goserelin and Puberty--Precocious

Topics: Buserelin; Delayed-Action Preparations; Goserelin; Humans; Puberty, Precocious

To assess the efficacy of a longer acting preparation of the gonadotrophin releasing hormone (GnRH) analogue goserelin (Zoladex LA, 10.8 mg) in 12 girls with central precocious or early puberty.. Two girls started treatment de novo; the remainder had been on suppressive treatment for a median duration of 1.5 (range, 0.2-5.6) years. Assessment comprising auxology, pubertal staging, and pelvic ultrasound examination was carried out at weeks 0, 4, 8, 10, and 12 (first cycle) and weeks 8, 10, and 12 (second cycle) to evaluate the required injection frequency. Thereafter, assessment was performed on the day of injection. Zoladex LA was given every 12 weeks unless pubertal progression occurred.. Satisfactory control was achieved in eight patients using this regimen, and three patients required more frequent injections. One girl was removed from the study because of clinical progression and extreme mood swings. No serious adverse effects occurred. Mean height velocity during the study period was 4.5 cm/year (range, 3.1-6.6) compared with 6.5 cm/year (range, 3.8-9.6) before treatment in nine patients for whom data were available.. Zoladex LA was effective in controlling precocious puberty in girls when given at intervals of 9-12 weeks and it is recommended that an initial assessment is made eight weeks after beginning treatment.

Topics: Antineoplastic Agents, Hormonal; Child; Child, Preschool; Delayed-Action Preparations; Female; Gonadotropin-Releasing Hormone; Goserelin; Growth; Humans; Ovary; Puberty, Precocious; Ultrasonography; Uterus

To compare the efficacy of goserelin and leuprolide on initial deceleration of growth and weight gain during the first 12 months of GnRH analogue treatment for precocious puberty.. Retrospective cohort analysis.. Forty children with precocious puberty treated with either goserelin or leuprolide (33 females, mean age 7.3 and 7.7 years, respectively, at the start of treatment).. The primary outcomes were baseline-to-6-months and 6-months-to-12-months change in height standard deviation score (SDS) and body mass index (BMI). Relative tall stature was calculated as the difference between height SDS and mid-parental height (MPH) SDS at baseline.. Goserelin and leuprolide were associated with similar suppression of serum LH during the first 12 months of treatment (P = 0.62). Greater relative tall stature was strongly associated with more advanced bone age, greater BMI SDS and with greater reduction in height SDS in the first 6 months. Adjusted for relative tall stature, goserelin therapy was associated with significantly greater suppression of growth than leuprolide (P = 0.025) in the first 6 months of treatment, with no subsequent change in the second 6 months. A similar, significant increase in BMI was seen with both analogues.. Both GnRH analogues were associated with effective biochemical suppression of puberty; however, goserelin was more effective at reducing linear growth during the first 6 months. Relative tall stature was a major determinant of the initial response to treatment.

Topics: Adolescent; Age Determination by Skeleton; Body Height; Child; Child, Preschool; Cohort Studies; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Infant; Leuprolide; Luteinizing Hormone; Male; Puberty, Precocious; Retrospective Studies; Time Factors; Weight Gain

Several factors can affect adult height (AH) of patients with gonadotropin-dependent precocious puberty (GDPP) treated with depot GnRH analogs.. Our objective was to determine factors influencing AH in patients with GDPP treated with depot GnRH analogs.. A total of 54 patients (45 girls) with GDPP treated with depot GnRH analog who reached AH was included in the study.. Univariate and multivariate analyses of the factors potentially associated with AH were performed in all girls with GDPP. In addition, clinical features of the girls who attained target height (TH) range were compared with those who did not. Predicted height using Bayley and Pinneau tables was compared with attained AH.. In girls the mean AH was 155.3 +/- 6.9 cm (-1.2 +/- 1 sd) with TH range achieved by 81% of this group. Multiple regression analysis revealed that the interval between chronological age at onset of puberty and at the start of GnRH analog therapy, height sd scores (SDSs) at the start and end of therapy, and TH explained 74% of AH variance. The predicted height at interruption of GnRH therapy, obtained from Bayley and Pinneau tables for average bone age, was more accurate than for advanced bone age in both sexes. In boys the mean AH was 170.6 +/- 9.2 cm (-1 +/- 1.3 SDS), whereas TH was achieved by 89% of this group.. The major factors determining normal AH in girls with GDPP treated with depot GnRH analogs were shorter interval between the onset of puberty and start of therapy, higher height SDS at the start and end of therapy, and TH. Therefore, prompt depot GnRH analog therapy in properly selected patients with GDPP is critical to obtain normal AH.

