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Background: Buserelin has been used to treat central precocious puberty (CPP). However, it could potentially result in immune dysregulation to undermine patients' health. Therefore, it is necessary to elucidate the effects of buserelin on immune cells. Here we explored buserelin-induced impacts on the differentiation and function of macrophage-colony-stimulating factor-producing T helper (ThGM) cells to uncover the immunoregulatory role of buserelin. Methods: Rat CPP was induced by danazol injection followed by buserelin treatment. The frequencies of ThGM cells in the spleen and lymph nodes were evaluated by flow cytometry. ThGM cell generation and function were analyzed in cell culture assays. Cell signaling was measured by Immunoblotting. Results: Buserelin increased the frequencies of splenic and lymph node ThGM cells. Buserelin promoted the in vitro differentiation and proliferation of ThGM cells. Buserelin-treated ThGM cells showed stronger supportive effects on other effector T helper cells. Buserelin induced the activation of the nuclear factor of activated T cells and extracellular signal-regulated kinase 1/2 in ThGM cells. Conclusion: Buserelin enhances the differentiation and function of pro-inflammatory ThGM cells, thus increasing the risk of autoimmune or inflammatory disorders. Therefore, it is necessary to monitor ThGM cells in buserelin-treated children to prevent latent immune dysregulation. [ABSTRACT FROM AUTHOR]

Cotyledonoid-dissecting leiomyoma, a very unusual form of uterine leiomyoma, often leads to misdiagnosis as a malignant tumor. Here, we describe a case of a 45-year-old nulliparous woman who underwent a laparoscopic biopsy of a large pelvic mass consisting of multiple flaps. Histologically, the mass was composed of smooth muscle fascicle nodules separated by hydropic connective tissue, and exhibited extensive stromal hyalinization. The tumor was diagnosed as a cotyledonoid-dissecting leiomyoma based on the laparoscopic, pathological, and image findings. Prior to performing radical laparotomy, two courses of leuprorelin were administered in anticipation of tumor reduction and hypoperfusion, and the tumor size reduced remarkably. We demonstrated the utility of laparoscopic biopsy, considering its minimal invasiveness and diagnostic accuracy. Furthermore, the preoperative use of Gonadotropin-releasing hormone (GnRH) analogs to reduce surgical stress may be useful for treating cotyledonoid-dissecting leiomyomas. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the height growth pattern and the incidence of significant growth deceleration in girls with CPP and EFP on GnRHa treatment, and thereby identify relevant predictors of growth deceleration. The data of 99 girls diagnosed with CPP and 47 girls with EFP were included in this retrospective analysis. The incidence of growth deceleration was calculated in both the first and second years. Multivariate logistic regression analysis was used to identify predictors indicative of growth deceleration. Growth velocity (GV) trajectories showed gradual decreases to the nadir at 18 months of treatment, and then they recovered till the 24th month of treatment, especially in girls with CPP. Nevertheless, the recovery was significantly greater in the CPP group than EFP. In the first year, no significant difference in the incidence of growth deceleration was found between the CPP group and the EFP group [17.35 vs. 25.53 %, p=0.249]; in the second year, the CPP group had a lower incidence than the EFP group [42.86 vs. 76.92 %, p=0.027]. The multivariate logistic regression analysis suggested that bone age (BA) was an independent predictor of growth deceleration (OR=2.264, 95 % CI: 1.268–4.042, p=0.006). The result of ROC curves showed the cut-off value of BA was 11.05 years. GV varies at different periods during GnRHa treatment. GnRHa should be used with more caution for EFP treatment than for CPP. BA can be used to predict the occurrence of growth deceleration during GnRHa treatment. [ABSTRACT FROM AUTHOR]

Abstract Background This retrospective study explored the effect on adult height of a combination of recombinant human growth hormone (rhGH) and aromatase inhibitors (AIs), or rhGH and a gonadotropin-releasing hormone analog (GnRHa), and compared their effects with rhGH alone in males at advanced bone age with idiopathic short stature (ISS). Methods In this retrospective study, rhGH or rhGH combined with GnRHa or rhGH combined with AI therapy was given to males with advanced bone age (13–15 years) and diagnosed with ISS. The patients were followed to assess their adult height. Results (1) A total of 68 patients were reviewed; 22 males were treated with rhGH for 24.9 ± 4.47 months, 22 males were treated with GnRHa + rhGH for 34.1 ± 3.36 months, and 24 males were treated with AI + RHGH for 22.7 ± 2.49 months. (2) Before treatment, the HtSDS-CA for the three groups were -1.04 ± 0.95, -1.23 ± 1.06, and -0.85 ± 0.98, respectively, and the HtSDS-BA were -2.14 ± 0.29, -2.14 ± 0.21, and-2.26 ± 0.31, respectively. The target heights for each group were 169.7 ± 4.0 cm, 169.7 ± 3.9 cm, and 169.1 ± 3.9 cm, respectively. The predicted adult heights were 161.7 ± 3.35 cm, 162.3 ± 1.75 cm, and 161.6 ± 2.89 cm, respectively. (3) After treatment, the HtSDS-CA for the rhGH group increased by 1.30 ± 0.58, and the HtSDS-BA increased by 2.00 ± 0.27. For the GnRHa + rhGH group, the HtSDS-CA and HtSDS-BA increased by1.42 ± 0.73and 2.74 ± 0.28, respectively. The AI + RHGH group increased by1.39 ± 0.64 and 2.76 ± 0.31, respectively. (4) There was no significant difference between the adult height (170.9 ± 0.7 cm) and target height for the rhGH group (P > 0.05), but the adult heights for the GnRHa + rhGH and AI + RHGH groups (173.2 ± 1.5 cm and 173.5 ± 1.0 cm, respectively, P > 0.05) were higher than the target height (P

Short stature in puberty significantly affects the physical and mental health of adolescents. The continuous acceleration of skeletal maturation, caused by sex hormones during puberty, limits the time available for growth and poses a considerable challenge for the treatment of short stature. To date, there is still no standardized treatment protocol for this disorder. However, puberty is the last period to improve the final adult height. Currently, commonly used pharmacological treatments in clinical settings include recombinant human growth hormone, gonadotropin-releasing hormone analogs, and third-generation aromatase inhibitors. In recent years, personalized treatment aiming to improve the final adult height has become a key focus in clinical practice. This article provides a comprehensive summary of research on pharmacological therapies for height improvement in pubertal children with short stature, offering valuable insights for healthcare professionals. [ABSTRACT FROM AUTHOR]

