Treatment Of Central Precocious Puberty Research Articles

Changes in body mass index during gonadotropin-releasing hormone agonist treatment for central precocious puberty and early puberty.

Gonadotropin-releasing hormone agonists (GnRHa) have been widely used for decades to treat patients with central precocious puberty (CPP). Several studies have investigated changes in body composition in patients with CPP following GnRHa treatment, but the results are inconsistent. The aim of this study was to investigate changes in body mass index (BMI) in children treated with GnRHa for 2 years. We also assessed whether BMI affects treatment outcomes. This study included 383 girls (214 girls with central precocious puberty and 169 girls who underwent early puberty) treated with depot leuprolide acetate monthly for at least 2 years. We analyzed changes in BMI standard deviation score (SDS). Furthermore, blood luteinizing hormone (LH) levels were determined 30 min after depot leuprolide acetate administration every 6 months to evaluate adequate suppression of the hypothalamic-pituitary-gonadal axis. Pretreatment mean BMI SDS values were 0.07 ± 0.69, 1.29 ± 0.16, and 1.95 ± 0.32 in the normal weight, overweight, and obese subjects, respectively. Mean BMI SDS values after 2 years of treatment increased significantly only in normal weight children (0.07 ± 0.69 vs. 0.25 ± 0.73, P < 0.001). LH levels 30 min after leuprolide injection after 2 years of treatment were not different among normal weight, overweight, and obese subjects. Although the difference in BMI SDS was relatively small, it standard deviation score increased significantly after 2 years of treatment in normal weight girls with early pubertal development.

Cognitive, Emotional, and Psychosocial Functioning of Girls Treated with Pharmacological Puberty Blockage for Idiopathic Central Precocious Puberty.

Central precocious puberty (CPP) develops due to premature activation of the hypothalamic-pituitary-gonadal (HPG) axis, resulting in early pubertal changes and rapid bone maturation. CPP is associated with lower adult height and increased risk for development of psychological problems. Standard treatment of CPP is based on postponement of pubertal development by blockade of the HPG axis with gonadotropin releasing hormone analogs (GnRHa) leading to abolition of gonadal sex hormones synthesis. Whereas the hormonal and auxological effects of GnRHa are well-researched, there is a lack of knowledge whether GnRHa treatment influences psychological functioning of treated children, despite the fact that prevention of psychological problems is used as one of the main reasons for treatment initiation. In the present study we seek to address this issue by exploring differences in cognitive function, behavior, emotional reactivity, and psychosocial problems between GnRHa treated CPP girls and age-matched controls. Fifteen girls with idiopathic CPP; median age 10.4 years, treated with slow-release GnRHa (triptorelin acetate—Decapeptyl SR® 11.25) and 15 age-matched controls, were assessed with a comprehensive test battery consisting of paper and pencil tests, computerized tasks, behavioral paradigms, heart rate variability, and questionnaires filled in by the children's parents. Both groups showed very similar scores with regard to cognitive performance, behavioral and psychosocial problems. Compared to controls, treated girls displayed significantly higher emotional reactivity (p = 0.016; Cohen's d = 1.04) on one of the two emotional reactivity task conditions. Unexpectedly, the CPP group showed significantly lower resting heart rates than the controls (p = 0.004; Cohen's d = 1.03); lower heart rate was associated with longer treatment duration (r = −0.582, p = 0.037). The results suggest that GnRHa treated CPP girls do not differ in their cognitive or psychosocial functioning from age matched controls. However, they might process emotional stimuli differently. The unexpected finding of lower heart rate that was associated with longer duration of the treatment should be further explored by methods appropriate for assessment of cardiac health.

Central precocious puberty: revisiting the diagnosis and therapeutic management.

