Effectiveness of leuprolide acetate administered monthly compared to three-monthly in the treatment of central precocious puberty: evaluation at the end of treatment.

Introduction: Gonadotropin-releasing hormone (GnRH) analogs are the standard treatment for central precocious puberty (CPP). Although there are numerous varieties of GnRH agonists, the effectiveness of 1-monthly compared with 3-monthly Leuprolide acetate is still restricted. The objective of this study was to evaluate the outcomes of CPP treatment with Leuprolide acetate at a 1-monthly dosage of 3.75 mg, in comparison to a dosage of 11.25 mg administered every 3 months. Method: This retrospective cohort study involved 143 girls diagnosed with CPP with 72 of them receiving the monthly treatment regimen and 71 receiving the 3-monthly treatment regimen. Anthropometric measurements were compared at the start and end of the therapy. The rates and level of LH suppression were assessed six months after therapy. Results: The regimen administered every 3 months showed more significant suppression of LH. The 3-monthly group showed lower actual height and degree of bone age advancement at the end of therapy. However, the predicted adult height (PAH) remained comparable in both groups. Conclusion: The 3-monthly treatment showed greater hormonal and growth suppression effects, but there was no significant difference in PAH between the two groups.

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.

A pediatric case of two Nicolau syndrome lesions following leuprolide injection in the upper extremity.

ABSTRACT: Nicolau syndrome (NS) is a rare and unpredictable adverse reaction that can occur after the administration of certain medications. A 9-year-old girl, accompanied by her father, visited the outpatient dermatology clinic with complaints of wounds on both upper arms. Upon reviewing her medical history, it was discovered that she had been receiving leuprolide for precocious puberty, and the symptoms began after the last two injections. The patient experienced pain during the leuprolide injection, and redness and swelling were noticed in the injection area on the same day. A few days later, the redness turned into ulcers. The fact that the development of NS cannot be detected in advance and the risk of rapid progression of tissue necrosis make disease management difficult. The prognosis of NS significantly depends on the patient, and when a developing lesion is noticed early, it is crucial to minimize the risk of complications.

The effectiveness of relugolix compared with leuprorelin for preoperative therapy before laparoscopic myomectomy in premenopausal women, diagnosed with uterine fibroids: protocol for a randomized controlled study (MyLacR study).

BACKGROUND: The oral gonadotropin-releasing hormone antagonist relugolix, which temporarily stops menstruation, is used to treat heavy menstrual bleeding, pelvic pressure, and low back pain in women with uterine fibroids. Treatment can also help women recover from low hemoglobin levels and possibly shrink the fibroids. However, evidence of preoperative use of relugolix before laparoscopic myomectomy is limited. Nevertheless, the treatment could reduce interoperative blood loss, decrease the risk of developing postoperative anemia, and shorten the operative time. Thus, we aim to test whether 12-week preoperative treatment with relugolix (40 mg orally, once daily) is similar to or not worse than leuprorelin (one injection every 4 weeks) to reduce intraoperative blood loss. METHODS: Efficacy and safety of preoperative administration of drugs will be studied in a multi-center, randomized, open-label, parallel-group, noninferiority trial enrolling premenopausal women ≥ 20 years of age, diagnosed with uterine fibroids and scheduled for laparoscopic myomectomy. Participants (n = 80) will be recruited in the clinical setting of participating institutions. The minimization method (predefined factors: presence or absence of fibroids ≥ 9 cm and the International Federation of Gynecology and Obstetrics [FIGO] type 1-5 fibroids) with randomization is used in a 1:1 allocation. Relugolix is a 40-mg oral tablet taken once a day before a meal, for 12 weeks, up to the day before surgery. Leuprorelin is a 1.88 mg, or 3.75 mg subcutaneous injection, given in three 4-week intervals during patient visits before the surgery. For the primary outcome measure of intraoperative bleeding, the blood flow is collected from the body cavity, surgical sponges, and collection bag and measured in milliliters. Secondary outcome measures are hemoglobin levels, myoma size, other surgical outcomes, and quality-of-life questionnaire responses (Kupperman Konenki Shogai Index and Uterine Fibroid Symptoms-Quality of Life). DISCUSSION: Real-world evidence will be collected in a clinical setting to use pre-treatment with an oral gonadotropin-releasing hormone antagonist to reduce intraoperative bleeding in women who undergo laparoscopic myomectomy. TRIAL REGISTRATION: jRCTs031210564 was registered on 19 January 2022 in the Japan Registry of Clinical Trials ( https://jrct.niph.go.jp ).