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Background: This retrospective study explored the effect on adult height of a combination of recombinant human growth hormone (rhGH) and aromatase inhibitors (AIs), or rhGH and a gonadotropin-releasing hormone analog (GnRHa), and compared their effects with rhGH alone in males at advanced bone age with idiopathic short stature (ISS). Methods: In this retrospective study, rhGH or rhGH combined with GnRHa or rhGH combined with AI therapy was given to males with advanced bone age (13–15 years) and diagnosed with ISS. The patients were followed to assess their adult height. Results: (1) A total of 68 patients were reviewed; 22 males were treated with rhGH for 24.9 ± 4.47 months, 22 males were treated with GnRHa + rhGH for 34.1 ± 3.36 months, and 24 males were treated with AI + RHGH for 22.7 ± 2.49 months. (2) Before treatment, the HtSDS-CA for the three groups were -1.04 ± 0.95, -1.23 ± 1.06, and -0.85 ± 0.98, respectively, and the HtSDS-BA were -2.14 ± 0.29, -2.14 ± 0.21, and-2.26 ± 0.31, respectively. The target heights for each group were 169.7 ± 4.0 cm, 169.7 ± 3.9 cm, and 169.1 ± 3.9 cm, respectively. The predicted adult heights were 161.7 ± 3.35 cm, 162.3 ± 1.75 cm, and 161.6 ± 2.89 cm, respectively. (3) After treatment, the HtSDS-CA for the rhGH group increased by 1.30 ± 0.58, and the HtSDS-BA increased by 2.00 ± 0.27. For the GnRHa + rhGH group, the HtSDS-CA and HtSDS-BA increased by1.42 ± 0.73and 2.74 ± 0.28, respectively. The AI + RHGH group increased by1.39 ± 0.64 and 2.76 ± 0.31, respectively. (4) There was no significant difference between the adult height (170.9 ± 0.7 cm) and target height for the rhGH group (P > 0.05), but the adult heights for the GnRHa + rhGH and AI + RHGH groups (173.2 ± 1.5 cm and 173.5 ± 1.0 cm, respectively, P > 0.05) were higher than the target height (P < 0.05). (5) Compared with the predicted adult height, the adult heights for the three groups improved significantly (P < 0.05). (6) No severe adverse reactions during the treatment occurred in any of the children. However, the total incidence of side effects in the three groups was significant (χ2 = 20.433, P = 0.00). Conclusion: Different therapeutic approaches have been investigated to improve the final adult height of males at advanced bone ages with ISS, and the optimal strategy remains controversial. In children at advanced bone ages with ISS, clinicians should carefully consider the advantages and disadvantages prior to treatment. [ABSTRACT FROM AUTHOR]

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 (R2 = 0.66 and adjusted R2 = 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. [ABSTRACT FROM AUTHOR]

Background/AimsCentral 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.MethodsIn 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.ResultsChildren with idiopathic CPP (iCPP) reached higher FH (p=0.002) than children with non-idiopathic CPP. After the diagnosis, the treated group gained 7.0 cm more than the untreated group. Yet, attributable to individualized decision-making, the FH in both groups was comparable (161.5 cm in treated, 161.0 cm 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).ConclusionChildren 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.

Gonadotropin-releasing hormone analogs (GnRHas) are used for treating central precocious puberty (CPP). However, their roles in the regulation of immune cells especially regulatory T cells (Tregs) remains elusive. Therefore, we characterized buserelin-induced phenotypical and functional changes of Tregs. A rat CPP model was established followed by administration of buserelin acetate. Flow cytometry was used to evaluate the expression of functional molecules in splenic Tregs. The suppressive activity of Tregs was determined by the suppression assay. GnRHR expression in Tregs was assessed by flow cytometry analysis and Immunoblotting. Normal Tregs were then stimulated and treated with buserelin acetate in vitro. After that, Foxp3 expression, Treg proliferation, and cytokine production were analyzed by flow cytometry. Intracellular signaling was evaluated by Immunoblotting, and Treg function was determined by the suppression assay. After in vivo buserelin treatment, the frequency of splenic Tregs was decreased, with the reduction in the expression of Foxp3, IL-10, and TGF-β. The suppressive activity of Tregs was weakened. Buserelin down-regulated Foxp3 expression while promoting the expression of RORγt and IL-17 in Tregs through activating the protein kinase A (PKA) pathway in vitro. The PKA inhibitor H-89 abolished the effect of buserelin and enhanced Treg function. Buserelin impaired the immunosuppressive activity of Tregs through the PKA signal pathway. Buserelin-induced activation of PKA signaling down-regulated Foxp3 expression while promoting RORγt expression in Tregs, and subsequently weakened Treg function. Our study indicates the necessity of monitoring Treg activity in CPP patients to avoid potential autoimmunity or inflammation. [ABSTRACT FROM AUTHOR]

Background and Objective: Darolutamide is an androgen receptor inhibitor that increases overall survival in combination with androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive and nonmetastatic castration-resistant prostate cancer (PCa). This phase 2 study assessed the efficacy and safety of darolutamide as monotherapy without ADT in patients with eugonadal testosterone levels., Methods: This was a 24-wk, open-label, randomized study of patients with hormone-sensitive, histologically confirmed PCa requiring gonadotropin-releasing hormone (GnRH); an Eastern Cooperative Oncology Group performance status score of 0/1; and life expectancy >1 yr. All patients received darolutamide 600 mg bid or a commercially available GnRH analog. The primary endpoint is a prostate-specific antigen (PSA) response, defined as a ≥80% decline at week 24 relative to baseline in the darolutamide study arm. The GnRH arm is used as an internal control. The secondary endpoints included changes in T levels, safety/tolerability, and quality of life., Key Findings and Limitations: Among 61 men enrolled, the median (range) age was 72 yr (53-86 yr); 42.6% of them had metastases. In the darolutamide arm, the evaluable population with available PSA values at baseline and week 24 consisted of 23 patients. Twenty-three (100%) evaluable darolutamide patients achieved a PSA decline of >80% at week 24 (primary endpoint), with a median (range) decrease of -99.1% (-91.9%, -100%). Serum T levels increased by a median (range) of 44.3 (5.7-144.0) at week 24, compared with baseline. In the darolutamide arm, 48.4% of men reported drug-related adverse events (AEs; mostly grade 1 or 2). The most frequent treatment-emergent AEs included gynecomastia (35.5%), fatigue (12.9%), hot flush (12.9%), and hypertension (12.9%). Health-related quality of life measures are descriptive, and GnRH arm results will be presented as an internal reference., Conclusions and Clinical Implications: Darolutamide monotherapy was associated with a significant PSA response in nearly all men with hormone-naïve PCa. Testosterone-level changes and most common AEs (gynecomastia, fatigue, hypertension, and hot flush) were consistent with potent androgen receptor inhibition., Patient Summary: In this study, we report the first use of darolutamide, a novel antiandrogen, as monotherapy without androgen deprivation therapy (ADT). The study shows that darolutamide induce a profound suppression of prostate-specific antigen in all patients, with a safety profile different from that of ADT., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The benefits of gonadotropin-releasing hormone analogues (GnRHa) in the treatment of central precocious puberty are well established, and their use is regarded as both safe and effective. Possible adverse effects on blood pressure (BP) and cardiac outcomes, body composition, bone health and brain development, however, continue to be of some concern. The aim of this study was to analyze BP changes in transgender female adolescents before and after receiving GnRHa and after adding estrogen treatment. This was a retrospective pilot study. We analyzed systolic BP (SBP) and diastolic BP (DBP) before and after GnRHa initiation and after adding estrogen. Nineteen transgender female adolescents received GnRHa and 15 continued to estrogen treatment. Their baseline SBP and DBP percentiles did not change significantly after either GnRHa or the addition of estrogen treatment. Blood pressure is apparently not affected by GnRHa or GnRHa + estrogen treatment in transgender female adolescents. Further larger studies are indicated to confirm these findings. [ABSTRACT FROM AUTHOR]