Clinical and laboratory diagnosis and treatment of central precocious puberty (CPP) remain challenging due to lack of standardization. The aim of this revision was to address the diagnostic and therapeutic features of CPP in Brazil based on relevant international literature and availability of the existing therapies in the country. The diagnosis of CPP is based mainly on clinical and biochemical parameters, and a period of follow-up is desirable to define the "progressive" form of sexual precocity. This occurs due to the broad spectrum of pubertal development, including isolated premature thelarche, constitutional growth and puberty acceleration, progressive and nonprogressive CPP, and early puberty. Measurement of basal and stimulated LH levels remains challenging, considering that the levels are not always in the pubertal range at baseline, short-acting GnRH is not readily available in Brazil, and the cutoff values differ according to the laboratory assay. When CPP is suspected but basal LH values are at prepubertal range, a stimulation test with short-acting or long-acting monthly GnRH is a diagnostic option. In Brazil, the treatment of choice for progressive CPP and early puberty is a long-acting GnRH analog (GnRHa) administered once a month or every 3 months. In Brazil, formulations of GnRHa (leuprorelin and triptorelin) are available and commonly administered, including 1-month depot leuprorelin 3.75 mg and 7.5 mg, 1-month depot triptorelin 3.75 mg, and 3-month depot leuprorelin 11.25 mg. Monthly or 3-month depot GnRHa are effective and safe to treat CPP. Arch Endocrinol Metab. 2016;60(2):163-72.

MANAGEMENT OF ENDOCRINE DISEASE: Long-term outcomes of the treatment of central precocious puberty.

GnRH analogues (GnRHa) are the treatment of choice for central precocious puberty (CPP), with the main objective to recover the height potential compromised by the premature fusion of growth cartilages. The aim of this review was to analyze long-term effects of GnRHa on height, body weight, reproductive function, and bone mineral density (BMD) in patients with CPP, as well as the potential predictors of outcome. Because randomized controlled trials on the effectiveness and long-term outcomes of treatment are not available, only qualified conclusions about the efficacy of interventions can be drawn. GnRHa treatment appears to improve adult height in girls with CPP, especially if diagnosed before the age of 6, whereas a real benefit in terms of adult height is still controversial in patients with the onset of puberty between 6 and 8 years of age. No height benefit was shown in patients treated after 8 years. Gonadal function is promptly restored in girls after cessation of treatment, and reproductive potential appears normal in young adulthood. Data are conflicting on the long-term risk of polycystic ovarian syndrome in both treated and untreated women. Fat mass is increased at the start of treatment but normalizes thereafter, and GnRHa itself does not seem to have any long-term effect on BMI. Similarly, analogue treatment does not appear to have a negative impact on BMD. Owing to the paucity of data available, no conclusions can be drawn on the repercussions of CPP and/or its treatment on the timing of menopause and on the health of the offspring.

Experience with the Histrelin Implant in Pediatric Patients.

The histrelin implant has emerged as a therapeutic option for the treatment of central precocious puberty that has been favorably received by patients and providers. Inserted subcutaneously, the 50-mg implant provides continuous release of the potent gonadotropin-releasing hormone analog (GnRHa) histrelin. Profound suppression of the hypothalamic-pituitary-gonadal (HPG) axis occurs within 1 month of its placement resulting in pubertal arrest, attenuation of skeletal advancement and a progressive increase in predicted adult height. Although marketed for annual use, suppression lasting 2 years from a single implant has been demonstrated. Placing and removing the device is a minor outpatient procedure easily accomplished by a pediatric surgeon using local anesthesia. The major downside to the implant is a ∼25% rate of breakage upon removal. Information about the recovery of the HPG axis following histrelin explantation is limited but suggests an average time to menarche comparable with depot GnRHa formulations albeit with wide individual variation.

Central precocious puberty following the diagnosis and treatment of paediatric cancer and central nervous system tumours: presentation and long-term outcomes.

