Final adult height in girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analogue and growth hormone
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Abstract:
Objective To evaluate the long-term final adult height outcome of combined treatment with gonadotropin-releasing hormone analogue(GnRHa)and recombinant human growth hormone(rhGH)in girls with idiopathic central precocious puberty(ICPP).Methods Out of 49 sirls with ICPP[treated with GnRHa at a dose of 60-80 μg/kg every 4 weeks for at least 6 months,whose height velocity fell below 4 cm/year and showed no improvement of predicted adult height(PAH)in 6 months],26 received(rhGH-combined group),in addition to chronological age,and duration of GnRHa treatment,who showed the same growth pattern but refused rhGH treatment,served to evaluate the efficacy of rhGH in addition.At the conclusion of the smdy,all the girls had been followed up for(3.3±1.9)years,and(3.2±0.9)years in rhGH-combined group and control group,respectively;and had achieved adult heisht.To compare the PAH with the final adult height(FAH)before and after treatment in the two groups.Results During rhGH treatment, height velocity of the rhGH-combined girls increased significantly[(6.7±2.0 vs <4)cm/year baseline],RhGH-combined gids showed an adult height far higher than pretreatment PAH [(157.5±4.5 vs 148.1±4.6)cm,P<0.01],and target height[(154.4±4.6)cm] was,significantly excceded.The control group reached an adult heisht also significandy higher than pretreatment PAH[(154.7±5.5vs 150.3±6.0)cm,P<0.01],while target height[(155.6±4.3)cm]was just reached but not significantlyexcceded.The gain in height obtained,calculated between pretreatment PAH and final heisat,(9.4±4.9)cm in rhGH-combined group was much more than that(4.3±4.2)cm in the control group(P<0.01).Conclusion RhGH may accelerate the linear growth and improve adult height of GnRHa-treated ICPP girls.
Key words:
Gonadotropin-releasing hormone analogue; Growth hornmne; puberty,precocious; Adult heightKeywords:
Growth velocity
Objective
To investigate clinical effect of recombinant human growth hormone (rhGH) for interventing central precocious puberty in children, to provide reference for clinical treatment.
Methods
80 patients with growth deceleration slows CCP were selected, when height growth rate below 4cm/year, 40 patients on the basis of joint GnRHa used rhGH treatment were selected as the observation group, and the remaining 40 patients refused to use rhGH, continued to use of GnRHa treatment were selected as the control group.After treatment predicted height, height, bone age, growth rate and other indicators were compared.
Results
In observation group, the actual height Ht, predicted height PAH, the growth rate Gv, serum insulin-like growth factor-1 (IGF-1) after treatment were (144.48±6.59)cm, (154.94±4.52)cm, (4.43±0.64)cm/6months, (132.25±8.84)ng/mL, compared to before treatment, the differences were statistically significant (t=6.548, P<0.01; t=5.734, P<0.01; t=28.869, P<0.01; t=20.65, P<0.01), compared with the control group, the differences were significant (t=3.943, P<0.01; t=4.759, P<0.01; t=28.247, P<0.01; t=20.882, P<0.01), there were no differences in other indices; hormones FSH, LH and other indicators of the two groups before and after treatment, and blood sugar, thyroid indicators showed no abnormality.
Conclusion
Recombinant human growth hormone in the treatment of central precocious puberty deceleration in children does not increase bone age, which will help improve the growth rate and predicted height, which worthy of clinical application.
Key words:
Human growth hormone; Gonadotropin-releasing hormone; Child development; Sex characteristics
Human growth hormone
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Article Effects of Combined Gonadotropin-Releasing Hormone Agonist and Growth Hormone Therapy on Adult Height in Precocious Puberty: A Further Contribution was published on September 1, 2003 in the journal Journal of Pediatric Endocrinology and Metabolism (volume 16, issue 7).