Relatively little is known of the effects of time of day of hormone injection on latency period in most fishes. Interest in improved culture techniques for White Crappie (Pomoxis annularis) has led to advances in tank holding and induced spawning methods. However, an understanding of latency period is needed for synchronizing and optimizing White Crappie hatchery production. Therefore, the effects of hormone injection timing on latency period and egg viability were examined. Crappie were injected with gonadotropin‐releasing hormone analog (GnRHa) at 1600 (evening treatment) and 0800 (morning treatment), monitored for latency period duration, and spawning success was determined using percent of females ovulated, ovulated egg volume and egg fertilization percent. In the evening treatment group, 75% of the females ovulated 48.40 ± 2.70 (mean ±SE) hours post initial injection and had a mean egg fertilization rate of 63%, while in the morning injection treatment, 91% of females ovulated 44.58 ± 1.36 h post initial injection and had a mean fertilization rate of 56%. No significant difference in mean latency period or spawning success was observed between treatments. Therefore, diel timing of hormone injection did not affect latency period or spawning success in White Crappie, allowing for flexibility in production. [ABSTRACT FROM AUTHOR]

Objective: To investigate the long‐term efficacy and safety of gonadotropin‐releasing hormone analog (GnRHa) treatment in children with idiopathic central precocious puberty (CPP). Method: The protocol was registered with International Prospective Register of Systematic Reviews (CRD42018102792). PubMed, EMBASE and the Cochrane Library were searched for eligible comparative and single‐arm studies. Results: We identified a total of 98 studies that included 5475 individuals. The overall risk of bias of the eligible studies ranged from critical to moderate. The overall quality of evidence for each outcome ranged from very low to moderate. Evidence‐based comparative studies showed that GnRHa treatment increase final adult height (FAH, cm; studies = 4, n = 242; mean difference [MD] = 4.83; 95% confidence interval [CI], 2.32 to 7.34; I2 = 49%) and decrease body mass index (BMI, kg/m2; studies = 3, n = 334; MD = −1.01; 95% CI, −1.64 to −0.37; I2 = 0%) in girls with idiopathic CPP compared with no treatment. The incidence of polycystic ovary syndrome (PCOS) did not significantly differ with and without GnRHa treatment (studies = 3, n = 179; risk ratio = 1.21; 95% CI, 0.46 to 3.15; I2 = 48%). The evidence for other long‐term outcomes was very weak to deduce the effects of GnRHa treatment. Further, limited evidence is available on its effects in boys. Conclusion: Compared with no treatment, evidence indicates that GnRHa treatment increase FAH and decrease BMI in girls with idiopathic CPP. GnRHa treatment did not evidently increase the risk of PCOS. However, evidence regarding other key long‐term outcomes (such as infertility and malignant or metabolic diseases) was considered very weak to suggest the benefits or side effects of GnRHa treatment. Additional high‐quality evidence is needed before firm conclusions can be drawn. [ABSTRACT FROM AUTHOR]

Abstract Purpose To evaluate the efficacy and safety of self‐injections of the prefilled recombinant human chorionic gonadotropin (r‐hCG) in a syringe in assisted reproductive technology (ART) treatment for the maturation trigger (MT), as compared to self‐injections of conventional hCG and intranasal administration of gonadotropin‐releasing hormone agonist (GnRH‐a). Methods Between January and April, 2017, 396 patients who underwent oocyte retrieval were recruited. Of these, 396 patients were classified into three groups, according to the types of MT: (1) the urinary human chorionic gonadotropin (u‐hCG) group that consisted of patients who had a self‐injection of u‐hCG (n = 127); (2) the GnRH‐a group that received nasal administration of GnRH‐a (n = 159); and (3) the r‐hCG group that had a self‐injection of r‐hCG (n = 110). Several ART outcomes were evaluated. Results The mature oocyte retrieval rate was not different between the u‐hCG, r‐hCG, and GnRH‐a groups and the fertilization and cleavage rates were similar between the three groups. The clinical pregnancy rates did not significantly differ between the GnRH‐a group and the u‐hCG group; however, it was significantly lower in the GnRH‐a group, compared to the r‐hCG group. No difference was observed in the incidence of moderate or more severe ovarian hyperstimulation syndrome among the three groups. Conclusion The self‐injection of the prefilled r‐hCG is a favorable MT for ART patients.

Introduction: About 8% of children born small for gestational age (SGA) do not reach a final height within the normal range. Recombinant human growth hormone (rhGH) has been shown to be effective in increasing the final height in children born SGA. Our objective was to identify predictive factors of final height in children born SGA treated with rhGH. Materials and Methods: In this retrospective study, conducted in a tertiary pediatric endocrinology referral center, we recruited all patients born SGA (defined as birth length or weight <10th percentile) treated with rhGH for more than 12 months for whom final height data were available. Some patients had received gonadotropin-releasing hormone (GnRH) analog therapy. Results: We included 252 patients with an average birth length of −2.0 ± 0.7 SD and birth weight of −1.7 ± 1.0 SD. After 4.6 ± 2.8 years of rhGH treatment, their height increased from −2.2 ± 0.9 SD to −1.5 ± 0.9 SD. In multivariate analysis, we identified 8 factors that predict 46% of the final height, namely, cause of SGA (p < 0.0001), GnRH analog therapy >2 years (p = 0.006), birth length (p < 0.02), height at the start of rhGH (p < 0.0001), IGF-1 level at the start of rhGH (p = 0.0002), growth velocity during the 1st year of treatment (p = 0.0002), and age and height at the onset of puberty (p < 0.0001, p = 0.0007, respectively). Conclusion: In this large cohort of SGA patients who had reached their final height, we were able to confirm that growth hormone increases final height in short SGA children. In addition, we identified several factors associated with a better response to growth hormone treatment. [ABSTRACT FROM AUTHOR]

