Efficacy and uterine bleeding patterns in initiating goserelin therapy during different menstrual phases in patients with adenomyosis: a prospective cohort study.

OBJECTIVE: We carried out this study to explore the possibility of initiating goserelin therapy during the non-menstrual period in patients diagnosed with adenomyosis. METHODS: 115 premenopausal adenomyosis patients were enrolled and divided into three groups based on their menstrual cycle phase during the initial outpatient visit: menstrual, follicular, and luteal. Each received a 3.6 mg subcutaneous dose of goserelin monthly for three months. The endpoints encompassed alterations in uterine volume, dysmenorrhea Numerical Rating Scale (NRS) score, CA125 level, hemoglobin (HGB) after a 12-week treatment course, and the occurrence and duration of uterine hemorrhage during the first treatment cycle. RESULTS: Analysis revealed that the timing of goserelin therapy initiation in the menstrual cycle did not significantly impact its effectiveness in reducing uterine size, alleviating pain, lowering CA125 levels, or improving hemoglobin concentrations. However, patients starting treatment during the luteal phase experienced increased uterine bleeding (reference: menstrual period, OR = 4.33, 95% CI 1.23-15.25, p = .023). CONCLUSIONS: The results suggested non-inferiority of goserelin therapy initiated during the non-menstrual period, but the uterine bleeding rate was higher in the luteal phase group. Therefore, goserelin treatment for outpatient adenomyosis patients should not be limited to starting during the menstrual period; it can also be initiated outside the menstrual period, providing more convenience for patients as most consultations occur outside the menstrual period. However, the use of goserelin during the luteal phase should be avoided to reduce the risk of exacerbated bleeding, especially in anemic patients with heavy menstrual bleeding. This study highlights the importance of individualizing treatment initiation based on the patient's health profile to optimize therapeutic outcomes and minimize adverse effects. TRIAL REGISTRATION: ChiCTR2200059548.

A Retrospective Study of the Use of Gonadotropin-Releasing Hormone Analogs and Testosterone in Transgender Boys: Who, What, When, and for How Long?

A retrospective review of gender-affirming hormone therapy was conducted in 101 transgender boys followed in the pediatric endocrine clinic. Eighty-seven percent were postmenarchal at the initial visit. Of the 44% prescribed gonadotropin-releasing hormone analogs (GnRHas), insurance coverage was denied in 34% and an average of 4.5 months elapsed before treatment could be started in the remainder. Patients prescribed GnRHas were younger than those who were not, 13.7±2.1 versus 15.5±2.0 years, p<0.001. Continued menstrual bleeding was reported by patients receiving testosterone alone at doses ranging from 50 to 200 mg every 2 weeks.

Regarding "Outcomes of vaginal repair and vaginal repair combined with GnRHa administration in the treatment of cesarean section scar defects: A randomized clinical trial".

First, Table 2 of this study[1] compares the differences in menstruation, menstrual cycle, and thickness of the remaining muscular layer (TRM) between before VR and after VR. These measurements were taken at two different time points for the same indicators, suggesting that the appropriate statistical analysis should involve a paired sample t-test[2] rather than ANOVA. The paired sample t-test is specifically designed to account for the fact that the same subjects are being measured before and after an intervention, thereby controlling for intra-subject variability and providing a more accurate assessment of the changes induced by the treatment. Second, the description in Table 4 of this study[1] is inappropriate. For example, Table 4 describes the odds ratio (OR) for persistent CSD as 0.365 with a 95% confident interval (CI) of (-1.933, -0.083), which is clearly incorrect because the OR value does not fall within the 95% CI range, indicating a statistical error. Similarly, the OR for optimal healing is given as 3.254 with a 95% CI of (0.210, 2.150), where again the OR value is not within the 95% CI range. This error is present for all parameters in Table 4, including TRM ≥ 5.39 mm and menstruation ≤ 7 days. Therefore, it is recommended that the data undergo a thorough review and appropriate statistical analysis be performed to obtain accurate conclusions.

Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation combined with different drugs in the treatment of adenomyosis.