Topics: Adolescent; Adult; Body Height; Child; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Goserelin; Humans; Leuprolide; Luteinizing Hormone; Male; Puberty, Precocious; Regression Analysis; Triptorelin Pamoate

To compare the efficacy of goserelin 10.8 mg (Zoladex LA-ZLA) administered 9-12 weekly with 3.6 mg (Zoladex-Z) given monthly in suppressing pubertal development, and effect on body mass index (BMI).. Children with central precocious puberty (CPP) treated with Z (n = 34) or ZLA (n = 28) were studied retrospectively. Pubertal scores and BMI SDS during 24 months' treatment were compared.. To attain adequate pubertal suppression, more patients on ZLA than Z required increase in injection frequency (p = 0.02) and this was so for 7/8 patients with a structural aetiology for CPP on ZLA and 2/8 on Z. A greater proportion of patients on ZLA had BMI >+2 SDS before (p = 0.05), and at 18 and 24 months (p = 0.02 and 0.04). BMI SDS transiently increased during the first 6 months on ZLA (p = 0.04).. Both Z and ZLA were effective in suppressing puberty. To achieve adequate suppression, increased injection frequency was more likely with ZLA than Z, and particularly in patients with structural defects. Children with CPP had an elevated BMI at the onset of therapy and ZLA had a transient positive influence on BMI.

Topics: Body Height; Body Mass Index; Child; Delayed-Action Preparations; Drug Administration Schedule; Female; Gonadotropin-Releasing Hormone; Goserelin; Growth and Development; Humans; Male; Puberty, Precocious; Retrospective Studies; Treatment Outcome

Turner syndrome (TS) affects approximately 1 in 2000 liveborn girls. It is a common cause of short stature and is often, but not universally, associated with characteristic dysmorphic features and ovarian dysgenesis. Genotype/phenotype correlation in TS is generally poor and girls with TS may occasionally have normal functioning ovarian tissue, with approximately 30-40% entering puberty, 4% achieving menarche and 1% being fertile. In this report, we describe a girl with mosaic TS who unusually experienced spontaneous precocious puberty with associated accelerated longitudinal growth during mid childhood. This case acts as a useful clinical vignette with which to highlight important aspects of diagnosis and treatment in children with TS, particularly in relation to future growth potential and issues relating to fertility.

Topics: Body Height; Child; Child, Preschool; Female; Goserelin; Humans; Mosaicism; Puberty, Precocious; Turner Syndrome

An 8-year-old girl with idiopathic central precocious puberty experienced multiple episodes of anaphylaxis after receiving a goserelin acetate implant. She was hospitalized and treated with epinephrine, antihistamine, and corticosteroids. The goserelin implant was surgically excised; however, anaphylactic symptoms continued for 4 days after excision. Less severe systemic symptoms recurred 6 weeks after removal; these were possibly due to leakage of the depot drug into subcutaneous tissues. It was noted that 3 years earlier, the patient had developed a similar, milder systemic allergic reaction to leuprolide acetate that required treatment with oral prednisone and antihistamines. Intradermal testing yielded positive results for leuprolide. Gonadotropin-releasing hormone (GnRH) analogs, including leuprolide acetate and goserelin acetate, are commonly prescribed for patients with prostatic carcinoma, endometriosis, and precocious puberty. A literature review identified a single case report of a systemic hypersensitivity reaction involving goserelin acetate and several reports of systemic hypersensitivity reactions associated with leuprolide acetate. We found no reports of systemic reactions to GnRH analogs in pediatric patients. Clinicians should be aware of the potential association of GnRH analogs with systemic reactions. They should also recognize that recurrent anaphylaxis may occur due to the long half-life of these therapeutic agents in tissue.