Introduction: Loss-of-function mutation of MKRN3 represents the most frequent genetic cause of familial central precocious puberty (CPP). The outcomes of gonadotropin-releasing hormone analog (GnRHa) treatment in CPP patients with MKRN3 defects are unknown. Objective: To describe the clinical and hormonal features of patients with CPP with or without MKRN3 mutations after GnRHa treatment. Anthropometric, metabolic and reproductive parameters were evaluated. Patients and Methods: Twenty-nine female patients with CPP due to loss-of-function mutations in the MKRN3 and 43 female patients with idiopathic CPP were included. Their medical records were retrospectively evaluated for clinical, laboratory, and imaging study, before, during, and after GnRHa treatment. All patients with idiopathic CPP and 11 patients with CPP due to MKRN3 defects reached final height (FH). Results: At the diagnosis, there were no significant differences between clinical and laboratory features of patients with CPP with or without MKRN3 mutations. A high prevalence of overweight and obesity was observed in patients with CPP with or without MKRN3 mutations (47.3 and 50%, respectively), followed by a significant reduction after GnRHa treatment. No significant differences in the values of mean FH and target height were found between the 2 CPP groups after GnRHa treatment. Menarche occurred at the expected age in patients with or without CPP due to MKRN3 mutations (11.5 ± 1.3 and 12 ± 0.6 years, respectively). The prevalence of polycystic ovarian syndrome was 9.1% in patients with CPP due to MKRN3 mutations and 5.9% in those with idiopathic CPP. Conclusion: Anthropometric, metabolic, and reproductive outcomes after GnRHa treatment were comparable in CPP patients, with or without MKRN3 mutations, suggesting the absence of deleterious effects of MKRN3 defects in young female adults' life. [ABSTRACT FROM AUTHOR]

In order to accurately estimate body composition at slaughter and to meet specific market targets, the influence of age at time of castration (surgical or immunological) on body composition and boar taint indicators must be determined for male pigs. In all, 48 males were randomly assigned to one of four management regimens: (1) entire male pigs (EM), (2) EM surgically castrated at ~40 kg BW and 10 weeks of age (late castrates; LC), (3) conventional, early surgical castrates (within 4 days of birth; EC) and (4) EM immunized with a gonadotropin-releasing hormone (GnRH) analog (primary dose at 30 kg BW and 8 weeks of age; booster dose at 70 kg and 14 weeks of age; IM). Pigs were fed corn and soybean meal-based diets that were not limiting in essential nutrients. Back fat was sampled on days −3, 8, 18 and 42, relative to administering the booster dose of GnRH analog at day 0, to determine androstenone concentrations (n=8 or 9/group). Fat androstenone concentrations in IM were lower than EM between days 8 and 42 after administering the booster dose (173 v. 863 ng/g, respectively; P

Aaron Spitz,1 Marc Gittelman,2 Lawrence I Karsh,3 Sanja Dragnic,4 Ahmed M Soliman,5 Aditya Lele,6 Damian Gruca,7 Michael Norton4 1Orange County Urology Associates, Laguna Beach, CA, 221st Century Oncology/UroMedix-Aventura Division, Aventura, FL, 3The Urology Center of Colorado, Denver, CO, 4US Medical Affairs, 5Health Economics and Outcomes Research, 6Data and Statistical Sciences, AbbVie Inc., North Chicago, IL, USA; 7Global Medical Affairs, AbbVie Deutschland, Ludwigshafen, Germany Introduction: Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) analogs is a standard treatment for advanced prostate cancer. GnRH analog therapy can reduce testosterone to “castrate” levels, historically defined as

Short stature in puberty significantly affects the physical and mental health of adolescents. The continuous acceleration of skeletal maturation, caused by sex hormones during puberty, limits the time available for growth and poses a considerable challenge for the treatment of short stature. To date, there is still no standardized treatment protocol for this disorder. However, puberty is the last period to improve the final adult height. Currently, commonly used pharmacological treatments in clinical settings include recombinant human growth hormone, gonadotropin-releasing hormone analogs, and third-generation aromatase inhibitors. In recent years, personalized treatment aiming to improve the final adult height has become a key focus in clinical practice. This article provides a comprehensive summary of research on pharmacological therapies for height improvement in pubertal children with short stature, offering valuable insights for healthcare professionals.

With the changes in various factors such as genetics and the environment, the incidence of childhood precocious puberty has been gradually increasing. Improving height is one of the key issues in the clinical management of precocious puberty. Currently, gonadotropin-releasing hormone analogs (GnRHa) remain the preferred treatment for precocious puberty, but their effect on height improvement is influenced by multiple factors, which may result in lower-than-expected height benefits. Combining recombinant human growth hormone (rhGH) therapy with GnRHa treatment is an alternative strategy to enhance the efficacy of GnRHa, but there is still no clear recommendation regarding the timing of their combination. Considering the current status of precocious puberty treatment, it is crucial to reevaluate the effects of GnRHa monotherapy and combination therapy with rhGH on height improvement. This article discusses strategies such as combination therapy indications to guide clinical medication and help children with precocious puberty achieve optimal height benefits.

