Effect Of GnRH Analogue Research Articles

Effect of GnRH analogue, buserelin acetate, on semen quality of subfertile male dogs

Effect of GnRH analogue, buserelin acetate, on semen quality of subfertile male dogs

Effect of GnRH analogs in advanced male breast cancer: 10-year experience from the Henan Breast Cancer Center and literature review.

Effect of GnRH analogs in advanced male breast cancer: 10-year experience from the Henan Breast Cancer Center and literature review.

Back to the Future: Is GnRHa Treatment in Transgender and Gender Diverse Adolescents Only an Extended Evaluation Phase?

The role of body modifications induced by gonadal suppression in transgender and gender diverse adolescents on psychological functioning has not yet been evaluated. The main aim of the present study was to explore several hormone, physical and psychological functioning changes during gonadotropin-releasing hormone analog (GnRHa) treatment in transgender and gender diverse adolescents (TGDAs). The potential relationship between the physical and hormone effects of GnRHa and psychological well-being, along with its magnitude, was assessed for the first time. This prospective multidisciplinary study included 36 TGDA (22 assigned female at birth, and 14 assigned male at birth) who received psychological assessment followed by triptorelin prescription after referring to the Florence Gender Clinic. This study consisted of 3 time points: first referral (T0), psychological assessment (T1); and treatment with intramuscular injections of triptorelin for 3 up to 12 months (T2). Psychometric questionnaires were administered at each time point, and clinical and biochemical evaluations were performed at T1 and T2. The following results were found: (1) GnRHa showed efficacy in inhibiting puberty progression in TGDAs; (2) an increase in psychopathology was observed before starting GnRHa (T1) compared with baseline levels; (3) during GnRHa treatment (T2), a significant improvement in psychological functioning, as well as decrease in suicidality, body uneasiness, depression, and anxiety levels were observed; (4) hormone and physical changes (in terms of gonadotropin and sex steroid levels, height and body mass index percentiles, waist-hip ratio, and acne severity) observed during triptorelin treatment significantly correlated with a reduction in suicidal ideation, anxiety, and body image concerns. Psychological improvement in TGDA on GnRHa seems to be related to the objective body changes induced by a GnRHa. Therefore, the rationale for treatment with a GnRHa may not only be considered an extension of the evaluation phase, but also the start of a medical (even if reversible) gender-affirming path, especially in TGDAs whose puberty has already progressed.

Puberty Assessment and Consideration of Gonadotropin-Releasing Hormone Agonists in Transgender and Gender-Diverse Youth.

Transgender and gender-diverse (TGD) youth may pursue gender-affirming medical therapy in the form of gonadotropin-releasing hormone analogues (GnRHa), or "puberty blockers," if pubertal changes result in the development or worsening of gender dysphoria. GnRHa monotherapy can allow TGD youth to explore gender without the distress of unwanted secondary sexual characteristics. However, given the potential effects of GnRHa on growth, skeletal development, neurodevelopment, fertility, and future surgical outcomes, it is critical to accurately assess pubertal status to facilitate fully informed conversations with TGD youth and families about risks, benefits, and unknown consequences of GnRHa monotherapy. The focus of this discussion will be on the approach to puberty assessment in TGD youth as well as the different effects of GnRHa monotherapy that may be important to TGD youth and their families. [Pediatr Ann. 2023;52(12):e462-e466.].

Effects of GnRH analogs on strip spawning and steroid plasma levels of Colossoma macropomum

Effects of GnRH analogs on strip spawning and steroid plasma levels of Colossoma macropomum

Final adult height in children with central precocious puberty - a retrospective study.

