Impact of Regulatory Interventions on Ulipristal Acetate 5 mg (Esmya) Use in Spain: An Interrupted Time-Series Analysis.

PURPOSE: Since late 2017, the use of ulipristal acetate 5 mg (UPA; Proprietary name: Esmya) has been under review in the European Union, due to an emerging hepatic risk. In February 2018 and in July 2018, the Spanish Agency of Medicines and Medical Devices and the marketing authorization holder put two risk minimization measures (RMM) in place, in order to inform about new safety information and to mitigate this risk. This study aims to assess RMM effectiveness in Spain, by performing an interrupted time-series (ITS) analyses, between 2014 and 2019. METHOD: Two quasi-experimental ITS analyses to examine the use of UPA before and after the RMM release were performed: (a) an ecological study using aggregated data from a drug consumption database; and (b) a study using primary healthcare data gathered from electronic clinical records. RESULTS: Regulatory interventions were associated with an immediate and significant decrease level of DID (the number of DDD dispensed per 100 000 inhabitants and day) and incidence. The DID was 70% less than expected 12 months after the interventions. This value was 59% for the incidence. However, a change in the slope was not observed and the use started rising again in the last segment of the study period. CONCLUSION: Despite RMM had an immediate strong impact on UPA use, the last segment upward trend in the long-term might have been affected by the lack of comparable therapeutic alternatives. Further studies should be performed to confirm the increase trend observed and analyze subsequent measures and additional data.

[Is there still a place for progesterone receptor modulators in chronic use ?] / Cas clinique. Y a-t-il encore une place pour les modulateurs du récepteur de la progestérone en continu ?

Selective progesterone receptor modulators (SPRMs) are synthetic steroid compounds that interact with the progesterone receptor, inducing various agonist, antagonist or mixed responses. First identified with mifepristone, they are now represented by ulipristal acetate (UPA), used for emergency contraception and uterine fibroids. Despite a few rare cases of severe hepatic insufficiency, SPRMs offer advantages in the treatment of uterine fibroids, reducing their volume without the hypoestrogenic side-effects of GnRH agonists, thus preserving patients' bone capital and quality of life. Despite temporary suspension of UPA administrated on a daily basis, research is exploring the potential of SPRMs in the management of endometriosis, adenomyosis and breast cancer. Despite certain concerns, SPRMs offer promising prospects in gynecological pathologies, opening up new therapeutic avenues to improve women's health and quality of life. This article describes the case of a patient with peritoneal leiomyomatosis for whom UPA significantly alleviated symptoms, reduced disease progression and improved quality of life, even allowing a pregnancy.

Les modulateurs sélectifs des récepteurs de la progestérone (SPRMs) sont des composés stéroïdiens synthétiques qui interagissent via le récepteur de la progestérone, induisant diverses réponses, agonistes, antagonistes ou mixtes. Les SPRMs ont d'abord été représentés par la mifépristone, utilisée pour ses propriétés antagonistes dans la gestion de l'interruption de la grossesse, puis par l'acétate d'ulipristal, qui est indiqué en contraception d'urgence, mais aussi pour la gestion de myomes utérins symptomatiques. Les SPRMs permettent de réduire le volume des myomes utérins, sans induire les effets secondaires d'hypo-œstrogénie des agonistes de la GnRH, préservant ainsi le capital osseux et la qualité de vie des patientes. Néanmoins, quelques cas graves d'insuffisance hépatique ont conduit à la suspension temporaire de l'acétate d'ulipristal en traitement chronique. En dépit de certaines réserves, les SPRMs offrent des perspectives dans les affections gynécologiques, ouvrant de nouvelles voies thérapeutiques pour améliorer la santé et la qualité de vie des femmes. Des recherches explorent leur potentiel dans l'endométriose, l'adénomyose et la chimioprévention du cancer du sein. Nous décrivons ici le cas d'une patiente avec léiomyomatose péritonéale pour laquelle l'acétate d'ulipristal a significativement réduit les symptômes et l'évolution de la maladie, tout en améliorant la qualité de vie de la patiente, avec même l'obtention d'une grossesse menée à terme.

