Patients with hepatic encephalopathy (HE) experience both cognitive and motor coordination alterations, which lead to a decrease in quality of life. During the progression of this disease, the cerebellum is one of the most affected brain regions due to elevated blood ammonia levels that cause neuronal damage and contribute to motor dysfunction. Leuprolide acetate (LA), a gonadotropin-releasing hormone (GnRH) receptor agonist, has demonstrated neurotrophic effects in various regions of the central nervous system. Therefore, this study evaluated the potential neurotrophic effect of LA on the cerebellum in a rat model of HE induced by portocaval anastomosis (PCA). For the experimental design, male Wistar rats were divided into three groups: SHAM, PCA with saline solution (PCA+SS), and PCA treated with LA (PCA+LA). Motor function was assessed using rotarod and open field tests. Histological assessment of the cerebellum was performed using H&E staining, while immunoreactivity of the apoptotic markers caspase-8 and caspase-3 were analyzed to evaluate apoptosis. In addition, the expression of proteins associated with neuronal integrity and recovery, including NF200, neurabin II, and BDNF, were examined. The results showed that LA administration significantly improved motor coordination. Treated animals exhibited reduced neuronal loss in the Purkinje and granular layers, decreased activation of caspase-8 and caspase-3, and increased expression of neurabin II and BDNF. Collectively, these findings indicate that LA has therapeutic potential to attenuate cerebellar neuronal damage and promote functional recovery during HE.

Obesity is associated with disrupted estrous cyclicity, impaired follicular development, and altered uterine responses. Leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, produces time-dependent effects on the reproductive axis; however, its actions under severe obesity remain poorly defined. This study evaluated the effects of LA on metabolic parameters, estrous cyclicity, ovarian morphology, and uterine morphometry in obese Zucker rats. Thirty-six adult female rats were used: normal-weight Long-Evans (LE) and obese Zucker (OZ) rats were assigned to untreated control, vehicle, or LA-treated groups (n = 6/group). LA was administered subcutaneously at 2.5 μg/rat/day for 21 consecutive days. Estrous cyclicity was evaluated before and during treatment, and metabolic, ovarian, and uterine outcomes were assessed after treatment. Obese Zucker rats exhibited greater adiposity, metabolic alterations, prolonged and disrupted estrous cycles, impaired follicular development, increased follicular atresia, fewer corpora lutea, and altered uterine morphometry. LA produced condition-dependent reproductive responses. In obese rats, LA shortened the prolonged estrous cycle and shifted estrous-stage distribution toward the pattern observed in normal-weight animals. LA also increased healthy, developing, antral, and preovulatory follicles, markedly increased corpora lutea, and reduced follicular atresia and cystic structures. In contrast, LA produced predominantly suppressive follicular and estrous-cycle changes in normal-weight rats. LA markedly reduced total cholesterol in obese rats without modifying serum glucose, whereas no condition-specific treatment effect on triglycerides was detected. At the uterine level, LA reduced uterine diameter in obese rats but did not modify endometrial thickness. These findings indicate that LA produces markedly different reproductive responses according to the metabolic and reproductive context, improving several follicular and luteal histomorphometric indices in obese Zucker rats without a parallel restoration of uterine morphometry.

Endometriosis is a chronic, estrogen dependent condition affecting up to 10% of women of reproductive age, characterized by dysmenorrhea, dyspareunia, and nonmenstrual pelvic pain. Conventional treatments are often limited by inadequate efficacy or tolerability. Elagolix, an oral nonpeptide gonadotropin releasing hormone (GnRH) antagonist approved by the Food and Drug Administration in 2018, offers dose dependent estrogen suppression with rapid reversibility upon discontinuation. This systematic review synthesizes the current evidence on elagolix for the management of endometriosis associated pain. A comprehensive search was conducted across PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov from inception to September 2024. Studies were screened per Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines and quality appraised using the a measurement tool to assess systematic reviews 2. (AMSTAR 2) checklist. From 103 identified records, 20 studies were included, encompassing Phase II/III randomized controlled trials, long term extension studies, systematic reviews, network meta analyses, real world data analyses, postmarketing safety reports, and cost effectiveness studies. Elagolix significantly reduced dysmenorrhea (up to ~75% responder rate), nonmenstrual pelvic pain (~55%-69%), and dyspareunia (~60%) compared to placebo, with benefits sustained at 12 months. Efficacy was dose dependent; higher doses yielded greater symptom relief but increased hypoestrogenic adverse effects, primarily hot flushes and decreased bone mineral density (BMD). BMD loss remained minimal (<2% annually) with add back estradiol/norethindrone acetate therapy. Network meta analyses demonstrated comparable or superior efficacy versus other oral GnRH antagonists. Elagolix was cost effective compared to leuprolide acetate in the US settings, and patients favored its oral administration. Elagolix represents an effective, patient centered therapeutic option for moderate to severe endometriosis associated pain, with a well characterized safety profile. Future research should address long term safety beyond 48 months, direct comparisons with first line hormonal therapies, and cost effectiveness in non US healthcare settings.