Central precocious puberty (CPP) is due to premature activation of the hypothalamic-pituitary-gonadal axis. It predominantly affects girls. CPP leads to lower final height (FH), yet the treatment benefit in girls between 6 and 8 years is equivocal. Our main goal was to evaluate the effects of gonadotropin-releasing hormone analog (GnRHa) on FH and identify factors that predict FH. In a retrospective study, children with CPP (12 boys, 81 girls) that reached FH were included. Their clinical data at diagnosis and up to their final height was compared by descriptive statistics among idiopathic (iCPP) (n=68) and non-idiopathic CPP (nCPP) and between GnRHa treated (n=48) and untreated (n=15) girls with iCPP. The treatment effect of body weight (BW) adjusted GnRHa dosing was evaluated. Univariate linear regression and step-wise multivariable regression including 48 girls with iCPP treated with GnRHa were performed to identify predicting factors for FH. Children with idiopathic CPP (iCPP) reached higher FH (p=0.002) than children with non-idiopathic CPP. After the diagnosis, the treated group gained 7.0cm more than the untreated group. Yet, attributable to individualized decision-making, the FH in both groups was comparable (161.5cm in treated, 161.0cm in untreated girls with iCPP), although the onset of menarche was 2.5 years earlier among untreated girls. BW-adjusted dosing suppressed peak luteinizing hormone (LH) below 4.5 IU/L in 95% of children; however, bone age further advanced during therapy in 38% of patients. Predicting factors revealed by multivariable regression were bone age at diagnosis, BMI SDS at diagnosis, LH basal, age at start and cessation of treatment, predicted adult height and target height. (R2 = 0.72). Children with nCPP had worse FH outcome compared to iCPP despite similar CPP onset and therapeutic characteristics. Treatment by GnRHa using BW-adjusted dosing was effective in delaying menarche onset and reaching target height in girls with iCPP. Multiple factors affecting FH outcome indicated individualized decision-making regarding therapeutic intervention remains challenging. In the treated patients, among the factors that can be influenced, height at treatment cessation most significantly influenced the outcome.

RF33 | PSAT68 Gonadotropin-Releasing Hormone Agonist Therapy Does Not Affect Bone Mineral Density in Congenital Adrenal Hyperplasia: a Clinical Study

Abstract Background Children with congenital adrenal hyperplasia (CAH) are at risk for early central puberty, and gonadotropin-releasing hormone analogs (GnRHa) are frequently used aiming to improve adult height. However, their effect on bone health among the CAH population has not been previously studied. GnRHa reduce sex steroid levels and delay central puberty, which may negatively affect the achievement of peak bone mass. In healthy children, bone mass increases with time, reaching its peak between the second and third decades of life. The purpose of this study was to investigate the short-term and long-term effect of GnRHa therapy on the bone mineral density (BMD) of patients with classic CAH. Methods Sixty patients with classic CAH due to 21OH deficiency were followed longitudinally at our institution with DXA scans at the time they achieved adult height. Adult height was considered attained when bone age exceeded 15 years in girls and 17 years in boys. Twenty-one patients treated with GnRHa (81% male, 57% salt wasting, treated for mean ± SD: 4.3 ±2 years) were compared to 39 patients not treated with GnRHa (49% male, 79.5% salt wasting). BMD z scores, adjusted for height and age, were evaluated at the time they reached adult height and on average 8.3 years later. Results There was no difference between GnRHa groups in total body (p=0.96), femoral neck (p=0.24), lumbar spine (p=0.59), forearm (p=0.38), and total hip (p= 0.31) z scores at adult height attainment. In multivariable analyses, there was no effect of GnRHa on BMD z scores at any site. In reduced models, increased 17-hydroxyprogesterone (17-OHP) levels correlated with higher BMD z scores for total body (p=0.003), lumbar spine (p<0.001), and forearm (p<0.001). Higher BMI (p=0.014) and no treatment with dexamethasone (p=0.022) were also associated with higher femoral BMD z score. Overall, the follow up DXA during young adulthood (n=28) showed significant decreases in z scores at total body (p=0.019), femoral neck (p=0.036), lumbar spine (p<0.001), forearm (p<0.001), and total hip (p=0.024), and use of GnRHa did not contribute. Interestingly, when adjusting for midparental height, those treated with GnRHa had lower adult height z scores than those without GnRHa (p=0.037). Conclusion Treatment with GnRHa for approximately 4 years does not impact BMD in adolescents and young adults with CAH, and exposure to adrenal androgens may play a protective role. In patients with CAH, BMD decreases with time and during the second and third decades of life, which may reflect the effect of long-term supraphysiologic glucocorticoid therapy. Although intended to preserve height, children with CAH who experience early puberty have loss of adult height, despite treatment with GnRHa. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:54 p.m. - 12:59 p.m.