Advancements and Emerging Therapies in the Medical Management of Uterine Fibroids: A Comprehensive Scoping Review.

Uterine fibroids, benign tumors originating from uterine smooth muscle cells, vary in prevalence depending on patient ethnicity, hormonal exposure, and genetics. Due to their high incidence, these neoplasms pose a significant burden on healthcare systems. Current treatment strategies range from routine monitoring in asymptomatic cases to surgical procedures such as myomectomy or hysterectomy in symptomatic patients, with an increasing trend toward uterus-preserving or non-surgical alternatives. This review examines the existing medical treatments for uterine fibroids and delves into the potential of emerging therapies. A scoping review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Medical therapies are divided into hormonal and non-hormonal treatments; however, long-term, safe, and effective treatments in the treatment of uterine fibroids are limited. In addition to established therapies, there is an increasing number of studies investigating the effect of substances such as vitamin D or green tea extract on uterine fibroids. Some studies investigate acupuncture as a possible alternative therapy. While existing treatments offer symptomatic relief and preparation for surgery, our findings point to a significant need for further research into long-term solutions, especially owing to recent limitations in the use of ulipristal acetate due to risk of liver damage. Initial studies involving vitamin D and epigallocatechin gallate are encouraging; however, additional research is required to establish definitive therapeutic roles.

Changes in symptom burden and quality of life among women with uterine fibroids receiving relugolix combination therapy: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of findings from two research studies (known as clinical trials). The studies looked at how well a medicine called relugolix combination therapy worked in women with heavy menstrual bleeding (heavy bleeding during a period) with uterine fibroids (noncancerous or benign growths in the uterus). In this analysis of the studies, researchers looked at how patients self-reported their uterine fibroid symptoms before and after taking relugolix combination therapy. Researchers also looked at how patients self-reported the impact of uterine fibroids on their health-related quality of life before and after taking relugolix combination therapy. WHAT WERE THE RESULTS?: Women took either relugolix combination therapy or placebo (a pill that contains no medicine) by mouth once daily for 24 weeks. Women completed the Uterine Fibroid Symptom and Quality of Life questionnaire (where "quality of life" refers to the women's health-related quality of life related to uterine fibroids) before, during, and after treatment. The questionnaire let researchers see if the women felt that relugolix combination therapy decreased the burden of uterine fibroid symptoms and improved the women's health-related quality of life related to uterine fibroids. More women said that they felt less distress due to their uterine fibroid symptoms and that their health-related quality of life related to uterine fibroids was better after taking relugolix combination therapy compared with women who took placebo. WHAT DO THE RESULTS MEAN?: Relugolix combination therapy may lessen distress associated with uterine fibroid symptoms and improve health-related quality of life related to uterine fibroids.

The use of oral nomegestrol acetate/estradiol in rapid and random start preparation of endometrium before office hysteroscopic polypectomies: A multicenter, prospective, randomized controlled trial.

OBJECTIVE: To evaluate the use of oral nomegestrol acetate/estradiol in random start rapid preparation of endometrium before office hysteroscopic polypectomy. STUDY DESIGN: Multicenter, prospective, randomized controlled trial. SETTING: University hospitals. PARTICIPANTS: 80 adult women undergoing office hysteroscopic polypectomy between January 2023 and March 2024 were randomized to intervention (n = 40) or control (n = 40). Exclusion criteria included the presence of endouterine pathology other than endometrial polyps solely. METHODS: Subjects in the intervention group were treated with oral nomegestrol acetate/estradiol 1.5 mg/2.5 mg/day started taking the drug from an indefinite time in the menstrual cycle (random start) for 14 days. Subjects in the control group did not receive any pharmaceutical treatment and underwent polypectomy between days 8 and 11 of the menstrual cycle. RESULTS: On the day of the procedure, the difference in pre- and post-office hysteroscopic polypectomy endometrial ultrasound thickness was statistically significant between the two groups, with endometrial thickness in both measurements being thinner for the intervention group (p < 0.001). In the nomegestrol acetate/estradiol-treated group, compared with the control, there was also a statistically significant difference in the physician's assessment of the quality of endometrial preparation (p < 0.001), the quality of visualization of the uterine cavity (p < 0.001), and satisfaction with the performance of the procedure (p < 0.001). Finally, all surgical outcomes analyzed were better in the treatment group. CONCLUSION: Treatment with nomegestrol acetate/estradiol could provide rapid, satisfactory and low-cost preparation of the endometrium before office polypectomy, thus improving surgical performance and woman's compliance. TRIAL REGISTRATION: ClinicalTrials.gov NCT06316219.

