Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty

Objective: Depot GnRH agonists are commonly used in the treatment of central precocious puberty (CPP). The triptorelin 11.25 mg 3-month depot, currently used in adult indications, had not previously been evaluated in CPP. Design: This was a multicenter, open-label, 12 month trial conducted in 64 CPP children (54 girls and 10 boys), treated quarterly. Methods: Children with a clinical onset of pubertal development before the age of 8 years (girls) or 9 years (boys), pubertal response of LH to GnRH ≥7 IU/l, advanced bone age >1 year, enlarged uterus (≥36 mm) and testosterone level ≥0.5 ng/ml (boys), were included. Suppression of gonadotropic activation, as determined from serum LH, FSH, estradiol or testosterone, and pubertal signs were assessed at Months 3, 6 and 12. Results: GnRH-stimulated peak LH ≤3 IU/l, the main efficacy criterion, was met in 53 out of 62 (85%), 60 out of 62 (97%) and 56 out of 59 (95%) of the children at Months 3, 6 and 12 respectively. Serum FSH and sex steroids were also significantly reduced, while pubertal development regressed in most patients. Mean residual triptorelin levels were stable from Month 3 through to Month 12. The triptorelin 3-month depot was well tolerated. Severe injection pain was experienced in only one instance. Five girls experienced mild-to-moderate or severe (one girl) withdrawal bleeding. Conclusions: The triptorelin 3-month depot efficiently suppresses the pituitary–gonadal axis and pubertal development in children with CPP. This formulation allows a 3-fold reduction, over the once-a-month depot, in the number of i.m. injections required each year.

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Circulating ghrelin levels in girls with central precocious puberty are reduced during treatment with LHRH analog

Acta Endocrinologica ◽

10.1530/eje.1.02320 ◽

2007 ◽

Vol 156 (1) ◽

pp. 99-103 ◽

Cited By ~ 11

Author(s):

Claudio Maffeis ◽

Roberto Franceschi ◽

Paolo Moghetti ◽

Marta Camilot ◽

Silvana Lauriola ◽

...

Keyword(s):

Precocious Puberty ◽

Pubertal Development ◽

Central Precocious Puberty ◽

Bone Age ◽

Serum Levels ◽

Gnrh Analog ◽

Therapy Discontinuation ◽

17Β Estradiol ◽

Therapy Withdrawal ◽

Ghrelin Secretion

Decreased levels of ghrelin have been measured in growing children during puberty. No data are available for girls with central precocious puberty (CPP). Aims: To explore ghrelin changes before, during, and after GnRH analog treatment in girls with CPP. Subjects and methods: A sample of 20 Caucasian girls (8.08 ± 0.65 years of age) with CPP was recruited. Height and weight, bone age, LH, FSH, 17β estradiol (E2), and ghrelin were measured before starting treatment with GnRH analog, 18 months after therapy began and again 6 months after therapy discontinuation. Results: LH and E2 serum levels decreased significantly during treatment (2.45 ± 2.03 vs 0.67 ± 0.49 UI/l, P < 0.01 and 28.17 ± 9.7 vs 15 pmol/l, P < 0.01 respectively), returning to baseline levels after the discontinuation of therapy (4.75 ± 1.66 UI/l and 29.23 ± 6.99 pmol/l respectively). LH peaked following LHRH stimulation significantly (P < 0.01) decreased during treatment (24.45 ± 14.17 vs 1.3 ± 0.18 UI/l) and then increased after therapy discontinuation (12.58 ± 6.09, P < 0.01). Ghrelin decreased significantly (P < 0.05) during treatment (1849 ± 322 vs 1207 ± 637 pg/ml), and increased, though not significantly (P = 0.09) after therapy withdrawal (1567 ± 629 pg/ml). Conclusions: Contrary to what is expected in physiologic puberty, where ghrelin is progressively reduced, the prepubertal hormone milieau induced by GnRHa treatment in patients suffering from central precocious puberty (CPP) did not promote an increase in ghrelin circulating levels. Therefore, in CPP, ghrelin secretion seems to be independent from pubertal development per se. Concomitant estrogen suppression during treatment may play a potential role in the regulation of ghrelin secretion in these girls.

