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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.

Background/Aims: Treatment with quarterly gonadotropin-releasing hormone (GnRH) analogs may improve compliance and optimize outcome in girls with central precocious puberty (CPP), but long-term comparative data between the new and the monthly formulations are very scarce. Methods: A group of girls with idiopathic CPP (n = 13; age 7.9 ± 0.6 years) were treated from the beginning with quarterly triptorelin (11.25 mg/90 days) and followed up to the achievement of adult height (AH). A group of girls with idiopathic CPP (n = 12; age 8.0 ± 0.6 years) treated with monthly triptorelin (3.75 mg/28 days) served as controls. Results: The AH (157.1 ± 4.9 cm) of girls treated with quarterly triptorelin was not significantly different from their mid-parental height (159.7 ± 3.8 cm) and significantly increased in comparison with predicted AH (average tables) at the beginning of GnRH analog therapy. The AH of girls treated with quarterly triptorelin was not significantly different in comparison with that of girls treated with the monthly formulation (158.1 ± 6.6 cm; mid-parental height 158.4 ± 5.0 cm). Conclusion: Treatment with quarterly triptorelin formulation permitted to achieve an AH adequate for mid-parental height in girls with CPP. Significant differences of AH between girls with CPP treated with quarterly or monthly formulations were not found.

To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare growth hormone (GH) profiles and fasting insulin-like growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) levels after 3 months of GnRHa treatment with those at baseline. After measurement of baseline overnight profiles and IGF-I and IGFBP-3 levels, 14 short pubertal SGA boys received leuprorelide acetate depots of 3.75 mg subcutaneously, every 4 weeks. At baseline, mean GH levels were comparable with those of controls, whereas IGF-I and IGFBP-3 standard deviation scores (SDS) were significantly lower than zero SDS. After 3 months of GnRHa treatment, all boys showed clinical arrest of puberty. The area under the curve above zero, mean and maximum LH and FSH had significantly decreased to prepubertal levels. Peak LH during the GnRH agonist test, however, indicated insufficient pubertal suppression in 43% of boys. Overnight GH profile characteristics and IGF-I and IGFBP-3 levels did not significantly change. Puberty was sufficiently suppressed by GnRHa treatment, as shown by the prepubertal LH and FSH profiles. After 3 months of GnRHa treatment, overnight GH profile characteristics had not significantly changed, reflecting that GH levels are comparable for prepubertal and early pubertal boys.

Background A consensus has been reached on the preferred primary outcome of all infertility treatment trials, which is the cumulative live birth rate (CLBR). Some recent randomized controlled trials (RCTs) and retrospective studies have compared the effectiveness of GnRH-antagonist and GnRH-agonist protocols but showed inconsistent results. Studies commonly used conservative estimates and optimal estimates to described the CLBR of one incomplete assisted reproductive technology (ART) cycle and there are not many previous studies with data of the complete cycle to compare CLBRs in GnRH-antagonist versus GnRH-agonist protocols. Methods A total of 18,853 patients have completed their first IVF cycle including fresh and subsequent frozen-thawed cycles during 2016–2019, 16,827 patients were treated with GnRH-a long and 2026 patients with GnRH-ant protocol. Multivariable logistic analysis was used to evaluate the difference of GnRH-a and GnRH-ant protocol in relation to CLBR. Utilized Propensity Score Matching(PSM) for sampling by up to 1:1 nearest neighbor matching to adjust the numerical difference and balance the confounders between groups. Results Before PSM, significant differences were observed in baseline characteristics and the CLBR was 50.91% in the GnRH-a and 33.42% in the GnRH-ant (OR = 2.07; 95%CI: 1.88–2.28; P  < 0.001). Stratified analysis showed the CLBR of GnRH-ant was lower than GnRH-a in suboptimal responders(46.89 vs 27.42%, OR = 2.34, 95%CI = 1.99–2.74; P  < 0.001) and no differences of CLBR were observed in other patients between protocols. After adjusting for potential confounders, multivariable logistic analysis found the CLBR of GnRH-ant group was lower than that of GnRH-a group (OR = 2.11, 95%CI:1.69–2.63,  P  < 0.001). After PSM balenced the confounders between groups, the CLBR of GnRH-a group was higher than that of GnRH-ant group in suboptimal responders((38.61 vs 28.22%, OR = 1.60, 95%CI = 1.28–1.99; P  < 0.001) and the normal fertilization rate and number of available embryo in GnRH-a were higher than these of GnRH-ant groups in suboptimal responders (77.39 vs 75.22%; 2.86 ± 1.26 vs 2.61 ± 1.22; P  < 0.05). No significant difference was observed in other patients between different protocols. Conclusions It is crucial to optimize the utilization of protocols in different ovarian response patients and reconsider the field of application of GnRH-ant protocols in China.