Pharmacist recommendations for emergency contraception in Belgium: a simulated user study.

BACKGROUND: Emergency contraception reduces the risk of unintended pregnancy, after unprotected sexual intercourse or contraceptive failure. In Belgium, emergency contraception is available without a prescription and pharmacists play therefore a crucial role in dispensing emergency contraception. AIM: This study assesses the dispensing practices of emergency contraception by pharmacists in two regions of Belgium. METHOD AND DESIGN: Simulated patient study, using a predefined scenario, evaluating a request for emergency contraception. The scenario involves a 25-year-old woman not using contraception, who had unprotected sexual intercourse 84 h (3.5 days) ago. Her last menstrual period was 10 days ago. POPULATION: 260 pharmacies were randomly selected. Principal outcome: proportion of pharmacists who deliver the adequate emergency contraception. We considered the following responses as adequate: Prescribing ulipristal acetate or redirecting to another pharmacy, in case of unavailability, or referring for a copper IUD. RESULTS: We analysed the data obtained in 216 pharmacies (216/260 = 83.1%). In 64% of cases, adequate dispensing of emergency contraception (dispensing of ulipristal acetate or referral for intrauterine device insertion) occurred. There was an association between correct dispensing and asking appropriate questions, such as the date of the last menstrual period and the date of the risky sexual intercourse. CONCLUSION: More than one-third of visited pharmacies did not distribute appropriate emergency contraception, underlining the need for improvement. We hypothesise that this may be achieved with appropriate training, use a dispensing checklist.

We assesses the dispensing of emergency contraception by pharmacists using a simulated patient. More than one-third of visited pharmacies did not distribute appropriate emergency contraception, underlining the need for improvement.

Functional evidence for two distinct mechanisms of action of progesterone and selective progesterone receptor modulator on uterine leiomyomas.

OBJECTIVE: To study the specific mechanisms through which progesterone and selective progesterone receptor modulators impact the growth, synthesis, and accumulation of the extracellular matrix in uterine leiomyomas. DESIGN: Laboratory study. SETTING: Academic Research Institutions. PATIENTS (S): This study involved reproductive-age women diagnosed with infertility associated uterine leiomyomas who underwent myomectomy either after selective progesterone receptor modulator ulipristal acetate (UA) treatment or without any pharmacological pretreatment. Control samples included healthy myometrium tissue (n = 100). Specimens were obtained from the Department of Reproduction and Gynecological Endocrinology and Biobank, Medical University of Bialystok, Poland. INTERVENTIONS: Daily (5 mg/d) UA treated for 2 months (n = 100) and untreated (n = 150) patients with uterine leiomyomas or normal healthy myometrium (n = 100) tissue samples immediately after surgery were collected for transcriptional analysis and assessments. MAIN OUTCOME MEASURES: Progesterone-induced activation of the signaling pathways related to uterine leiomyomas extracellular matrix synthesis, deposition, and growth, as well as the expression profile of progesterone receptors in uterine leiomyomas, were assessed. RESULTS: The results indicated that progesterone activated the transforming growth factor-ß and SMAD3 signaling pathways and promoted proliferation, growth, and extracellular matrix remodeling in uterine leiomyomas by up-regulating SMAD3, transforming growth factor-ß (TGF-ß) receptor type 1 and II, Ras homolog A, vascular endothelial growth factor, or increasing the fibrosis-related gene collagen, type I, ɑ-1, and procollagen, type I, ɑ-1 production. In contrast, UA had inhibitory effects on these processes. The study also showed that both nuclear and membrane progesterone receptors play distinct roles in uterine leiomyoma pathobiology. CONCLUSIONS: We showed that both nuclear and membrane progesterone receptors were relevant in the treatment of uterine leiomyomas, especially when combined with selective progesterone receptor modulators. Novel therapeutic approaches combining selective progesterone receptor modulators with or without direct and indirect extracellular matrix targeting through selected specifically TGF-ß and SMAD3 (SMAD3, TGF-ß receptor types 1 and II, Ras homolog A, vascular endothelial growth factor, collagen, type I, ɑ-1) signaling pathways could therefore be a treatment option for uterine leiomyomas.