Hormonal Therapy and Radiation Therapy in Prostate Cancer: 5-Year Outcomes From a Trial Evaluating Combined Androgen Blockade With 5-Alpha Reductase Inhibitors as an Alternative to Gonadotropin Releasing Hormone Agonists.

BACKGROUND: We previously reported that for men undergoing combined androgen deprivation therapy (ADT) and radiation therapy (RT) for prostate cancer, substitution of LHRH-agonists with 5-α- reductase inhibitors (5-ARIs) led to improved preservation of 6-month hormonal quality of life (hQOL). With longer term follow-up, we evaluated disease control. METHODS: In this non-randomized trial, men with unfavorable intermediate or high-risk prostate cancer, aged ≥70 years or with Charlson Comorbidity Index ≥2, were treated with RT (78-79.2 Gy in 39-44 fractions) and either oral ADT (oADT; 5-ARI with antiandrogen) or standard of care ADT (SOC; leuprolide with antiandrogen) for up to 28 months. The primary endpoint was EPIC hQOL; secondary endpoints included biochemical control and survival as well as changes in cholesterol and hemoglobin levels. RESULTS: Between 2011 and 2018, 70 men were enrolled (40 in oADT; 30 in SOC). Median follow-up was 65 months [IQR 36-94]. Five-year freedom from biochemical failure for oADT and SOC was 89% versus 86%, disease free survival was 62% versus 69%, cancer-specific survival was 100% versus 96%, and overall survival was 70% versus 81% (all P>.1). Testosterone (2 mo through 3 yr) and hemoglobin levels (2 mo through 2 yr) were higher, and cholesterol levels (1 yr) were lower in the oADT groups (all P < .05). CONCLUSIONS: In this non-randomized study, men treated with combined RT and oADT had better preservation of hQOL and comparable 5-year disease outcomes to men treated with SOC. Eugonadal testosterone with this approach may yield measurable benefits in cholesterol and hemoglobin levels.

Anastrozole monotherapy further improves near-adult height after the initial combined treatment with leuprorelin and anastrozole in early-maturing girls with compromised growth prediction: results from the second phase of the GAIL study.

Background: The first phase of the GAIL study ("Girls treated with an Aromatase Inhibitor and Leuprorelin," ISRCTN11469487) has shown that the combination of anastrozole and leuprorelin for 24 months is safe and effective in improving the predicted adult height (PAH) in girls with early puberty and compromised growth prediction by +1.21 standard deviation score (SDS; +7.51 cm) compared to inhibition of puberty alone, +0.31 SDS (+1.92 cm). Objectives and hypotheses: In the second phase of the GAIL study, we assessed the adult height (AH)/near-adult height (NAH) at the end of the first phase and, in addition, the efficacy of anastrozole monotherapy thereafter in further improving NAH. Methods: We measured the AH (age 16.5 years)/NAH [bone age (BA), 15 years] of the 40 girls included, divided into two matched groups: group A (20 girls on anastrozole + leuprorelin) and group B (20 girls on leuprorelin alone). Group A was further randomized into two subgroups: A1 and A2. Group A1 (n = 10), after completion of the combined therapy, received anastrozole 1 mg/day as monotherapy until BA 14 years, with a 6-month follow-up. Group A2 (n = 10) and group B (n = 20), who received only the combined treatment and leuprorelin alone, respectively, were recalled for evaluation of AH/NAH. Results: AH or NAH exceeded the PAH at the completion of the 2-year initial phase of the GAIL study in all groups, but the results were statistically significant only in group A1: NAH-PAH group A1, +3.85 cm (+0.62 SDS, p = 0.01); group A2, +1.6 cm (+0.26 SDS, p = 0.26); and group B, +1.7 cm (+0.3 SDS, p = 0.08). The gain in group A1 was significantly greater than that in group A2 (p = 0.04) and in group B (p = 0.03). Anastrozole was determined to be safe even as monotherapy in Group A1. Conclusions: In early-maturing girls with compromised growth potential, the combined treatment with leuprorelin and anastrozole for 2 years or until the age of 11 years resulted in a total gain in height of +9.7 cm when continuing anastrozole monotherapy until the attainment of NAH, as opposed to +7.4 cm if they do not continue with the anastrozole monotherapy and +3.6 cm when treated with leuprorelin alone. Thus, the combined intervention ends at the shortest distance from the target height if continued with anastrozole monotherapy until BA 14 years.

