Leuprolide Research Articles

Relugolix in combination with abiraterone acetate, apalutamide, or docetaxel in men with advanced prostate cancer (aPC): A phase 1, three-part, open-label, parallel-cohort study.

TPS207 Background: Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) analogs or receptor antagonists is a cornerstone of prostate cancer treatment. As disease progresses, agents with complementary mechansims are co-prescribed with ADT to suppress extra-testicular testosterone production or block androgen receptors on cancer cells. Relugolix (120 mg) is an oral non-peptide GnRH receptor antagonist approved in the US for the treatment of aPC. In the phase 3 study, relugolix maintained suppression of testosterone to castration levels in 96.7% of men for up to 48 weeks (wks), with superiority to leuprolide acetate. Relugolix was well tolerated and associated with a 54% lower risk of major adverse cardiovascular events relative to leuprolide acetate (Shore N, NEJM 2020;382;23). To formally assess the safety and tolerability of combination treatment with relugolix, a phase 1 study in men with aPC has been undertaken. Methods: This is a three-part, open-label, parallel-cohort safety and tolerability study of relugolix in combination with abiraterone acetate in men with metastatic castration-sensitive prostate cancer (mCSPC) or metastatic castration-resistant prostate cancer (mCRPC) (Part 1), apalutamide in men with mCSPC or non-metastatic catration-resistant prostate cancer (nmCRPC) (Part 2), or docetaxel in men with mCSPC or mCRPC (Part 3). Each part of the study consists of a 45-day screening period, a 12-wk primary study treatment period and a 40-wk safety extension treatment period. All of the men are required to have been treated with leuprolide acetate or a GnRH receptor antagonist (eg, degarelix) in combination with abiraterone acetate for a minimum of 12 wks, apalutamide for a minimum of 6 wks, or docetaxel for a minimum of one treatment cycle prior to the baseline (Day 1) visit. Men will be transitioned from leuprolide acetate or degarelix to relugolix (120 mg [Part 1 and 3] or 240 mg [Part 2] once daily after a single loading dose of 360 mg); on the approximate date the next analog or antagonist injection is scheduled; treatment with each combination treatment will continue as previously prescribed. Hence, the study will provide safety and tolerability of relugolix and the three different combination agents for up to 1 year and in addition, will provide safety and tolerability data as men transition from injectable leuprolide acetate or degarelix to oral treatment with relugolix. Enrollment into the study began in March 2021. A protocol amendment was approved in July 2021 to include Part 2 and Part 3 of the study and to add the 40-wk safety extension treatment period. Screening for Part 2 was initiated in August 2021 and for Part 3 it is expected to initiate in January 2022. Clinical trial information: NCT04666129.

Real-world analyses of major adverse cardiovascular event risk by drug class after initiation of androgen deprivation therapy.

46 Background: Recent literature has suggested an association between androgen deprivation therapy (ADT) and increased cardiovascular (CV) risk in prostate cancer (PCa) patients.1,2 The 1-year incidence of major adverse cardiovascular events (MACE) in patients ≥45 years old was 1.4%,3 whereas a recent study of PCa patients on ADT reported MACE in 2.9% of patients treated with an LHRH antagonist (relugolix) and 6.2% of patients treated with an LHRH agonist (leuprolide acetate) over 48 weeks.4 Thus, MACE risk is an important consideration for PCa patients on ADT. This study aims to evaluate MACE risk after ADT initiation with LHRH agonists vs. LHRH antagonists using real-world data. Methods: Analyses of US electronic medical records (2010 to 2020) of PCa patients (n=45,059) receiving LHRH agonist and antagonist injections were conducted to evaluate the rate of MACE-free survival after ADT initiation by drug class. The database contained 178,388 LHRH agonist and antagonist injection entries and 965 documented MACE events. Exclusion criteria included taking more than one class of ADT and MACE within 6 months prior to ADT initiation. MACE was defined as myocardial infarction, stroke, and death from any cause based on a recent study in this field.4 Kaplan-Meier event-free survival curves were constructed to compare the risk of MACE between patients on agonist vs. antagonist. Statistical significance between survival curves was evaluated by log-rank test. Results: Overall MACE risk for all patients was 1.0% at one year. MACE risk was significantly higher for patients treated with LHRH antagonist compared to agonists in the first seven years after ADT initiation. Conclusions: Risk of MACE was lower than previously reported. Although this may potentially be due to underreporting, our analysis of data over 10 years from >45,000 PCa patients is likely an accurate reflection of the real world. A recent study using large real-world dataset with >50,000 PCa patients over approximately 2 years showed no difference in CV risk following treatment with GnRH agonists and antagonists.5 However, in our analyses MACE risk was lower in patients treated with LHRH agonists vs. antagonists in the first seven years after ADT initiation. Further, we plan to evaluate baseline comorbidities and demographics for imbalances. Future studies evaluating the impact of ADT class and comorbidities on MACE risk for PCa patients during ADT may be helpful to identify CV predictors. 1Ng C-F, et al. Scientific Reports. 2020. 2Zhao J, et al. PLoS One. 2014. 3Miao B, et al. J of the American Heart Association. 2020. 4Shore ND, et al. New England Journal of Medicine. 2020. 5George G, et al. Int J Cancer. 2021.

