The final adult height in the children with true precocious puberty are destined to be short due to excessive bone maturation, compared to the growth velocity, regardless of its etiologies. To improve this final shortness, long-acting GnRH analog have been tried to the children with true precocious puberty. We evaluated the parameters of the growth. including the growth velocity, height SDS, predicted final adult height obtained by Bayley-Pinneau method in the 12 children with true precocious puberty after treatment of long-acting GnRH analog, Decapeptyl, The results were as belows; 1) The mean age of pubertal onset was 5.0 +/-2.9 year of age (1~8.6 years of age). The bone age (10.2+/-3.5 years of age) at diagnosis were significantly higher than the chronological age (7.2 +/-3.0)(Fig. 1,p<0.001). 2) During treatment with Decapeptyl, the progression of bone maturation seemed to be reduced, compared to the progression of chronological age, but there was no statistically significant difference (p>0.05). 3) The responses of LH and FSH to GnRH administration at 6 months of treatment with Decapeptyl were significantly reduced to prepubertal level, compared to those before the initiation of Decapeptyl treatment. 4) The height SDS before and at the first year of treatment with Decapeptyl were 1.5+/-0.3 and 1.4 +/-0.2, which had no significant change during treatment (Fig, 3, p>0.05). But the height velocity during the first year of treatment (4.9+/-1.7 cm/year) was significantly reduced, compared to the height velocity during the one year before treatment (10.1+/-1.5 cm/year)(Fig, 4, p=0.01). 5) The predicted final adult height, obtained by Bayley-Pinneau method, at second year of treatment (174.4 +/-1.8 cm) were significantly improved, compared to those at initial treatment (151.7 +/-2.3 cm) and 6 months of treatment (156.9+/-2.5 cm)(Fig, 5, p<0.05). 6) The predicted final adult height, obtained at the first year of treatment had significant inverse correlation with the bone age at the initiation of treatment with Decapeptyl (Fig. 6, p<0.05,r=-0.84), but had no corrleation with the chronological age at the initiation of treatment. 7) During this study, we could not find any adverse reaction, which could come with the therapy of Decapeptyl, such as facial flushing and hypotension. With these result, we can conclude that the final adult height can be improved if true precocious puberty could be diagnosed early and treatment with long-acting GnRH analog be given early.
Adult* ; Child* ; Diagnosis ; Flushing ; Gonadotropin-Releasing Hormone ; Humans ; Hypotension ; Puberty, Precocious* ; Triptorelin Pamoate

OBJECTIVE: The purpose of this study was to evaluate the endocrine response to step-up microdose GnRH agonist. METHODS: Administration of triptorelin acetate was initiated from 2 mg and gradually increased to 50 mg during 6-day period to five normal menstruating women. Serum FSH, LH, and estradiol levels were serially measured for 6 days. The same set of experiment was duplicated after taking oral contraceptive for 3 weeks. Serum testosterone and progesterone levels were measured on day 1 and day 5 of experiment. RESULTS: The flare of gonadotropin continued for 6 days. When subjects were pretreated with oral contraceptive, serum FSH levels 4 hrs after GnRH agonist injection were 17.35+/-7.88 mIU/mL, 11.26+/-4.81 mIU/mL, and 9.60+/-4.08 mIU/mL for day 1, 2, and 3 respectively. The FSH levels were not statistically different when pretreatment with oral contraceptive was not applied. The level of serum LH was significantly lower in the cycle, which was pretreated by oral contraceptive (32.13+/-9.61 mIU/mL vs. 14.12+/-5.63 mIU/mL for day 1, 28.95+/-3.09 mIU/mL vs. 15.76+/-9.92 mIU/mL for day 2, and 24.45+/-2.52 mIU/mL vs. 16.86+/-8.56 mIU/mL for day 3). The sign of corpus luteum rescue was found in 2 out of 5 subjects only in non-treated cycle. CONCLUSION: Step-up microdose GnRH agonist protocol could induce persistent gonadotropin flare for 6 days and this regimen could be applied in controlled ovarian hyperstimulation especially for poor responders. The pretreatment with oral contraceptive is necessary to prevent supraphysiologic LH elevation and corpus luteum rescue.
Corpus Luteum ; Estradiol ; Female ; Gonadotropin-Releasing Hormone* ; Gonadotropins ; Humans ; Progesterone ; Testosterone ; Triptorelin Pamoate