18. Continuation of Gonadotropin-Releasing Hormone Analogue Use Among Transgender and Gender-Diverse Adolescents With Access to Low- or no-Cost Gender-Affirming Medical Care

The Endocrine Society Guideline for Transgender Care and the World Professional Association for Transgender Health Standards of Care recommend the use of gonadotropin-releasing hormone analogues (GnRHa) as a treatment option for adolescents with gender dysphoria who have not completed puberty. These medications attenuate sex hormone production and pause development of secondary sex characteristics. The effects of GnRHa are reversible, allowing adolescents time to explore their gender identity before determining if they would benefit from interventions with partially irreversible effects, such as gender-affirming hormones.

The expression of Annexin A1 and A5 mRNA by gonadotropin-releasing hormone in LβT2 gonadotrope cells.

Gonadotropin-releasing hormone (GnRH) stimulation of annexin A1 (ANXA1) and A5 (ANXA5) mRNA expression was analyzed in LβT2 gonadotrope cells. Quantitative polymerase chain reaction results showed that a GnRH analog (GnRHa) stimulated the expression of both ANXA1 and A5 mRNA with a peak at 12 h of incubation; however, ANXA1 mRNA was extremely stimulated (60 folds). Immunocytochemical analysis confirmed these findings. A GnRH antagonist inhibited the effect of GnRHa. ANXA1 and A5 mRNA levels were significantly increased by protein kinase C (PKC) activator (12-O-Tetradecanoylphorbol-13-acetate; TPA), but not by dibutyryl cAMP. GnRHa-stimulated induction of ANXA1 and A5 mRNA was inhibited by PKC (GF109203) and MEK inhibitors (PD98059). TPA increased ANXA1 and A5 mRNA expression in a dose-dependent manner (1 nM to 10 μM), while the extent of the increase was much greater in ANXA1. After stimulation with 10 nM or 1 μM TPA, ANXA1 and A5 mRNA levels were increased at 6 h. ANXA1 mRNA levels were higher in the 1 μM TPA than in the 10 nM TPA treatment, whereas 1 μM TPA did not show further stimulation of ANXA5 mRNA compared to 10 nM TPA. These results clearly show that ANXA1 mRNA expression is stimulated by GnRH through PKC like ANXA5, and the response of ANXA1 is much larger than that of ANXA5. A close relationship between these annexins and a significant role for ANXA1 in GnRH action at gonadotropes is suggested.

Effects of Gonadotropin-Releasing Hormone Analogs on Ovarian Function Against Chemotherapy-Induced Gonadotoxic Effects in Premenopausal Women With Breast Cancer in China

Studies of the use of gonadotropin-releasing hormone analogs (GnRHa) to protect ovarian function have shown mixed results. To determine whether administering GnRHa during chemotherapy in premenopausal women with breast cancer can reduce ovarian impairment. This randomized clinical trial, conducted at the Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital and Zhejiang Cancer Hospital in China, was an open-label trial involving premenopausal women aged 18 to 49 years with operable stage I to III breast cancer for which treatment with adjuvant or neoadjuvant cyclophosphamide-containing chemotherapy was planned in 2 parallel groups: treatment with chemotherapy with or without GnRHa. Enrollment occurred from September 2015 to August 2017, and follow-up ended December 2020. The data were analyzed in March 2021. A total of 405 patients were enrolled in the study, among whom 27 patients (6.7%) quit participation voluntarily, 33 (8.1%) did not meet the inclusion criteria and were excluded, and 15 (3.7%) were lost to follow-up. Ultimately 330 patients were included in the primary analysis, including 29 patients with baseline anti-Müllerian hormone levels less than 0.5ng/ mL. Eligible patients were randomly assigned (1:1) to receive chemotherapy with (n = 165) or without (n = 165) GnRHa. In patients randomized to receive GnRHa, 3.6 mg of goserelin or 3.75 mg of leuprorelin was injected subcutaneously once every 28 days from 1 to 2 weeks before the first cycle of chemotherapy to 4 weeks after the last cycle of chemotherapy. The primary end point was the rate of premature ovarian insufficiency (POI) at 12 months after chemotherapy. Premature ovarian insufficiency was defined as anti-Müllerian hormone levels of less than 0.5 ng/mL in this study. The secondary end point was overall survival (OS) and tumor-free survival (TFS). A total of 330 eligible patients could be evaluated with complete data, among whom 301 patients (91.2%; GnRHA group: mean [SD] age, 40.6 [6.7] years; control group: mean [SD] age, 40.2 [5.9] years) were eligible for primary end point analysis. At 12 months after the completion of chemotherapy, the POI rate was 10.3% (15 of 146) in the GnRHa group and 44.5% (69 of 155) in the control group (odds ratio, 0.23; 95% CI, 0.14-0.39; P < .001). Anti-Müllerian hormone resumption in the GnRHa group was significantly better than that in the control group (15 of 25 vs 6 of 44; odds ratio, 4.40; 95% CI, 1.96-9.89; P < .001). After a median follow-up of 49 months (range, 25-60 months), the differences in 4-year OS and TFS between the 2 groups were not significant. A post hoc analysis showed that in patients younger than 35 years, the TFS was higher in the GnRHa group than in the control group (93% vs 62%; P = .004; hazard ratio, 0.15; 95% CI, 0.03-0.82; P = .03). This randomized clinical trial found that administering GnRHa in treatment with chemotherapy for premenopausal patients with breast cancer reduces the risk of POI, which promotes the recovery of ovarian function. ClinicalTrials.gov Identifier: NCT02518191.