Leuprolide Acetate and QTc Interval in Gender-Diverse Youth.

Puberty suppression is a standard of care for gender-affirming therapy in gender-diverse youth. Leuprolide acetate is a gonadotropin-releasing hormone agonist (GnRHa) commonly used for pubertal suppression. There are concerns that GnRHa agents prolong the rate-corrected QT interval (QTc) when used as androgen deprivation therapy in management of prostate cancer; however, there is a paucity of literature regarding the effect of leuprolide acetate on QTc intervals in gender-diverse youth. To determine the proportion of gender-diverse youth with QTc prolongation on leuprolide acetate therapy. A retrospective chart review of gender-diverse youth initiated on leuprolide acetate between July 1, 2018 and December 31, 2019 was conducted at a tertiary care pediatric hospital in Alberta, Canada. Youth aged 9-18 years were included if a 12-lead electrocardiogram was completed after initiating leuprolide acetate. The proportion of adolescents with clinically significant QTc prolongation was assessed, defined as QTc >460 milliseconds (ms). Thirty-three pubertal youth were included. The cohort had a mean age of 13.7 years (standard deviation [SD] 2.1) and 69.7% identified as male (assigned female at birth). The mean post-leuprolide acetate QTc was 415 ms (SD 27, range 372-455). Twenty-two (66.7%) of youth were prescribed concomitant medications, including QTc-prolonging medications in 15.2%. None of the 33 youth on leuprolide acetate had QTc prolongation. Only 24.2% patients had a borderline QTc (QTc 440-460 ms). No gender-diverse youth on leuprolide acetate demonstrated clinically significant QTc prolongation.

Fertility preservation in transgender men without discontinuation of testosterone

ObjectiveTo report two cases of fertility preservation in two transgender men without an extended period of higher dose testosterone cessation.DesignChart abstraction was completed for two cases of oocyte preservation in transgender men without stopping testosterone gender-affirming therapy before controlled ovarian stimulation (COS).SettingA university-affiliated fertility clinic in San Francisco, California.Patient(s)Two 27-year-old transgender men on higher dose testosterone undergoing oocyte cryopreservation.Intervention(s)Not applicable.Main Outcome Measure(s)Both patients had been on 6 and 20 months of testosterone therapy, respectively, and continued throughout COS. A random start antagonist plus letrozole protocol was used for the patient in case 1, with a leuprolide acetate trigger. A luteal start antagonist protocol was applied to the patient in case 2 with a leuprolide acetate trigger.Result(s)In case 1, a total of 35 oocytes were retrieved, with a total of 23 metaphase II (MII) oocytes cryopreserved. An additional 7 MII oocytes were obtained after in vitro maturation for a total of 30 MII oocytes that were vitrified. In case 2, 14 oocytes were retrieved, and 9 mature oocytes (MII) were vitrified.Conclusion(s)Transgender men have historically been advised to discontinue testosterone before COS, a process that may be distressing for many individuals. This is the first published case report demonstrating the proof of concept of COS without cessation of high-dose testosterone therapy in two transgender men. Future studies with larger sample sizes should be performed to confirm these findings.

