Abstract
Purpose
Gonadotropin-releasing hormone agonists are the standard treatment for central precocious puberty (CPP). These agonists include leuprolide acetate and triptorelin pamoate, but research data for the relative effectiveness of these 2 treatments in overweight and obese girls experiencing CPP are lacking. In this study, we compared the effectiveness of these 2 therapeutics, leuprolide acetate and triptorelin pamoate, in the treatment of overweight and obese girls affected by CPP.
Methods
We enrolled 69 overweight and obese girls with CPP in this retrospective cohort study and classified these participants according to their baseline body mass index (BMI) status, BMI≥1 standard deviation scoer. Leuprolide acetate was administered to 48 of the participants, and the other 21 were treated with triptorelin pamoate. The anthropometric measurements were compared at the beginning and conclusion of the therapy, and luteinizing hormone (LH) suppression levels were assessed 6 months following the completion of treatment.
Results
Leuprolide acetate and triptorelin pamoate substantially suppressed LH when administered to overweight and obese girls with CPP. The predicted adult height (PAH) at the conclusion of treatment was comparable between the 2 groups.
Conclusions
There was no significant difference in the level of LH suppression and PAH between the 2 groups, overweight and obese girls with CPP treated with leuprolide acetate and those treated with triptorelin pamoate.
Keywords: Central precocious puberty, Obesity, Overweight, Triptorelin pamoate, Leuprolide acetate
Highlights
· Both Leuprolide acetate and Triptorelin pamoate were effective in suppressing luteinizing hormone (LH) levels and improving predicted adult height (PAH) in overweight and obese girls with central precocious puberty (CPP).
· The study found no significant difference in LH suppression and PAH outcomes between the two treatment groups.
· The findings suggest these 2 gonadotropin-releasing hormone agonists offer comparable therapeutic benefits in treating CPP in overweight and obese girls with CPP.
Introduction
Central precocious puberty (CPP) is characterized by the early activation of the hypothalamic-pituitary-gonadal (HPG) axis in girls who are younger than 8 years old [1]. Girls account for nearly 90% of CPP cases for which the etiology is unknown [2]. The diagnosis of CPP in girls is based on the physical examination findings of early initiation of menstruation, stunted growth caused by the premature fusion of growth plates, and mental and social dysfunction [1]. Obesity is more prevalent in girls with CPP than in those without the condition.
Standard treatments for CPP are the administration of gonadotropin-releasing hormone (GnRH) agonists [3]. These analogs prevent pubertal activation and suppress gonadotropin production by persistently adhering to pituitary GnRH receptors. This process involves the downregulation of GnRH receptors that subsequently leads to the suppression of the HPG axis [4,5]. The essential findings for assessing treatments as successful are deceleration of bone aging, attainment of final adult height that is near the normal range, regression of pubertal development, and reduction of growth velocity [3,6,7].
Currently, a variety of GnRH analog formulations are available for the treatment of CPP. These include leuprolide acetate and triptorelin pamoate, 2 therapeutics that have been demonstrated to effectively suppress the pituitary-gonadal axis and pubertal development. However, data on the relative effectiveness of the different formulations are scarce, particularly data on the relative effectiveness of these therapies in the overweight and obese population of young female CPP patients. A previous study using fixed and weight-based dosages did demonstrate no significant differences in GnRH agonist treatment outcomes [8]; but no data on the relative effectiveness of various GnRH agonist medications, particularly in overweight and obese young girls with CPP, are available. Therefore, the objective of our study was to assess the relative effectiveness of leuprolide acetate and triptorelin pamoate in suppressing luteinizing hormone (LH) levels at 6 months posttreatment and to assess predicted adult height (PAH) at the conclusion of the treatment in overweight and obese girls experiencing CPP.
Materials and methods
1. Participants
Sixty-nine girls who had been diagnosed with CPP were patients in the Pediatric Endocrinology Clinic at King Chulalongkorn Memorial Hospital from December 2018 to December 2022. Overweight and obese girls with CPP, defined as a baseline body mass index (BMI)≥1 standard deviation score (SDS), with onset of breast growth before the age of 8 years were included in the study. Participants’ hormonal profiles needed to demonstrate a baseline LH level of over 0.3 IU/L or a peak LH level of over 5 IU/L following a GnRH stimulation test, and the treatment regimen included intramuscular administration of a GnRH agonist. Individuals with a history of congenital adrenal hyperplasia or exogenous hormone therapy were excluded from the study.