Testosterone Recovery after Neoadjuvant Gonadotropin-Releasing Hormone Antagonist versus Agonist on Permanent Iodine-125 Seed Brachytherapy in Prostate Cancer Patients: A Propensity Score Analysis.

Optimal neoadjuvant hormone therapy (NHT) for reducing prostate cancer (PC) patients' prostate volume pre-brachytherapy is controversial. We evaluated the differential impact of neoadjuvant gonadotropin-releasing hormone (GnRH) antagonist versus agonist on post-brachytherapy testosterone recovery in 112 patients treated pre-brachytherapy with NHT (GnRH antagonist, n=32; GnRH agonists, n=80) (Jan. 2007-June 2019). We assessed the effects of patient characteristics and a GnRH analogue on testosterone recovery with logistic regression and a propensity score analysis (PSA). There was no significant difference in the rate of testosterone recovery to normal levels (> 300 ng/dL) between the GnRH antagonist and agonists (p=0.07). The GnRH agonists induced a significantly more rapid testosterone recovery rate at 3 months post-brachytherapy versus the GnRH antagonist (p<0.0001); there was no difference in testosterone recovery at 12 months between the GnRH antagonist/agonists (p=0.8). In the multivariate analysis, no actor was associated with testosterone recovery. In the PSA, older age and higher body mass index (BMI) were significantly associated with longer testosterone recovery. Post-brachytherapy testosterone recovery was quicker with the neoadjuvant GnRH agonists than the antagonist, and the testosterone recovery rate was significantly associated with older age and higher BMI. Long-term follow-ups are needed to determine any differential effects of GnRH analogues on the quality of life of brachytherapy-treated PC patients.

Effect of gonadotropin-releasing hormone analogue treatment in improving final adult height of children with central precocious puberty or early and fast puberty: a Meta analysis.

To systematically evaluate the effect of gonadotropin-releasing hormone analogue (GnRHa) treatment on the final adult height of children over 6 years of age with central precocious puberty (CPP) or early and fast puberty (EFP). PubMed, MEDLINE, Embase, Cochrane Library, CNKI, and Wanfang Data were searched for related articles on GnRHa treatment for children with CPP or EFP. Stata 12.0 software was used to perform a Meta analysis of related data. A total of 10 studies were included, and the total sample size was 720 children, with 475 children in the GnRHa treatment group and 245 children in the control group. The Meta analysis showed that compared with the control group, the GnRHa treatment group had significantly better final adult height (WMD=3.30, 95%CI: 2.49-4.12, P<0.001), standard deviation score of final adult height (WMD=0.51, 95%CI: 0.29-0.73, P<0.001), and height gain (WMD=2.89, 95%CI: 2.17-3.60, P<0.001). No severe adverse events were reported in these studies. GnRHa treatment is safe and effective in improving the final adult height of children over 6 years of age with CPP or EFP.

