Ulipristal Acetate Therapy Research Articles

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 < 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

Nutraceuticals in fibroid management after ulipristal acetate administration: An observational study on patients' compliance.

On May 13, 2020, the Italian government Pharmaceutical Agency (AIFA) stopped ulipristal acetate (UPA) treatments for uterine fibroids (UFs), so patients shifted to other natural treatments. The authors tested the patients' compliance with UF natural treatments. Thirty patients of reproductive age (30-45years) affected by UFs stopped UPA intake and started epigallocatechin gallate (EGCG) plus vitamin D3 treatment. Patients were asked to complete the Uterine Fibroid symptoms and Quality of Life (UFS-QOL) questionnaire, divided into symptoms severity (SS) and health-related quality of life (HRQL), after UPA suspension and to repeat it after 3months of natural treatment. Collected data were analyzed using paired Student's t test, considering a P value less than 0.05 to be significant. The SS score was significantly lower (-12.19%) for natural treatment when compared with UPA administration. The HRQL score significantly improved (+11.79%) after shifting treatment from UPA to natural therapy. All the investigated parameters appeared improved by 10% after the natural treatment. No adverse effects were reported following the natural treatment. Natural treatments showed positive compliance in patients with UFs, based on HRQL score, representing an alternative therapeutic opportunity for patients forced to stop UPA therapy.

Progesterone Modulator May Offer PMDD Relief

Progesterone Modulator May Offer PMDD Relief

Series of 55 pregnancies following ulipristal acetate treatment of symptomatic uterine fibroids

Introduction: Treatment with ulipristal acetate effectively controls excessive bleeding due to uterine fibroids and reduces their size. Uterine fibroid size reduction is expected to improve the results of the myomectomy and the reproductive prospects of the patient. Methods: Retrospective and descriptive analysis of a series of 53 patients who achieved pregnancy after being treated for symptomatic uterine fibroids. The primary endpoints were pregnancy and birth outcomes in women with symptomatic uterine fibroids that conceived following at least one course of therapy with ulipristal acetate 5 mg/day. The secondary endpoints were time until pregnancy, reasons for ulipristal acetate treatment, number of treatment courses completed, hemorrhagic control achievement, hemoglobin levels, fibroid FIGO classification, largest fibroid diameter, and type of myomectomy (if any). Results: Fifty-five pregnancies were registered in 53 patients following ulipristal acetate therapy (43 live births, 9 miscarriages, and 3 ongoing pregnancies). Half of the patients became pregnant without interval surgery. Bleeding control was achieved in 96% 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. No malformations were reported among newborns after ulipristal acetate therapy. Conclusion: So far, this is the largest case series reporting both pregnancy and birth outcomes following ulipristal acetate therapy for uterine fibroids. Our data support favorable outcomes after therapy for this population subset.

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.

Predictive Factors of Response to Selective Progesterone Receptor Modulator (Ulipristal Acetate) in the Pharmacological Treatment of Uterine Fibroids.

Background: Selective progesterone receptor modulator ulipristal acetate (UPA) is a drug used in management of symptomatic myomas. It was observed that the response to UPA treatment in uterine myomas varied amongst patients. An attempt was thus made at establishing predictive factors conducive to better reaction to treatment with UPA. The aim of this study was to assess the efficacy of UPA treatment in women with myomas, depending on pretreatment myomas’ volume, number of myomas, age of patients, estrogenic status of women, and pretreatment blood flow in uterine arteries. Materials and methods: The study included patients with one to four myomas. The UPA treatment was a preparation stage for surgical treatment in all patients. The study group was divided into the subgroups according to pretreatment myomas’ volume, number of myomas, age of patients, estrogenic status of women, and pretreatment blood flow in uterine arteries. Results: A better effect of reduction in size of myomas after UPA treatment was noted when pretreatment myomas’ volume was lower than 30 cm3. A significant reduction in fibroids’ size was observed after UPA therapy independently of the number of myomas and age of patients. A good response after the UPA therapy was observed when pretreatment estradiol concentration was below 50 pg/mL and when uterine artery resistance index (RI) was above 0.8. Conclusions: Our research demonstrates that treatment with ulipristal acetate is an efficient method in preoperative preparation of patients with uterine fibroids. The most important factor of positive response to UPA therapy is myoma volume. The number of myomas and patient’s age do not interfere with effects of UPA therapy. Pretreatment estradiol concentration is significant, yet secondary for the effects of therapy. The UPA therapy has no impact on blood flow in the uterine arteries and no adverse influence on estradiol concentrations.