2. Methodology
The data for this retrospective cohort study were collected at the time of diagnosis and periodically during follow-up. The data collected included age (in years) at the onset of breast development, chronological age (in years), weight (SDS), height (SDS), body mass index (BMI) (SDS), Tanner stage of breast development, bone age (in years), and PAH at treatment initiation (cm, SDS) were all included in the data collection. We utilized the World Health Organization growth curve to determine the SDS values for weight, height, and BMI. The Greulich and Pyle approach was implemented by the pediatric endocrinologist to estimate bone age, and the Bayley-Pineau method was implemented to calculate PAH [9].
3. LH suppression
The efficacy of GnRH agonist therapy was assessed by examining the degree of LH suppression 6 months after treatment. Serum LH levels were quantified using electrochemiluminescent immunoassay 2 hours posttreatment with the GnRH agonist. LH suppression was defined as a decrease in serum LH concentration to below 4 IU/L [10-12].
4. Growth parameters
The growth outcomes were evaluated, particularly those associated with final height attainment. Height at the conclusion of treatment, degree of bone age advancement, and PAH at the conclusion of treatment were assessed.
5. Ethical statement
This study was a retrospective analysis conducted through the review of medical records and does not involve an examination of the treatment decisions made by physicians. The requirement for informed consent was waived because of the retrospective nature of the study and record review data collection method. Approval for the study was obtained from the Institutional Review Board (IRB) of the Faculty of Medicine, Chulalongkorn University (IRB No. 0726/66). The study protocol complied with all international guidelines for human research protection, including the Declaration of Helsinki, the Belmont Report, the CIOMS Guideline, and the International Conference on Harmonization in Good Clinical Practice (ICH-GCP) findings.
6. Statistical analysis
IBM SPSS Statistics ver. 29.0 (IBM Co., USA) was used to conduct statistical analyses. Means (standard deviations) are reported for both continuous variables, and each of these had a normal distribution. To evaluate the distinctions in continuous variables between the 2 groups, an independent t-test was utilized. Statistical significance was defined as a P-value of less than 0.05.
Results
Data from a cohort of 69 overweight or obese girls who were diagnosed with CPP were analyzed in this study. Of these subjects, 48 were treated with leuprolide acetate; the remaining 21 participants were administered triptorelin pamoate therapy. The initial clinical characteristics of the patients and dosage of the 2 medications are shown in Table 1. The demographic data, including the age at onset; auxological data; bone age; and PAH were compared between the 2 groups. No significant differences between the groups were observed. GnRH agonists are typically administered to patients until a bone age of approximately 12 years is achieved. This process usually requires 2 to 3 years of treatment. In this study, the level of LH suppression was assessed at 6 months posttherapy. The LH suppression results are illustrated in Table 2. The average LH level was comparable in the 2 treatment groups, those that received leuprolide acetate and those that were administered triptorelin pamoate, 2.31±1.34 and 1.95±1.45, respectively, with a P-value=0.46.
Table 1.
Demographic data on overweight and obese CPP girls
| Variable | GnRH agonist |
||
|---|---|---|---|
| Leuprolide acetate (N=48) | Triptorelin pamoate (N=21) | P-value | |
| Age of onset (yr) | 7.23±0.90 | 7.55±0.66 | 0.17 |
| Weight (kg) | 39.12±7.31 | 37.98±7.48 | 0.56 |
| Weight SDS | 2.23±0.75 | 2.10±0.94 | 0.56 |
| Height (cm) | 136.85±9.80 | 135.72±6.41 | 0.57 |
| Height SDS | 1.89±1.04 | 1.75 ±1.01 | 0.60 |
| BMI (kg/m2) | 20.67±1.56 | 20.45±2.48 | 0.72 |
| BMI SDS | 1.88±0.55 | 1.82±0.89 | 0.78 |
| MPH (cm) | 157.35±4.31 | 157.38±3.91 | 0.98 |
| Bone age (yr) | 10.87±1.63 | 10.60±1.15 | 0.44 |
| PAH-av | 152.30±7.52 | 152.79±5.69 | 0.77 |
| PAH-av SDS | -0.98±1.59 | -0.88±1.20 | 0.76 |
| PAH-ac | 156.67±8.15 | 157.64±6.61 | 0.62 |
| PAH-ac SDS | -0.61±1.72 | 0.14±1.38 | 0.61 |
| BA–CA | 2.56±1.15 | 2.25±0.81 | 0.22 |
| BA/CA | 1.32±0.24 | 1.27±0.10 | 0.22 |
| Dosage (μg/kg every 4 wk) | 99.7±22.3 | 101.9±17.4 | 0.66 |
| Duration of treatment (mo) | 27.9±9.01 | 28.44±4.47 | 0.88 |
Values are presented as mean±standard deviation.