Emergency contraception - A review.

Emergency contraception (EC), or postcoital contraception, is a therapy aimed at preventing unintended pregnancy after an act of unprotected or under-protected sexual intercourse. Options include both emergency contraceptive pills (most commonly containing levonorgestrel or ulipristal acetate) and insertion of an intrauterine device. The aim of this paper is to summarize current evidence surrounding the use of emergency contraceptives and to present an evidence-based approach to EC provision. Emergency contraception is a safe and effective option in preventing unwanted pregnancy, irrespective of age, weight, or breastfeeding status. Efforts should be made to increase their availability, as well as knowledge of these methods, both among patients and healthcare providers.

Effects of long-term intermittent pharmacological therapy with ulipristal acetate on reducing the volume of uterine fibroids and relieving symptoms.

BACKGROUND: The aim of this study was to compare the effects of a 12-week course and four repeated 12-week courses of daily 5 mg ulipristal acetate (UPA) on reducing the volume and relieving symptoms of uterine fibroids. METHODS: From 2016 to 2019, 287 female patients with uterine fibroids diagnosed using ultrasonography were recruited. The patients received four 12-week course treatments of daily UPA administration in the first and fourth sessions, respectively. During the first and fourth courses of UPA, we measured the volume of the fibroids using ultrasonography to study the effect on volume reduction. The measured outcomes included symptomatic relief and adverse effects. RESULTS: After the first UPA treatment course, menorrhagia was improved in 82.2% of patients. A total of 59.5% of patients were responsive to treatment, and the volume of the three largest fibroids decreased from 160.9 cm3 to 104.6 cm3. After the fourth treatment course, 87.4% of patients reported decreased bleeding. A total of 67.2% of patients were responsive to treatment, and the volume of the three largest fibroids decreased from 171.7 cm3 to 106.5 cm3. In 64 (38.1%) patients in group A and 36 (30.3%) in group B, the fibroid volume increased. Among them, 72% of patients showed improved symptoms. CONCLUSIONS: Uterine bleeding, pain, and reduced fibroid volume were adequately regulated in patients with symptomatic fibroids with four repeated 12-week courses of daily UPA.

Society of Family Planning Clinical Recommendation: Emergency contraception.

Emergency contraception (EC) refers to several contraceptive options that can be used within a few days after unprotected or under protected intercourse or sexual assault to reduce the risk of pregnancy. Current EC options available in the United States include the copper intrauterine device (IUD), levonorgestrel (LNG) 52 mg IUD, oral LNG (such as Plan B One-Step, My Way, Take Action), and oral ulipristal acetate (UPA) (ella). These clinical recommendations review the indications, effectiveness, safety, and side effects of emergency contraceptive methods; considerations for the use of EC by specific patient populations and in specific clinical circumstances and current barriers to emergency contraceptive access. Further research is needed to evaluate the effectiveness of LNG IUDs for emergency contraceptive use; address the effects of repeated use of UPA at different times in the same menstrual cycle; assess the impact on ovulation of initiating or reinitiating different regimens of regular hormonal contraception following UPA use; and elucidate effective emergency contraceptive pill options by body mass indices or weight.

Ultrasonographic appearance of the endometrium after saline infusion in women presenting with PRM-associated endometrial changes, due to the use of ulipristal acetate.