OBJECTIVES: To observe the therapeutic efficacy of high-intensity focused ultrasound (HIFU) combined with different pharmacological treatments for adenomyosis. MATERIALS AND METHODS: A total of 126 patients with adenomyosis who underwent HIFU combined with pharmacological treatment were retrospectively reviewed. Patients were treated with either dienogest (DNG) (Group A, N = 38) or GnRH-a (Group B, N = 88) for three months after HIFU, and received levonorgestrel-releasing intrauterine systems (LNG-IUS) at the end of the third month. Visual Analog Scale (VAS) and Pictorial Blood Loss Assessment Chart (PBAC) scores were used for evaluating symptom improvement. RESULTS: After propensity score matching (1:2), 38 patients were included in Group A and 76 in Group B. All patients showed significant improvement in VAS and PBAC scores after HIFU, but the PBAC score of Group A was significantly higher than that of patients in Group B at 18 months [11.50 (1.00, 29.50) vs. 0.00 (0.00, 16.50), p < 0.01] and 24 months [4.00 (0.25, 27.75) vs. 0.00 (0.00, 12.75), p = 0.04] after HIFU. Furthermore, patients in Group B had a greater uterine volume reduction at 24 months after HIFU than that of patients in Group A [51.00 (27.00, 62.00) vs. 30.00 (17.00, 42.75, p = 0.02)]. However, the adverse effects in Group A were lower than those in Group B [7 (15.79) vs. 35 (46.05), p < 0.01]. No significant difference was observed in the recurrence rate between the two groups. CONCLUSIONS: HIFU combined with DNG and LNG-IUS is a safe and effective treatment for patients with adenomyosis.

Shaping the skeleton: impact of GnRH analogue and sex hormone therapy on skeletal dimensions in transgender individuals.

CONTEXT: Skeletal dimensions vary between sexes. Men typically have broader shoulders and women a wider pelvis. If gender affirming hormone therapy (GAHT) with or without prior puberty suppression (PS) alters these dimensions in transgender individuals remains unclear. OBJECTIVE: To investigate impact of PS and GAHT on skeletal dimensions. DESIGN: Retrospective cross-sectional study. SETTING: Gender identity clinic. PARTICIPANTS: Transgender individuals assigned male at birth (AMAB) and assigned female at birth (AFAB) who underwent dual-energy X-ray absorptiometry (DXA) scanning between ages 18 and 28 years were divided into four groups: Early PS (Tanner G/B2-3)+GAHT, Late PS (Tanner G/B4-5)+GAHT, GAHT only, and Untreated. MAIN OUTCOME MEASURES: Shoulder and pelvis dimensions measured by DXA scan were compared between groups, with adjustment for height. RESULTS: A total of 121 individuals AMAB and 122 AFAB were included. Only in individuals AMAB who underwent early PS had smaller shoulders compared to untreated individuals AMAB (-1.3 cm; 95%CI -2.1; -0.5). In individuals AMAB from both the early and late PS group, pelvic inlet, pubic symphysis width and interischial distance were greater compared to untreated individuals AMAB resulting in dimensions comparable to untreated individuals AFAB. Only in early PS AFAB pelvic inlet width was smaller compared to untreated individuals AFAB (-1.0 cm; 95%CI -1.5; -0.6), and comparable to untreated individuals AMAB. CONCLUSIONS: The study results suggest that skeletal dimensions are only altered by GAHT if endogenous puberty has not yet been completed at start of PS. These findings enhance our understanding of hormonal effects on the skeleton and may hold clinical relevance for body image as well as for forensic anthropology. Future research should evaluate clinical implications for surgical or obstetrical outcomes in transgender individuals.

Pharmacological methods for ovarian function and fertility preservation in women with cancer: A literature review.

Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality. The effect of chemotherapy can range from minimal effects to complete ovarian atrophy. Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy decreases the gonadotoxic effect of chemotherapy, thereby diminishing the chance of developing premature ovarian insufficiency (POI). At present, the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function. Notably, most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer, with a considerably small number of studies on patients with hematological malignancies. Furthermore, most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk, regardless of the hormone receptor status. In addition, studies on hematological malignancies have yielded negative results; nevertheless, the findings must be interpreted with caution owing to numerous limitations. Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm, oocyte, and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible. In this manuscript, we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data, as well as future perspectives in this field that upcoming research should focus on.

The effect of gonadotropin-releasing hormone agonist downregulation in conjunction with hormone replacement therapy on endometrial preparation in patients for frozen-thawed embryo transfer.