Puberty Blocker, Leuprolide, Reduces Sex Differences in Rough-and-Tumble Play and Anxiety-like Behavior in Juvenile Rats.

We examined the effect of the puberty blocker, leuprolide acetate, on sex differences in juvenile rough-and-tumble play behavior and anxiety-like behavior in adolescent male and female rats. We also evaluated leuprolide treatment on gonadal and pituitary hormone levels and activity-regulated cytoskeleton-protein messenger RNA levels within the adolescent amygdala, a region important both for rough-and-tumble play and anxiety-like behavior. Our findings suggest that leuprolide treatment lowered anxiety-like behavior during adolescent development, suggesting that the maturation of gonadotropin-releasing hormone systems may be linked to increased anxiety. These data provide a potential new model to understand the emergence of increased anxiety triggered around puberty. Leuprolide also reduced masculinized levels of rough-and-tumble play behavior, lowered follicle-stimulating hormone, and produced a consistent pattern of reducing or halting sex differences of hormone levels, including testosterone, growth hormone, thyrotropin, and corticosterone levels. Therefore, leuprolide treatment not only pauses sexual development of peripheral tissues, but also reduces sex differences in hormones, brain, and behavior, allowing for better harmonization of these systems following gender-affirming hormone treatment. These data contribute to the intended use of puberty blockers in stopping sex differences from developing further with the potential benefit of lowering anxiety-like behavior.

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.

Cost-Effectiveness Analysis of Triptorelin, Goserelin, and Leuprolide in the Treatment of Patients With Metastatic Prostate Cancer: A Societal Perspective.

OBJECTIVES: Metastatic prostate cancer is the most common malignant cancer and the second leading cause of death due to various types of cancer among men after lung cancer. This study aimed to analyze the cost-effectiveness of triptorelin, goserelin, and leuprolide in the treatment of the patients with metastatic prostate cancer from the societal perspective in Iran in 2020. METHODS: This is a cost-effectiveness study in which a 20-year Markov transition modeling was applied. In this study, local cost and quality-of-life data of each health state were gathered from cohort of patients. The TreeAge pro 2020 and Microsoft Excel 2016 software were used to simulate cost-effectiveness of each treatment in the long term. The one-way and probabilistic sensitivity analyses were also performed to measure robustness of the model outputs. RESULTS: The findings indicated that the mean costs and utility gained over a 20-year horizon for goserelin, triptorelin, and leuprolide treatments were $ 13 539.13 and 6.365 quality-adjusted life-years (QALY), $ 18 124.75 and 6.658 QALY, and $ 26 006.92 and 6.856 QALY, respectively. Goserelin was considered as a superior treatment option, given the estimated incremental cost-effectiveness ratio. The one-way and probabilistic sensitivity analyses confirmed the robustness of the study outcomes. CONCLUSIONS: According to the results of the present study, goserelin was the most effective and cost-effective strategy versus 2 other options. It could be recommended to policy makers of the Iran healthcare system to prioritize it in clinical guidelines and reimbursement policies.

Timing of onset of menses after GnRH agonist treatment for central precocious puberty.

