Courses Of Ulipristal Acetate Research Articles

The use of a short course of Ulipristal Acetate for acute abnormal uterine bleeding in women without uterine fibroids.

Ulipristal Acetate (UPA) is a synthetic selective progesterone receptor modulator. It is used as emergency contraception and to reduce pain and blood loss in women of reproductive age with uterine fibroids. The first mechanism of action is myometrial apoptosis, the second is on the hypo-thalamic-pituitary-ovarian axis and the third action, is an anti-proliferative effect on the endometrium. Mainly based on the latter two, UPA is increasingly used off-label in women with abnormal uterine bleeding (AUB) without fibroids. The aim of this paper is to find evidence for a short course of UPA to treat acute AUB without fibroids, performing a systematic review as well as scrutinising literature data on the pharmacokinetics and on short term bleeding control in women with fibroids. A systematic electronic literature review was performed in February 2022. Inclusion criteria were UPA administered to women without myomas in a setting of acute uterine bleeding. Further criteria included papers describing early bleeding control using UPA, deemed independent of the presence of fibroids, with specific attention to the median time to amenorrhoea. The main outcome measured was the bleeding control within 10 days. One case report was identified. The data on symptomatic women with fibroids using 5 mg or 10 mg daily revealed bleeding control was reported within 10 days in 81% and 89% respectively, with amenorrhoea in 57% and in 78% respectively. A short-term administration may prove effective in abnormal uterine bleeding irrespective of the presence of uterine fibroids. However, more randomised controlled trials are needed and should be performed before implementation in general clinical practice. A short course of Ulipristal acetate as promising treatment for acute uterine bleeding without fibroids.

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

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. 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. 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. Uterine bleeding, pain, and reduced fibroid volume were adequately regulated in patients with symptomatic fibroids with four repeated 12-week courses of daily UPA.

Safety and efficacy of two repeated cycles of ulipristal acetate in the management of symptomatic uterine fibroid among Indian women.

IntroductionTo evaluate the safety and efficacy along with the impact on uterine and fibroid vascular indices of 2 repeat 12-week courses of ulipristal acetate (UPA) among Indian women.Material and methodsNinety-four premenopausal women aged 18-45 years with at least 1 symptomatic fibroid of size ranging from 1 cm to 10 cm were included in the study. All participants received 2 courses of 5 mg of UPA orally for 12 weeks starting from the 5th day of their menstrual cycle with a 2-menstrual-cycle break in between. The efficacy was measured in terms of time to amenorrhoea, percentage of women who achieved amenorrhoea for the last 35 consecutive days, reduction in uterine and fibroid volume, as well as its vascularity at the end of the first and second treatment cycle.ResultsEighty-six women completed the first treatment cycle whereas only 65 women completed the second treatment course. Seventy-nine per cent of women achieved amenorrhoea for 35 consecutive days during the first treatment cycle. Median time to amenorrhoea was 7 days and 5 days during the first and second treatment cycle, respectively. Percentage reduction of the mean fibroid volume was 32% and 52% after the first and second treatment cycle, respectively. We observed an increase in fibroid vascular indices (pulsatility index and resistive index) suggesting reduction in fibroid vascularity. Serum oestradiol remained at mid-follicular phase. No serious drug emergent side effect was noted.ConclusionsTwo interrupted repeat course of 5mg UPA is well tolerated efficient and safe in symptomatic fibroid among Indian women.

Progression of adenomyosis magnetic resonance imaging features under ulipristal acetate for symptomatic fibroids

Research questionWhat is the evolution of adenomyosis on magnetic resonance imaging (MRI) after a 3-month treatment course of daily 5 mg doses of ulipristal acetate (UPA) for symptomatic fibroids? DesignA monocentric prospective pilot study on patients who underwent a 3-month treatment course of UPA for symptomatic fibroids between January 2014 and December 2017. Patients underwent pelvic MRI shortly before (pre-MRI) and after treatment (post-MRI). The diagnosis of adenomyosis on MRI was defined by the observation of intramyometrial cysts and/or haemorrhagic foci within these cystic cavities and/or a thickening of the junctional zone >12 mm. The progression of adenomyosis was defined by the presence of at least one of the aforementioned criteria of adenomyosis on the pre-MRI and by at least one of the following on the post-MRI: (i) increased thickness of the junctional zone ≥20% and/or (ii) increased number of intramyometrial cysts. The appearance of adenomyosis was defined by the absence of the aforementioned criteria of adenomyosis on the pre-MRI and the presence of at least one of these criteria on the post-MRI. ResultsSeventy-two patients were included. The MRI features of adenomyosis progressed for 12 of 15 patients (80.0%) for whom adenomyosis was identified on the pre-MRI. An appearance of adenomyosis was identified after treatment for 15 of 57 patients (26.3%) for whom adenomyosis was not identified on the pre-MRI. ConclusionsA 3-month treatment course of daily 5 mg doses of UPA could provoke a short-term progression or an emergence of typical adenomyosis intramyometrial cysts on MRI examinations.