Abstract Introduction Gender-affirming hormone treatment is known to affect adrenal androgen levels in adult individuals with gender dysphoria (GD). This may be clinically relevant because the adrenal gland plays a critical role in many different metabolic processes. Aim This study aims to assess the effects of gonadotropin-releasing hormone analogs (GnRHa) treatment and gender-affirming hormone treatment on adrenal androgen levels in adolescents with GD. Methods In this prospective study, dehydroepiandrosterone-sulfate (DHEAS) and androstenedione values were measured every 6 months during 2 years of GnRHa treatment only, and 2 years of GnRHa combined with gender-affirming hormone treatment (estradiol or testosterone) in 73 transgirls and 54 transboys. To determine trends in adrenal androgen levels a linear mixed model was used to approximate androgen levels. Main Outcome Measures DHEAS and androstenedione levels were the main outcome measures. Results DHEAS levels rose in transboys during GnRHa treatment, which may represent the normal increase during adolescence. In transgirls no change in DHEAS levels during GnRHa treatment was found. Gender-affirming hormone treatment did not affect DHEAS levels in either sex. In transboys androstenedione levels decreased during the first year of GnRHa treatment, which may reflect reduced ovarian androstenedione synthesis, and rose during the first year of gender-affirming hormone treatment, possibly due to conversion of administered testosterone. In transgirls androstenedione levels did not change during either GnRHa or gender-affirming hormone treatment. Clinical Implications No deleterious effects of treatment on adrenal androgen levels were found during approximately 4 years of follow-up. Strengths & Limitations This is one of the largest cohort of adolescents with GD, treated using a uniform protocol, with standardized follow-up. The lack of a control group is a limitation. Conclusion The changes in androstenedione levels during GnRHa and gender-affirming hormone treatment in transboys may not be of adrenal origin. The absence of changes in androstenedione levels in transgirls or DHEAS levels in either sex during gender-affirming hormone treatment suggests that gender-affirming hormone treatment does not significantly affect adrenal androgen production. Schagen SEE, Lustenhouwer P, Cohen-Kettenis PT, et al. Changes in Adrenal Androgens During Puberty Suppression and Gender-Affirming Hormone Treatment in Adolescents With Gender Dysphoria. J Sex Med 2018;15:1357–1363. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the effect of leuprolide acetate, a synthetic gonadotropin‐releasing hormone analog (GnRH‐a) on ovarian function preservation in systemic lupus erythematosus (SLE) patients treated with cyclophosphamide (CYC) in clinical practice. Methods: We enrolled 30 premenopausal female SLE patients who fulfilled the 1997 American College of Rheumatology revised criteria and were treated with intravenous CYC (IVCY) in 2008–2017. We used Kaplan–Meier survival estimates to compare the GnRH‐a‐treated patients and those not treated with GnRH‐a as controls. We performed Cox regression analyses to identify factors associated with premature ovarian failure (POF), incidences of cardiovascular events, strokes and osteoporosis after IVCY therapy. Results: After a mean follow‐up of 41 months, POF developed in one of the 16 GnRH‐a‐treated patients (6%) versus seven of the 14 controls (50%). Significantly improved cumulative ovarian protection over time was observed in the GnRH‐a‐treated group (P = 0.030). The hazard model analysis showed that treatment with GnRH‐a during IVCY therapy is an independent factor associated with POF after IVCY therapy (adjusted hazards ratio = 0.12, 95% CI 0.01–0.67, P = 0.013) but not incidences of cardiovascular events, strokes or osteoporosis. Conclusion: The combined use of GnRH‐a with IVCY therapy was associated with a significant reduction of POF among premenopausal women with SLE, suggesting that the addition of GnRH‐a can be a strategy to prevent POF among premenopausal women with SLE after IVCY therapy. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate the efficacy and safety of self‐injections of the prefilled recombinant human chorionic gonadotropin (r‐hCG) in a syringe in assisted reproductive technology (ART) treatment for the maturation trigger (MT), as compared to self‐injections of conventional hCG and intranasal administration of gonadotropin‐releasing hormone agonist (GnRH‐a). Methods: Between January and April, 2017, 396 patients who underwent oocyte retrieval were recruited. Of these, 396 patients were classified into three groups, according to the types of MT: (1) the urinary human chorionic gonadotropin (u‐hCG) group that consisted of patients who had a self‐injection of u‐hCG (n = 127); (2) the GnRH‐a group that received nasal administration of GnRH‐a (n = 159); and (3) the r‐hCG group that had a self‐injection of r‐hCG (n = 110). Several ART outcomes were evaluated. Results: The mature oocyte retrieval rate was not different between the u‐hCG, r‐hCG, and GnRH‐a groups and the fertilization and cleavage rates were similar between the three groups. The clinical pregnancy rates did not significantly differ between the GnRH‐a group and the u‐hCG group; however, it was significantly lower in the GnRH‐a group, compared to the r‐hCG group. No difference was observed in the incidence of moderate or more severe ovarian hyperstimulation syndrome among the three groups. Conclusion: The self‐injection of the prefilled r‐hCG is a favorable MT for ART patients. [ABSTRACT FROM AUTHOR]

In order to accurately estimate body composition at slaughter and to meet specific market targets, the influence of age at time of castration (surgical or immunological) on body composition and boar taint indicators must be determined for male pigs. In all, 48 males were randomly assigned to one of four management regimens: (1) entire male pigs (EM), (2) EM surgically castrated at ~40 kg BW and 10 weeks of age (late castrates; LC), (3) conventional, early surgical castrates (within 4 days of birth; EC) and (4) EM immunized with a gonadotropin-releasing hormone (GnRH) analog (primary dose at 30 kg BW and 8 weeks of age; booster dose at 70 kg and 14 weeks of age; IM). Pigs were fed corn and soybean meal-based diets that were not limiting in essential nutrients. Back fat was sampled on days -3, 8, 18 and 42, relative to administering the booster dose of GnRH analog at day 0, to determine androstenone concentrations (n = 8 or 9/group). Fat androstenone concentrations in IM were lower than EM between days 8 and 42 after administering the booster dose (173v . 863 ng/g, respectively;P <0.01), and were not different from surgically castrated males (EC and LC) after day 18. Slaughter occurred at ~115 kg BW, 42 days (6 weeks) after administering the booster dose for IM, and 10 and 20 weeks after surgical castration for LC and EC, respectively (n = 8 or 9/group). At slaughter, live BW, liver weight as a percent of live BW, dissectible bone as a percent of cold carcass side, body protein and water contents and whole-body protein deposition decreased with time after surgical castration (linear;P <0.05), whereas dressing percentage, dissectible fat, probe fat depth and body fat content increased with time after surgical castration (linear;P <0.05). The IM had intermediate dressing percentage and dissected fat to EM and EC, whereas liver weight as a percent of live BW and body protein and lipid contents were not different from EM. Whole-body lipid deposition tended to be greater in IM than in EM between 14 and 20 weeks of age (373v . 286g/d;P = 0.051). In conclusion, castration of male pigs after 6 weeks of age has a lasting effect on physical and chemical body composition. The relationship between time after castration and body composition may be developed to predict carcass composition and can be used to determine the ideal immunization schedule aimed at specific markets in the future. [ABSTRACT FROM AUTHOR]

Background: In central precocious puberty (CPP), the pulse secretion and release of gonadotropin-releasing hormone (GnRH) are increased due to early activation of the hypothalamic-pituitary-gonadal axis, resulting in developmental abnormalities with gonadal development and appearance of secondary sexual characteristics. The CPP without organic disease is known as idiopathic CPP (ICPP). The objective of the study was to evaluate the clinical efficacy and safety of domestic leuprorelin (GnRH analog) in girls with ICPP. Methods: A total of 236 girls with ICPP diagnosed from April 2012 to January 2014 were selected and were randomized into two groups. One hundred fifty-seven girls in the test group were treated with domestic leuprorelin acetate, 79 girls in the control group were treated with imported leuprorelin acetate. They all were treated and observed for 6 months. After 6-month treatment, the percentage of children with peak luteinizing hormone (LH) ≤3.3 U/L, the percentage of children with peak LH/peak follicle stimulating hormone (FSH) ratio 0.05). Conclusions: Domestic leuprorelin is effective and safe in the treatment of Chinese girls with ICPP. Its effectiveness and safety are comparable with imported leuprorelin.

Pituitary stimulation with pulsatile gonadotropin-releasing hormone (GnRH) analogs induces both follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Pituitary gonadotropin secretions are blocked upon desensitization when a continuous GnRH stimulus is provided by means of an agonist or when the pituitary receptors are occupied with a competitive antagonist. GnRH antagonists were not available originally; therefore, prolonged daily injections of agonist with its desensitizing effect were used. Today, single- and multiple-dose injectable antagonists are also available to block the LH surge and thus to cause desensitization. This review provides an overview of the use of GnRH analogs which is potent therapeutic agents that are considerably useful in a variety of clinical indications from the past to the future with some limitations. These indications include management of endometriosis, uterine leiomyomas, hirsutism, dysfunctional uterine bleeding, premenstrual syndrome, assisted reproduction, and some hormone-dependent tumours, other than ovulation induction.