OBJECTIVES: To understand possible predictors of the onset of menses after gonadotropin-releasing hormone agonist treatment cessation in girls with central precocious puberty (CPP). METHODS: This exploratory post hoc analysis of a phase 3 and 4 trial of girls with CPP treated with once-monthly intramuscular leuprolide acetate examined onset of menses after treatment completion using a time-to-event analysis. Pretreatment and end-of-treatment chronologic age (CA), bone age (BA)/CA ratio, and Tanner breast stage; pretreatment menses status; and end-of-treatment BA and body mass index (BMI) were studied as potential factors influencing the onset of menses. RESULTS: Median time to first menses after stopping treatment was 18.3 months among 35 girls (mean age at onset of treatment, 6.8 years) examined. Of 26 girls experiencing menses, 11 (42 %) menstruated at 16-21 months after stopping treatment. Most girls with pretreatment BA/CA≥1.4 started menstruating very close to 18 months after stopping treatment; those with less advanced BA/CA experienced menses at 9-18 months. End-of-treatment BA/CA≥1.2 was associated with a quicker onset of menses (14.5 vs. 18.5 months for BA/CA<1.2, p=0.006). End-of-treatment BA≥12 years predicted longer time to menses. No relationship with time to menses was observed for pretreatment menarche status, pretreatment or end-of-treatment Tanner breast stage (<3/≥3) or CA (<6/≥6 or ≤11/>11), or end-of-treatment BMI percentiles (<85.6/≥85.6 and <92.6/≥92.6). CONCLUSIONS: Pretreatment menarche status or CA do not appear to predict onset of menses, but pre- and end-of-treatment BA/CA may be helpful in anticipating time to first menses after stopping treatment.

The effect of antiangiogenic agent aflibercept on surgically induced endometriosis in a rat model.

OBJECTIVE: The aim of the study is to show for the first time how aflibercept affects endometriosis lesions. MATERIAL AND METHODS: Surgically induced endometriosis in Wistar albino female rats. Rats with endometriosis were randomly divided into three groups: control (Co), aflibercept (Af), and leuprolide acetate (Le). Then, Af, aflibercept, and Le received leuprolide acetate. The control group was not treated. The weights and changes in intra-abdominal adhesions of the rats before and after treatment were recorded according to the Blauer adhesion score. Blood extracted for sacrifice was analyzed. Endometriotic lesions were evaluated for size, volume, histology, and immunohistochemistry (vascular endothelial growth factor [VEGF] and CD31). Significance level was accepted as p < 0.05. RESULTS: Aflibercept significantly reduced endometrial implant volume (p = 0.002). The explant epithelial histological score showed a significant difference between aflibercept and leuprolide acetate (p = 0.006) and between aflibercept and control groups (p = 0.002). Aflibercept decreased VEGF-H and CD31 expression (p = 0.001) more than leuprolide acetate. Aflibercept improved adhesions (p = 0.006). CONCLUSION: Aflibercept is more successful than leuprolide acetate in the treatment of endometriosis.

OBJETIVO: Mostrar por primera vez cómo afecta aflibercept a las lesiones de endometriosis. MATERIAL Y MÉTODOS: Endometriosis inducida quirúrgicamente en ratas hembras albinas Wistar. Las ratas con endometriosis se dividieron aleatoriamente en tres grupos: control (Co), aflibercept (Af) y acetato de leuprolida (Le). Luego, Af, aflibercept y Le recibieron acetato de leuprolida. El grupo de control no fue tratado. Los pesos y cambios en las adherencias intraabdominales de las ratas antes y después del tratamiento se registraron de acuerdo con la puntuación de adherencia de Blauer. La sangre extraída para el sacrificio fue analizada. Las lesiones endometriósicas se evaluaron en tamaño, volumen, histología e inmunohistoquímica (factor de crecimiento endotelial vascular [VEGF] y CD31). El nivel de significación se aceptó como p < 0.05. RESULTADOS: Aflibercept redujo significativamente el volumen del implante endometrial (p = 0.002). La puntuación histológica epitelial (EHS) del explante mostró una diferencia significativa entre aflibercept y acetato de leuprolida (p = 0.006) y entre los grupos de aflibercept y control (p = 0.002). Aflibercept disminuyó la expresión de VEGF-H y CD31 (p = 0.001) más que el acetato de leuprolida. Aflibercept mejoró las adherencias (p = 0.006). CONCLUSIÓN: Aflibercept tiene más éxito que el acetato de leuprolide en el tratamiento de la endometriosis.