PURPOSE: The objective of this study was to evaluate the effect of gonadotropin releasing hormone analog (GnRHa) treatment on bone mineral density (BMD) in girls with central precocious puberty (CPP). Further we investigated the differences in the effect on BMD by using the GnRHa leuprolide-acetate and triptorelin. METHODS: Sixty-one females with CPP were enrolled in the study, the lumbar spine BMD was measured by dual energy x-ray absorptiometry before treatment, after one year (n = 61) and after two years (n = 24) of treatment. Lumbar spine BMD standard deviation scores (SDS) were compared according to chronological age (CA) and bone age (BA) for the whole group, as well as for the group A, treated with leuprolide-acetate (n = 40), and the group B, treated with triptorelin (n = 21). RESULTS: All subjects showed significant increment in BMD during treatment (P < 0.05). Lumbar spine BMD SDS for CA and BA showed no significant changes before and during treatment. Group A and group B, within each group, showed no significant changes in lumbar spine BMD SDS for CA and BA during treatment. CONCLUSION: Our study suggests that lumbar spine BMD was not impaired in girls treated with GnRHa for CPP and both leuprolide-acetate and triptorelin showed comparable effects on lumbar spine BMD during treatment.
Absorptiometry, Photon ; Bone Density ; Female ; Gonadotropin-Releasing Hormone ; Humans ; Leuprolide ; Piperazines ; Puberty, Precocious ; Spine ; Triptorelin Pamoate

Long-acting formulations of gonadotropin-releasing hormone (GnRH) agonists are indicated for treating central precocious puberty. Leuprolide acetate and triptorelin acetate are widely used in Korea. Local reactions related to GnRH agonists, including erythematous macules, granulomas, subcutaneous nodules, and sterile abscesses, are the most side effects and sterile abscesses occur in less than 2-3% of treated patients. We report on two patients who had been injected with leuprolide acetate for the treatment of central precocious puberty and who subsequently presented with a sterile abscess at the injection sites. After the patients were switched to triptorelin acetate, one patient had another subcutaneous abscess at the injection site, and the other patient had no further problems. There are many theories as to the cause of these local reactions, but the mechanism has still not been elucidated. Further studies are required to identify the mechanism and the relationship between treatment effect and local reaction.
Abscess ; Gonadotropin-Releasing Hormone ; Granuloma ; Humans ; Korea ; Leuprolide ; Puberty, Precocious ; Triptorelin Pamoate

Long-acting formulations of gonadotropin-releasing hormone (GnRH) agonists are indicated for treating central precocious puberty. Leuprolide acetate and triptorelin acetate are widely used in Korea. Local reactions related to GnRH agonists, including erythematous macules, granulomas, subcutaneous nodules, and sterile abscesses, are the most side effects and sterile abscesses occur in less than 2-3% of treated patients. We report on two patients who had been injected with leuprolide acetate for the treatment of central precocious puberty and who subsequently presented with a sterile abscess at the injection sites. After the patients were switched to triptorelin acetate, one patient had another subcutaneous abscess at the injection site, and the other patient had no further problems. There are many theories as to the cause of these local reactions, but the mechanism has still not been elucidated. Further studies are required to identify the mechanism and the relationship between treatment effect and local reaction.
Abscess ; Gonadotropin-Releasing Hormone ; Granuloma ; Humans ; Korea ; Leuprolide ; Puberty, Precocious ; Triptorelin Pamoate

