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In boys, central precocious puberty （CPP） is the appearance of secondary sex characteristics driven by pituitary gonadotropin secretion before the age of 9 years. In the last years, relevant improvements in the treatment of CPP have been achieved. Because CPP is rare in boys, the majority of papers on this issue focus on girls and do not address specific features of male patients regarding end results and safety. In the present paper, recent advances of CPP management with GnRH analogs in men are summarized. End results in untreated and treated patients are also reviewed by an analysis of the recently published literature on treatment of CPP in men. The available data indicate that therapy with GnRH analogs can improve final height into the range of target height without significant adverse short-term and long-term effects, but longer follow-up of larger series of patients is still required to draw definitive conclusions.

The Chinese Expert Consensus on central precocious puberty (CPP) defines girls’ rapid sexual development before age 8 as CPP; while after age 8 as early normal puberty (ENP). And the use of recombinant human growth hormone (rhGH) for CPP and ENP is off-label and lacks reliable evidence for clinical practice. This study only included girls due to the low prevalence among boys. We aimed to compare the long-term efficacy and safety of gonadotrophin releasing hormone analogue (GnRHa) in combination with or without rhGH for the treatment of CPP and ENP, and to explore the differences in the efficacy of different age of intervention. The medical information of girls with CPP or ENP at a women’s and children’s hospital from January 2013 to December 2018 was retrospectively collected. The primary outcome of efficacy was final adult height (FAH), and the secondary outcome included height gain, genetic height gain, standard deviation score of final adult height (FAHSDS), and standard deviation score of height (HSDS) gain. The safety outcomes were the rate of at least one adverse event of any type and the rate of each adverse event. We included factors with P  < 0.05 in baseline analysis, and factors from systematic review and clinical experience as covariates in multivariable linear regression to adjust the clinical treatment choice, and subgroup analysis was taken to explore the efficacy of interventions at different ages. A total of 182 girls with CPP or ENP were finally included in this study. The adjusted results of multivariable linear regression showed that the mean(SD) of FAH in the combination therapy group (CG) (162.58 [0.46] cm) was higher than the monotherapy group (MG) (160.25 [0.35] cm) and the no treatment group (NG) (158.39 [0.47] cm) ( P  < 0.001), and the height gain(CG: 4.00 [0.46] cm, MG: 1.68 [0.36] cm, NG: − 0.18 [0.47] cm, P  < 0.001), genetic height gain(CG: 6.18 [0.46] cm, MG: 3.85 [0.35] cm, NG: 1.99 [0.47] cm, P  < 0.001), FAHSDS (CG: 0.66 [0.08], MG: 0.24 [0.06], NG: − 0.13 [0.08], P  < 0.001), and HSDS gain(CG: 0.26 [0.08], MG: − 0.17 [0.06], NG: − 0.54 [0.08]) in CG were all higher than MG and NG. Besides, the incidence of at least one adverse event of any type in the CG was higher than MG and NG (CG: 83.30%, MG: 15.00%, NG: 16.70%, P  < 0.001), among which the incidence of fasting insulin elevation (CG: 55.60%, MG: 1.25%, NG: 2.08%, P  < 0.001) and hypothyroidism(CG: 44.4%, MG: 0.00%, NG: 0.00%, P  < 0.001) was higher than the other two groups. Subgroup analysis indicated that, compared with the NG, the MG showed no differences in FAH in girls who entered puberty after the age of 8 years (1.46 [− 0.01, 2.93], P  = 0.051) and those treated with GnRHa for less than 1 year (0.30 [− 1.34, 1.94], P  = 0.718). Compared with the NG, there were no differences in FAH between the CG and MG (1.41 [− 0.76, 3.58], P  = 0.204, 1.70 [− 0.77, 4.16], P  = 0.178) in girls who initiated pharmacotherapy at the age of 10–12 years. Compared with the MG, the CG showed no differences in FAH in girls treated with rhGH in combination for less than 1 year (1.48 [− 0.09, 3.05], P  = 0.064). The combination of GnRHa and rhGH can improve the FAH of girls with CPP and ENP to a certain extent, especially for those who began pharmacotherapy before 10 years of age and continued treatment for more than 1 year, but meanwhile increased the incidence of adverse events. The benefits, risks, and affordability of medication should still be comprehensively considered before decisions on pharmacotherapy.