To our knowledge, bacterial meningitis following radical prostatectomy has not been previously reported. We present a 69-year-old male who had phosphatase and tensin homolog (PTEN)-deficient high-risk locoregional prostate cancer and received neoadjuvant leuprolide, abiraterone, prednisone, and capivasertib in the Single-Arm Phase II Study of Neoadjuvant Intensified Androgen Deprivation in Combination with protein kinase B (AKT) Inhibition (SNARE) trial and developed bacterial meningitis following robot-assisted radical prostatectomy. Diagnosis was established by cerebrospinal fluid analysis demonstrating leukocytosis and markedly elevated protein, although cultures were negative following prior antibiotic exposure. Though capivasertib is not considered overtly immunosuppressive, it is possible that a combination of androgen deprivation, low-dose steroids, alcohol use disorder, and surgical intervention resulted in a permissive immunologic environment for infection. This represents, to our knowledge, the first documented case of bacterial meningitis arising after radical prostatectomy. The relationship to his neoadjuvant therapy remains unclear.

A man in his 70s with high-risk localized prostate adenocarcinoma underwent definitive external beam radiotherapy (EBRT) to the prostate and pelvis with concurrent androgen deprivation therapy using leuprolide. Eight days after completion of radiotherapy, he developed acute urinary retention (AUR) with overflow incontinence, constipation, and post-renal acute kidney injury (AKI), requiring hospitalization and bladder decompression with Foley catheter placement. Initial urine output was approximately 1 liter, and creatinine improved from 4.89 mg/dL to 1.46 mg/dL after decompression. Imaging demonstrated mild left hydronephrosis and chronic renal disease without an obstructing calculus. He was discharged home on tamsulosin and a bowel regimen with a Foley catheter in place. Persistent catheter dependence subsequently required transurethral resection of the prostate (TURP) with improvement in symptoms. This case report describes a case of severe acute urinary retention with post-renal acute kidney injury occurring shortly after prostate and pelvic radiotherapy. The obstruction was likely multifactorial, with radiation-associated inflammation or edema potentially aggravating the underlying outlet issues and constipation. Prompt recognition and bladder decompression may permit rapid renal recovery and are important in patients with reduced renal reserves.

Premenstrual dysphoric disorder (PMDD) is a hormone-sensitive mood disorder characterized by cyclical psychiatric and physical symptoms that impair functioning. Despite inclusion in DSM-5 and ICD-11, PMDD is frequently misdiagnosed or overlooked due to clinical unfamiliarity, lack of structured assessment, and systemic minimization of hormone-linked distress. Women routinely face delays in diagnosis and often only receive definitive treatment through self-advocacy. This report describes a 35-year-old cisgender female with treatment-resistant PMDD, whose symptoms began after menarche and worsened over two decades. Despite multiple psychiatric and medical encounters, her condition was misattributed to obesity, mood disorders, or trauma. After a diagnostic delay and multiple first and second-line treatment failures, a trial of leuprolide acetate confirmed a hormonal etiology of her symptoms, and she subsequently underwent total hysterectomy with bilateral salpingo-oophorectomy. Although she experienced a severe depressive episode in the immediate postoperative period, she has since remained in sustained symptom remission on an SSRI and estrogen replacement. This case demonstrates the need to recognize cyclic symptom patterns and potential hormonal etiology in treatment-resistant mood disorders.