Objective: To investigate the effects of combining gonadotropin-releasing hormone agonist (GnRHa) downregulation with hormone replacement therapy (HRT, GnRHa-HRT) on the clinical outcomes of patients undergoing frozen-thawed embryo transfer (FET). Methods: In this retrospective study, we included patients who had FET between January 2018 and December 2022. They were categorized into HRT and GnRHa-HRT groups based on the endometrial preparation protocol. The study compared the clinical outcomes of patients in two groups. Possible factors affecting clinical outcomes were analyzed using univariate analysis. To analyze the impact of two endometrial preparation methods on clinical outcomes, multifactorial logistic regression was performed. Results: The rates of clinical pregnancy (47.31% vs. 59.60%), embryo implantation (37.58% vs. 49.65%), biochemical pregnancy (52.36% vs. 64.31%), and early abortion (7.07% vs. 10.77%) were statistically different between the two groups (p < 0.05). Analysis using multifactorial logistic regression showed that there was a 1.65-fold increase in clinical pregnancy rates (OR = 1.65, 95% CI: 1.29-2.12, p < 0.001) and a 1.55-fold increase in embryo implantation rates (OR = 1.55, 95% CI: 1.27-1.90, p < 0.001) in the GnRHa-HRT group when compared to the HRT group. For blastocyst transfer, the clinical pregnancy and implantation rates of the GnRHa-HRT group were significantly higher than those of the HRT group (OR = 1.75, 95% CI: 1.30-2.37, p < 0.001; OR = 1.73, 95% CI: 1.35-2.21, p < 0.001). Conclusion: In FET cycles, leuprorelin (as a GnRHa) downregulation combined with HRT may improve the clinical outcome of patients compared to the HRT cycle, especially for the clinical pregnancy and embryo implantation rates of patients with blastocyst transfer.

Fertility preservation in lymphoma patients treated with immunochemotherapy regimens with or without radiotherapy: results of a retrospective multicenter Italian study (Ferty care).

This is a retrospective, multicentric study, aimed to describe the real-life application of fertility preservation methods during treatment in female lymphoma patients, aged 18-40 years old, diagnosed between Oct 1st/2010 and May 31st/2018. Among 414 women included, median age was 28 years old, histologies were: HL 74%, PMBCL 13%, DLBCL 10%, others 3%. First line treatments were: ABVD in 295 (71%), R-CHOP like in 102 (25%), higher intensity regimens in 17 (4%) cases. Fertility preservation strategies were: GnRHa in 315 (78%), Oral Contraceptive in 41 (10%), oocytes and ovarian tissue cryopreservation in 55 and 42 patients, respectively. After therapy, we observed a restored regular period in 293 (70%) and premature ovarian failure (POF) in 33 (8%), Furthermore we recorded 43 pregnancies, all spontaneous with 5 years median follow-up. Median age at diagnosis and number of lines of treatment correlate with higher rate of amenorrhea, risk of POF and menopause (p < 0.001).

Revisiting ovarian function suppression with GnRH agonists for premenopausal women with breast cancer: Who should use and the impact on survival outcomes.

Breast cancer diagnosed in premenopausal women tends to be more aggressive and the benefit of ovarian function suppression (OFS), at least in certain groups of patients, is well known. There is hesitancy in using OFS in some groups of patients who may otherwise benefit from the treatment. For instance, it is clear that in premenopausal patients with hormone receptor-positive (HR+), high-risk, early-stage breast cancer, gonadotropin-releasing hormone agonists (GnRHa) should be given in the adjuvant setting; however, confusion remains whether premenopausal patients with intermediate-risk disease benefit from GnRHa, given the lack of consensus on its definition in guidelines and clinical practice. Most recent evidence on the long-term efficacy of GnRHa, with up to 20-years of follow-up, reinforced its benefits in premenopausal patients with early-stage breast cancer. In this comprehensive review, we reviewed the long-term efficacy in terms of improvement in disease-free survival (DFS) and overall survival (OS) for early-stage HR+ breast cancer and examined evidence from multiple randomized clinical studies to identify the clinicopathological characteristics that correlated with improved DFS and OS with the addition of OFS to adjuvant endocrine therapy. Other aspects of GnRHa, including its efficacy in advanced breast cancer, safety profile, evidence in ovarian function preservation, and the advantages of long-acting formulations were also discussed. By addressing the existing gaps and grey areas regarding the inclusion of OFS as a crucial treatment component for premenopausal breast cancer patients, physicians are more aware of who to administer and the potential impact on survival outcomes.