The Role of the EZH2 and H3K27me3 Expression as a Predictor of Clinical Outcomes in Salivary Duct Carcinoma Patients: A Large-Series Study With Emphasis on the Relevance to the Combined Androgen Blockade and HER2-Targeted Therapy.

ObjectiveSalivary duct carcinoma (SDC) is a highly aggressive and uncommon tumor arising not only de novo but also in pleomorphic adenoma. Androgen receptor (AR)- and HER2-targeted therapy have recently been introduced for SDC as promising treatment options; however, no predictive biomarkers have yet been established. EZH2 and H3K27me3 are closely linked to the development and progression of various cancers, and EZH2 is also expected to be a desirable therapeutic target. We therefore explored the clinicopathological and prognostic implications of EZH2 and H3K27me3 in a large cohort of SDC patients, focusing on their impact on the therapeutic efficacy of AR- or HER2-targeted therapy.Materials and MethodsThe EZH2 and H3K27me3 immunohistochemical expression and EZH2 Y646 gain-of-function mutation status were examined in 226 SDCs, and the relationship with the clinicopathological factors as well as clinical outcomes were evaluated within the three groups depending on the treatment: AR-targeted (combined androgen blockade with leuprorelin acetate and bicalutamide; 89 cases), HER2-targeted (trastuzumab and docetaxel; 42 cases), and conventional therapy (112 cases).ResultsEZH2 and H3K27me3 were variably immunoreactive in most SDCs. A positive correlation was found between the expression of EZH2 and H3K27me3. The EZH2 expression in the SDC component was significantly higher than that in the pre-existing pleomorphic adenoma component. EZH2 Y646 was not identified in any cases. EZH2-high cases more frequently had an advanced clinical stage and aggressive histological features than EZH2-low cases. An EZH2-high status in patients treated with AR-targeted therapy was associated with a significantly shorter progression-free and overall survival as well as a lower objective response rate and clinical benefit rate. In addition, a H3K27me3-high status in patients treated with AR-targeted therapy was related to a shorter overall survival. Conversely, there was no association between the EZH2 and H3K27me3 expression and the clinical outcomes in the conventional or HER2-targeted therapy groups.ConclusionsA high expression of EZH2 and H3K27me3 in SDC might be a predictor of a poor efficacy of AR-targeted therapy. Our data provide new insights into the role of EZH2 and H3K27me3 in therapeutic strategies for SDC.

Treatment with gonadotropin-releasing hormone analogs (GnRHa) in childhood and adolescence

For several decades, gonadotropin releasing hormone analogs (GnRHa) are the medical treatment selected for central precocious puberty (CPP) in girls and boys. They generate an inhibition of the hypothalamus-pituitary-gonadal axis decreasing LH, FSH, estradiol and testosterone secretion and, in this way, they produce a regression of secondary sexual characters under treatment. In the last years, these analogs are also used in trans adolescents, in adolescents and young adults with oncological diseases, in some very particular situations in children with short stature and in patients with neurodevelopmental disorders. In Argentina the most commonly used formulations are triptorelin and leuprolide acetate depot forms. These analogs have proven both their efficacy and their safety. The aim of this paper is to review and update about the use of GnRHa in children and adolescents.

ELIGANT: a Phase 4, interventional, safety study of leuprorelin acetate (ELIGARD®) in Asian men with prostate cancer.

BackgroundThe incidence and mortality rate of men with prostate cancer have been increasing in Asia. ELIGARD® is a formulation of leuprorelin acetate whose safety and efficacy have been well-established in Western regions. However, limited safety data are available for Asian populations.MethodsELIGANT (ELIGard AsiaN sTudy) was a Phase 4, multicenter, prospective, single-arm, interventional study. Men with locally advanced or metastatic prostate cancer without concomitant chemotherapy, or another androgen receptor pathway inhibitor, were enrolled across Asia to receive ELIGARD® (22.5 mg subcutaneous depot injection) every 3 months for 15 months, with a follow-up visit at 18 months. The primary objective was to establish the safety of ELIGARD® in Asian men with hormone-dependent prostate cancer. The secondary objectives were to assess efficacy, via prostate-specific antigen (PSA) progression and testosterone levels, and health-related quality of life (HRQoL).ResultsIn total, 106 patients were included in the safety analysis set (SAF). The most common treatment-emergent adverse events (TEAEs) included PSA increase, cough, back pain, hot flush, anemia, and upper respiratory tract infection. TEAEs considered related to ELIGARD® were reported in 13.2% of patients (n=14), two of which were serious. In the full analysis set (FAS) (n=105), 81.2% (n=56) and 68.5% (n=61) of patients achieved a PSA reduction of ≥90% from baseline at 12 and 18 months, respectively. At 18 months, the numbers of patients with testosterone levels <20, 20–50, and >50 ng/dL were 65 (61.9%), 17 (16.2%), and two (1.9%), respectively; 20% had missing testosterone measurements. HRQoL remained stable throughout the study with minimal change from baseline at study completion.ConclusionsIn conclusion, the safety profile of ELIGARD® (22.5 mg) in Asian men with hormone-dependent prostate cancer is comparable to previous studies in Western regions.Trial RegistrationClinical trial registration number NCT03035032.