Management of symptomatic uterine fibroids with ulipristal acetate: A retrospective, multicentric and nationwide study

ObjectiveTo evaluate symptomatic uterine fibroid outcomes following at least one course of ulipristal acetate (UPA) 5 mg/day therapy in the hospital setting, during the year 2017. Study designA retrospective and descriptive analysis involving women with symptomatic fibroids was conducted in 15 hospital centers in Portugal in 2017 to assess fibroid size, bleeding control and hemoglobin levels following at least one course of UPA 5 mg/day. Secondary outcomes were the reasons for the treatment, type of surgery, fibroid classification, patient satisfaction with the treatment, and adverse events. ResultsFive-hundred and twenty-six patients were enrolled in this survey, and 93 % of the women completed, at least, 1 treatment course with UPA. Uterine bleeding control was achieved in 81 % of the cases. A significant increase (p < 0.001) in hemoglobin levels and a reduction (p < 0.001) in uterine fibroid size was observed after treatment, with a median reduction of 24 % from the baseline. Forty-seven percent of the patients underwent subsequent surgery and there were no serious adverse events reported in this multicentric nationwide study. ConclusionsSo far, this is the largest case series reporting on symptomatic uterine fibroid outcomes after UPA therapy in Portugal. Our data are in line with published literature and confirm favorable outcomes after UPA therapy for women of childbearing age and premenopausal.

Pathologic Changes in Uterine Leiomyomas After Extended Treatment With Ulipristal Acetate

Ulipristal acetate is a selective progesterone receptor modulator that acts on progesterone receptors in uterine muscle and endometrium. It is effective in reducing the size of uterine leiomyomas (fibroids) and in managing associated menorrhagia. Although ulipristal acetate-associated pathologic changes have been previously documented in the endometrium, it is unclear what morphology can be expected in posttreatment fibroids. We herein report 2 cases in which patients underwent hysterectomy, after at least two 3-mo courses of ulipristal acetate. The fibroids demonstrated some pathologic changes that have previously been described associated with gonadotropin-releasing hormone agonist treatment and other progestogens. In addition, both cases demonstrated plexiform/"patchwork" fibrosis and vascular medial myxoid degeneration. Mitotic activity was absent; however, the presence of ischemic necrosis and mild nuclear atypia may mimic a more aggressive neoplasm in some areas. Awareness of these histopathologic patterns is important in the setting of ulipristal acetate treatment, to avoid over-diagnosis of "uncertain malignant potential" or malignant smooth muscle tumors.

What does non-eligibility for myoma surgery mean in the context of sequential prescription of ulipristal acetate?

Ulipristal Acetate (UPA) is the only selective progesterone receptor modulator currently approved for medical management of myomas. Following several cases of liver toxicity during UPA treatment, new recommendations of PRAC (Pharmacovigilance Risk Assessment Committee) and EMA (European Medicines Agency) have been proposed, including a pre-therapeutic assessment of liver function and a close monitoring during treatment. Repeated courses of UPA have also been restricted to women who are defined as “non-eligible” for surgery. This article raises important questions and tries to provide clarification about the concept of ‘non-eligibility’ for myoma surgery.

1953 Ulipristal Acetate for Adenomyosis: A Multicenter Randomized Trial

Study Objective To evaluate efficacy of a 3 months course of ulipristal acetate on abnormal uterine bleeding in adenomyosis Design A multicenter randomized trial with a 3:1 ratio. Setting In five different teaching hospitals Patients or Participants Women with adenomyosis confirmed on MRI or sonography and abnormal uterine bleeding with PBAC score more than 100 Interventions Women were randomly assigned for a 3 months course of either 10mg Ulipristal acetate or a placebo Measurements and Main Results Main objective was the rate of women with a PBAC score under 75 after 3 months of treatment. The secondary objectives included rate of PBAC score under 75 at 6 months, rate of amenorrhea at 3 and 6 months, evolution of the pain and of the quality of life at 3 and 6 months and finally, tolerance. Forty women were included, 30 in the UPA group and 10 in the placebo group. The two groups were comparable particularly for PBAC score and analgesic consumption before the treatment. At 3 months, a significant difference was observed between UPA group and placebo group for the rate of PBAC score under 75 (0 versus 95.2%), p Conclusion Ulipristal acetate seems to stop abnormal uterine bleeding due to adenomyosis but also pain during a three months course but both of these symptoms reappeared at the stop of the medication. Other studies are needed to conclude and to try different doses.