Efficacy and Safety of Radiotherapy Plus Relugolix in Men With Localized or Advanced Prostate Cancer.

Importance: Combination androgen deprivation therapy (ADT) with radiotherapy is commonly used for patients with localized and advanced prostate cancer. Objective: To assess the efficacy and safety of the oral gonadotropin-releasing hormone antagonist relugolix with radiotherapy for treating prostate cancer. Design, Setting, and Participants: This multicenter post hoc analysis of patients with localized and advanced prostate cancer receiving radiotherapy in 2 randomized clinical trials (a phase 2 trial of relugolix vs degarelix, and a subset of the phase 3 HERO trial of relugolix vs leuprolide acetate) included men who were receiving radiotherapy and short-term (24 weeks) ADT (n = 103) from 2014 to 2015 and men receiving radiotherapy and longer-term (48 weeks) ADT (n = 157) from 2017 to 2019. The data were analyzed in November 2022. Interventions: Patients receiving short-term ADT received relugolix, 120 mg, orally once daily (320-mg loading dose) or degarelix, 80 mg, 4-week depot (240-mg loading dose) for 24 weeks with 12 weeks of follow-up. Patients receiving longer-term ADT received relugolix, 120 mg, orally once daily (360-mg loading dose) or leuprolide acetate injections every 12 weeks for 48 weeks, with up to 90 days of follow-up. Main Outcomes and Measures: Castration rate (testosterone level <50 ng/dL [to convert to nmol/L, multiply by 0.0347) at all scheduled visits between weeks 5 and 25 for patients receiving short-term ADT and weeks 5 and 49 for patients receiving longer-term ADT. Results: Of 260 patients (38 Asian [14.6%], 23 Black or African American [8.8%], 21 Hispanic [8.1%], and 188 White [72.3%] individuals), 164 (63.1%) received relugolix. Relugolix achieved castration rates of 95% (95% CI, 87.1%-99.0%) and 97% (95% CI, 90.6%-99.0%) among patients receiving short-term and longer-term ADT, respectively. Twelve weeks post-short-term relugolix, 34 (52%) achieved testosterone levels to baseline or more than 280 ng/dL. Ninety days post longer-term ADT, mean (SD) testosterone levels were 310.5 (122.4) (106.7) ng/dL (relugolix; n = 15) vs 53.0 ng/dL (leuprolide acetate; n = 8) among the subset assessed for testosterone recovery. Castration resistance-free survival was not statistically different between the relugolix and leuprolide acetate cohorts (hazard ratio, 0.97; 95% CI, 0.35-2.72; P = .62). Adverse events grade 3 or greater for short-term or longer-term relugolix (headache, hypertension, and atrial fibrillation) were uncommon (less than 5%). Conclusions and Relevance: The results of these 2 randomized clinical trials suggest that relugolix rapidly achieves sustained castration in patients with localized and advanced prostate cancer receiving radiotherapy. No new safety concerns were identified when relugolix was used with radiotherapy.

Systemic therapies for salivary gland carcinomas: an overview of published clinical trials

Background: There is no consensus about effective systemic therapy for salivary gland carcinomas (sgcs). Our aim was summarized the clinical trials assessing the systemic therapies (ST) on sgcs.Material and Methods: Electronic searches were carried out through MEDLINE/pubmed, EMBASE, Scopus, Web of Science, and the Cochrane Library databases, and gray literature. Results: Seventeen different drugs were evaluated, and the most frequent histological subtype was adenoid cysticcarcinoma (n=195, 45.5%). Stable disease, observed in 11 ST, achieved the highest rate in adenoid cystic carcinoma treated with sunitinib. The highest complete (11.1%) and partial response (30.5%) rates were seen in androgen receptor-positive tumors treated with leuprorelin acetate. Conclusions: Despite all the advances in this field, there is yet no effective evidence-based regimen of ST, with all the clinical trials identified showing low rates of complete and partial responses. Further, translational studies are urgently required to characterize molecular targets and effective ST. (AU)

Systemic and Tumor-directed Therapy for Oligorecurrent Metastatic Prostate Cancer (SATURN): Primary Endpoint Results from a Phase 2 Clinical Trial.