Background: Early puberty (EP) is due to the activation of gonadotropin-releasing hormone (GnRH) pulse generator in lower ages; EP may be a potential cause for impairment of adult height, leading to short stature. The aim of this study was to determine the effects of GnRH analog (GnRHa) and GnRHa plus recombinant human growth hormone (rhGH) treatment on final height in healthy girls with EP. Materials and Methods: Fifty EP girls (sexual maturity rating: 2–3) with chronological age (CA) 9.22 ± 0.56 and bone age (BA) 9.74 ± 0.59 years were treated with GnRHa (Triptorelin) at a dose of 100 μg/kg body weight (BW) as intramuscular every 28 days for 2.82 ± 0.57 years; 45 EP girls with CA 9.84 ± 0.57 and BA 10.14 ± 1.02 years were also treated with the same GnRHa plus rhGH (Norditropin) at a dose of 0.1 unit/kg BW daily for 6 days in a week for 2.55 ± 0.6 years. In the control group, 33 EP girls followed for the same period without treatment. Height, weight, and body mass index of girls and parents were assessed. Predicted adult height (PAH) at the start and the end of the study and target height were assessed.Results: PAH at the end of the study in the GnRHa group was not different with untreated girls. PAH at the end of the treatment in GnRHa plus rhGH group was significantly higher than both untreated and GnRHa group. PAH at the end of therapy in GnRHa plus rhGH group was significantly more than their target height. Conclusion: GnRHa therapy has a benefit effect in achievement of target height. Combination therapy with GnRHa plus rhGH increased their PAH more than both untreated and GnRHa groups.

The present study was designed to examine the potential for inducing ovulation in starry flounder ( Platichthys stellatus) using gonadotropin-releasing hormone analog (GnRHa) and human chorionic gonadotropin (hCG) to assess whether starry flounder are differentially responsive to GnRHa and hCG. Female starry flounder were injected or implanted with different doses of hCG or GnRHa pellets to examine their ovulation-inducing potential and effects on plasma levels of testosterone (T), 17β-estradiol (E2), and 17,20β-dihydroxy-4-pregnen-3-one (17,20βP). Blood samples were collected for up to 10 or 25 days post-injection or post-implantation in two separate experiments designed to mimic the early and middle stages of spawning, respectively. Fish treated with the GnRHa pellets (100 µg) showed a significant increase in the total number of stripped eggs relative to the controls. GnRHa administration had no effect on the floating rate or fertilization rate of ovulated eggs in the both experiments, whereas hCG injection affected both of these rates. Plasma T levels were not significantly different between the exogenous hormone-treated and control fish. In contrast, the plasma E2 level was elevated in those fish treated with GnRHa, regardless of injection or implantation, and was accompanied by increased numbers of stripped eggs in both experiments. Treatment with GnRHa resulted in higher 17,20βP levels compared to the controls, and there was a positive relationship between elevated plasma 17,20βP and an increase in ovulated eggs in response to GnRHa treatment. The implantation of starry flounder with GnRHa-containing pellets was effective at inducing sustained ovulation compared to hCG treatment. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of treatment with gonadotropin-releasing hormone analog (GnRHa) on final height in girls who experienced moderately early puberty with symptoms beginning at 7-8.5 years of age. Methods: Female cases diagnosed with moderately early puberty which had started between ages 7 to 8.5 years were included in the study. In the treatment groups, all cases with a bone age ≤10.5 years constituted group 1 (n=18) and those with a bone age >10.5 years constituted group 2 (n=23). The 8 patients for which treatment approval could not be obtained constituted group 3. The 49 cases in all three groups were observed until they reached their final height. Results: Target height, target height standard deviation score (SDS), final height, and final height SDS values were similar in all 3 groups. Final height showed a significant positive correlation with target height (p=0.000, r=0.54) and height at diagnosis (p=0.003, r=0.467) in all groups. Linear regression analysis revealed that a 1 cm longer height at diagnosis increased the final height 0.213 fold, and a 1 cm longer target height at diagnosis increased the final height 0.459 fold. Conclusion: We found that GnRHa did not make a positive contribution to final height in cases of moderately early puberty. [ABSTRACT FROM AUTHOR]

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Study Objectives To evaluate bone quantity and quality in postmenarchal adolescents treated for idiopathic central precocious puberty (CPP) in childhood with a gonadotropin-releasing hormone analog (GnRHa) and to determine the serum concentrations of bone remodeling markers. Design and Participants This cross-sectional study included 53 postmenarchal adolescent girls who were divided into 2 groups: 27 adolescents who were treated with GnRHa in childhood for idiopathic CPP (the CPP group) and 26 women who presented with physiological development of secondary sex traits (the control group). Interventions: None. Main Outcome Measures Weight, height, body mass index, age at menarche, time since menarche, body composition, bone mineral density (BMD), bone quality, and serum insulin, glucose, osteocalcin, and carboxyl-terminal telopeptide of type I collagen concentrations were compared in the 2 groups. BMD data were analyzed by using both dual-energy x-ray absorptiometry (DXA) and osteosonography, and body composition was measure with the use of DXA and electrical bioimpedance. Results BMD and bone quality did not differ significantly between the CPP and control groups when analyzed by using DXA or osteosonography. Serum osteocalcin concentration was significantly lower ( P = .02) in the CPP than in the control group. Insulin was higher in the CPP group, and hyperinsulinemia was an independent predictor of bone quantity and quality assessed by using osteosonography. Body mass index and percent fat were determined by using DXA, and the duration of use of GnRHa treatment and the time since GnRHa discontinuation were not independent predictors of bone quantity and quality. Conclusion Postmenarchal adolescents treated with GnRHa for CPP in childhood did not show a reduction in bone quantity or quality. [ABSTRACT FROM AUTHOR]

Pituitary stimulation with pulsatile gonadotropin-releasing hormone (GnRH) analogs induces both follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Pituitary gonadotropin secretions are blocked upon desensitization when a continuous GnRH stimulus is provided by means of an agonist or when the pituitary receptors are occupied with a competitive antagonist. GnRH antagonists were not available originally; therefore, prolonged daily injections of agonist with its desensitizing effect were used. Today, single- and multiple-dose injectable antagonists are also available to block the LH surge and thus to cause desensitization. This review provides an overview of the use of GnRH analogs which is potent therapeutic agents that are considerably useful in a variety of clinical indications from the past to the future with some limitations. These indications include management of endometriosis, uterine leiomyomas, hirsutism, dysfunctional uterine bleeding, premenstrual syndrome, assisted reproduction, and some hormone-dependent tumours, other than ovulation induction. [ABSTRACT FROM AUTHOR]