Precocious Puberty and GnRH Analogs: Current Treatment Practices and Perspectives among US Pediatric Endocrinologists.

INTRODUCTION: Gonadotropin releasing hormone analogs (GnRHas) are used for treatment of precocious puberty. Over the last decade, several new formulations have been approved. METHODS: The Drugs and Therapeutics Subcommittee of the Pediatric Endocrine Society (PES) undertook a review to ascertain the current treatment options, prescribing behaviors, and practices of GnRHas among pediatric endocrinologists practicing within the USA. The survey consisted of four main subsections: (1) description of clinical practice; (2) self-assessment of knowledge base of pediatric and adult GnRHa formulations; (3) current practice for treating central precocious puberty (CPP); and (4) utilization of healthcare resources. RESULTS: There were 223 survey respondents. Pediatric endocrine practitioners were most familiar with the pediatric one-monthly preparation, the 3-month preparation, and the histrelin implant (Supprelin®) (88%, 96%, and 91%, respectively), with lower familiarity for 24-week triptorelin intramuscular (Triptodur®) (65%) and 6-month subcutaneous leuprolide (Fensolvi®) (45%). Only 23% of the respondents reported being extremely familiar with the availability of adult formulations, and 25% reported being completely unaware of cost differences between pediatric and adult GnRHa preparations. The implant was the most preferred therapy (44%), but in practice, respondents reported a higher percentage of patients treated with the 3-month preparation. While family preference/ease of treatment (87%) was the key determinant for using a particular GnRHa preparation, insurance coverage also played a significant role in the decision (64%). Responses regarding assessment for efficacy of treatment were inconsistent, as were practices and criteria for obtaining an MRI. CONCLUSIONS: The survey indicated there is more familiarity with older, shorter acting GnRHas, which are prescribed in greater numbers than newer, longer acting formulations. There is lack of consensus on the need for central nervous system (CNS) imaging in girls presenting with CPP between 6 and 8 years of age and use of laboratory testing to monitor response to treatment. Insurance requirements regarding CNS imaging and laboratory monitoring are highly variable. Despite having similar constituents and bioavailability, there are substantial cost differences between the pediatric and adult formulations and lack of evidence for safe use of these formulations in children. The survey-based analysis highlights the challenges faced by prescribers while reflecting on areas where further research is needed to provide evidence-based practice guidelines for pediatric endocrinologists.

Safety profiles of offspring born from early-follicular long-acting GnRH agonist protocol and daily mid-luteal GnRH agonist protocol: a retrospective study.

BACKGROUND: The gonadotropin hormone-releasing hormone agonists (GnRH-a) have been widely used for controlled ovarian stimulation in assisted reproductive technology (ART). The early-follicular long-acting GnRH-a long protocol (EFL) and the luteal phase short-acting GnRH-a long protocol (LPS) are commonly used GnRH agonist protocols. We conducted a retrospective analysis to assess and compare the rates of congenital abnormalities and safety profiles in offspring born from the EFL and LPS protocols. METHODS: We conducted a retrospective cohort study to analyze and compare neonatal data from patients who using EFL or LPS protocols at our center between January 1, 2014, and June 30, 2017. The study ultimately included 1810 neonates from 1401 cycles using the EFL protocol and 2700 neonates from 2129 cycles using the LPS protocol.The main outcome measures are gestational age at delivery, birth weight, and congenital anomaly rate.To assess the influence of various factors on congenital abnormalities, a random-effects logistic regression model was employed. RESULTS: The EFL and LPS protocols led to similar congenital anomaly rates (1.64% vs. 2.35%, P = 0.149). No significant differences were found between the two groups regarding birth weight and its categories, newborn gender and congenital anomaly rate. The results of the multivariate logistic regression model indicated no association between congenital anomaly and BMI, duration of infertility, treatment protocol, fertilization method, or embryo transfer stage. Compared with singleton pregnancies, the probability of congenital defects in multiple pregnancies was 2.64 times higher (OR: 2.64, 95% CI: 1.72-4.05, P < 0.0001). Newborns with congenital defects were born with a lower gestational age compared with full-term pregnancies. CONCLUSION: In conclusion, the EFL protocol is considered a safe option for ensuring offspring safety, comparable with the LPS protocol; however, multiple pregnancies represent an independent risk factor for congenital abnormalities. This approach can be widely adopted; however, prioritizing single embryo transfers is strongly recommended to minimize the potential risks associated with multiple pregnancies in offspring.