Adverse symptoms during short‐term use of ulipristal acetate in women with uterine myomas and/or adenomyosis

To evaluate various adverse symptoms during short-term use of ulipristal acetate in women with uterine myomas (n = 90), adenomyosis (n = 3) or both (n = 7). One hundred premenopausal women who received ulipristal acetate for 4-12 weeks during 2016 to 2017 were selected. The medical records were reviewed and the following information was collected; adverse symptoms during medication, presence of menorrhagia or menstrual cramps, blood hemoglobin and liver function test. Adverse symptoms were recorded in the medical records as a checklist form including 76 specific progestin-related symptoms. Overall, the most frequent adverse symptom was amenorrhea (43%), followed by weight gain (29%), fatigue (27%), abdominal discomfort (21%), decreased menstrual flow (19%) and dizziness (18%). In 89 symptomatic women (with heavy menstrual bleeding and/or menstrual cramping pain and/or anemia), the most frequent adverse symptom was weight gain (27%) and fatigue (27%), followed by abdominal discomfort (21%), dry eye (18%), facial flushing (17%), dizziness (17%), headache (17%) and increased vaginal discharge (15%). Fourteen women stopped the medication due to unwanted adverse symptoms. Of this discontinuation group, major complaint was fatigue (50%), followed by weight gain (36%) and breast discomfort (35.7%). Adverse symptoms were common and discontinuation rate was somewhat higher during short-term course of ulipristal acetate. Information about incidence of various adverse symptoms should be given to women who willing to take ulipristal acetate.

The Use of Ulipristal Acetate (Esmya) Prior to Laparoscopic Myomectomy: Help or Hindrance?

Introduction:The aim of this study was to assess the operative effects, both positive and negative, of pretreatment with ulipristal acetate (UPA) on laparoscopic myomectomy.Materials and Methods:We conducted a retrospective analysis of prospectively collected data from patients who underwent a laparoscopic myomectomy over a 2-year period.Results:A total of 62 patients were included, of which 10 received a 3-month preoperative course of UPA, and 52 patients received no pretreatment. There was no statistically significant difference between the two groups (no pretreatment vs. UPA pretreatment) with regard to blood loss (214.4 [±214.96] vs. 160 [±51.64], P = 0.432), operating time (111.64 [±41.8] vs. 117.5 [±50.4], P = 0.694), and duration of inpatient stay (1.27 [±0.56] vs. 1.11 [±0.33], P = 0.419). There were no complications in either group. In 100% of cases with UPA pretreatment, a distortion of the fibroid capsule with a more technically challenging dissection was noted, compared to 0% in the no pretreatment group. This anatomical distortion may result in more cases of incomplete resection and a potentially higher risk of recurrence.Conclusion:We conclude that UPA confers no operative benefits and should be used with caution in the presurgical treatment of fibroids. The use of UPA may indeed result in a more technically difficult myomectomy with distorted cleavage planes and carry a potential risk of incomplete resection.

Absence of predictable long-term molecular effect of ulipristal acetate (UPA) on the endometrium.

What are the effects of ulipristal acetate (UPA) on the expression of endometrial proliferation and maturation markers? A total of 45 endometrium-containing blocks of hysterectomy samples from non-menopausal women with a diagnosis of moderate to severe symptoms of uterine fibroids: 14 women operated on at the end of a 3-month course of UPA; four women who had discontinued UPA treatment 1-12 months before surgery; 27 control unexposed samples (14 in the proliferative and 13 in the secretory phase). Immunohistochemical staining of Ki67, vascular endothelial growth factor-receptor 2 (VEGFR2), oestradiol receptor, progesterone receptor, interleukin-15 (IL-15), indoleamin-2,3-dioxygenase (IDO) and C-C motif chemokine ligand-2 (CCL2) markers were analysed in both endometrial compartments and layers. Under UPA, oestradiol receptor and progesterone receptor expression is similar to the proliferative phase in both layers, although with a decrease in cell proliferation. IL-15, IDO and CCL2 expressions are similar to the proliferative phase, suggesting a progesterone-antagonist effect of UPA. VEGFR2 staining suggests a trend to a mixed agonist-antagonist effect. No significant difference is observed in the post-UPA proliferative phase group compared with the control group in both layers of the endometrium. The effect of 3-month UPA treatment is mostly progesterone receptor antagonist-like. After treatment is discontinued, there are no signs of any long-term effects of this molecule on endometrial proliferation and maturation. Therefore, UPA may be administered to women willing to conceive in the short term without consequences for further implantation.