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.

Objective To compare the efficacy of three protocols for ovarian stimulation in patients with diminished ovarian reserve during in vitro fertilization (IVF) treatment. Methods This prospective randomized study enrolled patients with diminished ovarian reserve who underwent cycles of IVF or intracytoplasmic sperm injection. The patients were randomly divided into three groups: a modified gonadotrophin releasing hormone (GnRH) agonist protocol (group A); (ii) a mild stimulation protocol (group B); or (iii) an antagonist protocol (group C). Demographic characteristics, clinical variables and pregnancy outcomes were compared between the groups. Results A total of 116 patients were enrolled in the study: 54 in group A, 52 in group B and 60 in group C. Group B (32.69%) had a significantly higher cycle cancellation rate compared with groups A (11.11%) and C (16.67%). The early abortion rate of group C (44.44%) was significantly higher than group A (12.50%), but not significantly different from group B (16.67%). There were no significant differences in the clinical pregnancy rates and live birth rates among the three groups. Conclusion A modified GnRH agonist protocol achieved a comparable pregnancy rate to those of the mild stimulation protocol and antagonist protocol, whilst having lower cycle cancellation and early abortion rates.

Objective In boys during puberty who were undergoing recombinant human growth hormone (rhGH) treatment, we compared the therapeutic efficacy on growth, and any adverse reactions, of co-therapy with either letrozole or gonadotropin-releasing hormone analog (GnRHa). Methods Fifty-six pubertal growth hormone deficiency (GHD) boys were studied, they were treated with the combination of letrozole and rhGH (letrozole group, n  = 28) or the combination of GnRHa and rhGH (GnRHa group, n  = 28) for at least one year. Eighteen patients in the letrozole group and seventeen patients in the GnRHa group attained final adult height (FAH). Results The increase in height of the letrozole group was significantly more than the GnRHa group both in the first year [(10.37 ± 2.19) vs. (7.78 ± 1.55) cm] and at two years [(18.82 ± 2.49) vs. (13.84 ± 2.17) cm] ( p  < 0.05), however, there was no significant group difference in the advancement of bone age (BA) of in the first year or at two years ( p  > 0.05). The mean FAH in two groups were similar, but the treatment duration of the letrozole group was significantly less than GnRHa group. There was a significant body mass index (BMI) SDS increase in the letrozole vs. GnRHa groups. Of concern, bone mineral density (BMD) decreased in both groups after treatment, but more so in the letrozole cohort. Conclusion The combination of letrozole/rhGH in pubertal GHD boys was similar to GnRHa/rhGH in terms of the progression of BA and FAH, but the former co-therapy was superior in the gain of height. Disconcertingly, however, this combination may adversely affect BMI and BMD. Clinical trial registration number ChiCTR2300068405.

