LH responses were found in 14 girls. Mean basal oestradiol levels were low (20 ± 9 pg/ml) (X̄ ± sd) at the end of therapy but increased significantly (P < 0.0025) to levels similar to different stages of the menstrual cycle after 4 weeks. In contrast mean basal prolactin levels were elevated (21±9 ng/ml) (X̄ ± sd) when therapy was stopped. Within one week a significant (P < 0.01) decrease to values averaging 13 ± 4 ng/ml (sd) was seen. A further but only moderate decline occurred until the 12th week after therapy. The decrease of prolactin paralleled to same extend the increase of endogenous oestradiol. All girls experienced spontaneous menstrual bleedings within 3 to 22 weeks after termination of therapy. In all cases but one menses have been regular since. The data presented suggest that no major functional disturbance of the hypothalamo-pituitary axis has to be expected after long-term steroid treatment in excessively tall girls.

Treatment of Excessively Tall Girls and Boys With Sex Hormones

PEDIATRICS ◽  
1978 ◽  
Vol 62 (6) ◽  
pp. 1202-1210
Author(s):  
Andrea Prader ◽  
Milo Zachmann
Keyword(s):  
Sex Hormones ◽  
Adult Height ◽  
Bone Age ◽  
Short Term ◽  
Contraceptive Pill ◽  
Physical Handicap ◽  
Tall Girls ◽  
High Doses ◽  
Spontaneous Onset

Sex hormones in high doses administered over a period of one to two years are today the only effective medical way to decrease future adult height in excessively tall adolescents. Such treatment is not physiological and should be considered only if a careful growth prediction gives an excessive adult height that is a severe psychological or physical handicap to the patient. The most effective and safest way of treatment is not yet fully worked out, but the principles are simple: The hormone preparations used should be as natural as possible, the dosage as low as possible for producing the desired effect, and treatment should start only after the spontaneous onset of puberty and be discontinued at a bone age of about 15 years in girls and 17 years in boys. The risks are probably similar to those of the contraceptive pill and of pregnancy. The short-term risks are small in the adolescent age period. Fertility does not seem to be impaired. The long-term risks are not yet completely known.

scholarly journals Long-term outcomes after gonadotropin-releasing hormone agonist treatment in boys with central precocious puberty

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243212
Author(s):  
Young Suk Shim ◽  
Kyung In Lim ◽  
Hae Sang Lee ◽  
Jin Soon Hwang
Keyword(s):  
Precocious Puberty ◽  
Adult Height ◽  
Treatment Initiation ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Gonadotropin Releasing Hormone ◽  
Gonadotropin Releasing Hormone Agonist ◽  
Final Adult Height ◽  
The Mean

Objective Gonadotropin-releasing hormone agonist (GnRHa) treatment improves the potential for gaining height in patients with central precocious puberty (CPP). However, most studies have focused on girls because CPP in boys is relatively rare. Therefore, we aimed to determine the effect of GnRHa treatment on auxological outcomes in boys with CPP. Methods Eighty-five boys with CPP were treated with leuprolide or triptorelin acetate 3.75 mg over 2 years. Anthropometry, bone age, sexual maturity rating, and predicted adult height (PAH) were assessed every 6 months. Furthermore, 20 boys were followed up after treatment discontinuation until achievement of the final adult height (FAH). Results The mean chronological age (CA) and bone age (BA) of the patients with CPP at treatment initiation were 9.5 ± 0.5 years and 11.7 ± 0.9 years, respectively. The mean duration of treatment was 2.87 ± 0.63 years. The PAH at treatment initiation was 172.1 cm (-0.23 ± 1.05 PAH standard deviation score). The PAH at treatment discontinuation (176.2 ± 6.6 cm) was significantly higher than the pretreatment PAH. In addition, the mean final adult height in the 20 boys who were followed up after discontinuation of treatment was 173.4 ± 5.8 cm, which was significantly higher than the initial PAH (170.1 ± 4.5 cm; p = 0.006). In multivariate analysis, the height gain (the difference between the FAH and PAH at treatment initiation) significantly correlated with the target height. Conclusion Long-term GnRHa treatment significantly improved the growth potential and FAH in boys with CPP.

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.