126P Effects of GnRHa on ovarian function against chemotherapy-induced gonadotoxicity in premenopausal women with breast cancer in China: A prospective randomized controlled trial (EGOFACT)

Premature ovarian insufficiency (POI) is a common toxic effect of chemotherapy in premenopausal female patients. Studies of the use of gonadotropin-releasing hormone analogs (GnRHa) to protect ovarian function have shown mixed results. There has never been any randomized controlled study data on Chinese patients.

P–644 Effect of a reduced dose of long-acting gonadotropin releasing hormone (GnRH) agonist versus short-acting GnRH agonist on pregnancy outcome in patients undergoing ICSI/ET cycles

Abstract Study question Are pregnancy outcome different between reduced dose of long-acting GnRH agonist and short-acting GnRH agonist in patients undergoing ICSI/ET cycles? Summary answer Clinical outcomes were not significantly different between the two group. What is known already There is no consensus on which of two GnRH agonist protocol is the most effective form and it has been challenging which one improves the clinical pregnancy rate. Study design, size, duration This is randomized clinical trial that 394 patients, who were candidates for ICSI/ET, were included in this study between April 2019 and January 2020. Participants/materials, setting, methods Patients were randomly divided into two groups using blocks of 8; hereby every 8 subjects were randomized, four were allocated to the long-acting GnRH agonist, and four were allocated to the short-acting GnRH agonist randomly. Main results and the role of chance No significant difference was noted between the two groups in progesterone and estradiol levels at hCG administration day. Despite no significant difference between the two groups in ART outcomes, interestingly rate of ovarian hyperstimulation syndrome (OHSS) occurrence was significantly higher in the short-acting group (P = 0.005). Limitations, reasons for caution We couldn’t evaluate the long-term consequence of pregnancy including live birth rate and effect of GnRH analogue on fetus. Wider implications of the findings: A lower rate of OHSS occurrence in the long-acting group, and similar ART outcomes in both groups. Trial registration number IRCT20190609043845N1

Effects of GnRHa and hCG with or without dopamine receptor antagonists on the spawning efficiency of African catfish (Clarias gariepinus) reared in hatchery conditions

Optimization of artificial reproduction is essential for minimizing genetic diversity, especially when fish are captured from their natural habitats and spawned in controlled conditions. In the present study, there was evaluation of the effects of gonadotropin-releasing hormone analogue (GnRHa) and human chorionic gonadotropin (hCG) with or without dopamine receptor antagonists such as domperidone (DOM) and metoclopramide (MET) on the spawning efficiency of African catfish (Clarias gariepinus) reared in captivity. The control group was intramuscularly (IM) injected with 1 mL of sterile saline solution. The fish specimens of the other six groups were injected IM with GnRHa or hCG, or in combination with either DOM or MET. None of the specimens had ovulations in the control group. There was the longest latency period in specimens treated with only GnRHa or hCG. There were the largest egg mass weight, fecundity, and hatchability (%) in specimens of the GnRHa + MET group. These findings indicate that GnRHa or hCG combined with dopamine receptor antagonists such as DOM and MET resulted in a marked enhancement of ovulation rate and increased the egg mass, fecundity, and hatchability of the treated C. gariepinus, and the values when there was inclusion of the MET treatment exceeded those when there was treatment with DOM.

The effect of gonadotropin-releasing hormone analogues on the preservation of ovarian function against cyclophosphamide-induced damage in adult mice

<strong>Objective: </strong> To assess the effect of gonadotropin-releasing hormone analogue (GnRHa) on the preservation of ovarian function against cyclophosphamide-induced gonadal toxicity. <strong>Materials and Methods: </strong> In a controlled, experimental study, 64 female mice were divided into four groups: control (C), triptorelin acetate (T), cyclophosphamide (CY), and triptorelin plus cyclophosphamide (T+CY) groups. Mice in the group (T) were subcutaneously injected with GnRHa (triptorelin acetate) in a dose of 0.5 mg/kg daily for 21 days. In contrast, mice in the (CY) group and (T+CY) group were injected intraperitoneally with 75 mg/kg of CY on day 15. After 21 days, half of the mice in each group were sacrificed, and their ovaries were removed. The rest of the mice in each group were left without any intervention for an additional 21 days, and the same procedures were repeated to assess the ovarian follicles. <strong> </strong> <strong>Results: </strong> There was significant depletion of ovarian follicles in the CY group compared to the control group (p<0.05). There were significant decreases in the number of secondary and antral follicles at late stage as compared to early stage in the CY group (p<0.05). There was also a significant increase in the number of primordial and primary follicles in the T+CY group as compared with the CY group early post-treatment, while the increase was significant in all follicles after 42 days (p<0.05). <strong>Conclusion: </strong> Cyclophosphamide destroys primordial and primary follicles at an early stage while damage in secondary and antral follicles was prominent after 42 days. Triptorelin acetate reduces the toxic effect of CY; it has early and late protective effects and preserves ovarian function in mice.