Triptorelin
Gonadotropin-releasing hormone agonist
Central precocious puberty
Bone maturation
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Citations (63)
Combined treatment with GH and GnRH analogs (GnRHa) has been proposed to improve final adult height in true precocious puberty, GH deficiency, and short normal subjects with early or normal timing of puberty with still controversial results. We treated 12 girls with idiopathic short stature and normal or early puberty with GH and GnRHa and followed them to adult height; 12 girls comparable for auxological and laboratory characteristics treated with GH alone served to better evaluate the efficacy of addition of GnRHa. At the start of combined treatment, the chronological age of the girls (CA; mean ± sd) was 10.2 ± 0.9 yr, bone age (BA) was 10.6 ± 1.9 yr, height sd score for BA was −1.81 ± 0.8, PAH was 146.3 ± 5.0 cm. PAH was significantly lower than target height (TH 152.7 ± 3.6 cm; P < 0.005). GH was given at a dose of 0.3 mg/kg·week, sc, 6 days weekly, and GnRHa (depot-triptorelin) was given at a dose of 100 μg/kg every 21 days, im. The 12 girls were treated with GH alone at the same dose; at the start of therapy their CA was 10.7 ± 1.0, BA was 10.1± 1.4 yr, height sd score for BA was −1.65 ± 0.8, PAH was 145.6 ± 4.4 cm, and TH was 155.8 ± 4.6 cm. Pubertal Tanner stage in both groups was B2P2 or B3P3. LHRH test and pelvic ultrasound showed the beginning of puberty. The GH response to standard provocative tests was 10 g/L or more. The mean period of treatment was 4.6 ± 1.7 yr in the group treated with GH plus GnRHa and 4.9± 1.4 yr in the group treated with GH alone; both groups discontinued treatment at comparable CA and BA. Adult height was considered to be attained when growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients in the group treated with GH plus GnRHa showed an adult height significantly higher (P < 0.001) than the pretreatment PAH (156.3 ± 5.9 vs. 146.3 ± 5 cm); the gain in centimeters calculated between pretreatment PAH and adult height was 10 ± 2.9 cm, and 7 of 12 girls had a gain over 10 cm. Target height was significantly exceeded. Height sd score for BA increased from −1.81 ± 0.8 to− 0.85 ± 1.0. The GH alone group reached an adult height higher than the pretreatment PAH (151.7 ± 2.7 vs. 145.6 ± 4.4 cm); the gain in final height vs. pretreatment PAH was 6.1 ± 4.4 cm, and 5 of 12 girls did not gain more than 4 cm. TH was even not reached. The height sd score did not significantly change. No adverse effects were observed in either group. All of the girls showed good compliance and were satisfied with the results. Our experience suggests that the combination of GH and GnRHa is significantly more effective in improving adult height than GH alone in girls with idiopathic short stature, early or normal onset of puberty, and low PAH well below the third percentile and TH. As the cost-benefit of such invasive treatment must be seriously considered, further studies are needed due to the small sample of our patients as well as in other studies reported to date.