Zhibai dihuang pill (ZBDH) exhibits therapeutic effects on idiopathic central sexual precocity in rats by modulating the gut microflora.

To reveal the role of gut microbiota (GM) in the occurrence and development of idiopathic central precocious puberty (ICPP) using 16S rDNA sequencing and bioinformatics analysis. The Danazol-induced ICPP model was successfully constructed in this study. ZBDH and GnRHa treatments could effectively inhibit ICPP in rats, as manifested by the delayed vaginal opening time, reduced weight, decreased uterine organ coefficient, and decreased uterine wall thickness and corpus luteum number, as well as remarkably reduced serum hormone (LH, FSH, and E2) levels. According to 16S rDNA sequencing analysis results, there was no significant difference in the GM community diversity across different groups; however, the composition of the microbial community and the abundance of the dominant microbial community were dramatically different among groups. ZBDH and GnRHa treatments could effectively reduce the abundance of Muribaculateae and Lactobacillus and promote Prevotella abundance. ZBDH and GnRHa were effective in treating Danazol-induced ICPP model rats. The therapeutic effects of ZBDH and GnRHa could be related to the changes in GM in rats.

Pubertal Suppression in Early Puberty Followed by Testosterone Mildly Increases Final Height in Transmasculine Youth.

Context: Treatment for transmasculine youth (TMY) can involve testosterone treatment and is sometimes preceded by gonadotropin-releasing hormone agonist (GnRHa) treatment for puberty blockade. GnRHas can increase final height in birth-assigned females with central precocious puberty. Maximizing final adult height (FAH) is an important outcome for many TMY. Objective: Our objective was to determine how GnRHa treatment before testosterone impacts FAH. Methods: Retrospective cohort study at 5 US transgender health clinics. Participants were 32 TMY treated with GnRHas in early to midpuberty before testosterone (GnRHa + T group) and 62 late/postpubertal TMY treated with testosterone only (T-only group). Results: The difference between FAH minus midparental target height (MPTH) was +2.3 ± 5.7 cm and -2.2 ± 5.6 cm in the GnRHa + T and T-only groups, respectively (P < .01). In the GnRHa + T group, FAH was 1.8 ± 3.4 cm greater than predicted adult height (PAH) (P < .05) and FAH vs initial height (IH) z-score was 0.5 ± 1.2 vs 0.16 ± 1.0 (P < .05). After adjusting for patient characteristics, each additional month of GnRHa monotherapy increased FAH by 0.59 cm (95% CI 0.31, 0.9 cm), stage 3 breast development at start of GnRHa was associated with 6.5 cm lower FAH compared with stage 2 (95% CI -10.43, -2.55), and FAH was 7.95 cm greater in the GnRHa + T group than in T-only group (95% CI -10.85, -5.06). Conclusion: Treatment with GnRHa in TMY in early puberty before testosterone increases FAH compared with MPTH, PAH, IH, and TMY who only received testosterone in late/postpuberty. TMY considering GnRHas should be counseled that GnRHas may mildly increase their FAH if started early.

Early GnRH-agonist therapy does not negatively impact the endometrial repair process or live birth rate.