Effect of gonadotropin-releasing hormone analog on ovarian reserve in children with central precocious puberty.

Gonadotropin-releasing hormone analog (GnRHa) is the mainstream treatment for central precocious puberty (CPP). However, its effect on the ovarian reserve in CPP girls remains unclear. This study was designed to analyze the changes of ovarian reserve in CPP girls during and after GnRHa therapy, with an attempt to achieve the early prediction of the effect of GnRHa treatment on the reproductive function of CPP girls, eliminate the concerns of girls and their parents on the potential toxicities of GnRHa treatment, and improve the patients' adherence to treatment. The clinical data of 383 CPP girls who had been treated with GnRHa for more than half a year in our hospital within the past 10 years were retrospectively analyzed. The serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), FSH/LH, estradiol (E2), and anti-Müllerian hormone (AMH) levels, as well as uterine and ovarian volumes, were measured before treatment, at various time points during treatment, and after menarche or resumption of menses (ROM) after treatment discontinuation. GnRHa treatment had similar effects on uterine/ovarian volumes, LH, FSH, and E2: these indicators were significantly inhibited during the treatment (compared with the pre-treatment levels), gradually returned normal after drug withdrawal, and became significantly higher than the pre-treatment levels after menarche or ROM (both P<0.05 for LH and FSH levels and P>0.05 for E2 and uterine/ovarian volumes). AMH level transiently decreased 6 months after GnRHa treatment (2.70±1.76 vs. 3.56±2.21, t=3.227, P=0.001); however, the AMH levels after 12, 18, and 24 months of treatment were similar to the pre-treatment level (P>0.05). The FSH/LH ratio significantly increased after 12 months of treatment compared with the pre-treatment (P<0.05), and the FSH/LH ratio after menarche or ROM was significantly lower than the pre-treatment value (1.34±0.66 vs. 5.69± 6.85, t=3.068, P=0.006). When FSH/LH and FSH level were used to reflect the ovarian reserve, the proportion of CPP girls with normal ovarian reserve after menarche or ROM was higher than at pre-treatment (FSH/LH ratio: 100% vs. 46%, χ2=27.586, P<0.05; FSH level: 100% vs. 99%, P>0.05). When AMH level was used to reflect the ovarian reserve, the proportion of CPP girls with normal ovarian reserve after menarche or ROM was slightly lower than at pre-treatment (87% vs. 93%, P>0.05). The ovarian reserve of CPP girls is somehow inhibited during GnRHa treatment but is gradually restored after drug discontinuation. Thus, GnRHa treatment does not affect ovarian reserve in CPP children after the treatment stops.

Long-Term Outcomes of Treatments for Central Precocious Puberty or Early and Fast Puberty in Chinese Girls.

Gonadotropin-releasing hormone analogues (GnRHa) and recombinant human growth hormone (rhGH) have been widely used to treat idiopathic central precocious puberty (CPP) or early and fast puberty (EFP). However, large-scale studies to evaluate the treatment effects on final adult height (FAH) are still lacking. To assess the effects of long-term treatment for CPP/EFP on FAH and its main influencing factors. Retrospective, multicenter observational study from 1998 to 2017. Four hundred forty-eight Chinese girls with CPP/EFP received GnRHa and rhGH treatment (n = 118), GnRHa alone (n = 276), or no treatment (n = 54). FAH, target height (Tht), and predictive adult height (PAH). The height gain (FAH-PAH) was significantly different among the GnRHa and rhGH treatment, GnRHa alone, and no treatment groups (P < 0.05; 9.51 ± 0.53, 8.07 ± 0.37, and 6.44 ± 0.91 cm, respectively). The genetic height gain (FAH-Tht) was 4.0 ± 0.5 cm for the GnRHa + rhGH group and 2.0 ± 0.27 cm for the GnRHa group, while the control group reached their Tht. In addition, 5 critical parameters derived from PAH, bone age, and Tht, showed excellent performance in predicting which patients could gain ≥5 cm (FAH-PAH), and this was further validated using an independent study. The overall beneficial effect of GnRHa + rhGH or GnRHa on FAH was significant. The control group also reached their genetic target height. Clinicians are recommended to consider both the potential gains in height and the cost of medication.