CPP, central precocious puberty; GnRH, gonadotropin-releasing hormone; SDS, standard deviation score; BMI, body mass index; MPH, midparental height; PAH, predicted adult height; PAH-av, PAH with average bone age; PAH-ac, PAH with accelerated bone age; BA, bone age; CA, chronological age.
Table 2.
Hormonal suppression at 6 months of treatment
| Variable | 3-Month GnRH agonist |
||
|---|---|---|---|
| Leuprolide acetate | Triptorelin pamoate | P-value | |
| LH (IU/L) | 2.31±1.34 | 1.95±1.45 | 0.46 |
| FSH (IU/L) | 3.79±2.08 | 3.40±1.88 | 0.56 |
| Estradiol (pg/mL) | 15.69±12.08 | 12.55±10.69 | 0.41 |
Values are presented as mean±standard deviation.
GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone.
Subjects in both groups exhibited an increase in PAH at the conclusion of treatment (Table 3) compared to their PAHs at the initiation of treatment. At the conclusion of treatment, there was no statistically significant difference in the PAH and average bone age (PAH-av) between the 2 groups, 159.06±56.7 and 157.60±7.00 with a P-value of 0.60 (Fig. 1). Compared to baseline BMI SDS measurements, both treatment groups demonstrated substantial increases in BMI SDS at the end of therapy (Table 4).
Table 3.
Growth parameter at end of treatment
| Variable | GnRH agonist |
P-value | |
|---|---|---|---|
| Leuprolide acetate | Triptorelin pamoate | ||
| Height | |||
| Ht last treatment | 148.95±6.52 | 150.53±6.79 | 0.53 |
| Ht last treatment SDS | 1.19±1.07 | 1.24±1.28 | 0.92 |
| BA–CA | |||
| 0 Mo | 2.56±1.15 | 2.25±0.81 | 0.22 |
| End of treatment | 1.25±1.11 | 1.30±0.89 | 0.88 |
| BA/CA | |||
| 0 Mo | 1.27±0.14 | 1.21±0.16 | 0.11 |
| End of treatment | 1.13±0.19 | 1.12±0.08 | 0.62 |
| PAH-av | |||
| 0 Mo | 152.30±7.52 | 152.79±5.69 | 0.77 |
| 0-Mo SDS | -0.98±1.59 | -0.88±1.20 | 0.77 |
| End of treatment | 159.06±56.7 | 157.60±7.00 | 0.60 |
| End of treatment SDS | 0.44±1.41 | 0.13±1.47 | 0.60 |
| PAHend–PAHstart | 5.08±5.80 | 3.87±2.61 | 0.36 |
| PAH-ac | |||
| 0 Mo | 156.67±8.15 | 157.64±6.61 | 0.62 |
| 0-Mo SDS | -0.61±1.72 | 0.14±1.38 | 0.62 |
| End of treatment | 162.34±7.20 | 160.12±7.56 | 0.46 |
| End of treatment SDS | 1.13±1.50 | 0.66±1.58 | 0.46 |
| PAHend–PAHstart | 6.17±5.13 | 4.99±2.00 | 0.28 |
Values are presented as mean±standard deviation.
GnRH, gonadotropin-releasing hormone; Ht, height; SDS, standard deviation score; BA, bone age; CA, chronological age; PAH, predicted adult height; PAH-av, PAH with average bone age; PAH-ac, PAH with accelerated bone age; PAHend, PAH at end of treatment; PAHstart, PAH at start treatment; MPH, midparental height.
Fig. 1.
Mean predicted adult height (PAH). MPH, midparental height.
Table 4.
Comparison of BMI SDS at the start and end of various GnRH agonist treatments
| Variable | BMI SDS Start the treatment | BMI SDS End of the treatment | P-value |
|---|---|---|---|
| Drugs | |||
| Leuprolide acetate | 1.88±0.55 | 2.10±0.82 | <0.05 |
| Triptorelin pamoate | 1.82±0.89 | 2.27±1.14 | <0.05 |
Values are presented as mean±standard deviation.