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Evaluation and significance of the degree of pituitary-gonadal inhibition during intranasal administration of buserelin

Acta Endocrinologica ◽

10.1530/acta.0.1160519 ◽

1987 ◽

Vol 116 (4) ◽

pp. 519-525 ◽

Cited By ~ 4

Author(s):

J. P. Bourguignon ◽

C. Heinrichs ◽

G. Van Vliet ◽

M. Vandeweghe ◽

M. Vanderschueren-Lodeweyckx ◽

...

Keyword(s):

Intranasal Administration ◽

Pubertal Development ◽

Age At Onset ◽

Central Precocious Puberty ◽

Bone Age ◽

Height Velocity ◽

Breast Development ◽

Variable Degree ◽

Oestradiol Level ◽

Serum Lh

Abstract. In 12 patients (11 girls, 1 boy) with central precocious puberty and 4 patients (3 girls, 1 boy) with idiopathic short stature treated for 1 year with a GnRH superagonist, buserelin (0.3 mg intranasally, 4 times a day), a variable degree of inhibition of sex steroid secretion and pubertal development was observed. Regression of breast or genital development required a daily dosage of buserelin ≥ 34 μg/kg. After 3, 6, 9 and 12 months of treatment, the serum oestradiol level in the girls was positively related (r = 0.69) to basal serum LH measured at the same time and to change in breast development during the previous 3 months. In contrast, LH response to GnRH was very low in all the patients and not related to the degree of oestradiol inhibition. Height velocity and bone age velocity during the year of treatment showed no significant correlation with mean oestradiol level. Bone age velocity during treatment was inversely related to bone age at onset of buserelin. These data show that 1) the pituitary gonadal suppression during intranasal administration of buserelin is variable and dose-dependent; 2) gonadotropin response to GnRH is not a sensitive indicator of incomplete pituitary suppression during buserelin treatment; and 3) bone age velocity during treatment is more reduced the more advanced bone age is at onset of treatment.

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Effectiveness of basal LH in monitoring central precocious puberty treatment in girls

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0386 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Valeria Calcaterra ◽

Gianpaolo De Filippo ◽

Riccardo Albertini ◽

Domenico Rendina ◽

Beatrice Messini ◽

...

Keyword(s):

Precocious Puberty ◽

Pubertal Development ◽

Central Precocious Puberty ◽

Reliable Indicator ◽

Gnrh Agonists ◽

Basal Serum ◽

Serum Lh ◽

Before And After ◽

Hypothalamic Pituitary Axis ◽

Efficacy Of Treatment

AbstractObjectivesTreatment of central precocious puberty (CPP) is based on administration of GnRH agonists in order to suppress hypothalamic-pituitary-gonadal axis and thus induce the stabilization or regression of pubertal development. Our aim was to determine whether the single basal serum LH and/or FSH concentration could be an effective tool to assess the efficacy of treatment to suppress activation of hypothalamic-pituitary axis.Patients and methodsSerum LH and FSH were measured before and after the GnRH injection, as well as E2 basal levels in 60 girls with documented idiopathic CPP at diagnosis and 18 and 30 months after the beginning of therapy.ResultsAt diagnosis, peaks of >5 IU/L of LH and of FSH were observed in 100 and 91.6% of girls, respectively, with basal LH values of <1 IU/L in 70% and basal FSH levels of <1 IU/L in 10%. E2 were <20 pg/mL in 36.6%. After 18 months, a suppressed peak (i.e. <3 IU/L) was recorded in 85% of girls (p<0.01) for LH and in 98.3% for FSH (p<0.01). Basal LH <1 IU/L was detected in 85% (p<0.01) and basal FSH ≤1 IU/L in 40% (p<0.01). Serum E2 ≤20 pg/mL was recorded in 61.6% (p<0.01). After 30 months, all patients showed LH suppressed peak (p<0.01) and 98.3% suppressed FSH peak (p<0.01). 100% showed basal LH concentrations <1 IU/L (p<0.01) and 38.3% FSH basal values <1 UI/mL (p<0.01). E2 ≤20 pg/mL was observed in 32.72% (p=NS).ConclusionsBasal LH values are a reliable indicator of the efficacy of GnRHa therapy after 30 months of GnRHa therapy.