Ulipristal acetate (UPA), used for the treatment in women with symptomatic fibroids, is associated with endometrial changes visualised on ultrasound as thickening up to more than 16 mm in approximately 10% of the patients. Is saline infusion sonography (SIS) a good alternative for more invasive techniques, to evaluate the presence of intrauterine pathology? Ten patients, presenting with UPA associated endometrial changes at their follow up ultra-sonographic evaluation, were included. Our study demonstrated that SIS is feasible and painless in patients presenting with UPA associated endometrial changes. The thickened endometrium appears to divide at the midline, making it possible to study both layers separately and exclude any suspected intrauterine pathology. Our findings suggest that SIS may be a first choice, non-invasive, painless technique to provide a proper visualisation to rule out intrauterine pathology when UPA associated endometrial changes are diagnosed after fibroid treatment. This is especially of clinical interest in front of assisted reproductive technology treatment. Invasive techniques can be withheld for patients in whom SIS examination is not contributive.Impact StatementWhat is already known on this subject? Reversible endometrial changes after ulipristal acetate (UPA) treatment in patients with symptomatic fibroids have been described. In patients who receive UPA, especially if planned to undergo ART, assessment of potential endometrial pathology is important as such interfere with proper implantation after ART. Consequently, clinicians may consider ruling out intrauterine pathology by invasive examinations such as biopsy or hysteroscopy after visualisation of the thickened endometrium.What do the results of this study add? Saline infusion sonography (SIS) was feasible and painless in patients presenting with UPA associated endometrial changes.What are the implications of these findings for clinical practice and/or further research? SIS may be a first choice, non-invasive, painless technique to provide a proper visualisation to rule out intrauterine pathology when UPA associated endometrial changes are diagnosed after fibroid treatment. This is especially of clinical interest in front of assisted reproductive technology treatment. Invasive techniques can be withheld for patients in whom SIS examination is not contributive in excluding intrauterine pathology.

Evaluation of marketing authorization and clinical implementation of ulipristal acetate for uterine fibroids.

Ulipristal acetate (UPA) is a medical treatment for uterine fibroids and was authorized for surgical pre-treatment in 2012 after the conduct of the PEARL I and II randomized controlled trials and for intermittent treatment after the observational PEARL III and IV trials. However, UPA came into disrepute due to its temporary suspension in 2017 and 2020 because of an apparent association with liver injury. This clinical opinion paper aims to review the process of marketing authorization and implementation of UPA, in order to provide all involved stakeholders with recommendations for the introduction of future drugs. Before marketing authorization, the European Medicines Agency (EMA) states that Phase III registration trials should evaluate relevant outcomes in a representative population, while comparing to gold-standard treatment. This review shows that the representativeness of the study populations in all PEARL trials was limited, surgical outcomes were not evaluated and intermittent treatment was assessed without comparative groups. Implementation into clinical practice was extensive, with 900 000 prescribed treatment cycles in 5 years in Europe and Canada combined. Extremely high costs are involved in developing and evaluating pre-marketing studies in new drugs, influencing trial design and relevance of chosen outcomes, thereby impeding clinical applicability. It is vitally important that the marketing implementation after authorization is regulated in such way that necessary evidence is generated before widespread prescription of a new drug. All stakeholders, from pharmaceutical companies to authorizing bodies, governmental funding bodies and medical professionals should be aware of their role and take responsibility for their part in this process.

Dual agonist-antagonist effect of ulipristal acetate in human endometrium and myometrium.

The aim of this study was to assess the molecular effect of ulipristal acetate (UPA) on gene expression in myometrium and endometrium of patients with symptomatic fibroids. Tissues isolated from four women treated preoperatively with UPA (5 mg) were compared to those from untreated controls using NanoString platform to assess the expression of 75 candidate genes modulated by UPA and ovarian steroids. Deregulated genes were then validated by real-time PCR. In myometrium, UPA exerted an antagonistic effect similar to that observed in fibroids. In UPA-treated endometrium, six genes were identified as highly and significantly upregulated, including matricellular genes CCN1 (54-fold, P = 0.0018) and CCN2 (11-fold, P = 0.00044), Krüppel-like factor 4 (>3-fold, P = 0.0036), and mast cell markers including tryptases TPSAB1/TPSB2 (31-fold, P = 0.023) and carboxypeptidase A (CPA3, 17-fold, P = 0.05). In endometrium, UPA induced the expression of genes involved in fibrogenesis and mast cell function-some of them being widely involved in hepatic injury, which could explain the marked fibrosis and inflammatory cell infiltration observed in explanted livers from patients under UPA treatment.