Topics: Anaphylaxis; Child; Child, Preschool; Drug Hypersensitivity; Drug Implants; Drug Therapy, Combination; Female; Follicle Stimulating Hormone; Goserelin; Humans; Leuprolide; Luteinizing Hormone; Puberty, Precocious

Data concerning the effects of GnRHa on weight gain are scarce.. To assess the variation of the body mass index (BMI) in girls during GnRHa treatment for idiopathic central precocious puberty (CPP).. Semestral anthropometric data from 176 girls treated with goserelin or leuprorelin were analyzed.. BMI z-score increased from 1.5 +/- 0.1 SD before treatment (n = 176) to 1.7 +/- 0.2 SD after 24 months (n = 61, p = 0.008). In girls with normal weight before treatment, this variation was greater (n = 112, 0.2 +/- 0.1 SD, p = 0.01) than in those who were overweight (n = 63, -0.9 +/- 0.2 SD, p = 0.7). In the goserelin group the weight change adjusted for bone age was greater (n = 28, 0.4 +/- 0.1 SD) than in the leuprorelin group (n = 5, 0.04 +/- 0.1 SD, p = 0.05).. A slight increase in BMI was noted, mainly in girls with normal weight before treatment. The influence of different GnRHa on weight must be further investigated.

Topics: Body Height; Body Mass Index; Body Weight; Child; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Longitudinal Studies; Puberty, Precocious; Retrospective Studies

Following a successful clinical trial in 1996, the long-acting GnRH analogue goserelin (Zoladex LA 10.8 mg; Astra Zeneca) has been our preferred treatment for central early (CEP) or precocious puberty (CPP). However, some female patients have expressed concern about perceived weight gain during therapy and delay in the onset or resumption of menses on completion of therapy. The primary aim of this study was to investigate these concerns by determining the auxological parameters and timing of menarche or re-menarche in all girls with CEP/CPP who have completed a course of Zoladex LA treatment. The secondary aim was to assess auxological outcome in girls who have attained final height.. Case records of all girls with idiopathic CEP/CPP or CEP/CPP secondary to CNS pathology treated with Zoladex LA since 1996 were reviewed. A total of 46 girls who have completed therapy were identified, of whom 11 had reached final height. measurements Height, weight and bone age (RUS (TW2) method) were measured before treatment, when Zoladex LA was stopped and at final height. Body mass index (BMI) was calculated as a clinical measure of body fatness. Pubertal status was assessed pre- and post-treatment by Tanner staging and pelvic ultrasonography. Timing of menarche or re-menarche following cessation of treatment was recorded.. The mean (range) age of starting GnRH analogue therapy was 8.3 (1.8-10.5) years and the duration of treatment was 2.9 (0.7-8.9) years. Pre-treatment height was above average at 0.72 SD but had declined to 0.28 SD by the end of therapy. The 46 girls were heavier than average before treatment (Wt SDS 1.04) with no change in weight status on completion of therapy. Mean BMI SDS increased significantly from 0.93 to 1.2 during treatment, indicating that the girls became relatively fatter. Using recommended BMI cut-off values for defining overweight and obesity in children of the 85th and 95th centiles, 41% of the cohort were overweight and 28% were obese before treatment, rising to 59% and 39%, respectively, at the end of therapy. The average time interval to onset or resumption of menses after stopping treatment was 1.46 years (median 1.5, range 0.8-2.0 years). None of the following variables was found to be predictive of the time interval to menarche after completion of therapy: duration of treatment; chronological age; bone age; Tanner breast stage or uterine maturation at the end of treatment; the frequency of injections required to suppress puberty; or treatment with alternative GnRH analogue prior to Zoladex LA. Mean final height in 11 girls was 159.7 cm (-0.63 SD), close to the mean parental target height of 160.9 cm (-0.48 SD). Nine of the 11 girls (82%) attained final heights within or above their target range. In keeping with the whole cohort this subset of girls became fatter during treatment, although this difference was not statistically significant. However, they returned to their pretreatment size at final height (mean BMI SDS 1.18, 1.41 and 1.16 before, at the end of treatment and at final height, respectively).. Our cohort of 46 girls treated with long-acting goserelin was already considerably overweight at the start of therapy and became fatter during treatment. However, adiposity appeared to return to pretreatment levels in the 11 girls followed up to final height. Most of the girls who have attained final height are within or above their expected target range. The relatively long time interval to menarche of 1.5 years after stopping treatment is unexplained but may reflect a residual suppressive effect on the hypothalamo-pituitary axis of this long-acting GnRH analogue. Anticipation of the timing of menarche has proved to be of value in planning when to stop therapy in girls in whom treatment is mainly for practical and/or psychological reasons.