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Phase 3 Trial of a Small-volume Subcutaneous 6-Month Duration Leuprolide Acetate Treatment for Central Precocious Puberty

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa479 ◽

2020 ◽

Vol 105 (10) ◽

pp. e3660-e3671

Author(s):

Karen O Klein ◽

Analía Freire ◽

Mirta Graciela Gryngarten ◽

Gad B Kletter ◽

Matthew Benson ◽

...

Keyword(s):

Precocious Puberty ◽

Small Volume ◽

Study Drug ◽

External Genitalia ◽

Central Precocious Puberty ◽

Bone Age ◽

Leuprolide Acetate ◽

Open Label ◽

Phase 3 ◽

Pubertal Stage

Abstract Context Gonadotropin-releasing hormone agonists (GnRHas) are standard of care for central precocious puberty (CPP). A 6-month subcutaneous injection has recently been approved by the Food and Drug Administration. Objective Determine efficacy, pharmacokinetics, and safety of 6-month 45-mg subcutaneous leuprolide acetate for CPP. Design Phase 3 multicenter, open-label, single-arm study. Setting 25 sites in 6 countries. Subjects 64 GnRHa-naïve children with CPP (age: 7.5 ± 0.1 years) received study drug: 59 completed the study. Intervention(s) 2 doses of 45-mg subcutaneous leuprolide acetate (0.375 mL) at 0 and 24 weeks; children were followed for 48 weeks. Main Outcome Measure(s) Percentage of children with serum luteinizing hormone (LH) <4 IU/L 30 minutes following GnRHa stimulation at week 24. Results 54/62 (87%) children achieved poststimulation LH <4 IU/L at week 24; 49/56 (88%) girls and 1/2 boys maintained peak LH <4 IU/L at week 48. Mean growth velocity decreased from 8.9 cm/year at week 4 to 6.0 cm/year at week 48. Mean bone age was advanced 3.0 years beyond chronological age at screening and 2.7 years at week 48. Breast pubertal stage regressed or was stable in 97% of girls and external genitalia development regressed in both boys. Adverse events were mild and did not cause treatment discontinuation. Conclusions A small volume of 45-mg subcutaneous leuprolide acetate administered at a 6-month interval effectively suppressed pubertal hormones and stopped or caused regression of pubertal progression. This long-acting GnRHa preparation of leuprolide acetate is a new, effective, and well-tolerated therapy for children with CPP.

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Rapid progressive central precocious puberty: diagnostic and predictive value of basal sex hormone levels and pelvic ultrasound

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0577 ◽

2020 ◽

Vol 33 (6) ◽

pp. 785-791

Author(s):

Valeria Calcaterra ◽

Catherine Klersy ◽

Federica Vinci ◽

Corrado Regalbuto ◽

Giulia Dobbiani ◽

...

Keyword(s):

Precocious Puberty ◽

Tanner Stage ◽

Central Precocious Puberty ◽

Bone Age ◽

Diagnostic Value ◽

Sex Hormone ◽

Pelvic Ultrasound ◽

Predictive Values ◽

Hormone Levels ◽

Ultrasound Parameters

AbstractObjectivesData on the predictive values of parameters included in the diagnostic work-up for precocious puberty (PP) remain limited. We detected the diagnostic value of basal sex hormone levels, pelvic ultrasound parameters and bone age assessment for activation of the hypothalamic-pituitary-gonadal axis in girls with PP, in order to help in the decision to perform GnRH testing.Patients and methodsWe retrospectively considered 177 girls with PP. According to puberty evolution, the girls were divided into two groups: rapid progressive central precocious puberty (RP-CPP) and non/slowly progressive/transient forms (SP-PP). In all patients we considered Tanner stage, basal luteinizing hormone (LH) and estradiol (E2) values, bone age, and pelvis examination. We assessed the diagnostic value of each variable and identified the number of pathological parameters that best identify patients with RP-CPP.ResultsBasal LH ≥ 0.2IU/L, E2 level ≥ 50 pmol/L, uterine longitudinal diameter ≥ 3.5 cm, transverse uterine diameter ≥ 1.5 cm, endometrial echo and ovarian volume ≥ 2 cm3 were significantly associated with RP-CPP (p ≤ 0.01). The ability to diagnose RP-CPP was enhanced with increasing number of pathological hormonal and instrumental parameters (p < 0.001). With more than three parameters detected, sensitivity and specificity reached 58% (95%CI 48–67) and 85% (95%CI 74–92), respectively, with a PPV = 86% (95%CI 76–93) and PPN = 54% (95%CI 43–54); the area under the ROC curve was 0.71 (95%CI 0.65–0.78).ConclusionDespite the availability of different tests, diagnosing RP-CPP remains difficult. A diagnosis model including at least three hormonal and/or ultrasound parameters may serve as a useful preliminary step in selecting patients who require GnRH testing for early detection of RC-PP.