BMI, body mass index; SDS, standard deviation score; GnRH, gonadotropin-releasing hormone.
Discussion
Previously, depot GnRH agonist administration was the predominant treatment for CPP. However, Thailand has now approved 2 newer GnRH agonists for treatment of girls with CPP. Data on the relative effectiveness of these 2 therapeutics are lacking, though; studies comparing the benefits of these treatment regimens, particularly in overweight and obese girls with CPP, are necessary [1, 13, 14]. One of these therapeutics, leuprolide acetate, is a synthetic nonapeptide analog of GnRH that is more potent than this natural hormone. In triptorelin pamoate, another synthetic GnRH analog, D-tryptophan is substituted for L-glycine at the sixth amino acid position of the natural hormone. This modification to GnRH increases resistance to enzymatic degradation and pituitary receptor affinity for the pituitary receptor. Therefore, the treatment involves increased plasma half-life and effectiveness of this analog compared to GnRH. Triptorelin pamoate is 35 times more effective than leuprolide acetate and has a longer half-life than GnRH, but the comparative effectiveness of the 2 analogs after completion of therapy has never been tested in overweight and obese young girls with CPP. Childhood obesity is a predictor of morbidity and mortality in adulthood [15], and girls with CPP are substantially more likely to be overweight or obese than their counterparts without CPP. The effectiveness of GnRH agonist treatment in suppressing the HPG axis in overweight and obese girls with CPP has been a topic of debate, but this research question has not been tested. In our study, we identified no significant difference between the 2 treatment groups in terms of their dosage per kilogram over a four-week period, approximately 100 μg per kg. This amount is equal to the standard CPP treatment dosage used in Europe.
Initially, we primarily sought to conduct a comparative assessment of treatment effectiveness by documenting the reduction in LH levels after 6 months of treatment. However, the methods for clinical assessment of the biochemical efficacy of LH suppression during GnRH analog therapy are not universally accepted. GnRH-stimulated or -unstimulated serum LH or sex steroidal hormone levels can be measured to evaluate the HPG axis. However, a standard cutoff value for monitoring and adequate therapeutic LH suppression achievement has also not been universally accepted despite undergoing GnRH agonist-stimulated testing. The cutoff value for LH suppression in that International Consortium investigation was an LH level below 4 IU/L [15]. Using this standard, our results indicated that both treatments performed satisfactorily; both treatments resulted in GnRH-stimulated LH suppression test reductions to mean LH levels below 4 IU/L [12]. The findings are consistent with those of previous research conducted on girls diagnosed with CPP. Those results indicated that LH suppression rate was approximately 84%–100% with the use of either of the 2 medications [14,16-21]. Our results also agreed with those of previous studies conducted in predominantly Caucasian populations, and a meta-analysis of previous trials demonstrated that there were no significant differences in outcomes between Caucasian and Asian patients.
In previous assessments of growth parameters after 1 year of treatment, no statistically significant differences in height attainment, the rate at which height increased, or the degree to which bone age advanced were noted between the GnRH agonist preparations in tests on girls with CPP [17,22,23]. Nevertheless, medical effectiveness evaluation information on posttreatment growth characteristics are still lacking, particularly in the population of overweight and obese girls with CPP. Therefore, our research focused on this population. We expanded the scientific knowledge base concerning the long-term growth effects of these treatments in this population of overweight and obese girls diagnosed with CPP. Our testing of the therapies demonstrated that there was no statistically significant difference in the actual height of individuals who were administered leuprolide acetate and those who were administered triptorelin pamoate, and both treatments were clinically effective.
Comparisons of pretreatment and posttreatment PAHs demonstrated that all patients in our analysis experienced an increase in PAH after receiving treatment with either GnRH agonist. The restoration of growth potential was not substantially different between the 2 GnRH agonist regimens. At the conclusion of the treatment, the 2 patient groups did not demonstrate any significant differences in terms of weight, height, or PAH.
Our interpretation of the data is supported by our demonstration that the BMI SDS remained elevated throughout the duration of treatment, indicating that the expected reduction in growth velocity in overweight and obese girls was substantial. These patients exhibited comparable height SDS levels prior to and following GnRH agonist treatment. In conjunction with medical management, healthy lifestyle interventions such as dietary modifications, physical activity, and psychosocial support may offer significant benefits. These interventions may contribute to a slower rate of pubertal progression and improved overall health outcomes.