Oestrogen treatment to reduce the adult height of tall girls: long-term effects on fertility

The Lancet ◽  
2004 ◽  
Vol 364 (9444) ◽  
pp. 1513-1518 ◽  
Author(s):  
Alison Venn ◽  
Fiona Bruinsma ◽  
George Werther ◽  
Priscilla Pyett ◽  
Donna Baird ◽  
...  
Keyword(s):  
Adult Height ◽  
Long Term Effects ◽  
Oestrogen Treatment ◽  
Tall Girls

scholarly journals Adult height after GH therapy in 188 Ullrich-Turner syndrome patients: results of the German IGLU Follow-up Study 2001

2002 ◽  
pp. 625-633 ◽  
Author(s):  
MB Ranke ◽  
CJ Partsch ◽  
A Lindberg ◽  
HG Dorr ◽  
M Bettendorf ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
Adult Height ◽  
Bone Age ◽  
First Year ◽  
Gh Therapy ◽  
Gh Treatment ◽  
Height Gain ◽  
Puberty Onset

OBJECTIVES: We aimed to evaluate the factors influencing true adult height (HT) after long-term (from 1987 to 2000) GH treatment in Ullrich-Turner syndrome (UTS) based on modalities conceived in the 1980s. DESIGN: Out of 347 near-adult (>16 Years) patients from 96 German centres, whose longitudinal growth was documented within KIGS (Pharmacia International Growth Database), 188 (45, X=59%; bone age >15 Years) were available for further anthropometric measurements. RESULTS: At a median GH dose of 0.88 (10th/90th percentiles: 0.47/1.06) IU/kg per week, a gain of 6.0 (-1.3/+13) cm above the projected adult height was recorded. Variables were recorded at GH start, after 1 Year GH, puberty onset, and last visit on GH therapy. At these visits, the median ages were 11.7, 12.7, 14.2, 16.6 and 18.7 Years; and median heights, 0.4, 1.1, 1.7, 1.7 and 1.3 SDS (UTS) respectively. Height gain (DeltaHT) after GH discontinuation was 1.5 cm. Total DeltaHT correlated (P<0.001) negatively with bone age and HT SDS at GH start, but positively with DeltaHT after the first Year, DeltaHT at puberty onset, and GH duration. Final HT correlated (P<0.001) positively with HT at GH start, first-Year DeltaHT, and HT at puberty onset. Body mass index increased slightly (P<0.05), with values at start and adult follow-up correlating highly (R=0.70, P<0.001). No major side effects of GH occurred. CONCLUSIONS: GH dosages conceived in the 1980s are safe but too low for most UTS patients. HT gain and height are determined by age and HT at GH start. Height gain during the first Year on GH is indicative of overall height gain. After spontaneous or induced puberty, little gain in height occurs.

scholarly journals Increased Final Height in Precocious Puberty after Long-Term Treatment with LHRH Agonists: The National Institutes of Health Experience

2001 ◽  
Vol 86 (10) ◽  
pp. 4711-4716 ◽  
Author(s):  
Karen Oerter Klein ◽  
Kevin M. Barnes ◽  
Janet V. Jones ◽  
Penelope P. Feuillan ◽  
Gordon B. Cutler Jr.
Keyword(s):  
Precocious Puberty ◽  
Adult Height ◽  
Final Height ◽  
Bone Age ◽  
Chronological Age ◽  
Lhrh Agonist ◽  
Duration Of Treatment ◽  
Long Term Treatment ◽  
Predicted Height

We report 98 children who have reached final adult height in a long-term trial of LHRH agonist treatment. These children were 5.3± 2.1 yr old at the start of treatment and were treated with either deslorelin (4 μg/kg·d sc) or histrelin (4–10 μg/kg·d) for an average of 6.1 ± 2.5 yr. Final height averaged 159.8 ± 7.6 cm in the 80 girls, which was significantly greater than pretreatment predicted height (149.3 ± 9.6 cm) but still significantly less than midparental height (MPH) (163.7 ± 5.6). Final height averaged 171.1 ± 8.7 cm in the 18 boys, which was significantly greater than pretreatment predicted height (156.1 ± 14.2 cm) but still significantly less than MPH (178.3 ± 5.2 cm). However, the average adult height of the 54 children who had less than a 2-yr delay in the onset of treatment was not significantly different from their MPH, and 21 children exceeded MPH. Final height sd score correlated positively with duration of treatment (P &lt; 0.01), midparental height (P &lt; 0.001), predicted height at the start of treatment (P &lt; 0.001), and growth velocity during the last year of treatment (P &lt; 0.001) and correlated inversely with delay in the onset of treatment (P &lt; 0.001), age at the start of treatment (P &lt; 0.001), bone age at the start of treatment (P &lt; 0.001), bone age at the end of treatment (P &lt; 0.001), breast stage at the start of treatment (P = 0.02), and bone age minus chronological age at the start of treatment (P = 0.001). We conclude that LHRH agonist treatment improves the final height for children with rapidly progressing precocious puberty treated before the age of 8 yr for girls or 9 yr for boys. Less delay in the onset of treatment, longer duration of treatment, and lower chronological and bone age at the onset of treatment all lead to greater final height. All children with onset of pubertal symptoms before age 8 in girls and age 9 in boys should be evaluated for possible treatment. Treatment is appropriate in children with rapidly progressing puberty, accelerated bone maturation, and compromise of adult height prediction, regardless of bone age or chronological age at time of evaluation. However, once treatment is considered appropriate, it should be initiated quickly, because longer delays lead to shorter final height. In addition, the longer the treatment is continued, the greater is the final height outcome.