Lipid-based nanocarriers for oral delivery of peptides

Therapeutic peptides can treat a wide variety of diseases with selective and potent action. Their oral bioavailability is strongly limited by an important proteolytic activity in the intestinal lumen and poor permeation across the intestinal border. We have evaluated the capacity of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) to overcome both oral bioavailability limiting aspects, using leuprolide (LEU) as model peptide. Lipidization of LEU by formation of a hydrophobic ion pair (HIP) with sodium docusate enables a significant increase of peptide encapsulation efficiency in both SLN and NLC. The nanocarriers, obtained by high-pressure homogenization, measured 120 nm and were platelet shaped. Regarding the protective effect towards proteolytic degradation, only NLC maintained LEU integrity in presence of trypsin. Intestinal transport, evaluated on Caco-2 (enterocyte-like model) and Caco-2/HT29-MTX (mucin-secreting model) monolayers, showed nanocarriers internalization by enterocytes but no improvement of LEU permeability. Indeed, the combination of nanoparticles platelet-shape with the poor stability of the HIP in the transport medium induces a high burst release of the peptide, limiting nanoparticles capacity to transport LEU across the intestinal border. Stability of peptide lipidization needs to be improved to withstand biorelevant medium to benefit from the advantages of encapsulation in solid lipid nanocarriers and consequently improve their oral bioavailability.

Potential therapeutic response in a severe case of autosomal dominant osteopetrosis type I

The low-density lipoprotein receptor-related protein 5 gene (LRP5), which encodes a coreceptor within the canonical Wnt signaling pathway, plays a crucial role in bone mass regulation and has been associated with several bone disorders. Autosomal dominant osteopetrosis type I (ADO type I, OMIM 607634) is a rare disease caused by heterozygous, gain-of-function mutations in LRP5. Here we describe a 44-year-old female who presented with thickened calvarium, elevated bone density, torus palatinus, mandibular exostoses, enlarged mandible, and disabling headaches and bone pain. Exome sequencing revealed a previously reported heterozygous missense variant in the LRP5 gene (p.A242T). Post-diagnosis cranial vault volume measurement by computed tomography 3D reconstruction demonstrated decreasing intracranial volume over time. Off-label use of leuprolide acetate was associated with apparent stabilization of skull mineralization. This report documents a severe example of ADO type I and provides anecdotal evidence of the utility of therapy in need of formal evaluation.

The development of real–world evidence of leuprorelin acetate for spinal and bulbar muscular atrophy

The development of real–world evidence of leuprorelin acetate for spinal and bulbar muscular atrophy