Immunization against GnRH reduces the occurrence of boar-taint-causing compounds in entire male pigs and is likely to alter growth perfonnance, including whole-body protein deposition (PD; N reten-tion x 6.25). Thirty-six male pigs were used to determine the effects of immunization against GnRH with GnRH analog on N retention and plasma urea nitrogen (PUN; a measure of AA catabolism). Four treatments were used: 1 ) conventional, early castrates (EC), 2) entire male pigs (EM), 3) entire male pigs immunized with GnRH analog (IM), and 4) entire male pigs surgically castrated after 6 wk of age (between 25 and 40 kg BW; late castrates; LC). The GnRH analog was injected at 30 and 70 kg BW. Within each of 9 litters, 4 males were randomly assigned to the 4 treatments. Pigs were fed corn- and soybean-meal-based diets that were not limiting in essential nutrients for high PD. Five consecutive N balances were conducted between d -9 and -4,1 and 7,9 and 16,20 and 26, and 30 and 36, relative to administration of the boost-er dose of GnRH analog at d 0. Blood was sampled on d -4, -1,2, 5, 8,11,14,19,28, and 37. There was an inter-active effect of treatment and time on N retention (P < 0.001). Across periods, N retention for EC and LC were similar (32.7 vs. 33.6 g/d) and lower than EM (39.2 g/d, P < 0.001). The N retention in EM and IM were similar up to d 7 (37.8 vs. 38.5 g/d), tended to be greater for EM than IM between d 9 and 16 (38.4 vs. 34.9 g/d, P = 0.07) and was greater for EM than IM after d 20 (40.9 vs. 34.9 g/d, P < 0.05). Between d 9 and 36, N retention in IM was similar to EC and LC. The PUN concentrations were similar in EC and LC across sampling times (15.50 vs. 15.86 mg/dL) and greater than EM (9.33 mg/dL, P < 0.05). The PUN concentrations were similar in EM and IM up to d 5 (9.88 vs. 9.59 mg/dL), tended to be less in EM than IM on d 8 (9.08 vs. 11.85 mg/dL, P < 0.10), and were lower in EM than IM from d 11 to 37 (8.94 vs. 14.80 mg/dL, P < 0.05). After d 8, PUN concentra-tions were similar for IM, EC, and LC ( 14.31, 15.13, and 15.55 mg/dL, respectively). In conclusion, the results of the current study show that N retention and PUN pat-terns in EC and LC are very similar and lower than those in EM. Between d 7 and 16 after administration of the booster dose of GnRH analog, N retention and PUN in IM changed gradually from EM levels to approach levels in EC and LC, which should be considered when devel-oping feeding programs for IM. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical outcomes of gonadotropin-releasing hormone analog (GnRHa) combined with implantation of a levonorgestrel-releasing intrauterine system (LNG-IUS) in adenomyosis patients with significantly enlarged uteruses. Subjects and Methods: Twenty-one adenomyosis patients whose uterine volumes were greater in size than at 12 weeks' gestation were recruited for the study. Subcutaneous injection of GnRHa was administrated at an interval of 28 days for a total of 3-4 cycles when uterine length was determined to be less than 10 cm by ultrasound measurement. At 3, 6 and 12 months after LNG-IUS implantation, follow-up was performed to document the clinical values such as uterine volume, degree of dysmenorrhea and menstrual flow. Results: Twelve months after implantation, the menstrual flow was significantly lower than baseline values (53.8 ± 11.7 vs. 100, p = 0.03). The degree of dysmenorrhea (pain) was relieved 12 months after implantation (58.2 ± 11.5 vs. 93.7 ± 0.2, p = 0.005). Uterine volume was also below pre-GnRHa levels after implantation (276.6 ± 32.1 vs. 311.4 ± 32.3, p = 0.005). LNG-IUS was expelled in 3 patients, giving an expulsion rate of 14%. Side effects of GnRHa combined with LNG-IUS implantation were few. Conclusion: The findings indicate that combined GnRHa and LNG-IUS treatment was efficacious in patients with enlarged adenomyosis. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The role of aromatase inhibitors combined with gonadotropin-releasing hormone analog in metastatic male breast cancer patients remains unknown. In this retrospective study we evaluated the activity of letrozole combined with a gonadotropin-releasing hormone analog as a first- or second-line therapy for metastatic male breast cancer patients. 19 men entered the study. We did not observe any grade 3 or 4 adverse events. 2 patients (10.5 %) had complete response, 7 patients (36.8 %) experienced a partial response, 7 patients (36.8 %) had stable disease lasting ≥6 months, and 3 patients (15.8 %) had progressive disease. Overall, the disease control rate was 84.2 %. Median progression-free survival was 12.5 months (95 % CI 8.2-16.9), median overall survival was 35.8 months (95 % CI 24.4-49.2), 1- and 2-year survival rates were 89.5 and 67 %, respectively. Interestingly, 3 out of 4 patients treated with the combination following disease progression while on aromatase inhibitor monotherapy confirmed or improved the best overall response observed in the first-line setting. The combination of letrozole and gonadotropin-releasing hormone analog is effective and safe in hormone-receptor positive, metastatic male breast cancer patients. [ABSTRACT FROM AUTHOR]

Sexual offending is both a social and a public health issue. Evidence demonstrates that a combination of pharmacological and psychotherapeutic approaches may reduce or even eliminate deviant sexual behavior in sex offenders with paraphilic disorders. In this article, we will review pharmacological treatment options for sex offenders with paraphilias. Both serotonin selective reuptake inhibitors (SSRIs) and antiandrogen treatments have been used with reported success in decreasing recidivism. SSRIs have been used in mild types of paraphilias and juvenile paraphilias. Antiandrogen treatments seem to be effective in severe sex offenders with paraphilic disorders in order to reduce victimization. Combined pharmacological and psychotherapeutic treatment is associated with better efficacy. Imaging studies may improve the knowledge of paraphilic disorders and the mechanisms of action of current treatments. In spite of existing evidence, there is a need for independent, large-scale and good quality studies assessing the long-term efficacy and tolerance of treatments. [ABSTRACT FROM AUTHOR]

Abstract: Background: Normal brain maturation is the result of molecular changes that can be modulated by endocrine variables associated with brain plasticity and results in sex- and age specific changes in cognitive performance. Using a sheep model, we have previously shown that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) receptors results in increased sex-differences in cognitive executive function and emotional control. In this study we explore effects of this treatment regime on hippocampal gene expression and spatial orientation. Methods: The study was conducted with 30 same-sex twin lambs, half of which were treated with the GnRH analog (GnRHa) goserelin acetate every 4th week, beginning before puberty, until 50 weeks of age. Animals were tested in their spatial orientation ability at 48 weeks of age. Quantitative real time PCR analysis was conducted to examine effects of treatment on the expression of genes associated with synaptic plasticity and endocrine signaling. Results: GnRHa treatment was associated with significant sex- and hemisphere specific changes in mRNA expression for some of the genes studied. The treatment had no significant effect on spatial orientation. However, there was a tendency that females performed better than males in spatial orientation. Conclusion: Our results indicate that GnRH directly and/or indirectly, is involved in the regulation of sex- and side-specific expression patterns of genes. Hence, these results should be considered when long-term peri-pubertal GnRHa treatment is used in children. [Copyright &y& Elsevier]