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Assessment of gonadotropin concentrations stimulated by gonadotropin-releasing hormone analog by electrochemiluminescence (ECLIA) in girls with precocious puberty and premature thelarche

Hormone Research in Paediatrics ◽

10.1159/000521593 ◽

2021 ◽

Author(s):

Kamila Botelho Fernandes de Souza ◽

Melyna Shayanne Pessôa Veiga ◽

Gabriela Ráina Ferreira Martins ◽

Adriana Paula da Silva ◽

Lívia Grimaldi Abud Fujita ◽

...

Keyword(s):

Precocious Puberty ◽

Central Precocious Puberty ◽

Bone Age ◽

Gonadotropin Releasing Hormone ◽

Assay Method ◽

Premature Thelarche ◽

Releasing Hormone ◽

Cutoff Values ◽

Hormone Analog ◽

Hormone Analogs

Objective: The aim of this study is to determine the cutoff values of gonadotropin response to gonadotropin-releasing hormone analogs (GnRHas) corresponding to the activation of the hypothalamic–pituitary–gonadal axis that could differentiate central precocious puberty (CPP) from premature thelarche (PT) and using the electrochemiluminescence assay method. Methods: A total of 49 girls underwent the stimulation test with the intramuscular injection of 3.75 mg leuprolide acetate. Based on the clinical and laboratory characteristics, they were divided into two groups: CPP (n = 22) and PT (n = 27). Baseline estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were collected before GnRHa administration, and LH and FSH at 60 and 120 min, respectively, after GnRHa administration. Results: The girls with CPP presented an increased height Z-score, advanced bone age, and higher baseline LH, FSH, estradiol, and LH/FSH ratio in relation to PT (p < 0.001). Stimulated LH differed significantly between the two groups, and the LH cutoff values were ≥4.29 IU/L (p < 0.001) and ≥3.95 IU/L at 60 and 120 min, respectively (p < 0.001). LH peak was found at 60 min after stimulation. Conclusions: The GnRHa test is effective in distinguishing CPP from PT, and a single sampling, at 60 min, with LH concentrations above 4.29 may be the parameter of choice with the advantage of greater convenience and practicality.

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Update on the etiology, diagnosis and therapeutic management of sexual precocity

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302008000100005 ◽

2008 ◽

Vol 52 (1) ◽

pp. 18-31 ◽

Cited By ~ 44

Author(s):

Vinicius Nahime Brito ◽

Ana Claudia Latronico ◽

Ivo J. P. Arnhold ◽

Berenice Bilharinho Mendonça

Keyword(s):

Precocious Puberty ◽

Sex Steroids ◽

Therapeutic Option ◽

Receptor Gene ◽

Pubertal Development ◽

Protein A ◽

Activating Mutations ◽

Sexual Precocity ◽

Gonadotropic Axis ◽

Hormonal Evaluation

Precocious puberty is defined as the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Gonadotropin-dependent precocious puberty (GDPP) results from the premature activation of the hypothalamic-pituitary-gonadal axis and mimics the physiological pubertal development, although at an inadequate chronological age. Hormonal evaluation, mainly through basal and GnRH-stimulated LH levels shows activation of the gonadotropic axis. Gonadotropin-independent precocious puberty (GIPP) is the result of the secretion of sex steroids, independently from the activation of the gonadotropic axis. Several genetic causes, including constitutive activating mutations in the human LH-receptor gene and activating mutations in the Gs protein a-subunit gene are described as the etiology of testotoxicosis and McCune-Albright syndrome, respectively. The differential diagnosis between GDPP and GIPP has direct implications on the therapeutic option. Long-acting gonadotropin-releasing hormone (GnRH) analogs are the treatment of choice in GDPP. The treatment monitoring is carried out by clinical examination, hormonal evaluation measurements and image studies. For treatment of GIPP, drugs that act by blocking the action of sex steroids on their specific receptors (cyproterone, tamoxifen) or through their synthesis (ketoconazole, medroxyprogesterone, aromatase inhibitors) are used. In addition, variants of the normal pubertal development include isolated forms of precocious thelarche, precocious pubarche and precocious menarche. Here, we provide an update on the etiology, diagnosis and management of sexual precocity.