OBJECTIVES: The microdose of gonadotrophin-releasing hormone agonist (GnRHa) has been suggested as a beneficial method of ovulation induction for poor responders. However, the effect of microdose of GnRHa itself has not been evaluated yet. We performed a prospective sutdy to assess the effect of microdose of GnRHa (5 microgram of triptorelin acetate) on the luteinizing hormone (LH) and follicle stimulating hormone (FSH). Secondary objective of this study is to assess how long the down-regulation of gonadotrophin secretion by microdose GnRHa persists. METHODS: Five microgram of triptorelin was injected daily into five normally menstruating women for 7 days starting from cycle day 3. The blood sample was drawn for 12h with 4h interval, then for 6days with 4 h interval and once a day for 14days, In next cycle, same amount of triptorelin was injected into the same subjects daily for 3 days. The blood sample was drawn twice a day for 20days. Serum FSH, LH and extradiol level was measured. RESULTS: The serum LH and FSH level increased rapidly after injection of first GnRHa. The FSH level reached peak (27.53+/-6.34 IU/l) in 5h while LH level reached peak (34.35+/-7.18 IU/l) in 4h. The flare of gonadotrophins persisted even after second and third day injection of GnRHa, although the peak levels were not as high as first injection. The down regulation of gonadotrophin was established in 4-5 days. The estradiol level increased for 4-5 days then decreased. When GnRHa was given for 7days, the estradiol level began to rise 7-8 days after last injection; when given for 3days, the estradiol level began to rise 3-6 days after last injection. CONCLUSION: Even with ultra-low dose of GnRHa, the down-regulation of gonadotrophin could be achieved. The flare-up of gonadotrophin would persist for 3days with this dose. The duration of down regulation was influenced by the duration of GnRHa administration.
Down-Regulation ; Estradiol* ; Female ; Follicle Stimulating Hormone ; Gonadotropin-Releasing Hormone* ; Gonadotropins* ; Humans ; Luteinizing Hormone ; Ovulation Induction ; Prospective Studies ; Triptorelin Pamoate

OBJECTIVETo investigate the values of single or repeated luteinizing hormone (LH) releasing hormone analogue (triptorelin) stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism (IHH) and constitutional delayed puberty (CDP).

METHODSMale patients (n = 133) without puberty onset after the age of 14 were recruited for triptorelin stimulating test and were followed up for 24 - 48 months until the diagnosis were confirmed: 86 were IHH and the other 47 were CDP. Repeated triptorelin stimulating tests were conducted in 9 IHH patients and 13 CDP patients one year after the first stimulating tests with an attempt to evaluate the dynamic change of hypothalamus-pituitary-testis axis function. The relationship between the final diagnosis and the peak LH value (LH(max)), and the changes of repeated LH(max) were investigated.

RESULTSIn the single triptorelin stimulating test, LH(max) was (1.9 +/- 1.2) U/L in IHH group, which was significantly lower than that in CDP group [(13.7 +/- 8.3) U/L] (P < 0.01); 75 IHH patients (87.2%) had a LH(max) lower than 4 U/L, while only 2 CDP patients (4.3%) had a LH(max) lower than 4 U/L. When LH(max) < 4U/L was used as a criteria for the diagnosis of IHH, the single triptorelin stimulating test had a sensitivity of 87.2%, a specificity of 95.7%, and a positive predictive value of 97.4%. The repeated triptorelin stimulating tests performed one year later showed that the LH(max) in the 9 IHH patients increased from (4.7 +/- 2.5) U/L to (5.1 +/- 3.3) U/L (P = 0.78), while that in the 13 CDP patients increased from (10.7 +/- 3.3) U/L to (24.5 +/- 5.7) U/L (P < 0.05).

CONCLUSIONSA single triptorelin stimulating test is highly effective in differentiating IHH from CDP. For some patients without definitive diagnosis, a repeated triptorelin stimulating test performed one year later may provide more valuable information on the dynamic change of the hypothalamus-pituitary-testis axis function.

Adolescent ; Adult ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Hypogonadism ; diagnosis ; Male ; Puberty, Delayed ; diagnosis ; Triptorelin Pamoate ; Young Adult

The McCune-Albright Syndrome is characterized by polyostotic fibrous dysplasia, cafe-au-lait colored patches of the skin and endocrinological abnormalities, including precocious puberty. Affected patients progress from GnRH-independent puberty to GnRH-dependent puberty. GnRH analogues are ineffective in GnRH-independent precocious puberty. Three year and 2 month old girl with breast development(SMR B3) and irregular vaginal bleeding were seen & diagnosed as incomplete sexual precocity. Decapeptyl treatment was started for the purpose of regression of breast development & vaginal bleeding with no effect. After 10 months, cafe-au-lait skin lesion & polyostotic fibrous dysplasia were noted and diagnosed as McCune-Albright syndrome. Breast development regressed to SMR B2 and vaginal bleeding was controlled with ketoconazole. As our experience, ketoconazole treatment might be effective to delay the progression of sexual development in patients with precocious puberty in McCune-Albright Syndrome.
Adolescent ; Breast ; Female ; Fibrous Dysplasia, Polyostotic* ; Gonadotropin-Releasing Hormone ; Humans ; Infant ; Ketoconazole* ; Puberty ; Puberty, Precocious ; Sexual Development ; Skin ; Triptorelin Pamoate ; Uterine Hemorrhage