Evolution of drug delivery systems: From 1950 to 2020 and beyond

Modern drug delivery technology began in 1952 with the advent of the Spansule® sustained-release capsule technology, which can deliver a drug for 12 h after oral administration through an initial immediate dose followed by the remaining released gradually. Until the 1980s, oral and transdermal formulations providing therapeutic durations up to 24 h for small molecules dominated the drug delivery field and the market. The introduction of Lupron Depot® in 1989 opened the door for long-acting injectables and implantables, extending the drug delivery duration from days to months and occasionally years. Notably, the new technologies allowed long-term delivery of peptide and protein drugs, although limited to parenteral administration. The introduction of the first PEGylated protein, Adagen®, in 1990 marked the new era of PEGylation, resulting in Doxil® (doxorubicin in PEGylated liposome) in 1995, Movantik® (PEGylated naloxone - naloxegol) in 2014, and Onpattro® (Patisiran - siRNA in PEGylated lipid nanoparticle) in 2018. Drug-polymer complexes were introduced, e.g., InFed® (iron-dextran complex injection) in 1974 and Abraxane® (paclitaxel-albumin complex) in 2005. In 2000, both Mylotarg™ (antibody-drug conjugate – gemtuzumab ozogamicin) and Rapamune® (sirolimus nanocrystal formulation) were introduced. The year 2000 also marked the launching of the National Nanotechnology Initiative by the U.S. government, which was soon followed by the rest of the world. Extensive work on nanomedicine, particularly formulations designed to escape from endosomes after being taken by tumor cells, along with PEGylation technology, ultimately resulted in the timely development of lipid nanoparticle formulations for COVID-19 vaccine delivery in 2020.While the advances in drug delivery technologies for the last seven decades are breathtaking, they are only the tip of an iceberg of technologies that have yet to be utilized in an approved formulation or even to be discovered. As life expectancy continues to increase, more people require long-term care for various diseases. Filling the current and future unmet needs requires innovative drug delivery technologies to overcome age-old familiar hurdles, e.g., improving water-solubility of poorly soluble drugs, overcoming biological barriers, and developing more efficient long-acting depot formulations. The lessons learned from the past are essential assets for developing future drug delivery technologies implemented into products. As the development of COVID-19 vaccines demonstrated, meeting the unforeseen crisis of the uncertain future requires continuous cumulation of failures (as learning experiences), knowledge, and technologies. Conscious efforts of supporting diversified research topics in the drug delivery field are urgently needed more than ever.

In vitro and in vivo evaluations of a 3-month sustained-release microsphere depot formulation of leuprolide acetate

In vitro and in vivo evaluations of a 3-month sustained-release microsphere depot formulation of leuprolide acetate

Assessment of Gonadotropin Concentrations Stimulated by Gonadotropin-Releasing Hormone Analog by Electrochemiluminescence in Girls with Precocious Puberty and Premature Thelarche

Objective: The aim of this study is to determine the cutoff values of gonadotropin response to gonadotropin-releasing hormone analogs (GnRHas) corresponding to the activation of the hypothalamic-pituitary-gonadal axis that could differentiate central precocious puberty (CPP) from premature thelarche (PT) and using the electrochemiluminescence assay method. Methods: A total of 49 girls underwent the stimulation test with an intramuscular injection of 3.75 mg leuprolide acetate. Based on the clinical and laboratory characteristics, they were divided into two groups: CPP (n = 22) and PT (n = 27). Baseline estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were collected before GnRHa administration and LH and FSH at 60 and 120 min, respectively, after GnRHa administration. Results: The girls with CPP presented an increased height Z-score, advanced bone age, and higher baseline LH, FSH, estradiol, and LH/FSH ratio in relation to PT (p < 0.001). Stimulated LH differed significantly between the two groups, and the LH cutoff values were ≥4.29 IU/L (p < 0.001) and ≥3.95 IU/L at 60 and 120 min, respectively (p < 0.001). The LH peak was found at 60 min after stimulation. Conclusions: The GnRHa test is effective in distinguishing CPP from PT, and a single sampling, at 60 min, with LH concentrations above 4.29 may be the parameter of choice with the advantage of greater convenience and practicality.

Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain compared with leuprorelin in Japanese women: a phase 3, randomized, double-blind, noninferiority study

To evaluate the efficacy and safety of 40-mg relugolix (REL) compared with those of leuprorelin (LEU) in women with endometriosis-associated pain. Phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled study in Japanese patients. Hospitals and clinics. Women aged ≥20 years with regular menstrual cycles (25-38 days) experiencing endometriosis or ovarian endometrioma and reporting pelvic pain. In the REL group, 40 mg of REL was orally administered once a day for 24 weeks. In the LEU group, 3.75 or 1.88 mg of LEU was subcutaneously injected every 4 weeks for 24 weeks. The primary endpoint was the change in the maximum visual analog scale score for pelvic pain from baseline until 28 days before the end of treatment. Changes in the maximum visual analog scale score were -52.6 ± 1.3 for REL and -57.5 ± 1.4 for LEU. Ovarian endometrioma decreased by 12.26 ± 17.52 cm3 for REL and 14.10 ± 18.81 cm3 for LEU. Drug-related treatment emergent adverse events with an incidence of >10% for both groups were hot flush, metrorrhagia, headache, and genital hemorrhage. Discontinuations from treatment emergent adverse events were 2.9% for REL and 4.3% for LEU. Relugolix was noninferior to LEU for treating endometriosis-associated pelvic pain. Safety profiles of both medications were comparable, although menses returned earlier in patients taking REL, a huge benefit for women who plan to conceive after treatment. ClinicalTrials.gov: NCT03931915.