Histological pattern of leiomyomas after ulipristal acetate treatment in women: a case-control study

Purpose of Investigation: Assessing cytological and extracellular matrix histological patterns of uterine leiomyomas, in women previously treated with ulipristal acetate (UPA). Materials and Methods: Patients underwent surgical intervention for uterine leiomyomas between 2017 and 2018 were screened for previous use of UPA and were considered as cases. Controls were matched for race and nonmenopausal status among patients with surgeries for leiomyomas. Fibrosis, hyalinosis, edema, necrosis, cellularity, phlogosis, and mitosis were assessed in the specimens of fibroids by a semiquantitative score. The rates of scores for each histological pattern were compared among cases and controls, and described in a two-dimensional correspondence analysis. Results: There is not significance among scores between cases and controls fibroids, except than for the hyalinosis of moderate grade, that seems more likely in the ulipristal acetate group. The fibroids after ulipristals appear to have less mitosis and cellularity, while it seems to have more hyalinosis, edema and, in case of two cycles of ulipristal, fibrosis. Conclusions: Histological changes of leiomyomas after UPA therapy are heterogeneous. UPA mostly acts on extracellular matrix and, to a lesser extent, on histological parameters of smooth muscle cell proliferation.

Hormonal assessment of patients of reproductive age with uterine myoma for surgical treatment

Aim: To assess the efficacy and safety of ulipristal acetate (UA) use in uterine myoma patients before surgical treatment. Material and methods: 78 patients of reproductive age with uterine bleeding and anemia, who underwent laparoscopic myomectomy, were included in the study. Patients were divided into two groups: the first group consisted of 43 women who received 5 mg of ulipristal acetate daily for 3 months before the operation and the second group consisted of 35 patients without ulipristal treatment. A comparative analysis was made between clinical laboratory data groups, pathomorphological changes in myoma and endometrial nodes, and long-term treatment results. Results: As a result of UA therapy uterine bleeding stopped in all patients of the first group, the size of myoma nodes decreased by 25% according to visual diagnostics data, hemoglobin content normalized without iron-containing drugs. Duration of the operation and volume of intraoperative blood loss were less in the first group of patients in comparison with such parameters in the second group. Conclusion: Use of ulipristal acetate for preoperative assessment of patients with uterine myoma of reproductive age suffering from uterine bleeding and anemia is effective and safe.

Observation of Long-term Effects on Endometrium and Uterine Fibroids in Women With Ulipristal Acetate Therapy

Observation of Long-term Effects on Endometrium and Uterine Fibroids in Women With Ulipristal Acetate Therapy

Influence of Ulipristal Acetate Therapy on Uterine Fibroid-Related Symptoms and on Uterine and Fibroid Volumes and Vascularity Indices Assessed by Ultrasound.

To investigate the modifications of uterine and fibroid volume, to study Doppler changes in uterine arteries and fibroid-supplying vessels, and to assess possible symptomatic relief after 3 months of treatment with ulipristal acetate. Forty-two premenopausal women with symptomatic fibroids were included in the study. They were evaluated clinically for the symptoms reported and underwent ultrasound examinations before starting treatment and after 3 months of therapy with ulipristal acetate. Transvaginal scanning was performed by the same sonographer, who measured the uterine volume and uterine artery pulsatility index and resistive index. Considering that some patients had more than 1 fibroid, the vascularization (supplying vessel pulsatility and resistive indices), locations, and sizes of a total of 73 fibroids were also recorded. After 3 months of ulipristal acetate, patients had a significant improvement of all symptoms (P < .05). The percentage of uterine volume reduction was 14% (P = .03), with fibroid volume reduction of 32.8% (P = .01). Uterine artery vascular indices decreased after treatment, but their reduction did not reach significant results, whereas all fibroid vascular indices decreased significantly after 3 months of ulipristal acetate (P < .05). When the fibroids were divided according to their localization, all had significant volume reduction after therapy, but type 5 had the highest decrease (42%) compared to other fibroid types (P = .03). Fibroid treatment with ulipristal acetate resulted in a significant improvement of fibroid-related symptoms; moreover, it proved to be effective in decreasing both uterine and fibroid volumes and fibroid vascularization. Type 5 fibroids seem to have the most major response to treatment.