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Ovarian cysts and tumors as the cause of isosexual pseudoprecocious puberty

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0608305m ◽

2006 ◽

Vol 134 (7-8) ◽

pp. 305-309 ◽

Cited By ~ 4

Author(s):

Katarina Mitrovic ◽

Dragan Zdravkovic ◽

Tatjana Milenkovic ◽

Katarina Sedlecki ◽

Zoran Stankovic

Keyword(s):

Luteinizing Hormone ◽

Granulosa Cell ◽

Precocious Puberty ◽

Granulosa Cell Tumor ◽

Central Precocious Puberty ◽

Bone Age ◽

Cell Tumor ◽

Ovarian Cysts ◽

Pelvic Ultrasound ◽

Releasing Hormone

Introduction. Precocious puberty in girls is generally defined as appearance of secondary sexual characteristics before eight years of age. Menarche before the ninth birthday may serve as an additional criterion. Precocious puberty is divided in central precocious puberty and pseudoprecocious puberty. Central precocious puberty (GnRH dependent) occurs because of premature activation of hypothalamic-pituitarygonadal axis and activity of gonadotrophins. Pseudoprecocious puberty (GnRH independent) is caused by activity of sexual steroids that are not the result of gonadotrophin activity. Objective. Objective of our study was to examine the etiology, clinical and laboratory manifestations of isosexual pseudoprecocious puberty in girls. Method. In the period between 1995 and 2004, clinical and laboratory sings of 34 girls with precocious puberty were studied at the Endocrine Department of the Institute of Mother and Child Health Care of Serbia. Initial evaluations included height measurement, staging of puberty, bone age assessment and pelvic ultrasound. Important diagnostic sonographic parameters of precocious puberty were the volumes of ovaries and uterus as well as ovarian structure. The initial hormonal evaluation included measuring of plasma oestradiol, luteinizing hormone (LH) and follicle stimulating hormone (FSH). The luteinizing hormone releasing hormone (LHRH) stimulation test was used to evaluate LH and FSH responsiveness (60 ?g/m2 LHRH- Relefact LHRH?, Ferring). Blood samples were collected at 0, 20 and 60 minutes. Basal and GnRH stimulated LH and FSH were determined by immunoradiometric assay. Estradiol concentration was measured using the fluoroimmunometric assay. Results. Thirty-four girls aged 6 months to 9 years (mean age 4.5 years) with precocious puberty were studied during the period of 9 years. Eleven girls presented with breast development, six with vaginal bleeding and seventeen with signs of puberty. On the basis of clinical signs, bone age, estradiol levels and LHRH test, premature the larche was diagnosed in eleven patients (32.4%), premature menarche in six (17.6%) and central precocious puberty in ten girls (29.4%). Seven girls (20.6%) presented with pseudoprecocious puberty. Pelvic ultrasound examination revealed unilateral ovarian cysts in six patients and granulosa cell tumor in one. Elevated estrogen serum levels and failure of gonadotropin responses after gonadotropin releasing hormone were the classical findings in patients with isosexual pseudoprecocious puberty during the acute period of disease. In four patients, the cyst decreased spontaneously after several months, while in two patients, the cyst was removed by laparotomy. Surgical treatment was performed in a patient with granulosa cell tumor. Conclusion. Our work demonstrates that autonomous functional ovarian follicle cyst is the most often cause of isosexual pseudoprecocious puberty. Short period of observation is suggested because the cyst can resolve spontaneously. On the other hand, juvenile granulosa cell tumor, as highly malignant tumor, should be removed as soon as diagnosis is established.