Nearly all men with metastatic hormone-sensitive prostate cancer treated with intermittent androgen deprivation therapy (ADT) experience recurrence within 6 mo of testosterone recovery. We conducted a single-arm phase 2 trial to evaluate whether addition of dual androgen receptor pathway inhibitors (ARPIs) and metastasis-directed stereotactic body radiotherapy (SBRT) to intermittent ADT improves recurrence rates for men with between one and five nonvisceral, extrapelvic metastases on prostate-specific membrane antigen positron emission tomography/computed tomography after prior radical prostatectomy. Patients received 6 mo of androgen annihilation therapy (AAT; leuprolide, abiraterone acetate plus prednisone, and apalutamide) and metastasis-directed SBRT. The primary endpoint was the percentage of patients with prostate-specific antigen (PSA) <0.05 ng/ml 6 mo after testosterone recovery (≥150 ng/dl), with the study powered to detect an improvement from 1% to 12%. We enrolled 28 men between March 2021 and June 2022. Median follow-up was 20 mo (interquartile range 16-22). Twenty-six patients (93%) completed SBRT with 6 mo of hormone therapy, of whom six discontinued at least one ARPI; two patients withdrew prematurely. At 6 mo after testosterone recovery, PSA was maintained at <0.05 ng/ml in 13/26 patients (50%, 95% confidence interval 32-67%). Rates of grade 2 and 3 AAT toxicity were 21% and 21%. The results confirm that addition of metastasis-directed SBRT to highly potent systemic therapy can maintain low PSA after testosterone recovery, although further studies are needed to clarify the optimal systemic therapy regimen. PATIENT SUMMARY: We tested a combination of intensified hormone therapy (called androgen annihilation therapy) and radiotherapy targeted at metastases in men with recurrence of metastatic prostate cancer. We found that half of patients were recurrence-free 6 months after their testosterone level recovered, and that less than a quarter of patients experienced a severe drug-related side effect. Overall, this appears to be an effective therapy with acceptable side effects. This trial is registered on ClinicalTrials.gov as NCT03902951.

Efficacy of leuprorelin in spinal and bulbar muscular atrophy: a 3-year observational study.

OBJECTIVE: This study aimed to investigate the long-term effects and functional outcomes of androgen suppression therapy using leuprorelin among Korean patients with spinal and bulbar muscular atrophy (SBMA). METHODS: This observational study enrolled patients with genetically confirmed SBMA who provided informed consent. Leuprorelin was administered via subcutaneous injection every 12 weeks. The primary outcome measure was the change in total Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS) scores. RESULTS: A total of 48 SBMA patients were evaluated in this study. Among them, 39 patients underwent androgen suppression therapy over a 3-year period. The total SBMAFRS score decreased from 41.72 ± 5.55 to 36.74 ± 7.74 (p < 0.001) in patients who completed their treatment. The subgroup with a baseline SBMAFRS score of ≥ 42 had a significantly lower decline in SBMAFRS score than did those with a baseline SBMAFRS score of ≤ 41. We determined that at a baseline, SBMAFRS cutoff value of 41.5 could predict good prognosis, with a corresponding area under the curve of 0.689. CONCLUSION: Despite androgen suppression therapy, all enrolled participants exhibited a decrease in the overall SBMAFRS score. However, those with a baseline SBMAFRS of ≥ 42 showed a mild decrease in scores, indicating a more favorable prognosis. These findings suggest that a higher baseline motor function was a key prognostic indicator in SBMA treatment and that initiating early leuprorelin treatment in patients with high baseline function may lead to good clinical outcomes.

Postradical prostatectomy prostate-specific antigen outcomes after 6 versus 18 months of perioperative androgen-deprivation therapy in men with localized, unfavorable intermediate-risk or high-risk prostate cancer: Results of part 2 of a randomized phase 2 trial.