Ulipristal Acetate Improves Clinical Symptoms in Women with Adenomyosis and Uterine Myomas

Study ObjectiveTo study the effects of ulipristal acetate (UPA) on adenomyosis-associated clinical symptoms. DesignA retrospective, single-center observational study (Canadian Task Force classification II-2). SettingA university tertiary referral center. PatientsPremenopausal women (163) with adenomyosis and symptomatic uterine myomas (41 patients, A + F group) versus a control group with only myomas (122 patients, F group) treated with the first course of UPA. InterventionsThis was a retrospective study to assess the effects of a 12-week course of UPA (5 mg/d). Measurements and Main ResultsClinical symptoms including bleeding control, amenorrhea, pain outcomes, and self-perceived severity of the disease and quality of life. Amenorrhea was present in 90.4% of the A + F group compared with 77.6% in the F group (p = .0017). Optimal bleeding control was significantly higher in the adenomyosis group (pictorial blood loss assessment chart < 75) than in the F group (90.2% vs 73.8%, p = .028). At the end of the first UPA course, the self-reported visual analog scale scores in the A + F group were significantly higher than in the F group (p = .017), reflecting greater improvement in pain outcomes for women with adenomyosis. UPA treatment improved the quality of life in both study groups. Most of the women rated their global health status as “better” after the first UPA course than before the treatment (A + F group: 67.00% and F group: 80.50%, p = .223). ConclusionTreatment with UPA led to a significant reduction in the clinical symptoms of adenomyosis (bleeding and pain) and achieved a high rate of amenorrhea in a cohort of women with concomitant uterine myomas. Despite the limitations of the study, our results showed that UPA might be a good alternative treatment for adenomyosis.

Safety after extended repeated use of ulipristal acetate for uterine fibroids.

ObjectiveTo assess long term safety of extended repeated 3-month courses of ulipristal acetate (UPA) 10 mg/day, for up to 8 courses, with focus on endometrial and laboratory safety parameters.MethodsThis long-term, multi-center, open-label cohort, follow up study consisted of up to 8 consecutive 3-month courses of daily UPA 10 mg, each separated by a drug free period of 2 spontaneous menstrual bleeds. Sixty-four pre-menopausal women, with moderate to severe symptomatic uterine myoma(s) and heavy bleeding were enrolled and were studied for approximately 4 years. The main outcome measures were endometrial histology, laboratory parameters and general safety.ResultsAll data was reported in a descriptive manner with no formal statistical comparisons. In the 64 women, non-physiological changes (mostly cyst formation, epithelial and vascular changes) in endometrial histology at screening and after treatment courses 4 and 8 were observed in 18.0%, 21.4% and 16.3% of biopsies, respectively. After treatment cessation, such changes were observed in 9.1% of biopsies. All endometrial biopsies were benign after course 8. The median endometrial thickness was 7.0 mm, 10–18 days after the start of menses following treatment courses 5–8, compared to 9.0 mm at screening (before UPA treatment). No changes in the number and type of laboratory results outside the normal ranges were observed with the increasing treatment courses. In total, adverse events were reported in 10 (16%), 12 (19%), 8 (14%) and 5 (9%) subjects, during treatment courses 5, 6, 7 and 8, respectively of which the most frequent adverse events were headache and hot flush.ConclusionThe results of this study further support the safety profile of extended repeated 3 months treatment of symptomatic fibroids with ulipristal acetate 10 mg/day. Repeated UPA treatment courses did not result in any changes of concern in endometrial histology, endometrial thickness, or laboratory safety measures.