Transgender Youth Referred to Clinics for Gender-Affirming Medical Care in Canada.

Referrals of transgender and gender-diverse (trans) youth to medical clinics for gender-affirming care have increased. We described characteristics of trans youth in Canada at first referral visit. Baseline clinical and survey data (2017-2019) were collected for Trans Youth CAN!, a 10-clinic prospective cohort of n = 174 pubertal and postpubertal youth <16 years with gender dysphoria, referred for hormonal suppression or hormone therapy, and 160 linked parent-participants. Measures assessed health, demographics, and visit outcome. Of youth, 137 were transmasculine (assigned female) and 37 transfeminine (assigned male); 69.0% were aged 14 to 15, 18.8% Indigenous, 6.6% visible minorities, 25.7% from immigrant families, and 27.1% low income. Most (66.0%) were gender-aware before age 12. Only 58.1% of transfeminine youth lived in their gender full-time versus 90.1% of transmasculine (P < .001). Although transmasculine youth were more likely than transfeminine youth to report depressive symptoms (21.2% vs 10.8%; P = .03) and anxiety (66.1% vs 33.3%; P < .001), suicidality was similarly high overall (past-year ideation: 34.5%, attempts: 16.8%). All were in school; 62.0% reported strong parental gender support, with parents the most common support persons (91.9%). Two-thirds of families reported external gender-related stressors. Youth had met with a range of providers (68.5% with a family physician). At clinic visit, 62.4% were prescribed hormonal suppression or hormone therapy, most commonly depot leuprolide acetate. Trans youth in Canada attending clinics for hormonal suppression or gender-affirming hormones were generally healthy but with depression, anxiety, and support needs.

Evidence of Spermatogenesis in the Presence of Hypothalamic Suppression and Low Testosterone in an Adolescent Transgender Female: A Case Report.

To report a novel case of semen cryopreservation after testicular sperm extraction in an adolescent transgender female without cessation of gonadotropin-releasing hormone (GnRH) agonist therapy and feminizing hormone therapy. This is a case report of a 16-year-old transgender female using leuprolide acetate for 4 years and estradiol for 3 years requesting semen cryopreservation at the time of gender-affirming orchiectomy. She desired to proceed without cessation of gender affirming hormone therapy. The patient's consent was obtained for written publication. The patient underwent testicular sperm extraction followed by orchiectomy. The sample was processed and cryopreserved in a 1:1 Test Yolk Buffer. Multiple early and late spermatids were identified as well as spermatagonium in the TESE specimen. Advanced spermatogenesis may occur in the presence of a GnRH agonist. Cessation of GnRH agonist therapy may not be essential for semen cryopreservation in adolescent transgender females.

English

BACKGROUND We wanted to compare the effectiveness of the treatment and the adverse effects of ulipristal acetate and leuprolide acetate in the medical management of symptomatic uterine fibroids. METHODS This is a randomised controlled study conducted in the the Department of Obstetrics and Gynaecology in Chalmeda Anand Rao Institute of Medical Sciences from January 2019 to January 2020. 60 patients with symptomatic fibroids and excessive uterine bleeding were randomly divided. They were given daily therapy of ulipristal acetate 10 mg orally for 3 months or monthly injection leuprolide acetate 3.75 mg intramuscularly for 3 months. RESULTS Controlled uterine bleeding was observed in 98 % of patients who received oral therapy of ulipristal acetate of 10 mg, and 89 % of patients who received injections of leuprolide acetate, for differences in comparison with leuprolide acetate of 8.8 % points (95 % CI, 0.4 to 18.3) for ulipristal acetate of 10 mg. Median time of amenorrhea for those taking ulipristal acetate of 10 mg was 5 days, and 21 days for leuprolide acetate. 10 % of patients receiving ulipristal acetate reported moderateto-severe hot flashes and 40 % of patients receiving leuprolide acetate reported moderate to severe hot flashes (P &lt; 0.0010 for each dose of leuprolide acetate vs. ulipristal acetate). CONCLUSIONS Daily therapy of 10-mg ulipristal acetate was considered non inferior when compared to monthly injections of leuprolide acetate in control of uterine bleeding, moreover ulipristal acetate therapy was also significantly less likely to cause hot flashes. KEY WORDS Ulipristal Acetate; Leuprolide acetate; Abnormal Uterine Bleeding; Leiomyoma