Topics: Antineoplastic Agents, Hormonal; Body Height; Child; Child, Preschool; Female; Follow-Up Studies; Goserelin; Humans; Infant; Menarche; Puberty, Precocious; Time Factors; Weight Gain

Depot GnRH analogues are widely used in the treatment of precocious puberty, or suppression of relatively early puberty where growth or psychosocial well-being may be compromised. One example is Zoladex (Z goserelin 3.6 mg), which can be given every 4 weeks. This injection frequency may not always achieve adequate suppression of pubertal signs. A long-acting form, Zoladex-LA 10.8 mg, has now been introduced with a potential duration of action of 12 weeks. In order to assess the efficacy of Zoladex-LA in gonadotrophin suppression we have measured LH and FSH responses to GnRH at diagnosis and 8 and 12 weeks after injection in a group of children treated with Zoladex-LA for central precocious or early puberty.. Forty-nine children (40 girls) with clinical evidence of central precocious puberty (CPP) or early puberty (EP) were started on Zoladex-LA, either de novo (n = 29) or on changing from Zoladex. Ages at diagnosis ranged from 1.7 to 10.6 years (median 7.8 years). Twenty-three had a structural cause with abnormality on magnetic resonance/computerized tomography (MR/CT) head scan, nine had a syndrome or nonspecific brain injury, and in 17 the cause was idiopathic.. At diagnosis, in the de novo group, median peak LH was 13.6 IU/l and median peak FSH was 12.0 IU/l. By 12 weeks gonadotrophins were suppressed to 0.9 and 0.8 IU/l, respectively. In the previously treated group, median peak LH at diagnosis was 12.8 IU/l and median peak FSH was 15.0 IU/l with suppression to 0.8 and 1.1 IU/l, respectively, at 12 weeks. In the latter group peak FSH was higher than peak LH at both 8 and 12 weeks (P < 0.05) and there was a significant rise in peak LH (P < 0.05) and FSH (P = 0.01) between 8 and 12 weeks. There was no correlation between age at diagnosis and peak LH or FSH at 8 or 12 weeks. Nevertheless, individual patients in both groups showed evidence of incomplete gonadotrophin suppression at 12 weeks.. Zoladex-LA induces a significant reduction in gonadotrophins over 12 weeks. However, there are individuals, particularly those previously on Zoladex, in whom gonadotrophin suppression is waning by 12 weeks. As found with Zoladex, some children with precocious puberty treated with Zoladex-LA may require increased injection frequency, although correlation with clinical evidence of suppression needs to be studied further.