The retrospective design of our study resulted in occurrence of missing data, and the variable number of data points for specific parameters created difficulties in comparing the 2 treatment groups. Also, significantly, we did not evaluate the precise final adult height because the triptorelin pamoate group patients had not yet attained their final adult height. The initiation of their therapy was delayed until 2019. Despite these limitations, our research results do provide important insights into the comparable effectiveness of the 2 tested GnRH agonist regimens in the treatment of overweight and obese girls experiencing CPP.
In conclusion, the leuprolide acetate and triptorelin pamoate treatment regimens exhibited similar effectiveness in controlling LH levels and preventing the progression of bone age in overweight and obese young female patients who were receiving treatment for CPP. Both treatment protocols resulted in an improvement in PAH, and there were no significant differences in PAH between the 2 treatment groups. Additional longitudinal research is necessary to verify our findings and evaluate the final height achieved by the study subjects.
Footnotes
Conflicts of interest
No potential conflict of interest relevant to this article was reported.
Funding
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Data availability
The data that support the findings of this study can be provided by the corresponding author upon reasonable request.
Acknowledgments
The authors extend their gratitude to the patients and their families who participated in this study, contributing invaluable data for the advancement of our understanding of CPP treatment. We also express our appreciation to the healthcare professionals at the pediatric endocrinology clinic of King Chulalongkorn Memorial Hospital for their dedicated care and assistance in the collection of essential data.
Author contribution
Conceptualization: KS; Data curation: TT; Formal analysis: KS; Methodology: TT; Project administration: KS; Visualization: SA, NN, VS, SW; Writing - original draft: KS; Writing - review & editing: KS
References
- 1.Latronico AC, Brito VN, Carel JC. Causes, diagnosis, and treatment of central precocious puberty. Lancet Diabetes Endocrinol. 2016;4:265–74. doi: 10.1016/S2213-8587(15)00380-0. [DOI] [PubMed] [Google Scholar]
- 2.Carel JC, Leger J. Precocious puberty. N Engl J Med. 2008;358:2366–77. doi: 10.1056/NEJMcp0800459. [DOI] [PubMed] [Google Scholar]
- 3.Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR, ESPE-LWPES GnRH Analogs Consensus Conference Group et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics. 2009;123:e752–62. doi: 10.1542/peds.2008-1783. [DOI] [PubMed] [Google Scholar]
- 4.Kilberg MJ, Vogiatzi MG. Approach to the patient: central precocious puberty. J Clin Endocrinol Metab. 2023;108:2115–23. doi: 10.1210/clinem/dgad081. [DOI] [PubMed] [Google Scholar]
- 5.Eugster EA. Treatment of central precocious puberty. J Endocr Soc. 2019;3:965–72. doi: 10.1210/js.2019-00036. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Soriano-Guillén L, Argente J. Central precocious puberty, functional and tumor-related. Best Pract Res Clin Endocrinol Metab. 2019;33:101262. doi: 10.1016/j.beem.2019.01.003. [DOI] [PubMed] [Google Scholar]
- 7.Luo X, Liang Y, Hou L, Wu W, Ying Y, Ye F. Long-term efficacy and safety of gonadotropin-releasing hormone analog treatment in children with idiopathic central precocious puberty: a systematic review and meta-analysis. Clin Endocrinol (Oxf) 2021;94:786–96. doi: 10.1111/cen.14410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Jang S, Kim SJ, Lee M, Lee HI, Kwon A, Suh J, et al. Comparison of the effect of gonadotropin-releasing hormone agonist dosage in girls with central precocious puberty. Ann Pediatr Endocrinol Metab. 2023;28:283–8. doi: 10.6065/apem.2244210.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Greulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist. Stanford: Stanford University Press, 1959. [Google Scholar]