Recurrent Hemorrhagic Ascites in Endometriosis: A Case Series and Systematic Review

<h3>Study Objective</h3> To synthesize existing literature and contribute to the collective understanding of hemorrhagic ascites caused by endometriosis through a systematic review and description of three cases seen at our tertiary-care centre. <h3>Design</h3> The case series was conducted as a retrospective review of patients referred to our tertiary-care centre. The systematic review included all publications based on the keywords "endometriosis AND (plural effusion OR ascites) from CENTRAL (Cochrane Library, current issue), MEDLINE (Silver Platter) and EMBASE electronic databases between 1950-2021. <h3>Setting</h3> The three case series patients were seen at our tertiary-care centre. <h3>Patients or Participants</h3> All cases with endometriosis and ascites without any other identifiable cause were included in our systematic review. <h3>Interventions</h3> In Case 1, the patient underwent paracentesis and diagnostic laparoscopy followed by treatment with elagolix. In Case 2, the patient was treated conservatively with leuprolide acetate and norethindrone acetate. In Case 3, the patient underwent diagnostic laparoscopy followed by treatment with dienogest. <h3>Measurements and Main Results</h3> Data was collected from 130 cases (127 from the systematic review and 3 from our centre), including demographics, presenting symptoms, physical findings, management, and recurrence status. A strong correlation with nulliparity (78.2%) and black race (84.8%) was identified. Patients most commonly presented with bloating (62.1%) and abdominal distension on physical exam (54.4%). Ca-125 was frequently elevated (41.2%). A majority of patients received both medical (85.9%) and surgical management (85.7%). <h3>Conclusion</h3> This systematic review is the largest and most comprehensive review of hemorrhagic ascites in endometriosis. This rare form of endometriosis presents similarly to ascites of other etiologies, leading to diagnostic uncertainty, and may disproportionately affect black women. Although many patients undergo surgery as part of diagnosis, medical management may sufficiently treat this condition.

Parasitic Leiomyoma: A Rare Occurrence Following Robotic Hysterectomy

<h3>Study Objective</h3> To highlight the presentation and management of a symptomatic parasitic leiomyoma after a robotic assisted hysterectomy for a multi-fibroid uterus. <h3>Design</h3> Case report. <h3>Setting</h3> Lithotomy, Trendelenburg positioning. <h3>Patients or Participants</h3> C.B. is a 36-year-old G0. <h3>Interventions</h3> Index surgery – Robotic-assisted total laparoscopic hysterectomy and bilateral salpingectomy with mini-laparotomy 1. Robotic-assisted laparoscopic removal of pelvic mass <h3>Measurements and Main Results</h3> C.B. is a 36-year-old G0 who desired definitive management of a symptomatic multi-fibroid uterus. Preoperative ultrasound and MRI displayed an enlarged multi-fibroid 18-week uterus with a dominant 9cm fundal fibroid. Leuprolide acetate was administered for 6 months pre-operatively to reduce the myoma size and anticipated intra-operative blood loss. She underwent a robotic-assisted total laparoscopic hysterectomy and bilateral salpingectomy. A myomectomy was concurrently performed with diathermy to remove an obstructing fibroid for aid in visualization. A mini laparotomy was made to remove the surgical specimen, which was unable to be delivered through vagina. Pathology was benign. C.B. presented one year postoperatively with pelvic pain and bulk symptoms. Her exam was consistent with an adnexal mass and MRI revealed a 6cm pelvic mass. C.B. underwent a robotic-assisted laparoscopic removal of the mass, which was attached to the vaginal cuff. Pathology revealed an infarcted leiomyoma. She followed up postoperatively with complete resolution of her symptoms. <h3>Conclusion</h3> This case highlights a rare occurrence of a parasitic leiomyoma following a hysterectomy. There has been no publication to date describing the occurrence of parasitic myomas after concomitant myomectomy and hysterectomy without morcellation. The authors speculate that seeding of cells during the myomectomy may have been responsible for the development of a parasitic myoma; however, further investigation is needed. This case report also emphasizes the importance of being mindful of the occurrence of parasitic fibroids in a post-hysterectomy patient presenting with pain and pelvic mass.