Near final adult height, and body mass index in overweight/obese and normal-weight children with idiopathic central precocious puberty and treated with gonadotropin-releasing hormone analogs.

Background The standard treatment of central precocious puberty (CPP) is gonadotropin-releasing hormone analogues (GnRHa). It is a concern that children treated with GnRHa are at risk of developing obesity which could impair the treatment outcomes. This study aimed to investigate the effect of GnRHa on body mass index (BMI) standard deviation score (SDS), and the influence of BMI status on treatment outcomes in children with idiopathic CPP (iCPP). Methods A retrospective cohort study in children with iCPP who completed GnRHa treatment and had attained near final adult height (NFAH) was conducted. Children with a history of disease or drug ingestion which could affect their BMI were excluded. BMI, BMI SDS, height (Ht), Ht SDS, predicted adult height (PAH), and NFAH were compared at baseline, 1 and 2 years during treatment, and at NFAH according to the baseline BMI status; normal weight and overweight/obesity. Results Fifty-eight children with iCPP treated with GnRHa were enrolled. The BMI SDS was significantly increased at 1 and 2 years during treatment in the overweight/obese group and at 1 year during treatment in the normal-weight group. However, at NFAH (2 years after treatment discontinuation), the BMI SDS was not statistically different from baseline in both groups. Ht gain, change in Ht SDS and BMI SDS were not statistically different from the baseline in both groups. Conclusions GnRHa results in a transient increase in BMI SDS during treatment and returned to baseline after treatment cessation. The benefit of GnRHa treatment on final Ht improvement is similar between overweight/obese and normal-weight patients.

Gonadotropin-Releasing Hormone Analogs for Gonadal Protection During Gonadotoxic Chemotherapy: A Systematic Review and Meta-Analysis.

A systematic review and meta-analysis was conducted to investigate whether gonadotropin-releasing hormone analogs (GnRHa) have a protective role in women treated with alkylating agents. Major databases (PubMED, EMBASE, Cochrane Central Register of Controlled Trials), systematic snowballing, and trial registries were screened from the inception dates until September 2017. Comparative studies involving reproductive-aged women undergoing chemotherapy with or without coadministration of GnRHa were included. Spontaneous menstrual resumption was assessed as a main outcome. Statistical analyses were performed with STATA 14.2 statistical software. Effect estimates were presented as risk ratios (RR) with 95% confidence intervals (CIs). The literature search yielded 25 436 citations and 84 papers were assessed in full text. Eighteen studies (11 randomized controlled trials [RCTs] and 7 cohort studies) published between 1987 and 2015 were included in the analysis, revealing a significant protective effect of GnRHa (n = 1043; RR:1.38; 95% CI: 1.18-1.63) although with high heterogeneity (I2 = 83.3%). Subgroup analyses revealed a significant benefit of GnRHa cotreatment both in RCTs and in cohort studies. Statistical significance was found in all subgroups by the underlying disease, that is, hematological malignancies, autoimmune diseases, and breast cancer. Sensitivity analyses in GnRH agonist-treated patients, in patients younger than 40 years old, and in patients without supradiaphragmatic radiotherapy also revealed a significant benefit of GnRHa cotreatment. Our results indicate that concurrent GnRHa administration is an effective method to decrease gonadotoxicity of alkylating agents. The presence of low-quality evidence favoring gonadoprotective effect requires a strong recommendation for offering GnRHa coadministration to young women who are to undergo gonadotoxic chemotherapy. The present systematic review and meta-analysis shows a significant gonadoprotective effect of gonadotropin-releasing hormone analogs in women treated with alkylating agents.