Background Ganirelix, a third-generation GnRH antagonist, is widely used in assisted reproductive technology (ART) for rapid pituitary suppression to prevent premature luteinizing hormone (LH) surges. Despite its extensive clinical use, real-world evidence on its safety in large populations remains scarce. This study aimed to evaluate the safety profile of ganirelix by comprehensively analyzing adverse drug events (ADEs) using real-world data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japan Adverse Drug Event Reporting (JADER) database. Methods We extracted ADE data from FAERS (Q1 2004–Q2 2024) and JADER (Q1 2009–Q1 2024). Disproportionality analyses, including reporting odds ratios (ROR), proportional reporting ratios (PRR), Bayesian Confidence Propagation Neural Networks (BCPNN), and Multi-item Gamma Poisson Shrinkage (MGPS), were employed to identify significant associations between ganirelix and ADEs. Results In the FAERS database, we identified 1,096 ganirelix-related ADE reports, spanning 26 system organ classes (SOCs). A total of 65 positive signals were detected, including ADEs consistent with drug label such as ovarian hyperstimulation syndrome (OHSS) ( n  = 290, ROR 2462.76, PRR 2168.48, EBGM05 1655.59, IC025 9.18), injection site pain ( n  = 54, ROR 3.99, PRR 3.93, EBGM05 3.13, IC025 0.31), and fetal death ( n  = 6, ROR 21.05, PRR 21.00, EBGM05 10.72, IC025 2.72). Additionally, unexpected signals not listed in the drug label were identified, including ectopic pregnancy ( n  = 7, ROR 33.02, PRR 32.93, EBGM05 17.64, IC025 3.37), maternal exposure before pregnancy ( n  = 30, ROR 76.09, PRR 75.16, EBGM05 74.72, IC025 6.22), dermatitis allergic ( n  = 4, ROR 7.98, PRR 7.97, EBGM05 3.50, IC025 1.33), and bladder tamponade ( n  = 4, ROR 771.47, PRR 770.3, EBGM05 311.57, IC025 7.80). The median time to ADE onset was 13 days. External validation using the JADER database (62 ganirelix-related ADE reports) confirmed four signals, including abortion ( n  = 19), OHSS ( n  = 17), missed abortion ( n  = 9), and fetal death ( n  = 8), aligning with FAERS findings. Conclusion This study provides a robust real-world safety evaluation of ganirelix, with findings corroborated by two independent pharmacovigilance databases. While consistent with clinical observations, the identification of unexpected signals warrants further pharmacoepidemiological investigations to confirm these results.

Early puberty (EP) has been defined as the onset of puberty in the low-normal range; it may be a cause for concern regarding a possible impairment of adult height (AH). This paper meta-analysed data on AH after spontaneous growth or after gonadotropin-releasing hormone (GnRH) analog treatment in girls with EP. A computerized literature search was conducted from 1980 to June 30, 2016. Only published studies in English were considered. Eight papers were selected (483 cases). In untreated girls ( n  = 300), predicted adult height (PAH) at start of follow-up (−0.559 SDS (95%CI −1.110 to 0.001); P  = 0.050) was close to mid-parental height (MPH) (−0.557 SDS (95%CI −0.736 to −0.419); P <  0.0001) and AH (−0.663 SDS (95%CI −0.803 to −0.524); P <  0.0001). In GnRH analog treated girls ( n  = 183), PAH before the start of treatment was slightly reduced (−0.939 SDS (95%CI −1.401 to −0.477; P <  0.0001) vs MPH (−0.678 SDS (95%CI −0.942 to −0.414); P  < 0.0000), but AH (−0.604 SDS (95%CI −0.877 to −0.338); P  < 0.0000) was close to MPH. Conclusion : Present meta-analysis indicates that girls with EP spontaneously reach their MPH and that GnRH analog treatment does not widely change growth outcome. Differences among the selected studies for definition of EP, inclusion criteria, treatment duration, age at discontinuation of therapy, definition of AH may affect results. What is Known: • Early puberty represents a main cause of consultation in paediatric endocrinology offices due to concerns of both practitioners and parents. • Treatment with GnRH analogs is sometimes attempted with the aim to improve adult height. What is New: • Untreated and GnRH analog treated girls with early puberty reached similar adult height. • Adult height was consistent with mid-parental height in both untreated and GnRH analog treated girls with early puberty.