Topics: Antineoplastic Agents, Hormonal; Child; Child, Preschool; Delayed-Action Preparations; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Goserelin; Humans; Infant; Luteinizing Hormone; Male; Pituitary Gland; Puberty, Precocious; Testosterone; Time Factors

True gigantism is rare in early childhood and is usually due to excess GH secretion from a pituitary adenoma. We report a case in which the endocrine abnormality is secondary to an optic glioma. Careful endocrine evaluation has shown that GH peak amplitude was not increased but rather there was failure of GH levels to suppress to baseline and a lack of pulsatility. There is no evidence of a direct secretory role for the tumour and we postulate that the tumour is affecting GH secretion through an effect on somatostatin tone. Specific tumour therapy is not indicated for this patient in the absence of mass effect or visual disturbance. The GH excess is being treated with somatostatin analogue (Octreotide) and as he has developed precocious puberty he is also receiving long acting GnRH analogue (Zoladex). This boy appears likely to have neurofibromatosis type 1 (NF1) which raises the question of subtle GH excess in NF1 patients with tall stature.

Topics: Adult; Child, Preschool; Gigantism; Gonadotropin-Releasing Hormone; Goserelin; Growth Hormone; Humans; Magnetic Resonance Imaging; Male; Neurofibromatosis 1; Octreotide; Optic Nerve Glioma; Puberty, Precocious; Somatostatin

The gonadotropin releasing hormone (GnRH) secreting hypothalamic hamartoma (HH) is a congenital malformation consisting of a heterotopic mass of nervous tissue that contains GnRH neurosecretory neurons attached to the tuber cinereum or the floor of the third ventricle. HH is a well recognised cause of gonadotropin dependent precocious puberty (GDPP). Long term data are presented on eight children (five boys and three girls) with GDPP due to HH. Physical signs of puberty were observed before 2 years of age in all patients. At presentation with sexual precocity, the mean height standard deviation (SD) for chronological age was +1.60 (1.27) and the mean height SD for bone age was -0.92 (1.77). Neurological symptoms were absent at presentation and follow up. The hamartoma diameter ranged from 5 to 18 mm and did not change in six patients who had magnetic resonance imaging follow up. All patients were treated clinically with GnRH agonists (GnRH-a). The duration of treatment varied from 2.66 to 8.41 years. Seven of the eight children had satisfactory responses to treatment, shown by regression of pubertal signs, suppression of hormonal levels, and improvement of height SD for bone age and predicted height. One patient had a severe local reaction to GnRH-a with failure of hormonal suppression and progression of pubertal signs. It seems that HH is benign and that GnRH-a treatment provides satisfactory and safe control for most children with GDPP due to HH.

Topics: Antineoplastic Agents, Hormonal; Child; Child, Preschool; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Hamartoma; Humans; Hypothalamic Diseases; Leuprolide; Magnetic Resonance Imaging; Male; Puberty, Precocious

A 7-year-old boy with pituitary dependent Cushing's disease was treated with pituitary irradiation following unsuccessful microadenomectomy. This led to normalization of the hypercortisolaemia, but was followed by GH deficiency. Two years after radiotherapy he had the onset of pubertal development with testicular enlargement to 8 ml bilaterally. Pubertal regression was induced using the long-acting GnRH analogue goserelin. Acceleration of skeletal maturation was also arrested, resulting in improvement of final height prediction. Irradiation directly to the hypothalamo-pituitary region, as well as whole brain irradiation, may thus be associated with accelerated pubertal development.

Topics: Child; Cushing Syndrome; Goserelin; Humans; Male; Pituitary Gland; Puberty; Puberty, Precocious

Ten girls with early puberty secondary to cranial irradiation as a part of the treatment for acute lymphoblastic leukaemia (ALL) were treated with either gonadotropin-releasing hormone analogue (GnRHa) and human growth hormone (GH) (8 girls) or with GnRHa alone (2 girls). After 4 years of treatment, height SDS for bone age was improved in the group who received combined treatment (from -0.97 to +0.07, p < 0.001), in contrast to the 2 patients who received GnRHa alone in whom height standard deviation scores for bone age decreased (from -1.10 to -1.33). Sitting height in all patients was relatively shorter than leg length, and there was no significant alteration during the 4 years of treatment.

Topics: Age Determination by Skeleton; Body Height; Brain; Child; Child, Preschool; Female; Goserelin; Growth Hormone; Humans; Infant; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Puberty, Precocious

Topics: Child; Child, Preschool; Family; Female; Goserelin; Humans; Puberty, Precocious