Role of ethnicity in treating uterine fibroids with ulipristal acetate

To study differences in treatment effect between black and white premenopausal women prescribed ulipristal acetate (UPA) for symptomatic uterine fibroids. Prospective observational cohort study. Gynecology clinics. Premenopausal women aged 18-55years, at least one symptomatic uterine fibroid, UPA-naïve, and no contraindications for UPA treatment. One 3-month course of UPA at 5mg daily. Patients' ethnicity self-identification adapted from Statistics Canada National Household Survey. Change in fibroid symptoms according to Uterine Fibroid Symptoms Quality of Life Questionnaire symptom severity and health-related quality of life score. Bleeding symptoms and amenorrhea rates according to Aberdeen Bleeding Score. A total of 148 patients enrolled (45 black, 59 white, 44 other ethnicity). Black patients were younger (40.3y vs. 44.5y) with larger uteri (523mL vs. 351mL) than white counterparts. Baseline symptom severity was similar between groups. After 3months of UPA treatment, both groups experienced similar improvements in symptom severity. White women had 52% greater improvement in bleeding score (-40.3 vs. -26.5) and were more likely to be amenorrheic at the end of treatment (66% vs. 41%). Both groups experienced adverse events at similar frequencies. Black women were more dissatisfied with UPA compared with white women (27.3% vs. 8%). Black women had greater fibroid burden at baseline. Both ethnicities had similar improvement in fibroid symptomatology following UPA treatment, but white women experienced higher amenorrhea rates. Black women were more dissatisfied with UPA treatment, which may be related to the lower amenorrhea rates.

Repeated intermittent use of ulipristal acetate associated with rapid growth and multilocular cystic hydropic degeneration of a uterine fibroid: A case report

Introduction: Uterine fibroids or leiomyomas are common benign tumors often associated with menorrhagia, pressure symptoms and dysmenorrhea. selective progesterone receptor modulators (sPrMs) such as ulipristal acetate (UPA) have been proven a safe and effective treatment resulting in significant volume reduction of uterine fibroids and amenorrhea. safety concerns of long-term use of UPA have mainly focused on endometrial changes, which have been proven to be benign and self-resolving. case report: A 44-year-old woman presented with symptomatic subserosal fibroid of 7.5 cm in diameter and was prescribed UPA for three months. After a positive initial treatment response, a repeated three-month course of UPA was started. At the end of the second course the patient became symptomatic presenting with cyclic abdominal pain. Ultrasound imaging revealed a large multilocular cystic pelvic mass sized 10x11 cm suspicious of a malignant tumor and abdominal hysterectomy was performed.

Long-term medical management of uterine fibroids with ulipristal acetate

To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. Double-blind, randomized administration of four 12-week courses of ulipristal acetate. Gynecology centers. Four hundred fifty-one subjects with symptomatic uterine fibroid(s) and heavy menstrual bleeding. Four repeated 12-week treatment courses of daily 5 or 10 mg ulipristal acetate. Endometrial safety and general safety, laboratory parameters, amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), and pain. Efficacy results, such as bleeding control and fibroid volume reduction, were in line with previously published data. Pain and QoL showed marked improvements from screening, even during the off-treatment intervals. The safety profile of ulipristal acetate was confirmed, and repeated treatment courses did not increase the occurrence of adverse reactions. There were no significant changes in laboratory parameters during the study. The percentage of subjects with endometrial thickness ≥ 16 mm was 7.4% (all subjects) after the first treatment course and returned to below screening levels (4.9%) in subsequent treatment courses. As in previous studies, ulipristal acetate did not increase the occurrence of endometrial features of concern. The frequency of nonphysiological changes did not increase with repeated treatment. They were observed in 17.8% and 13.3% of biopsies after treatment courses 2 and 4, respectively, and were reversible after treatment cessation. The results of this study demonstrate the efficacy and further support the safety profile of repeated intermittent treatment of symptomatic fibroids with ulipristal acetate. NCT01629563.

Efficacy and safety of repeated use of ulipristal acetate in uterine fibroids

To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily of ulipristal acetate for intermittent treatment of symptomatic uterine fibroids. Double-blind, randomized administration of two 12-week courses of ulipristal acetate. Gynecology centers. A total of 451 patients with symptomatic uterine fibroid(s) and heavy bleeding. Two repeated 12-week treatment courses of daily 5 or 10 mg of ulipristal acetate. Amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), pain. In the 5- and 10-mg treatment groups (62% and 73% of patients, respectively) achieved amenorrhea during both treatment courses. Proportions of patients achieving controlled bleeding during two treatment courses were >80%. Menstruation resumed after each treatment course and was diminished compared with baseline. After the second treatment course, median reductions from baseline in fibroid volume were 54% and 58% for the patients receiving 5 and 10 mg of ulipristal acetate, respectively. Pain and QoL improved in both groups. Ulipristal acetate was well tolerated with less than 5% of patients discontinuing treatment due to adverse events. Repeated 12-week courses of daily oral ulipristal acetate (5 and 10 mg) effectively control bleeding and pain, reduce fibroid volume, and restore QoL in patients with symptomatic fibroids. NCT01629563 (PEARL IV).