Gonadotropin
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Combined gonadotrophin-releasing hormone analogue and recombinant human growth hormone therapy has been used in an attempt to improve the final height of short non-GH deficient adolescents with normally timed puberty; its use, however, is still controversial as only short-term studies in a very limited number of patients have been undertaken, with either improvement in height prognosis or no beneficial effect on predicted growth. We have treated a group of extremely short healthy children with very low predicted adult heights entering into normally timed puberty with combined therapy, in order to determine whether we could improve their final height above their pretreatment predicted adult height.We treated 10 healthy adolescent short children (7 girls and 3 boys) simultaneously for 30.0 +/- 5.2 months with the GnRH analogue leuprolide acetate (0.3 mg/kg im every 28 days) and with rhGH (0.1 U/kg/day, sc, 6 days a week). The mean chronological age of our patients was 11.8 +/- 1.3 years, with a mean bone age of 11.2 +/- 0.9 years, height of 128.9 +/- 7.5 cm (-2.4 +/- 0.4 SD below the mean) and a predicted adult height of 150.7 +/- 9.8 cm; they were all in Tanner stage II-III of puberty. Ten healthy short children (7 girls and 3 boys) in the early stages of puberty with a mean chronological age of 11.4 +/- 1.0 years, a mean bone age of 11.0 +/- 0.8 years, height of 128.9 +/- 7.8 cm (-2.3 +/- 0.4 SD below the mean) and a mean adult predicted height of 151.8 +/- 10.1 cm served as controls and were simultaneously followed without therapy for the same study period.Height and pubertal status were followed every 3 months during combined therapy and until final height of our patients was reached; bone ages were obtained every 6 months. Growth hormone deficiency was ruled out in all our subjects prior to beginning of the study by a normal response to oral clonidine and normal IGF-1 levels. Basal serum testosterone and/or oestradiol levels, as well as LH and FSH following administration of LH-releasing hormone were obtained before treatment and after 6 weeks and 4 months of combined therapy and every 6 months thereafter. Routine biochemistry as well as thyroid function tests were obtained at each visit.Combined treatment resulted in an interruption of pubertal development with a suppression of gonadal steroids and of the LH response to LH-releasing hormone. Growth velocity decreased from 6.5 +/- 1.6 cm/year before treatment to 5.5 +/- 1.5 cm/year and 3.9 +/- 1.3 cm/year during the first and second year of treatment (P < 0.02 and P < 0.05, respectively) resulting in a height Z score reduction, declining from -2.4 +/- 04 to -2.6 +/- 0.7 SD. Bone age maturation declined averaging 0.75 bone age year/year of treatment but height SDS for bone age declined from -1.7 +/- 0.7 to -2.2 +/- 0.5 at the end of the second year of therapy with no improvement in predicted adult height (150.7 +/- 9.8 cm before and 150.0 +/- 8.0 after 2 years of therapy). After discontinuing treatment growth velocity did not improve and bone maturation advanced more rapidly (averaging 2.0 +/- 0.4 year/year of follow up) and the mean final height of our patients was 151 +/- 2.4 cm (-2.6 +/- 0.6 SD below the mean) which was not greater than the mean pretreatment predicted adult height and well below their target height; these results were also similar to those of the control population in whom the predicted adult height at the beginning of the study and after 2 years of follow up, was not different from their final height and well below their target height.We conclude that combined rhGH and GnRH analogue therapy in short adolescents with normally timed puberty does not contribute to increase their final height above their pretreatment predicted adult height; we can therefore not recommend this form of therapy for this group of patients given the poor results obtained, as well as the cost of these medications and the
Bone maturation
Delayed puberty
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OBJECTIVE: To study the effects of treatment with gonadotropin-releasing hormone analogs (GnRHa) on final height, weight and pubertal development in girls with central precocious puberty. METHODS: Twenty-six girls with central precocious puberty were treated with GnRHa for an average of 19.2+/- 8.4 months. Pretreatment and posttreatment predicted adult heights (PAH) were evaluated based on the Bayley-Pineau table. The patients, heights and weights were measured monthly. Bone age (BA) was evaluated using Greulich-Plyle. Height standard deviation score for BA [HtSDS (BA)] was measured. After discontinuation of treatment, the patients were followed-up for the observation of height, weight, BA and menstruation. RESULTS: Final height averaged 158.0+/- 4.0 cm in the 26 girls, which was greater than their target height (155.3+/- 4.4 cm; P< 0.01) and consistent with their posttreatment PAH (158.4+/- 5.2 cm). The final height was positively corrrelated with initial height, PAH and HtSDS(BA). There was a positive correlation in the body mass index before and after treatment (r=0.724, P< 0.01). Menarche occurred 13.2+/- 6.1 months after discontinuation of treatment, with a mean menarche age of 12.2+/- 0.7 years. CONCLUSIONS: GnRHa may increase final height in girls with central precocious puberty. Their final heights may be correlated with their initial heights and PAH. The pubertal development after GnRHa treatment in girls with central precocious puberty may be matched with normal children.