Effects of ulipristal acetate in patients with symptomatic uterine fibroids. / Efectos del acetato de ulipristal en pacientes con miomas uterinos sintomáticos.

INTRODUCTION: Uterine fibroids are frequently encountered in gynecology and are a therapeutic challenge. New therapies, such as ulipristal acetate, could help with symptomatic relief, improve quality of life, and decrease uterine fibroid size. Notwithstanding, there is controversy about adverse effects, especially for hepatotoxicity. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis, and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified nine systematic reviews and included ten studies overall, of which five were randomized trials. We conclude that ulipristal increases the likelihood of amenorrhea, improves the quality of life, and decreases menstrual bleeding. However, there is also a likely increase in the risk of adverse effects. Furthermore, ulipristal could decrease the size of fibroids.

INTRODUCCIÓN: Los miomas uterinos son una patología frecuente en ginecología, que tiene como desafío el enfrentamiento terapéutico. Existen nuevas terapias como el uso de acetato de ulipristal que podrían ayudar con el alivio sintomático y mejoría de la calidad de vida, además de la disminución del tamaño de los miomas uterinos. No obstante, existe controversia respecto a los efectos adversos, especialmente frente a la hepatotoxicidad. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos nueve revisiones sistemáticas que incluyeron diez estudios primarios, de los cuales cinco son ensayos aleatorizados. Concluimos que el uso de ulipristal aumenta la probabilidad de amenorrea, mejora la calidad de vida y disminuye el sangrado menstrual. Además, el uso de ulipristal podría disminuir el tamaño de los miomas. Sin embargo, podría aumentar el riesgo de efectos adversos.

Efficacy of ulipristal acetate in women with fibroid induced menorrhagia: A systematic review and meta-analysis.

AIM: To evaluate the efficacy of UPA in women with fibroid induced menorrhagia. METHODS: Embase, MEDLINE, CAB Abstracts, Cochrane Central Register of Controlled Trials, PsychInfo were searched up to 18th May 2020 and updated on 7th February 2021. Randomised controlled trials evaluating the efficacy of UPA in women with fibroid induced menorrhagia were included in the study. RESULTS: Two authors independently reviewed and extracted the study data. Statistical heterogeneity was quantified using I2 statistics. Publication bias and data asymmetry was assessed by funnel plots. A meta-analysis was conducted where appropriate. Six studies were eligible for inclusion. UPA (5 mg and 10 mg) achieved statistically significant amenorrhoeic outcome when compared to placebo (p<0.00001). Increased adverse events (AE) profile was observed in the higher UPA dose, however, did not reach statistical significance. CONCLUSIONS: This review demonstrates the efficacy of UPA in achieving amenorrhoea in women with fibroid induced menorrhagia. However, the favourable dose of UPA remains inconclusive when AE profile is taken into account. Evidence remains obscure regarding liver damage and further research is warranted to attain a conclusive outcome.

The endometrial response to modulation of ligand-progesterone receptor pathways is reversible.