Objective: We studied the effect of gonadotropin-releasing hormone analogues (GnRHa) on weight gain as a possible side effect. Methods: We analyzed longitudinally changes in BMI-SDS in 92 children [median age 8.0 years (IQR 7.1-8.9), 88% females, mean BMI-SDS 0.69 ± 1.30] with idiopathic central precocious puberty or early puberty treated with GnRHa. Furthermore, 25 overweight children with GnRHa were compared to 25 overweight children without GnRHa matched by age, gender, degree of overweight, and pubertal stage. Results: The matched overweight children without GnRHa demonstrated a significant increase in their BMI-SDS in the course of 1 year (+0.18 ± 0.22). Normal-weight children treated with GnRHa demonstrated a significant increase in BMI-SDS in the course of 1 year (+0.32 ± 0.66) in contrast to overweight children treated with GnRHa who showed a stable BMI-SDS (-0.02 ± 0.27). This significant difference in changes in BMI-SDS between normal-weight and overweight children treated with GnRHa was also observed at the end of GnRHa treatment and 6 months later (p < 0.001). Conclusions: Change in weight status differed between overweight and normal-weight children during GnRHa treatment. We found no increased risk for the side effect of weight gain in overweight children treated with GnRHa. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Objective: To analyze the secondary efficacy and safety outcomes from a recent trial comparing dienogest (DNG) with leuprolide acetate (LA) in women with endometriosis. Methods: A 24-week, open-label, randomized, multicenter study of DNG versus LA in women with endometriosis-related pain was assessed for outcomes such as responder rates (using predefined thresholds of pain relief), changes in single symptoms/signs and sum scores from the Biberoglu and Behrman (B&B) scale, clinical laboratory parameters, and measures of quality of life. Results: Dienogest was non-inferior to LA for treatment response using all predefined thresholds of pain relief and provided equivalent improvements in B&B symptoms and signs. No clinically relevant changes in laboratory parameters were observed during DNG treatment, whereas estrogen levels decreased in the LA group. Compared with LA, DNG was associated with pronounced improvements in specific quality-of-life measures. Conclusion: The analyses provide supportive evidence that the efficacy of DNG is equivalent to that of LA for treating endometriosis symptoms, with specific quality-of-life benefits and a favorable safety profile. [Copyright &y& Elsevier]

Twenty-one boys with a height of 135 cm or less at onset of puberty were treated with a combination of GnRH analog and anabolic steroid hormone, and their pubertal height gain and adult height were compared with those of untreated 29 boys who enter puberty below 135 cm. The mean age at the start of treatment with a GnRH analog, leuprorelin acetate depot (Leuplin®) was 12.3 yr, a mean of 1.3 yr after the onset of puberty, and GnRH analog was administered every 3 to 5 wk thereafter for a mean duration of 4.1 yr. The anabolic steroid hormone was started approximately 1 yr after initiation of treatment with the GnRH analog. The mean pubertal height gain from onset of puberty till adult height was significantly greater in the combination treatment group (33.9 cm) than in the untreated group (26.4 cm) (p<0.0001). The mean adult height was significantly greater in the combination treatment group (164.3 cm) than in the untreated group (156.9 cm) (p<0.0001). The percentage of subjects with an adult height of 160 cm or taller was 90.5% (19/21) in the combination treatment group, and it was 13.8% (4/29) in the untreated group (p<0.0001). Since growth of the penis and pubic hair is promoted by the anabolic steroid hormone, no psychosocial problems arose because of delayed puberty. No clinically significant adverse events appeared. Combined treatment with GnRH analog and anabolic steroid hormone significantly increased height gain during puberty and adult height in boys who entered puberty with a short stature, since the period until epiphyseal closure was extended due to deceleration of the bone age maturation by administration of the GnRH analog and the growth rate at this time was maintained by the anabolic steroid hormone. [ABSTRACT FROM AUTHOR]

Purpose. Premature ovarian failure occurs in 40%-70% of patients who receive conventional chemotherapy alone. However, the incidence is higher, 70%-100%, in patients who undergo myeloablative chemotherapy with hematopoietic stem cell transplantation (HSCT). Gonadotropinreleasing hormone (GnRH) analogs, such as leuprolide, in a continuous-release formulation, may protect the ovaries from the gonadotoxic effects of chemotherapy. In non-HSCT settings, GnRH analogs have reduced the risk for premature ovarian failure to <10%. We conducted a phase II clinical trial based on the hypothesis that giving leuprolide before conditioning chemotherapy in HSCT patients reduces premature ovarian failure incidence. Patients and Methods. Eligible patients were women aged <40 years who were HSCT candidates, were premenopausal, and had both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels <20 IU/L. Two 22.5-mg leuprolide doses were delivered in 3-month depot i.m. injections, the first within 2 months before HSCT. Patients were monitored for menstruation return, and ovarian function tests (FSH, LH, and estradiol) were done every 2 months starting 90 days after the last leuprolide dose. Results. Sixty eligible patients were enrolled, 59 underwent HSCT, and 44 were evaluable (median age, 25 years; median follow-up, 355 days). Only seven of 44 patients (16%) regained ovarian function. Of the 33 who received myeloablative regimens, six (18%) regained ovarian function. However, among the 11 who received nonmyeloablative regimens, only one (9%) regained ovarian function (p = .66). Conclusion. Leuprolide did not preserve ovarian function in patients who underwent HSCT using either myeloablative or nonmyeloablative regimens. Other measures that protect ovarian function need to be investigated. [ABSTRACT FROM AUTHOR]

The purpose of this document is to review the non-barrier methods to prevent postoperative adhesion formation in humans. A MEDLINE computer search was performed to identify relevant articles using the keywords “postoperative adhesion prevention” “abdominal” and “humans”. Subsequent searches were performed using the keyword “non-barrier” to further supplement the information obtained. After careful review of the abstracts, 15 articles were selected for inclusion in the manuscript. Many methods, drugs and materials have been demonstrated effective for reducing postoperative adhesion in animal models. Among them, four types of drugs have been clinically used in attempts to reduce postoperative adhesions: gonadotropin-releasing hormone agonists, anti-inflammatory drugs, humidified CO2 and hydroflotation. Many clinical and meta-analyses revealed that hydroflotation materials do not increase adhesion-free outcome. GnRHa pretreatment using a standard clinical dose (3.75 mg monthly) before myomectomy do not decrease adhesion formation. The role of CO2 on the reduction and/or prevention of postoperative adhesions have been reported only in cardiac surgery. None of them have been adopted for clinical standard therapy, despite positive reports in animals or preclinical applications. In contrast to the results from animal studies, there is no substantial evidence that the use of non-barrier materials reduces postoperative abdominal adhesions in humans. [ABSTRACT FROM AUTHOR]