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 Long-Term Effect of Aromatase Inhibition in Aromatase Excess Syndrome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A679-A679
Author(s):  
Gerhard Binder ◽  
Akie Nakamura ◽  
Roland Schweizer ◽  
Tsutomu Ogata ◽  
Maki Fukami ◽  
...  
Keyword(s):  
Tandem Duplication ◽  
Low Dose ◽  
Adult Height ◽  
Bone Age ◽  
Sporadic Case ◽  
Term Treatment ◽  
Sibling Pairs ◽  
Long Term Effect ◽  
Long Term Treatment

Abstract Aromatase excess syndrome (AEXS) is a very rare disorder characterized by prepubertal gynecomastia, bone age acceleration and early growth arrest. Heterozygote submicroscopic rearrangements within the promotor of CYP19A1 result in overexpression of aromatase and enhanced aromatization of androgens. Long-term treatment effects of aromatase inhibitors are unknown. Retrospectively we collected data from file records of 7 boys (three sibling pairs and one sporadic case) with AEXS. Genetic analysis revealed upstream of CYP19A1 a 165,901 bp deletion in 4 German cousins, a 198,662 bp deletion in 2 Japanese brothers and a 387,622 bp tandem duplication in a Japanese boy. All boys developed prepubertal gynecomastia, at 9.0 yr of age (median; range: 7.0 - 11.0). Height was +1.20 SDS (-0.24 - +1.98); predicted adult height was -1.29 (-3.29 - +1.09 SDS). Four boys were treated with anastrozole 1.0 mg daily, while three reached adult height untreated. Treatment with anastrozole was stopped after 5.6 yr (4.0 - 6.8). Three treated boys exceeded height prognosis by 2.4, 6.9 and 8.1 cm; while one untreated fell below prognosis by 8.6 cm. One treated with a low dose and two untreated reached their prognosis. Adult heights were -0.91 SDS with anastrozole (-2.86 - -0.29) and -0.15 SDS without (-2.31 - -0.03). Distance to target height was -0.22 SDS with anastrozole (-1.72 - +0.52) and +0.54 SDS without treatment (+0.23 - +1.30). Spontaneous growth in AEXS varied, even in the same family. Our data suggest that early started, long-term inhibition by aromatase inhibitor anastrozole (1 mg daily) promotes adult height in boys with AEXS.

scholarly journals Final Height in Pubertal Short Stature Boys Treated with GH Combination with Letrozole: A retrospective study

2021 ◽  
Author(s):  
Yaping Ma ◽  
Ruofan Jia ◽  
Bingyang Xia ◽  
Bin Tang ◽  
Zhuangjian Xu
Keyword(s):  
Retrospective Study ◽  
Short Stature ◽  
Adult Height ◽  
Final Height ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Growth Potential ◽  
Target Height ◽  
Final Adult Height ◽  
Epiphyseal Fusion

Abstract BackgroundThe growth potential of pubertal short stature boys is limited by the effect of estrogen on epiphyseal fusion. This study aims to identify the efficacy and safety of growth hormone (GH) combination with letrozole on final adult height (FAH) in pubertal short stature boys. MethodsThis is a retrospective study. Among pubertal short stature boys who treated with GH and letrozole were be followed up in our hospital, 20 cases reached FAH. ResultsBaseline chronological age were 12.12±1.14yr, bone age were 13.00±0.93yr. The treatment duration was 1.94±0.67yr. The height standard deviation score for bone age was increased from -1.46±0.51 to -0.12±0.57 (p<0.000). The predicted FAH before treatment, predicted FAH after treatment, FAH, and genetic target height were 161.02 ±4.12 cm, 172.11±4.20 cm, 172.67±2.72cm and 167.67±3.56 cm, respectively. There was significant differences between predicted FAH before treatment and after treatment (p<0.000), as well as predicted FAH before treatment and genetic target height (p<0.000).The predicted FAH after treatment was higher than that of genetic target height (p<0.001), as well as FAH and genetic target height (p<0.000). ConclusionsThe GH combination with letrozole can enhance the FAH in pubertal short stature boys. No significant side effects were observed.

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