Uterine Artery Clipping at the Level of the Ureteric Tunnel for Reduction of Blood Flow

Study Objective Though cervical myomas comprise only 5% of total uterine myomas, they present unique surgical challenge due to proximity to the uterine vessels and ureters. We aim to highlight an approach to robotic-assisted hysterectomy with a large cervical fibroid, with minimal blood loss and clear visualization of the displaced anatomy. Design Video Case Presentation. Setting A robotic-assisted hysterectomy (RAH) was performed under general anesthesia in dorsal lithotomy position at a university-affiliated hospital. Patients or Participants 41-year-old G0 with abnormal uterine bleeding in the setting of 5 × 4 × 5 cm subserosal fibroid of the left posterior cervix. The patient was pretreated with leuprolide acetate injections then letrozole to reduce the fibroid volume, however, no change in size was observed. The patient desired definitive management of the fibroid. Interventions Once in the operating room, a uterine manipulator could not be placed due to displacement of the cervix by the fibroid. Careful retroperitoneal dissection was performed to identify the uterine artery coursing over the ureter at the ureteric tunnel of Wertheim. Laparoscopic clips were applied to the uterine artery to decrease blood supply to the fibroid. After completion of the hysterectomy, the fibroid capsule was entered and myomectomy was completed, resulting in separation of the fibroid from the vagina. Measurements and Main Results Estimated blood loss was 50 cc. Final specimen were uterus, fallopian tubes, and cervix weighing 54 g and cervical fibroid weighing 99 g. The patient had an uncomplicated postoperative course and was discharged home on postoperative day 1. Conclusion This case demonstrates the use of minimally-invasive surgical approach to safely complete a hysterectomy in the context of a large, cervical myoma. Our video demonstrates improved hemostasis and visualization of the ureters throughout the case due to placement of vessel clips at the level of the ureteric tunnel. Though cervical myomas comprise only 5% of total uterine myomas, they present unique surgical challenge due to proximity to the uterine vessels and ureters. We aim to highlight an approach to robotic-assisted hysterectomy with a large cervical fibroid, with minimal blood loss and clear visualization of the displaced anatomy. Video Case Presentation. A robotic-assisted hysterectomy (RAH) was performed under general anesthesia in dorsal lithotomy position at a university-affiliated hospital. 41-year-old G0 with abnormal uterine bleeding in the setting of 5 × 4 × 5 cm subserosal fibroid of the left posterior cervix. The patient was pretreated with leuprolide acetate injections then letrozole to reduce the fibroid volume, however, no change in size was observed. The patient desired definitive management of the fibroid. Once in the operating room, a uterine manipulator could not be placed due to displacement of the cervix by the fibroid. Careful retroperitoneal dissection was performed to identify the uterine artery coursing over the ureter at the ureteric tunnel of Wertheim. Laparoscopic clips were applied to the uterine artery to decrease blood supply to the fibroid. After completion of the hysterectomy, the fibroid capsule was entered and myomectomy was completed, resulting in separation of the fibroid from the vagina. Estimated blood loss was 50 cc. Final specimen were uterus, fallopian tubes, and cervix weighing 54 g and cervical fibroid weighing 99 g. The patient had an uncomplicated postoperative course and was discharged home on postoperative day 1. This case demonstrates the use of minimally-invasive surgical approach to safely complete a hysterectomy in the context of a large, cervical myoma. Our video demonstrates improved hemostasis and visualization of the ureters throughout the case due to placement of vessel clips at the level of the ureteric tunnel.