To estimate the prevalence of central precocious puberty (CPP) after treatment for tumours and malignancies involving the central nervous system (CNS) and examine repercussions on growth and pubertal outcomes. Retrospective study of patients with tumours near and/or exposed to radiotherapy to the hypothalamus/pituitary axis (HPA). Patients with CPP were evaluated at puberty onset, completion of GnRH agonist treatment (GnRHa) and last follow-up. Multivariable analysis was used to test associations between tumour location, sex, age at CPP, GnRHa duration and a diagnosis of CPP with final height <-2SD score (SDS), gonadotropin deficiency (LH/FSHD) and obesity, respectively. Eighty patients (47 females) had CPP and were followed for 11·4 ± 5·0 years (mean ± SD). The prevalence of CPP was 15·2% overall, 29·2% following HPA tumours and 6·6% after radiotherapy for non-HPA tumours. Height <-2SDS was more common at the last follow-up than at the puberty onset (21·4% vs 2·4%, P = 0·005). Obesity was more prevalent at the last follow-up than at the completion of GnRHa or the puberty onset (37·7%, 22·6% and 20·8%, respectively, P = 0·03). Longer duration of GnRHa was associated with increased odds of final height <-2SDS (OR = 2·1, 95% CI 1·0-4·3) and longer follow-up with obesity (OR = 1·3, 95% CI 1·1-1·6). LH/FSHD was diagnosed in 32·6%. There was no independent association between CPP and final height <-2SDS, and LH/FSHD and obesity in the subset of patients with HPA low-grade gliomas. Patients with organic CPP experience an incomplete recovery of growth and a high prevalence of LH/FSHD and obesity. Early diagnosis and treatment of CPP may limit further deterioration of final height prospects.

Severe allergic reaction following histrelin implant (Supprelin LA)

The histrelin implant (Supprelin LA) is an efficacious, safe and well tolerated medication for the treatment of central precocious puberty (CPP). Minor reactions such as bruising, redness, and pain at the implant site have commonly occurred, but only two cases of systemic allergic reaction leading to emergent removal of device have previously been reported. An otherwise healthy eleven-year-old female with CPP and no history of prior supprelin implantation, and a nine-year-old female with CPP and history of two prior supprelin implantations without complications, had a supprelin implant inserted on the same day. Within days of the procedure both presented with severe allergic reaction and underwent removal of the device. A few months after removal, both children had another supprelin implant placed without complications. It was determined that the device was not the cause of the allergic reaction, but rather the dressing material included in the implantation kit that was the offending agent. This report describes two patients with a severe systemic allergic reaction after histrelin implant necessitating urgent implant removal with resolution of allergic symptoms. It was later determined that the allergic reaction was caused by a substance in the self-adhering dressing wrap.

Central precocious puberty: consider early treatment with gonadotropin-releasing hormone analogues to preserve maximum height

The primary objective in the treatment of central precocious puberty is preservation of final adult height, with the greatest treatment benefit shown in children who are younger at the onset on the condition. Gonadotropin-releasing hormone analogues, the gold-standard treatment, are available in a range of preparations and delivery systems, with recent options having the benefit of less frequent dosing and potentially improved compliance.

Gonadotropin-Releasing Hormone Agonist Therapy and Obesity in Girls.

Background:Depot preparations of gonadotropin-releasing hormone agonists (GnRHa) are the gold standard drugs for the treatment of central precocious puberty. A concern about these drugs is obesity.Objectives:This study aimed to investigate the effect of gonadotropin-releasing hormone agonists (GnRHa) therapy on body mass index (BMI) in girls with central precocious puberty (CPP).Patients and Methods:The girls with onset of puberty before eight years of age or menarche before nine years of age were studied. The weight, height, BMI, and pubertal stage were determined before and at sixth and 12th months of treatment. The GnRHa (Triptorelin) was administered intramuscularly for patients with rapidly progressive forms of CPP. Patients with slowly progressive forms of CPP were considered as control group.Results:From 110 subjects with CPP, 46 girls (41.8%) were considered as intervention and 64 (58.2%) as control groups. The mean age at initial visit was 7.46 ± 1.03 years. The BMI standard deviation scores in both groups was not significantly different at sixth and 12th months of treatment compared with baseline (P = 0.257 and P = 0.839, respectively). The prevalence of obesity was not significantly different between study groups at baseline and at and sixth and 12th months of therapy (P = 0.11, P = 0.068, and P = 0.052, respectively).Conclusions:The GnRHa therapy has no effect on BMI and the prevalence of obesity.