The judicious selection of ovulation inhibitors in ovarian stimulation protocols is crucial for the success of assisted reproductive technology (ART). Herein, we investigate the dose-dependent effects of chlormadinone acetate (CMA) and cetrorelix, two distinct ovulation inhibitors, on oocyte maturation in patients with normal ovarian reserve, using univariable and multivariable Poisson regression analyses. Patients undergoing progestin-primed ovarian stimulation (PPOS) with CMA ( n = 299) or gonadotropin-releasing hormone antagonist (GnRH-ant) with cetrorelix ( n = 605) during their initial in vitro fertilization cycle were enrolled at our center from March 2018 to October 2020 ( N = 904). The primary and secondary outcomes were the oocyte maturation and fertilization rates, respectively. After adjusting for several covariates including age, anti-Müllerian hormone levels, total gonadotropin dose, and type of trigger, we calculated the dose-dependent adjusted relative risk (aRR) and 95% confidence interval (CI) for 1 mg of CMA or 0.25 mg of cetrorelix. In the PPOS group, the median age was 34.0 years, and the median total CMA dosage was 22 mg (interquartile range [IQR]: 18.0–32.0). In the GnRH-ant group, the median age was 35.0 years, and the median total cetrorelix dosage was 0.5 mg (IQR 0.5–0.5). The aRR of the maturation rate was 1.003 (95% CI: 0.999–1.007) with PPOS ( p = 0.194) and 1.009 (95% CI: 0.962–1.059) with GnRH-ant ( p = 0.717). The aRR of the fertilization rate was 1.002 (95% CI: 0.985–1.020) with PPOS ( p = 0.783) and 1.022 (95% CI: 0.839–1.246) with GnRH-ant ( p = 0.829). Collectively, these findings indicate that within the applied dosages, ovulation inhibitors do not significantly impact oocyte maturation or fertilization rates in patients with normal ovarian reserve. These valuable insights can be applied when designing ART protocols and may guide clinicians in optimizing infertility treatments.

Objective The psychological issues associated with idiopathic central precocious puberty (ICPP) in girls remain a contentious topic, particularly regarding the necessity and effectiveness of psychological interventions and pharmacological treatments such as gonadotropin-releasing hormone analog (GnRHa) or GnRHa combined with recombinant human growth hormone (rhGH). Methods This study aimed to assess the psychological profiles of 95 ICPP girls and their parents, comparing them with 70 healthy controls, and to investigate the potential therapeutic effects of pharmacological interventions. For parents, psychological evaluations were conducted using the Child Behavior Checklist, State Anxiety Inventory, and Positive and Negative Affect Schedule. Whereas for ICPP and control girls, the Children’s Depression Inventory and Social Anxiety Scale for Children were administered. Results Results indicated significant psychological challenges for ICPP girls, including issues with social competence, social withdrawal, defaulters, cruelty, depressive moods, and social anxiety. Correspondingly, their parents exhibited elevated anxiety levels. After 12 months of treatment, the GnRHa group demonstrated notable improvements in aggression, depressive moods, and social anxiety. Meanwhile, improvements were also observed in defaulter behaviors and depressive moods among the GnRHa plus rhGH treated group. Additionally, parental anxiety scores significantly decreased across both treatment groups. Conclusion ICPP girls face a spectrum of psychological difficulties, with their parents also experiencing notable anxiety. Both GnRHa and GnRHa combined with rhGH treatments can reduce parental anxiety and improve the psychological and behavioral problems of ICPP girls. This highlights the importance of addressing psychological health within medical treatment plans for ICPP.

Gonadotropin-releasing hormone analogues (GnRHa) are recommended as initial treatment for adolescents diagnosed with gender dysphoria, providing time to follow gender identity development and consider further treatment wishes without distress caused by unwanted pubertal changes. This has been described as an extended diagnostic phase. However, there are also concerns about the physical, neurocognitive, and psychosocial effects of this treatment. In this retrospective study, we document trajectories after the initiation of GnRHa and explore reasons for extended use and discontinuation of GnRHa. Treatment was considered appropriate in 143 (67%) of the 214 adolescents eligible for GnRHa treatment by virtue of their age/pubertal status, and all started GnRHa (38 transgirls, 105 transboys; median age, 15.0 years [range, 11.1–18.6] and 16.1 years [range, 10.1–17.9]). After a median duration of 0.8 years (0.3–3.8) on GnRHa, 125 (87%) started gender-affirming hormones (GAH). Nine (6%) discontinued GnRHa, five of whom no longer wished gender-affirming treatment. Thirteen had used GnRHa for longer than required by protocol for reasons other than logistics and regularly met with a mental health professional during this time, supporting the use of GnRHa treatment as an extended diagnostic phase. In conclusion, the vast majority who started GnRHa proceeded to GAH, possibly due to eligibility criteria that select those highly likely to pursue further gender-affirming treatment. Due to the observational character of the study, it is not possible to say if GnRHa treatment itself influenced the outcome. Few individuals discontinued GnRHa, and only 3.5% no longer wished gender-affirming treatment.