Study objective: To investigate whether different timings of GnRH-a downregulation affected assisted reproductive outcomes in infertile women with moderate-to-severe intrauterine adhesions (IUAs) accompanied by adenomyosis. Design: A retrospective case series. Setting: An assisted reproductive technology center. Patients: The study reviewed 123 infertile women with moderate-to-severe IUAs accompanied by adenomyosis undergoing their first frozen-thawed embryo transfer (FET) cycles between January 2019 and December 2021. Measurements and main results: The majority of patients had moderate IUA (n=116, 94.31%). The average Basal uterine volume was 73.58 ± 36.50 cm3. The mean interval from operation to the first downregulation was 21.07 ± 18.02 days (range, 1-79 days). The mean duration of hormone replacement therapy (HRT) was 16.93 ± 6.29 days. The average endometrial thickness on the day before transfer was 10.83 ± 1.75 mm. A total of 70 women achieved clinical pregnancy (56.91%). Perinatal outcomes included live birth (n=47, 67.14%), early miscarriage (n=18, 25.71%), and late miscarriage (n=5, 7.14%). The time interval between uterine operation and the first downregulation was not a significant variable affecting live birth. Maternal age was the only risk factor associated with live birth (OR:0.89; 95% CI: 0.79-0.99, P=0.041). Conclusions: The earlier initiation of GnRH-a to suppress adenomyosis prior to endometrial preparation for frozen embryo transfer did not negatively impact repair of the endometrium after resection.

Analysis of use of different rFSHs during IVF/ICSI-assisted conception in elderly population and effect of double trigger on clinical outcomes.

OBJECTIVE: To compare the number of oocytes retrieved and clinical outcomes of ovulation induction in an older population treated with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) (IVF/ICSI) using different rFSH options and the effectiveness of antagonist treatment to induce ovulation using gonadotropin-releasing hormone agonists (GnRH-a) in combination with an human chorionic gonadotropin (HCG) trigger. METHODS: A total of 132 fresh cycles were selected for this study, which were treated with IVF/ICSI in our hospital from March 2022 to December 2022. Observations were made according to different subgroups and the effects of different triggering methods on the number of oocytes obtained, embryo quality, and clinical outcomes. RESULTS: The initial gonadotropin (Gn) dose, the number of oocytes, and the number of MII oocytes were higher in group A than in group B (p < .05), and the clinical pregnancy rate was 29.41% in group A. Group B had a clinical pregnancy rate of 27.5%. The double-trigger group was superior to the HCG-trigger group in terms of the number of 2PN, the number of viable embryos, and the number of high-quality embryos (p < .05). The use of a double-trigger regimen (OR = 0.667, 95%CI (0.375, 1.706), p = .024) was a protective factor for the clinical pregnancy rate, whereas AFC (OR = 0.925, 95%CI (0.867, 0.986), p = .017) was an independent factor for the clinical pregnancy rate. CONCLUSIONS: The use of a dual-trigger regimen of GnRH-a in combination with HCG using an appropriate antagonist improves pregnancy outcomes in fresh embryo transfer cycles in older patients.

Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study.

PURPOSE: This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed. PATIENTS AND METHODS: Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30 pg/ml. Patient data was gathered from medical records for this comparison. RESULTS: Of the 264 patients enrolled in this study, 117 were administered 3.6 mg of goserelin monthly (goserelin 1 M group), 63 received 3.75 mg of leuprorelin monthly (leuprorelin 1 M group) and 84 were given 11.25 mg of leuprorelin every three months (leuprorelin 3 M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824-0.982), P = 0.018]. CONCLUSION: Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS.

The effect of GnRH-a on the angiogenesis of endometriosis.

PURPOSE: Neoangiogenesis is necessary for adhesion and invasiveness of endometriotic lesions in women affected by endometriosis. Vascular endothelial growth factor (VEGF) is one of the main components of angiogenesis and is part of the major pathway tissue factor (TF)-protease activated receptor-2 (PAR-2)-VEGF that leads to neoangiogenesis. Specificity protein 1 (SP1) is a transcriptional factor that has recently been studied for its crucial role in angiogenesis via a specific pathway. We hypothesize that by blocking angiogenetic pathways we can suppress endometriotic lesions. Gonadotrophin-releasing hormone-agonists (GnRH-a) are routinely used, especially preoperatively, in endometriosis. It would be of great interest to clarify which angiogenetic pathways are affected and, thereby, pave the way for further research into antiangiogenetic effects on endometriosis. METHODS: We used quantitative real-time polymerase chain reaction (qRT-PCR) to study mRNA expression levels of TF, PAR-2, VEGF, and SP1 in endometriotic tissues of women who underwent surgery for endometriosis and received GnRH-a (leuprolide acetate) preoperatively. RESULTS: VEGF, TF, and PAR-2 expression is significantly lower in patients who received treatment (p < 0,001) compared to those who did not, whereas SP1 expression is not altered (p = 0.779). CONCLUSIONS: GnRH-a administration does affect some pathways of angiogenesis in endometriotic lesions, but not all of them. Therefore, supplementary treatments that affect the SP1 pathway of angiogenesis should be developed to enhance the antiangiogenetic effect of GnRH-a in patients with endometriosis. TRIAL REGISTRATION: Clinicaltrial.gov ID: NCT06106932.