Central precocious puberty
Discontinuation
Menarche
Menstruation
Bone maturation
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To evaluate the effect of combined use of stanazolol (ST) on the final adult height (FAH) in girls with idiopathic central precocious puberty (ICPP) and apparently decreased linear growth during gonadotropin-releasing hormone analog (GnRHa) therapy.Sixty-three girls with ICPP and decreased velocity of growth of height (HV<4 cm/yr) during GnRHa therapy were divided into 3 groups based on the following types of interventions:group 1 (n = 20), GnRHa+ST [25-30 µg/(kg·d) every 3-month followed by 3-month discontinuation], group 2 (n = 21), GnRHa+recombinant human growth hormone [rhGH, 1-1.1 U/(kg·w)], group 3 (n = 22), GnRHa alone.HV, the advancement of bone age (BA) for chronological age (CA) (ΔBA/ΔCA) and FAH were compared among groups.(1)Total duration of ST combination therapy was (12.22 ± 3.62) months, while total duration of combination of rhGH was (13.22 ± 6.80) months. (2)HV increased significantly in both group 1 [ (2.79 ± 0.60) cm/yr vs. (6.27 ± 1.98) cm/yr, P < 0.01] and in group 2 [(2.80 ± 0.50) cm/yr vs. (6.25 ± 1.98) cm/yr, P < 0.01] during combined therapy, but maintained at low levels in group 3 [(3.95 ± 1.10) cm/yr vs. (3.34 ± 0.95) cm/yr, P > 0.05].No significant differences of ΔBA/ΔCA were found among the three groups [0.25(0.11∼0.28), 0.22(0.15∼0.31),0.19(0.10∼0.32), P > 0.05]. (3)FAH was significantly higher than predicted adult height (PAH) before combined therapy, as well as higher than target height (THt) in both group 1 [(156.25 ± 2.90) cm vs. (150.78 ± 3.70) cm, P < 0.01, (156.25 ± 2.90) cm vs. (153.94 ± 2.62) cm, P < 0.01], and in group2 [ (157.33 ± 4.69) cm vs. (152.61 ± 3.92) cm, P < 0.01, (157.33 ± 4.69) cm vs. (154.39 ± 4.72) cm, P = 0.01].In group 3, FAH was similar to PAH [(153.88 ± 2.6) cm vs. (152.54 ± 5.86) cm, P > 0.05], and was less than THt [(153.88 ± 2.6) cm vs. (155.60 ± 4.52) cm, P = 0.02]. (4)In girls treated with ST, no hirsutism, clitorism or hoarse voice was recorded.No polycystic ovary syndrome was found by B-mode ultrasound.Intermittent combined use of low dose ST therapy can increase HV and thus improve FAH in girls with ICPP and apparently decreased linear growth during GnRHa therapy.
Discontinuation
Gonadotropin
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This study aimed to investigate the outcomes of gonadotropin-releasing hormone agonist (GnRHa) therapy with or without growth hormone (GH) therapy for girls with idiopathic central precocious puberty (CPP).The medical records of 166 girls diagnosed with CPP from 2002 to 2017 were retrospectively reviewed. All included patients were treated with GnRHa for ≥36 months. Changes in height standard deviation score (SDS) for bone age, chronological age (CA), and predicted adult height (PAH) were assessed for the first three years of treatment. The final height gain SDS was calculated as the difference between the initial PAH SDS and adult height (AH) SDS; these were then compared between the GnRHa group (group A, n=135) and the combined GnRHa/GH group (group B, n=31).The initial mean CA was 7.89 years. The mean menarcheal age was 13.12 years (group A, 13.1±0.99; group B, 13.18±0.58 years; P=0.755). PAH SDS at the start of GnRHa treatment and AH SDS were significantly lower in group B than in group A (PAH SDS: -2.20±0.83 vs. -3.19±0.84, P<0.001; AH SDS: 0.18±084 vs. -0.30±0.66, P=0.021). The increase in PAH SDS was higher in group B than in group A for the first three years of GnRHa treatment (1.66±0.66 vs. 2.35±0.93, P<0.001). The height gain SDS was significantly higher in group B than in group A (2.5±0.75 vs. 2.93±1.02, P=0.048). Younger age, higher PAH at the start of treatment, and a greater increase in PAH SDS during the first year of GnRHa treatment positively affected AH.The combined GH group had more additional height gain than the GnRHa-alone group.