Bird's-Eye View of GnRH Analog use in a Pediatric Endocrinology Referral Center

Gonadotropin-releasing hormone analogs (GnRHa) are standard of care for the treatment of central precocious puberty (CPP). GnRHa have also been prescribed in other clinical settings with the hope of increasing adult stature, although evidence to support this practice is lacking. The degree to which GnRHa are being prescribed for indications other than CPP in routine clinical care has not been described. We sought to systematically examine GnRHa prescribing practices among the pediatric endocrinologists at our academic medical center. We reviewed medical records of children treated with GnRHa during a 6-year interval. Variables analyzed included gender, age at start of treatment, indication for therapy, and use of growth hormone as adjunctive treatment. Nonparametric analyses were utilized to compare treatment characteristics of those with CPP versus those without. A total of 260 patients (82% female) aged 8.06 ± 2.68 years were identified. Of these, 191 (73.5%) were treated for CPP, whereas 69 (26.5%) were treated for normally timed puberty in the context of idiopathic short stature/poor predicted height (n = 37), growth hormone deficiency (n = 17), congenital adrenal hyperplasia (n = 10), primary hypothyroidism (n = 4), and developmental delay (n = 1). Of the 161 girls with CPP, GnRHa therapy was initiated at ≥8 years of age in 62 (39%). Whereas most patients were treated for CPP, ~27% were treated for other indications. Of girls with CPP, 39% were treated at an age when benefit in terms of height is unlikely. This highlights the need for rigorous studies of GnRHa use for indications beyond CPP.

Treatment of Central Precocious Puberty Using Gonadotropin-releasing Hormone Agonists

Precocious puberty is treated with gonadotropin-releasing hormone agonists (GnRHa). In this study we describe our clinical experience with pubertal suppression from GnRHa, using monthly and 3-monthly formulations. A retrospective chart review for the period between 2006 and 2010 was done for 64 patients who were undergoing treatment for central precocious puberty. Two treatment cohorts were observed for 2+ years. Pubertal suppression was inadequate for 14 of 38 children (37%) on GnRHa given monthly and for 2 of 26 (8%) children given GnRHa every 3 months. Based on our findings of adequate pubertal suppression, decreased frequency of injections, and fewer facility visits, we consider GnRHa 3-monthly injection to be first-line therapy.

A Gonadotropin-Releasing Hormone (GnRH) Stimulation Test Before and After GnRH Analogue Treatment for Central Precocious Puberty: Has the GnRH Test been Adequately Simplified?

To investigate and simplify the gonadotropin-releasing hormone (GnRH) stimulation test for assessing pubertal activation and suppression. The authors identified 72 girls diagnosed with central precocious puberty who were treated with a GnRH analogue (GnRHa). Patients who underwent an assessment regarding GnRHa-mediated puberty suppression had been diagnosed via the GnRH stimulation test prior to GnRHa treatment. The authors analyzed the diagnostic values of the during/before-treatment LH levels at different time points by a receiver-operating characteristic (ROC) curve. Before GnRHa treatment, the mean luteinizing hormone (LH) level was higher at the 30-min test time point than at baseline or the 15, 60, 90, and 120-min points (P < 0.001). After GnRHa treatment, the LH levels were suppressed in 62 patients (86.1%) and inadequately suppressed in 10 (13.9%). The LH level was higher at the 30-min test time point than those at baseline or the 45 and 60-min level (P < 0.001). The area under the curve in a post-GnRHa treatment was greatest at 30min. The simplified GnRH test is adequate for evaluating pubertal activation (30 and/or 45-min time points of the GnRH test) and suppression (the 30-min time point).

Central Precocious Puberty: Update on Diagnosis and Treatment.