OBJECTIVE: To study the impact of the progesterone receptor modulator (PRM), ulipristal acetate (UPA), on endometrial morphology and function. DESIGN: Cross-sectional. SETTING: University Research Institute. PATIENT(S): Endometrial biopsies from 16 patients with heavy menstrual bleeding with a structurally normal uterus or in association with structural abnormalities identified on radiological imaging (fibroids, adenomyosis or a combination of fibroids and adenomyosis). INTERVENTION(S): Participants received UPA (5 mg once daily) for three 12-week courses, each separated by 4 weeks without treatment. MAIN OUTCOME MEASURE(S): Gene expression by real-time quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and digital image analysis were analyzed to investigate the endometrial impact of modulation of progesterone receptor pathways upon expression of steroid receptors, steroid metabolizing enzymes, cell proliferation, and progesterone-regulated genes in the same patients at 3 time points: before, during, and after discontinuation of PRM treatment. RESULT(S): Ulipristal acetate treatment resulted in increased messenger ribonucleic acid (mRNA) levels of steroid receptors compared with pretreatment secretory endometrium; decreased mRNA levels of 17- and 11-beta-hydroxysteroid dehydrogenases compared with pretreatment proliferative endometrium and pretreatment secretory endometrium; reduced cell proliferation compared with pretreatment proliferative endometrium; and altered mRNA levels of progesterone-regulated genes. A strong consistency between immunohistochemistry-digital image analysis and real-time quantitative reverse transcription polymerase chain reaction results was evident. Alterations in the mRNA levels and endometrial morphology returned to a pretreatment phenotype after the cessation of PRM exposure. CONCLUSION(S): The endometrial impact of the modulation of progesterone receptor pathways with PRM (UPA) treatment is reversible. CLINICAL TRIAL REGISTRATION NUMBER: Ulipristal acetate versus conventional management of heavy menstrual bleeding (UCON) trial (EudraCT 2014-003408-65; REC14/LO/1602).

Estradiol/nomegestrol acetate as a first-line and rescue therapy for the treatment of ovarian and deep infiltrating endometriosis.

PURPOSE: Estradiol valerate/nomegestrol acetate (E2V/NOMAC) is a new combined oral contraceptive with a good tolerability profile and low drop-out rates, which was shown to improve menstrual-related symptoms. This study aims to evaluate its effectiveness in the control of symptoms and progression of disease in women with ovarian endomestriomas and deep infiltrating endometriosis (DIE). METHODS: This was a retrospective cohort study on 39 women with pelvic endometriosis treated with E2V/NOMAC. We assessed for each patient, at the beginning of treatment and after 6 months, the painful symptoms, through a global VAS (Visual Analogue Scale) index and the size of the greatest ovarian and/or deep infiltrating endometriotic lesions. RESULTS: After 6 months of treatment, a significant reduction was observed for the global VAS score for pain symptoms and for the mean size of ovarian endometriomas, whereas DIE lesions did not present significant changes in mean size. CONCLUSIONS: E2/NOMAC was effective in reducing pain symptoms associated with pelvic endometriosis and the size of ovarian endometriomas, whereas DIE lesions remained stable. This therapy could provide good results in the control of symptoms and disease progression in women with pelvic endometriosis.

Ulipristal acetate compared with leuprorelin acetate for Japanese women with symptomatic uterine fibroids: a phase III randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of ulipristal acetate (UPA) for uterine fibroids (UFs), a phase III study was conducted with leuprorelin (LEU) as a comparator. This is the first confirmatory trial of UPA for UFs among Asians. DESIGN: Multicenter, randomized, double-blind, double-dummy, parallel-group study. SETTING: Thirty-two sites in Japan. PATIENT(S): Patients were assigned to 2 arms, with 82 patients in the UPA group and 79 patients in the LEU group. INTERVENTION(S): In the UPA group, 10 mg of UPA was orally administered once a day for 12 weeks. In the LEU group, 1.88 mg or 3.75 mg of LEU was subcutaneously administered at weeks 0, 4, and 8. MAIN OUTCOME MEASURE(S): The primary endpoint was the percentage of patients with amenorrhea for 35 days. For safety evaluation, adverse events (AEs) were recorded. RESULT(S): The percentage of patients with amenorrhea for 35 days was 87.0% in the UPA group and 81.8% in the LEU group, and the efficacy of UPA for causing amenorrhea for 35 days was confirmed to be noninferior to that of LEU. AEs occurred in 78.0% of the patients in the UPA group and 88.8% of the patients in the LEU group. CONCLUSION(S): The effect of UPA on heavy menstrual bleeding was shown to be comparable with that of LEU in Japanese patients with symptomatic UFs. No notable AEs occurred because of the UPA treatment, and the incidence of AEs in the UPA group was comparable with that of AEs in the LEU group. This result demonstrates the clinical utility of UPA for Asians.