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Clinical data and basal gonadotropins in the diagnostic of central precocious puberty in girls

Endocrine Connections ◽

10.1530/ec-20-0651 ◽

2021 ◽

Author(s):

Teodoro Durá-Travé ◽

Fidel Gallinas-Victoriano ◽

María Malumbres-Chacon ◽

Lotfi Ahmed-Mohamed ◽

María Jesús Chueca Guindulain ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Age At Onset ◽

Area Under The Curve ◽

High Specificity ◽

Central Precocious Puberty ◽

Bone Age ◽

Height Velocity ◽

Pubertal Status ◽

Serum Lh ◽

Before And After

Objective. The objective of this study was to analyze whether some auxological characteristics or a single basal gonadotropin measurement will be sufficient to distinguish the prepubertal from pubertal status. Methods. Auxologycal characteristics were recorded and serum LH and FSH were measured by immunochemiluminescence assays before and after GnRH stimulation test in a sample of 241 Caucasian girls with breast budding between 6- to 8- years old. Peak LH levels higher than 5 IU/L were considered a pubertal response. Area under the curve, cut-off points, sensitivity, and specificity for auxologycal variables and basal gonadotropins levels were determined by receiver operating curves. Results. There were no significant differences in age at onset, weight, height, BMI and height velocity between both groups. Bone age was significantly higher in pubertal girls (p<0.05), although with limited discriminatory capacity. The sensitivity and specificity for the basal LH levels were 89% and 82% respectively, for a cut off point of 0.1 IU/L. All girls in the pubertal group had a basal LH higher than 1.0 IU/L (positive predictive value of 100%). There was a wide overlap of basal FSH and LH/FSH ratio between prepubertal and pubertal girls. Conclusions. Auxologycal characteristics should not be used only in the differential diagnosis between prepubertal from pubertal status in 6- to 8-year-old girls. We found a high specificity of a single basal LH sample and it would be useful for establishing the diagnosis of puberty in this age group, eliminating the need for GnRH stimulation testing.

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Anthropometric, metabolic, and reproductive outcomes of patients with central precocious puberty treated with leuprorelin acetate 3-month depot (11.25 mg)

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2021-0142 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Carolina O. Ramos ◽

Ana P M Canton ◽

Carlos Eduardo Seraphim ◽

Aline Guimarães Faria ◽

Flavia Rezende Tinano ◽

...

Keyword(s):

Precocious Puberty ◽

Adult Height ◽

Central Precocious Puberty ◽

Bone Age ◽

Overweight And Obesity ◽

Leuprorelin Acetate ◽

The Mean ◽

Hormone Analogs

Abstract Objectives Longer-acting gonadotropin-releasing hormone analogs (GnRHa) have been widely used for central precocious puberty (CPP) treatment. However, the follow-up of patients after this treatment are still scarce. Our aim was to describe anthropometric, metabolic, and reproductive follow-up of CPP patients after treatment with leuprorelin acetate 3-month depot (11.25 mg). Methods Twenty-two female patients with idiopathic CPP were treated with leuprorelin acetate 3-month depot (11.25 mg). Their medical records were retrospectively evaluated regarding clinical, hormonal, and imaging aspects before, during, and after GnRHa treatment until adult height (AH). Results At the diagnosis of CPP, the mean chronological age (CA) was 8.2 ± 1.13 year, and mean bone age (BA) was 10.4 ± 1.4 year. Mean height SDS at the start and the end of GnRHa treatment was 1.6 ± 0.8 and 1.3 ± 0.9, respectively. The mean duration of GnRHa treatment was 2.8 ± 0.8 year. Mean predicted adult heights (PAH) at the start and the end of GnRH treatment was 153.2 ± 8.6 and 164.4 ± 7.3 cm, respectively (p<0.05). The mean AH was 163.2 ± 6.2 cm (mean SDS: 0.1 ± 1). All patients were within their target height (TH) range. There was a decrease in the percentage of overweight and obesity from the diagnosis until AH (39–19% p>0.05). At the AH, the insulin resistance and high LDL levels were identified in 3/17 patients (17.6%) and 2/21 patients (9.5%), respectively. The mean CA of menarche was 12.2 ± 0.5 years. At the AH, PCOS was diagnosed in one patient (4.8%). Conclusions Long-term anthropometric, metabolic, and reproductive follow-up of patients with CPP treated with longer-acting GnRHa revealed effectivity, safety, and favorable outcomes.

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