Central precocious puberty (CPP) is characterized by the same biochemical and physical features as normally timed puberty but occurs at an abnormally early age. Most cases of CPP are seen in girls, in whom it is usually idiopathic. In contrast, ~50% of boys with CPP have an identifiable cause. The diagnosis of CPP relies on clinical, biochemical, and radiographic features. Untreated, CPP has the potential to result in early epiphyseal fusion and a significant compromise in adult height. Thus, the main goal of therapy is preservation of height potential. The gold-standard treatment for CPP is gonadotropin-releasing hormone (GnRH) analogs (GnRHa). Numerous preparations with a range of delivery systems and durations of action are commercially available. While the outcomes of patients treated for CPP have generally been favorable, more research about the psychological aspects, optimal monitoring, and long-term effects of all forms of GnRHa treatment is needed. Several potential therapeutic alternatives to GnRHa exist and await additional investigation.

Histrelin for central precocious puberty—a single surgeon experience

BackgroundThe most common cause of precocious puberty is idiopathic central precocious puberty (CPP), which is usually treated with monthly injections. An alternative treatment of precious puberty is a subcutaneous implant that contains histrelin acetate, which is continuously released for more than 1 y and then removed or replaced with a new implant. MethodsThe aim of this study was to conduct a retrospective review of one surgeon's experience with the histrelin implant and to examine patient satisfaction. After obtaining institutional review board approval, the charts of all children who had undergone at least one implant were reviewed. ResultsFifty-eight children, average age 8.4 y old (range 7–14), underwent at least one histrelin implant insertion for treatment of CPP. Parents of 44 patients were able to be reached by telephone for this study and rated the histrelin implant treatment highly. All implants were placed, replaced, or removed without significant difficulty, and there were no complications. ConclusionsThis study suggests that the use of a histrelin subcutaneous implant for control of CPP is a safe and effective method for the treatment of this condition.

Psychological assessment of mothers and their daughters at the time of diagnosis of precocious puberty.

BackgroundConcerns about psychological distress are often used to justify treatment of girls with precocious puberty, but there is little evidence to support these concerns. The extent to which psychological problems are associated with central precocious puberty (CPP) compared with other forms of early puberty in girls has likewise not been established.MethodsGirls presenting with untreated CPP, premature adrenarche (PA) or early normal puberty (ENP) were recruited from our pediatric endocrine clinic along with their mothers. Child psychological adjustment was assessed by child self-report and parent report. Parent self-reported personality, anxiety, and depression were also assessed. Differences between groups were explored using one-way ANOVA and Dunnett’s T3 test.ResultsSixty-two subjects (aged 7.5 ± 1.4 years, range 4.8-10.5) were enrolled, of whom 19 had CPP, 22 had PA, and 21 had ENP. Girls with ENP were significantly older (8.9 ± .9 years) than girls with CPP (6.9 ± 1.1 years, p < .001) and PA (6.6 ± 1.0 years, p < .001). Girls with PA had significantly higher BMI z-scores (1.7 ± .8) than girls with CPP (1.1 ± .6, p = .01) and ENP (1.2 ± .6, p = .04). More girls with PA and ENP were from racial minorities (47% and 50% respectively) than girls with CPP (32%). No group differences were found for any child measure of psychological adjustment. However, mothers of girls with PA scored significantly higher than mothers of girls with ENP on one measure of depression (p = .04) and stress (p = .01).ConclusionsWhile mothers of girls with PA report increased psychological distress on some measures, no differences in psychological adjustment were found at baseline amongst the girls themselves. Whether these results will change as puberty progresses in the PA and ENP groups or with treatment of CPP is unknown. Long-term prospective studies are needed in order to further investigate psychological correlates of early puberty in girls.

An Examination of the Effects of Leuprolide Acetate Used in the Treatment of Central Precocious Puberty on Bone Mineral Density and 25-Hydroxy Vitamin D.