The aim was to develop a model to predict the adult height (AH) of idiopathic central precocious puberty (ICPP) girls who underwent gonadotropin-releasing hormone analog (GnRHa) treatment. Data analysis included 258 girls with ICPP. Among them, 101 girls who reached final AH (FAH) with GnRHa treatment were analyzed to verify three previous prediction models and develop a unique model based on multiple linear regression. The control group consisted of 41 untreated ICPP girls. Moreover, 116 girls treated with GnRHa who almost attained FAH were included for external validation. Based on our cohorts, all of the three previously published models underestimated the FAH with an R of 0.667, 0.793, and 0.664. The AH prediction model was built as follows: Calculated AH (cm) = 1.89630 * Height SDS + 2.29927 * Height SDS for bone age + 0.40776 * Target height + 100.16684 ( R 2  = 0.66 and adjusted R 2  = 0.65). Internal validation showed a mean root mean squared error (RMSE) of 2.16 cm and a mean absolute error (MAE) of 1.64 cm. External validation showed that a significant error (> 1 SD) appeared only in 7 of 116 girls (6.0%). The model is displayed on the website: http://cpppredict.shinyapps.io/dynnomapp . Conclusion : A model for predicting the AH of girls with ICPP was developed incorporating the variables of height SDS, height SDS for bone age, and target height. The internal and external validation ensures an appropriate degree of discrimination and calibration of the prediction model. What is Known: • Uncertainty prevails as how to predict the adult height of patients with central precocious puberty following gonadotropin-releasing hormone analog treatment. • Previous models for predicting adult height of girls with idiopathic central precocious puberty have not been proven translational to the Chinese population. What is New: • This study develops a new model for predicting the adult height of idiopathic central precocious puberty girls who underwent gonadotropin-releasing hormone analog treatment. • The internal and external validation assures a good degree of discrimination and calibration of the prediction model in this study.

Background Gender incongruence results from the mismatch between gender identity and thesex assigned at birth. The process of gender affirmation includes a series of procedures during which the transgender individual acquires phenotypic features of the desired sex. Hormonal therapy for transgender women aims to suppress endogenous androgens and replace them with estrogens. The present study sought to investigate the safety of feminizing therapy in transgender women in relation to somatometric and metabolic parameters. Methods The medical records of transgender women who received oral estradiol valerate and a gonadotropin-releasing hormone (GnRH) agonist for at least 18months were reviewed. The study population had estradiol levels within the normal limits of the follicular phase of cisgender women of reproductive age and suppressed blood testosterone levels after 18months of treatment. Changes in body mass index, glycemic and lipid profiles, hemoglobin and hematocrit, and liver function tests were examined. The paired t -test was used for statistical analysis. Results The mean blood estradiol and testosterone levels after approximately 18months of treatment were 85.65pg/mL and 24ng/dL, respectively. There was a statistically significant increase in blood triglycerides as well as a statistically significant decrease in hemoglobin and hematocrit. However, none of the participants developed severe hypertriglyceridemia or anemia. No significant changes were found in blood cholesterol (total, high-density lipoprotein, and low-density lipoprotein cholesterol), glucose, and liver enzymes. Conclusions Treatment with oral estradiol valerate and an intramuscular GnRH agonist is used in daily clinical practice to promote feminizing physical changes in transgender women. However, the possibility of side effects is not well documented. The present study demonstrated that achieving estradiol and testosterone levels within therapeutic targets is important for the safety of gender-affirming therapy.