BACKGROUND: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2. METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL). RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms. CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.

Effects of different treatment methods on clinical efficacy and fertility outcomes of patients with adenomyosis.

OBJECTIVE: This trial was to investigate the effect of different treatment methods on the clinical efficacy and fertility outcome of patients with adenomyosis. METHODS: In total, 140 patients with adenomyosis were evenly and randomly allocated into group A (laparoscopic surgery), group B (laparoscopic surgery combined with gonadotropin-releasing hormone analogs [GnRH-a]), group C (ultrasound-guided percutaneous radiofrequency ablation), and group D (ultrasound-guided percutaneous radiofrequency ablation combined with GnRH-a). On the 3rd day after surgery, patients in group B and group D were subcutaneously injected with GnRH-a (Leuprorelin Acetate SR for Injection) at 3.75 mg/time, once every 4 weeks, for a total of 3 months. The therapeutic effects of the 4 groups were compared, including menstrual volume, dysmenorrhea score, uterine volume, clinical efficacy, luteinizing hormone (LH), estradiol (E2), and follicle-stimulating hormone (FSH) levels, CA125 levels, recurrence, pregnancy status, and pregnancy outcomes. RESULTS: After treatment, the menstrual volume of 4 groups was lowered, dysmenorrhea, Visual Analog Scale (VAS) score, LH, FSH, E2, and CA125 levels were reduced, and uterine volume was decreased. The menstrual volume, VAS score, levels of LH, FSH, E2, and CA125, and uterine volume were reduced in groups B, C, and D compared with group A, and the decrease was more significant in group D. The total effective rate of group D was 100.00%, which was higher than that of group A (71.43%), group B (80.00%), and group C (82.86%). After one year of drug withdrawal, the recurrence of hypermenorrhea, dysmenorrhea, uterine enlargement, and excessive CA125 in group D was significantly lower than that in groups A, B and C, and the recurrence in groups B and C was significantly lower than that in group A (P < 0.05). Compared with groups A, B, and C, group D had a higher pregnancy rate, natural pregnancy rate, and lower in vitro fertilization-embryo transfer rate (P < 0.05), but showed no significant difference in pregnancy outcomes. CONCLUSION: Ultrasound-guided percutaneous radiofrequency ablation combined with Leuprorelin Acetate is effective in the treatment of adenomyosis, which can effectively relieve clinical symptoms, protect postoperative ovarian function, reduce recurrence rate, alleviate pain, and improve quality of life.

The Effect of Hormonal Treatment on Ovarian Endometriomas: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effect of hormonal suppression of endometriosis on the size of endometriotic ovarian cysts. DATA SOURCES: The authors searched MEDLINE, PubMed, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials.gov from January 2012 to December 2022. METHODS OF STUDY SELECTION: We included studies of premenopausal women undergoing hormonal treatment of endometriosis for ≥3 months. The authors excluded studies involving surgical intervention in the follow-up period and those using hormones to prevent endometrioma recurrence after endometriosis surgery. Risk of bias was assessed with the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool. The protocol was registered in PROSPERO (CRD42022385612). TABULATION, INTEGRATION, AND RESULTS: The primary outcome was the mean change in endometrioma volume, expressed as a percentage, from baseline to at least 6 months. Secondary outcomes were the change in volume at 3 months and analyses by class of hormonal therapy. The authors included 16 studies (15 cohort studies, 1 randomized controlled trial) of 888 patients treated with dienogest (7 studies), other progestins (4), combined hormonal contraceptives (2), and other suppressive therapy (3). Globally, the decrease in endometrioma volume became statistically significant at 6 months with a mean reduction of 55% (95% confidence interval, -40 to -71; 18 treatment groups; 730 patients; p <.001; I2 = 96%). The reduction was the greatest with dienogest and norethindrone acetate plus letrozole, followed by relugolix and leuprolide acetate. The volume reduction was not statistically significant with combined hormonal contraceptives or other progestins. There was high heterogeneity, and studies were at risk of selection bias. CONCLUSION: Hormonal suppression can substantially reduce endometrioma size, but there is uncertainty in the exact reduction patients may experience.