Leuprolide acetate is a gonadotropin-releasing hormone (GnRH) analogue frequently used in the treatment of central precocious puberty. Research is currently taking place into its effects on endocrine systems. The aim of this study is to investigate the effect of leuprolide acetate on vitamin D and bone mineral density. Twenty-three children diagnosed with central precocious puberty and receiving leuprolide acetate therapy for at least 12 months, and a control group of 17 healthy children were enrolled. In the study group, calcium, phosphorus, alkaline phosphatase, parathormone and 25-hydroxy vitamin D levels and bone mineral density were measured. The results were compared with those of the control group. 25-Hydroxy vitamin D levels in the study and control groups were 15.17 ± 7 mg/dL and 22.2 ± 6.1 mg/dL, respectively (p < 0.05). In terms of bone mineral density, osteopenia was determined in 13 (56.5%) patients in the study group and osteoporosis in one (4.3%), while osteopenia was identified in seven patients in the control group, with no osteoporosis being identified (p > 0.05). Gonadotropin-releasing hormone agonists may have an adverse effect on bone health. They may exhibit these effects by impacting on vitamin D levels. These levels should be periodically monitored in patients receiving treatment, and vitamin D support should be given in cases where the deficiency is identified.

Treatment of central precocious puberty and early puberty with GnRH analog in girls with Williams-Beuren syndrome.

Little has been published on treatment of precocious puberty in girls with Williams-Beuren syndrome (WBS), a condition occurring frequently in this group. We analyzed our own data on growth/age at menarche of now adult female patients with WBS being diagnosed with central precocious puberty or early puberty. Data of patients treated with gonadotropin-releasing hormone (GnRH) analog (n=13) were compared with those not treated (control group, n=11). Longitudinal data on the somatic development of 24 now adult female patients were analyzed. Medium final height was 157.2±6.5 cm compared to 151.4±5.6 cm in the control group. No significant difference could be found in the discrepancy of genetic target height and final height. Prepubertally girls were normal weight in both groups; in adulthood the majority of patients were overweight/obese. Menarche commenced 11 months after cessation of therapy. As already known from other studies, hormonal suppression via GnRH analog was well tolerated.

Evaluating the Efficacy of Treatment with a GnRH Analogue in Patients with Central Precocious Puberty.

Objective. GnRH analogues (GnRHa) are used in the treatment of central precocious puberty (CPP). The purpose of this study was to evaluate the efficacy of treatment with a GnRHa (leuprolide acetate) in patients with CPP. Subjects and Methods. A total of 62 female child patients who had been diagnosed with CPP, rapidly progressive precocious puberty (RP-PP), or advanced puberty (AP) and started on GnRHa treatment (leuprolide acetate, Lucrin depot, 3.75 mg once every 28 days) were included in the study. The efficacy of treatment was evaluated with anthropometric data obtained, progression of pubertal symptoms observed, as well as GnRHa tests, and, when necessary, intravenous GnRH tests carried out in physical examinations that were performed once every 3 months. Results. In the current study, treatment of early/advanced puberty at a dose of 3.75 mg once every 28 days resulted in the suppression of the HHG axis in 85.5% of the patients. Conclusion. The findings of this study revealed that a high starting dose of leuprolide acetate may not be necessary in every patient for the treatment of CPP. Starting at a dose of 3.75 mg once every 28 days and increasing it with regard to findings in follow-ups would be a better approach.

A Case of Gonadotropin-Releasing Hormone Agonist-Induced Sterile Abscess Showing a Good Response to Systemic Steroid Therapy.