Background: Radical radiotherapy (RT) combined with androgen deprivation therapy is currently the standard treatment for elderly patients with localized intermediate- or high-risk prostate cancer (PC). To increase the recurrence-free and overall survival, we conducted an adjuvant, randomized trial using docetaxel (T) in PC patients (Scandinavian Prostate Cancer Group trial 13). Methods: The inclusion criteria are the following: men >18 and ⩽75 years of age, WHO/ECOG performance status 0–1, histologically proven PC within 12 months before randomization and one of the following: T2, Gleason 7 (4+3), PSA >10; T2, Gleason 8–10, any PSA; or any T3 tumors. Neoadjuvant/adjuvant hormone therapy is mandatory for all patients. The patients were randomized to receive six cycles of T (75 mg m −2 d 1. cycle 21 d) or no docetaxel after radical RT (with a minimum tumor dose of 74 Gy). This study identifier number is NTC 006653848 ( http://www.clinicaltrials.org ). Results: In this preplanned safety analysis of 100 patients, T treatment induced grade (G) 3 adverse events (AEs) in 15 patients (30%) and G4 AEs in 30 patients (60%), mainly due to bone marrow toxicity. Neutropenia G3–4 was observed in 72% of the patients, febrile neutropenia was found in 24% of patients, neutropenic infection in 10% of patients and G3 infection without neutropenia in 4% of patients. Nonhematological G3 AEs were rare: anorexia, diarrhea, mucositis, nausea, pain (1 patient each) and fatigue (5). Other severe serious AEs related to T were pulmonary embolism and renal failure. However, only three patients discontinued T before completing the planned six cycles. No deaths had occurred. No patients in the control arm experienced G3–4 toxicities at 12 weeks after the randomization. Conclusions: Adjuvant docetaxel chemotherapy after radiotherapy has a higher frequency of neutropenia than previous studies on patients with metastatic disease. Otherwise, the treatment was quite well tolerated.

In 2007, a hydrogel histrelin implant was approved for the treatment of children with central precocious puberty (CPP). Children with CPP commonly have reduced height potential due to premature closure of the epiphyseal growth plates from exposure to sex steroids. Gonadotropin-releasing hormone analog (GnRHa) treatment halts puberty and allows for improvement of adult height. A hydrogel implant delivery system utilizing the potent GnRHa, histrelin, was first developed for use in men with prostate cancer. A once yearly histrelin subcutaneous implant was subsequently developed for the treatment of children with CPP. Studies to date have demonstrated safety, tolerability, and effectiveness of this treatment option in patients treated up to 2 years. The most common adverse effects of the implant relate to implant site pain or bruising. Cost of this treatment seems comparable to somewhat higher than the commonly used GnRHa treatment option, depot leuprolide. While long term studies are needed to establish continued efficacy and safety beyond 2 years of treatment, the histrelin implant appears to be an attractive option for GnRHa treatment in patients with CPP.

In two separate controlled clinical trials, the efficacy and safety of 2.2 mg of the GnRH analogue deslorelin, administered subcutaneously as a short-term implant to normally cycling mares in oestrus with a dominant ovarian follicle more than 30 mm in diameter, were evaluated, using a placebo as a negative control. The oestrous cycle of each mare was followed by teasing, palpation per rectum and transrectal ultrasonography. Follicles were monitored every 24 hours by ultrasonography until ovulation occurred. The mares were either mated naturally or inseminated artificially. In trial 1, 174 mares were treated at six locations in Canada, and in trial 2, 98 mares were treated at three locations in the USA. In trial 1, the treatment with deslorelin reduced the mean (sd) time to ovulation from 84.2 (48.4) hours to 50.2 (19.6) hours (P<0.001) and in trial 2 it reduced it from 88.8 (40.3) hours to 54.1 (26.5) hours (P<0.001). In trial 1, the percentage of mares ovulating within 48 hours increased from 37.7 per cent in control mares to 86.1 per cent in treated mares (P<0.001) and in trial 2 the percentage increased from 26.5 to 80.9 per cent (P<0.001). In trial 2, the duration of oestrus in the deslorelin-treated mares was reduced from 6.1 days to 4.3 days and the number of matings or artificial inseminations was reduced from 2.5 to 1.7 (P<0.001). In trial 1, days 12 to 20 pregnancy rates for matings at the treatment oestrus were not different for deslorelin-treated (75.6 per cent) and placebo-treated (66.1 per cent) mares. In trial 2, days 12 to 20 pregnancy rates from matings at the treatment oestrus were lower for deslorelin-treated (58.7 per cent) than for placebotreated (83.3 per cent) mares (P<0.05), although pregnancy rates were similar for deslorelin-treated (97.1 per cent) and placebo-treated (95.0 per cent) mares after mating at the second oestrus. In both trials, pregnancy losses due to early or late abortions were within the normally expected range and similar for deslorelin-treated (3.6 and 3.7 per cent, respectively) and placebo-treated (13.4 and 7.5 per cent) mares. The treatments did not cause systemic side effects and local reactions at the implantation sites were slight and of short duration.