PURPOSE:Precocious puberty is the development of secondary sexual characteristics before the age of 8 years in girls and 9.5 years in boys. It is usually associated with premature, rapid skeletal maturation and closure of the epiphyseal plates, resulting in short stature compared with genetic height potential and can produce significant psychological distress for patients. We examined effects of treatment with long-acting gonadotropin-releasing hormone(GnRH) agonist on somatic and skeletal growth in patients with central precocious puberty(CPP). MATERIALS & METHODS:Two male and seven female patients were diagnosed as having central precocious puberty(CPP) on the basis of onset age of secondary sexual characteristics, bone age, results of GnRH stimulation test and levels of sex hormones. They were treated with Triptorelin or Leuprorelin acetate(80-100ug/kg, IM every 4 weeks) for 1 year. The patients have been analyzed in terms of changes in auxological parameters including height velocity(HV), HV SDS CA, height SDS CA, height SDS BA and predicted adult height(PAH) SDS before and 1 year after treatment with GnRH agonist. RESULTS:The growth velocity a year after treatment was decreased to 4.1+/-0.9 from 7.5+/-1.2cm/year(P<0.01) and the height velocity standard deviation score(SDS) for chronologic age decreased to -1.6+/-0.4 from 2.8+/-0.8(P<0.01). The height SDS for chronologic age was increased to 2.0+/-0.7 from 3.8+/-1.0 a year after treatment (P<0.01). However, no significant difference were observed in height SDS for bone age(-1.9+/-0.2 from -2.1+/-0.3)(p>0.05) and predicted adult height SDS(-2.2+/-0.5 from -2.3+/-0.4)(p>0.05) one year after treatment. CONCLUSION: We observed a remarkable growth deceleration a year after treatment with GnRH agonist in CPP patients. However, the results of this study shows no benefit of GnRH agonist treatment in improving predicted adult height. It is still not clear whether GnRH agonist treatment will eventually help the patients with CPP achieve a final adult height within the range of their genetic target height or not. Further extensive long-term study using strict selection criteria for GnRH agonist treatment is required to address this issue.
Adolescent ; Adult ; Age of Onset ; Deceleration ; Female ; Gonadal Steroid Hormones ; Gonadotropin-Releasing Hormone* ; Growth Plate ; Humans ; Leuprolide ; Male ; Patient Selection ; Puberty ; Puberty, Precocious* ; Triptorelin Pamoate

PURPOSE: Long-acting gonadotropin-releasing hormone agonists (GnRHa) are commonly used to treat central precocious puberty (CPP) in Korea. Although rare, there have been reports on the characteristic of adverse reactions of GnRHa in CPP among the Korean population. This study was intended to report on our clinical experience regarding significant adverse reactions to long-acting GnRHa in CPP and early onset puberty and to evaluate the prevalence rate of serious side effects. METHODS: This retrospective study included children with CPP and early onset puberty, who were administered monthly with long-acting GnRHa (leuprolide acetate, triptorelin acetate) at the outpatient clinic of Department of Pediatrics, at Inha University Hospital, between January 2011 and December 2013. We analyzed the clinical characteristics of patients who experienced significant adverse reactions and evaluated the prevalence rate. RESULTS: Six serious side effects (0.9%) were observed among total of 621 CPP and early onset puberty children with GnRHa therapy. The number of sterile abscess formation was four in three patients (4 events of 621). Anaphylaxis occurred in only one patient, and unilateral slipped capital femoral epiphysis (SCFE) in another one patient. Anaphylaxis occurred after the 6th administration of the monthly depot triptorelin acetate. Unilateral SCFE developed in GnRHa therapy. CONCLUSION: Sterile abscess formation occurred in 0.6% of CPP and early onset puberty patients from the administration of a monthly depot GnRHa therapy. The occurrences of anaphylaxis and SCFE are extremely rare, but can have serious implications on patients. Clinicians should be aware of these potential adverse effects related to GnRHa therapy in CPP.
Abscess ; Adolescent ; Ambulatory Care Facilities ; Anaphylaxis ; Child ; Drug-Related Side Effects and Adverse Reactions ; Gonadotropin-Releasing Hormone* ; Humans ; Korea ; Leuprolide ; Pediatrics ; Prevalence ; Puberty* ; Puberty, Precocious* ; Retrospective Studies ; Slipped Capital Femoral Epiphyses ; Triptorelin Pamoate