Dear Editor: Prostate cancer is a common malignancy in men, and its incidence is increasing rapidly. Because prostate cancer shows androgen dependency in the early stages1, androgen-deprivation therapy with gonadotropin-releasing hormone (GnRH) agonists is the most effective systemic treatment2. Leuproreline (Lucrin; Abbot, Amstelveen, The Netherlands) is a GnRH agonist that blocks pituitary GnRH receptors, leading to the downregulation of luteinizing hormone and follicle-stimulating hormone3. This chemical castration provides long-term maximal androgen deprivation1. A 79-male-old man, who had painful tender erythematous subcutaneous nodules on the abdomen, visited our dermatologic department in June 2012. He received androgen-deprivation therapy consisting of pretreatment with leuprorelin 11.25 mg at 3-month intervals to treat underlying prostate cancer. A lesion arose from a previous leuprorelin injection site 2 weeks after the last injection (Fig. 1A). He was initially treated with antibiotics and non-steroidal anti-inflammatory drugs, but no improvement was observed. Subsequent histological examination showed neutrophilic and eosinophilic infiltration in the reticular dermis (Fig. 2). Laboratory examination results, including bacterial culture and tuberculosis polymerase chain reaction, were negative. Therefore, he was diagnosed with a sterile abscess caused by GnRH agonist injection and treated with systemic methylprednisolone 16 mg/day. The lesion had almost cleared after 4 weeks and remains in remission as of writing (Fig. 1B). Fig. 1 Painful tender erythematous subcutaneous swelling on abdomen. (A) Before treatment. (B) After 4 weeks of systemic steroid therapy. Fig. 2 Histologic slide stained with hematoxylin and eosin reveals neutrophilic and eosinophilic infiltrates in the reticular dermis. Leuprorelin, a GnRH agonist, is the most effective therapeutic modality for prostate cancer. Although GnRH agonist therapy appears to have significant benefits for patients, it also has serious side effects including anemia, cognitive changes, obesity, lipid alterations, insulin resistance, coronary artery disease, and osteoporosis2,3. The efficacy and side effects of GnRH agonists have recently been reported. In particular, sterile abscess formation has been reported in 3% of patients who received a GnRH agonist4. In Korea, only two patients, who were injected with a GnRH agonist for the treatment of central precocious puberty, have been reported to have developed a sterile abscess at the injection site5. Thus, our case is the first case of a sterile abscess in a Korean patient with prostate cancer treated with leuprorelin. There are many theories about the cause of sterile abscess5. One possible cause is an additive polymer of leuprorelin similar to that used in resorbable sutures. However, there is a report about granulomatous reactions induced by leuprorelin alone3. Thus, this could be thought of as a positive allergic reaction to leuprorelin. Furthermore, these reactions occurred in patients who received daily subcutaneous leuprorelin injections without additive polymer5. Thus, these cases suggest leuprorelin itself could be the cause of sterile abscess and granulomatous reaction. Previous reports describe spontaneous healing of sterile abscesses over several months without treatment4,5. Our patient was treated with a systemic steroid and remained in remission for 1 month. Thus, systemic steroid therapy may be a potential therapeutic modality for GnRH agonist-induced sterile abscess. Dermatologic clinicians should be aware of the potential adverse effects of leuprorelin injection, including sterile abscess and granulomatous reactions.

Long-term effects of gonadotropin-releasing hormone analogs in girls with central precocious puberty.

Gonadotropin-releasing hormone analogs (GnRHa) are widely used to treat central precocious puberty (CPP). The efficacy and safety of GnRHa treatment are known, but concerns regarding long-term complications are increasing. Follow-up observation results after GnRHa treatment cessation in female CPP patients up to adulthood showed that treatment (especially <6 years) was beneficial for final adult height relative to that of pretreated or untreated patients. Puberty was recovered within 1 year after GnRHa treatment discontinuation, and there were no abnormalities in reproductive function. CPP patients had a relatively high body mass index (BMI) at the time of CPP diagnosis, but BMI standard deviation score maintenance during GnRHa treatment seemed to prevent the aggravation of obesity in many cases. Bone mineral density decreases during GnRHa treatment but recovers to normal afterwards, and peak bone mass formation through bone mineral accretion during puberty is not affected. Recent studies reported a high prevalence of polycystic ovarian syndrome in CPP patients after GnRHa treatment, but it remains unclear whether the cause is the reproductive mechanism of CPP or GnRHa treatment itself. Studies of the psychosocial effects on CPP patients after GnRHa treatment are very limited. Some studies have reported decreases in psychosocial problems after GnRHa treatment. Overall, GnRHa seems effective and safe for CPP patients, based on long-term follow-up studies. There have been only a few long-term studies on GnRHa treatment in CPP patients in Korea; therefore, additional long-term follow-up investigations are needed to establish the efficacy and safety of GnRHa in the Korean population.