Outcome of patients with uterine fibroids after 3-month ulipristal acetate therapy

ObjectivesTo determine the proportion and the characteristics of patients who did or did not respond after 3 months of ulipristal acetate (UPA) therapy. Study designIn this retrospective cohort study conducted in the University Hospital of Bordeaux (France) and University Medical Center Ljubljana (Slovenia), symptomatic non-menopausal patients with fibroids that qualified for surgery were pretreated by 3 months of oral UPA 5 mg/day. Clinical success was defined by normalization of the bleeding score, and/or regression of pelvic pain, and/or abdominal distension. Imaging success was defined by reduction in fibroid volume ≥ 25%. ResultsThe clinical and imaging success rates were 54/66 (82%) and 39/66 (59%) respectively. The absence of previous pregnancy (p = 0.004) and the size of the dominant fibroid ≥ 80 mm (p = 0.004) were independent factors associated with clinical failure. Age <35 years (p = 0.02) was the only independent factor associated with imaging failure. ConclusionYoung women developing fibroids and/or women with large fibroids may be resistant to ulipristal acetate therapy.

OP24.09: Ulipristal acetate (UPA) therapy increased ultrasound features of adenomyosis: a good treatment given in an erroneous diagnosis of uterine fibroids

To describe sonographic findings in patients with adenomyosis erroneously treated with ulipristal acetate (UPA). This an observational ultrasound (US) study on premenopausal patients who were treated with UPA for menorrhagia and uterine fibroids. Patients undergoing UPA treatment (5mg/24h of oral UPA for 3 months) usually had a pre treatment scan to diagnose and evaluate uterine fibroid's volume and endometrial status. The US exam is usually repeated at the end of the 3months treatment in order to assess effects on UPA on fibroids and endometrium. Ideally both these ultrasound scans should be performed in the same unit however not always this occurs. On 42 patients treated with UPA and observed in our ultrasound unit, 18 were scheduled only at the end of the treatment. Of these 6 patients did not show typical fibroids at US but an enlarged uterus with typical US features of adenomyosis. All patients receiving UPA showed after treatment amenorrhea and improvement of symptoms related to their previous anemia. 36 out of 42 patients with US detected fibroids showed also an improvement of their pain due to their uterine pathology whereas in the 6 patients with adenomyosis pelvic pain was increased and 2 of this patients stopped the UPA treatment within the first 2 months. In 21% (10/42) patients we observed typical endometrial thickening induced by UPA therapy of these 3 had adenomyosis. The adenomyosis features and especially intramyometrial cystic areas seem to be enlarged compared to pre-treatment scan not performed in our unit. Our observations on patients with adenomyosis who underwent UPA treatment for an erroneously diagnosis of uterine fibroid showed a worsened of the US adenomyotic features and of their pelvic pain, with an improvement of the bleeding. After these observations we should be aware to prescribe UPA therapy in patients with adenomyosis and a correct US diagnose of fibroids in mandatory to start the UPA treatment.

CLINICAL AND MORPHOLOGICAL RATIONALE FOR THE ULIPRISTAL ACETATE PRE-OPERATION TREATMENT BEFORE ORGANPRESERVING OPERATIONS IN MYOMAS UTERUS PATIENTS WITH THE INTRAUTERINE BLEEDING AND ANAEMIA

Objective: assessment of the feasibility and safety of the use of ulipristal acetate on the basis of the clinical and morphological study. Materials and methods : the study involved 78 women with leiomyoma, abundant menstruation and anemia. Group I – 43 patients who underwent ulipristal acetate therapy for three months and then laparoscopic myomectomy. Group II – 35 patients who were myomectomyed without presurgical preparation. A comparative analysis was made of the clinic-laboratory data, operational parameters, pathomorphological changes in the nodes and endometrium. According to the original clinical laboratory study groups I and II were almost homogeneous. Results : in the case of ulipristal acetate therapy in all group I patients uterine bleeding ceased, the size of the myomatous nodules decreased by an average of 25 per cent according to the ultrasound and the MRI (p &lt; 0.05), the haemoglobin and the ferritin levels reached normal values (p &lt; 0.01). In group I there was a decline in the duration of the operation and blood loss compared to group II. Some leiomyoma reduction mechanisms have been identified. In endometrium of group I patients drug pathomorphosis after therapy was diagnosed. However, the immunohistochemical study made it possible to establish that these changes were benign and reversible. Conclusions : presurgical treatment by ulipristal acetate of reproductive age patients with myomas, uterine bleeding and anaemia is appropriate, safe and pathogenetically justified. The possibility to use repeated courses of the drug, which may eventually postpone or cancel the need for surgical treatment is promising.