Gonadotropin-releasing hormone agonist
Central precocious puberty
Gonadotropin
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Purpose:GnRH analogues(GnRHa) are used to treat central precocious puberty(CPP). However, in some patients, the GV decrease is so remarkable that it impairs predicted adult height(PAH); and there fore, the addition of growth hormone(GH) is suggested. We analysed the growth changes during two years and final adult height(FAH) in girls with idiopathic CPP treated with combined therapy, compared with those of girls treated with GnRHa alone. Methods:For the analysis, we classified the patients, who was treated for longer than two years, into three groups depending on the initial PAH and combination of GH; PAH_L, treated with GnRHa and PAH less than midparental height(MPH) - 5 cm. PAH_H, treated with GnRHa and PAH greater than MPH - 5 cm. GnRHa＋GH, combined GH treatment, regardless of PAH before treatment. We analysed the GV and PAH change during the first two years and FAH. Results:In PAH_L, the PAH(SDS) at first year of therapy was significantly increased to 153.5±6.5 cm(-1.4±1.3) from 149.7±6.4 cm(-2.1±1.3) before treatment(P=0.004). In PAH_H, there was no significant increase in PAH during the two years of treatment. During the first year of combination of GH and GnRHa, GV and PAH increased significantly. We observed significant increases in FAH, comparing to the initial PAH in the PAH_L and GnRHa＋GH groups. The height gains(FAH - initial PAH) were significantly higher in the PAH_L and GnRHa＋GH groups than that in the PAH_H group. Conclusion:This study suggests the FAH and height gains are improved in patients, whose predicted adult height before treatment was shorter than those with higher predicted adult height, with the treatment of GnRHa alone or in combination with GH. GH could not improve the final adult height, but compensated the growth in patients whose growth velocity was decelerated by GnRHa alone.
Gonadotropin-releasing hormone agonist
Central precocious puberty
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Objective To evaluate the effect of gonadotropin releasing hormone analogue (GnRHa) treatment on the actual final adult height (FH) in girls with idiopathic central precocious puberty (ICPP) and to observe the side effects.Methods Twenty-three girls with ICPP were followed for 45.0 ± 14.2 months after the discontinuation of GnRHa treatment.The FH,the time of menarche,menstrual cycle regulatory,and body mass index (BMI) were observed.The accuracy of predicted adult height (PAH) by three methods were compared.Results The 23 girls with ICPP were treated by GnRHa for (24.3 ± 13.1) months.The mean FH was (160.3 ± 4.2) cm,significantly higher than PAH before treatment (-0.01 ± 1.53 SD vs-1.58 ± 2.02 SD,P 0.01).The menarche occurred (11.5 ± 5.5) months after the discontinuation of the treatment.All girls have a regular menstrual cycle.The BMI was 20.81 ± 2.08 when the girls achieved FAH.The PAH by G-P and TW3 methods were not significantly different from FH,but both of them were significantly higher than PAH by growth curves when the treatment was discontined.Conclusions GnRHa treatment was effectively improved the FH in girls with ICPP and was no adverse effects.
Discontinuation
Central precocious puberty
Menarche
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The effect of gonadotropin-releasing hormone analogue(GnRHa) on lineafity growth and final height in 82 girls with central precocious puberty (CPP) was evaluated. The growth velocity in the second year was positively correlated with the difference value of bone age between the first year and the second year after treatment. The height standard deviation score for bone age and predicted aduh height increased after treatment. Twenty-six girls who had been followed to final height obtained better adult height than target height. GnRHa in combination with aerobic exercise increases linear growth and final height in girls with CPP.
Key words:
Gonadotropin-releasing hormone analogues; Precocious puberty; Girls; Final height
Central precocious puberty
Gonadotropin
Linear growth
Bone maturation
Growth velocity
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