Central precocious puberty secondary to postoperative craniopharyngioma: two case reports and a literature review.

BACKGROUND: Craniopharyngioma is a common intracranial tumour in children. Clinical manifestations are related to hypothalamic/pituitary deficiencies, visual impairment, and increased intracranial pressure. Defects in pituitary function cause shortages of growth hormone, gonadotropin, corticotropin, thyrotropin, and vasopressin, resulting in short stature, delayed puberty, feebleness, lethargy, polyuria, etc. However, manifestations involving precocious puberty (PP) are rare. CASE REPORT: In both patients, surgical resection was performed after the diagnosis of craniopharyngioma, and breast development occurred postoperatively at one month in one patient and at one year and three months in the other patient. Central precocious puberty (CPP) was diagnosed via relevant examinations. Leuprorelin was injected subcutaneously every 28 days, and changes in height, weight, bone age, gonadal ultrasound and sex hormones were recorded. During the follow-up of the two children, the sex hormone levels were significantly reduced, and significant acceleration in bone age was not observed. CONCLUSIONS: CPP was induced by craniopharyngioma surgery, and treatment with gonadotropin-releasing hormone analogues (GnRHa) inhibited sexual development and bone age progression. More attention should be given to monitoring for CPP during long-term follow-up of craniopharyngiomas in the clinic.

Systematic review and meta-analysis on the effect of adjuvant gonadotropin-releasing hormone agonist (GnRH-a) on pregnancy outcomes in women with endometriosis following conservative surgery.

BACKGROUND: Endometriosis frequently results in pain and infertility. While conservative surgery offers some relief, it often falls short of ensuring satisfactory pregnancy outcomes. Adjuvant GnRH-a is administered post-surgery to mitigate recurrence; however, its impact on pregnancy outcomes remains debated. This study endeavors to assess the efficacy of adjuvant GnRH-a in enhancing pregnancy outcomes post-conservative surgery in endometriosis patients. METHODS: Databases including PubMed, Embase, the Cochrane Library, Medline (Ovid), Web of Science, and Scopus were rigorously searched up to 02 August 2023, without linguistic constraints. Identified articles were screened using strict inclusion and exclusion criteria. Evaluated outcomes encompassed pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, multiple pregnancy rate, mean postoperative pregnancy interval, recurrence rate, and adverse reaction rate. The Cochrane risk of bias tool and the Jadad score evaluated the included studies' quality. Subgroup and sensitivity analysis were implemented to analyze the pooled results. A meta-analysis model expressed results as standardized mean difference (SMD) and Risk ratio (RR). RESULTS: A total of 17 studies about 2485 patients were assimilated. Meta-analysis revealed that post-surgery, the GnRH-a cohort experienced a marginally elevated pregnancy rate (RR = 1.20, 95% CI = 1.02-1.41; P = 0.03) and a reduced mean time to conceive (RR = -1.17, 95% CI = -1.70- -0.64; P < 0.0001). Contrarily, other evaluated outcomes did not exhibit notable statistical differences. CONCLUSIONS: Incorporating adjuvant GnRH-a following conservative surgery may be deemed beneficial for women with endometriosis, especially before Assisted Reproductive Technology (ART). Nonetheless, owing to pronounced heterogeneity, subsequent research is warranted to substantiate these potential advantages conclusively. REGISTRATION NUMBER: CRD42023448280.

Treatment of Central Precocious Puberty with a Focus on Girls.

The age of thelarche has declined in the past few decades but not the age of menarche. This is important when assessing girls who present with breast development between 6 and 8 years because not all of them will need treatment. The decision for treatment depends on age, bone age (BA), rate of pubertal progression, height velocity, psychosocial factors, and predicted adult height (PAH), with the caveat that height predictions are not precise and BA interpretation is variable.