- 10.Carel JC, Lahlou N, Jaramillo O, Montauban V, Teinturier C, Colle M, et al. Treatment of central precocious puberty by subcutaneous injections of leuprorelin 3-month depot (11.25 mg) J Clin Endocrinol Metab. 2002;87:4111–6. doi: 10.1210/jc.2001-020243. [DOI] [PubMed] [Google Scholar]
- 11.Carel JC, Blumberg J, Seymour C, Adamsbaum C, Lahlou N. Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty. Eur J Endocrinol. 2006;154:119–24. doi: 10.1530/eje.1.02056. [DOI] [PubMed] [Google Scholar]
- 12.Bangalore Krishna K, Fuqua JS, Rogol AD, Klein KO, Popovic J, Houk CP, et al. Use of gonadotropin-releasing hormone analogs in children: update by an international consortium. Horm Res Paediatr. 2019;91:357–72. doi: 10.1159/000501336. [DOI] [PubMed] [Google Scholar]
- 13.Lee PA, Klein K, Mauras N, Lev-Vaisler T, Bacher P. 36-month treatment experience of two doses of leuprolide acetate 3-month depot for children with central precocious puberty. J Clin Endocrinol Metab. 2014;99:3153–9. doi: 10.1210/jc.2013-4471. [DOI] [PubMed] [Google Scholar]
- 14.Durand A, Tauber M, Patel B, Dutailly P. Meta-analysis of paediatric patients with central precocious puberty treated with intramuscular triptorelin 11.25 mg 3-month prolonged-release formulation. Horm Res Paediatr. 2017;87:224–32. doi: 10.1159/000456545. [DOI] [PubMed] [Google Scholar]
- 15.Reilly JJ, Kelly J. Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: systematic review. Int J Obes (Lond) 2011;35:891–8. doi: 10.1038/ijo.2010.222. [DOI] [PubMed] [Google Scholar]
- 16.Freire AV, Gryngarten MG, Ballerini MG, Arcari AJ, Escobar ME, Bergadá I, et al. Assessment of Estradiol Response after Depot Triptorelin Administration in Girls with Central Precocious Puberty. Horm Res Paediatr. 2016;85:58–64. doi: 10.1159/000442523. [DOI] [PubMed] [Google Scholar]
- 17.Zenaty D, Blumberg J, Liyanage N, Jacqz-Aigrain E, Lahlou N, Carel JC. A 6-month trial of the efficacy and safety of triptorelin pamoate (11.25 mg) every 3 months in children with precocious puberty: a retrospective comparison with triptorelin acetate. Horm Res Paediatr. 2016;86:188–95. doi: 10.1159/000448840. [DOI] [PubMed] [Google Scholar]
- 18.Martínez-Aguayo A, Hernández MI, Beas F, Iñiguez G, Avila A, Sovino H, et al. Treatment of central precocious puberty with triptorelin 11.25 mg depot formulation. J Pediatr Endocrinol Metab. 2006;19:963–70. doi: 10.1515/jpem.2006.19.8.963. [DOI] [PubMed] [Google Scholar]
- 19.Chung LY, Kang E, Nam HK, Rhie YJ, Lee KH. Efficacy of triptorelin 3-month depot compared to 1-month depot for the treatment of korean girls with central precocious puberty in single tertiary center. J Korean Med Sci. 2021;36:e219. doi: 10.3346/jkms.2021.36.e219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Luo X, Zhang C, Yang Y, Xu X, Cheng X, Wei H, et al. Efficacy and safety of triptorelin 3-month formulation in chinese children with central precocious puberty: a phase 3, open-label, single-arm study. Adv Ther. 2023;40:4574–88. doi: 10.1007/s12325-023-02617-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Thaneetrakool T, Aroonparkmongkol S, Numsriskulrat N, Supornsilchai V, Wacharasindhu S, Srilanchakon K. Effectiveness of leuprolide acetate administered monthly compared to three-monthly in the treatment of central precocious puberty: evaluation at the end of treatment. Front Endocrinol (Lausanne) 2024;15:1390674. doi: 10.3389/fendo.2024.1390674. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Jeon MJ, Choe JW, Chung HR, Kim JH. Short-term efficacy of 1-month and 3-month gonadotropin-releasing hormone agonist depots in girls with central precocious puberty. Ann Pediatr Endocrinol Metab. 2021;26:171–7. doi: 10.6065/apem.2040134.067. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Yang J, Song Q, Gao S, Gao Y, Shang X, Li G, et al. Efficacy of leuprorelin 3-month depot (11.25 mg) compared to 1-month depot (3.75 mg) for central precocious puberty in chinese girls: a prospective cohort study. Int J Endocrinol. 2022;2022:1043293. doi: 10.1155/2022/1043293. [DOI] [PMC free article] [PubMed] [Google Scholar]