OC23.04: *Influence of ulipristal acetate therapy on uterine fibroid‐related symptoms and on uterine and fibroids volume and vascularity indices assessed by ultrasound

OC23.04: ^*Influence of ulipristal acetate therapy on uterine fibroid‐related symptoms and on uterine and fibroids volume and vascularity indices assessed by ultrasound

POSSIBILITIES TO APPLY PROGESTERONE RECEPTOR SELECTIVE MODULATORS IN WOMEN OF REPRODUCTIVE AGE WITH UTERINE MYOMA

Uterine myoma is the most common benign monoclonal tumor. The frequency of uterine myoma is 20–35% in women of reproductive age and reaches 70% after the age of 50. Modern strategy of treatment of uterine myomas are largely individualized and depends on the patient’s age, her desire to preserve reproductive function, as well as the size, location, nodes growth rate, hormone therapy possibility. In recent years more and more articles have been published about the successful use of the progesterone receptor selective modulator progesterone ulipristal acetate (UPA) for the treatment of uterine myoma. It is important to note that the interest in the problem of uterine myoma therapy by progesterone receptor selective modulators is not only associated with their inhibiting effect on the growth and size of uterine myoma, but with the effect on the endometrium, the mechanisms of occurrence of amenorrhea and anovulation without reducing endogenous secretion of estrogen. Drug therapy gives a possibility to postpone or to avoid surgical treatment. In this respect long-term intermittent courses of UPA therapy are currently regarded as the most promising. They allow you expanding the possibilities of conservative treatment of uterine myoma, providing a regression of symptoms of the disease and maintaining the effect after completion of therapy.

First series of 18 pregnancies after ulipristal acetate treatment for uterine fibroids

To study the pregnancy rate after ulipristal acetate (UPA) therapy for fibroids. Retrospective analysis of a series of 52 patients prospectively included in the PGL4001 (ulipristal acetate) Efficacy Assessment in Reduction of Symptoms Due to Uterine Leiomyomata (PEARL) II and III trials. Academic hospital. Among the 52 patients, 21 wished to conceive upon treatment completion. None. Pregnancy rate and live birth rate. Twenty-one patients attempted to get pregnant, among whom 15 (71%) succeeded, totaling 18 pregnancies. Among these 18 pregnancies, 12 resulted in the birth of 13 healthy babies and 6 ended in early miscarriage. No regrowth of fibroids was observed during pregnancy. We report the first series of pregnancies achieved after UPA treatment. Our data confirm a sustained long-term effect after UPA therapy.

Ulipristal acetate does not impact human normal breast tissue

Antiprogestins are of growing interest for the development of new treatments in the gynecological field. Ulipristal acetate (UPA) is a progesterone receptor (PR) modulator considered for long-term administration in contraception and is currently being registered for the treatment of uterine fibroids. In light of the influences of hormonal dysfunction in breast pathologies, the secondary consequences of chronic UPA therapy need to be established. The aim of this study was to determine UPA actions mediated by PR and glucocorticoid receptor (GR) in normal and transformed breast. UPA, progesterone (P) and dexamethasone (DEX) effects were observed on PR and GR responsive genes and on proliferation and apoptosis of normal human breast epithelial (HBE) and breast cancer cells. Human normal breast tissue samples were xenografted in athymic mice and treated with estradiol (E2), or E2 + P, or E2 + P + UPA. Analysis of PR and GR reporter gene transactivation and their respective endogenous target genes indicated that UPA exerted anti-progestational and anti-glucocorticoid activity in both types of cells with a more pronounced effect in cancer cells. When combined with P or DEX, UPA limits the proliferation of HBE cells but increases growth in breast cancer cell lines. UPA administration had no impact on the mitotic index on xenografted human breast tissue exposed to gonadal hormones at similar concentrations to those present in normal women. Although further clinical trials are required to confirm that the results from our experimental models can be extrapolated to women treated with UPA, they suggest that such treatment would not be deleterious to normal breast tissue at least for a cycle (28 days) of continuous administration.

Does the Selective Progesterone Receptor Modulator Ulipristal Normalize the Uterine Cavity in Women with Leiomyoma?

Objective: To determine if three months of chronic daily administration of ulipristal acetate (UPA), a selective progesterone receptor modulator, normalized the uterine cavity in women with leiomyoma. Methods: Saline sonograms with abnormal uterine cavities from patients participating in a placebo controlled double blind randomized controlled trial evaluating UPA effect on leiomyoma volume were identified prior to initiation of therapy. They were reexamined after 12 weeks of UPA therapy. Normal uterine cavity was defined as having zero percent of leiomyoma volume inside the cavity on repeat sonohysterography. Patients with normal saline sonograms after 12 weeks of UPA therapy were compared with patients with sonographically persistently abnormal uterine cavities. Statistical analysis was performed using the Fisher’s exact test. Results: 28 patients had abnormal sonohysterogram results at baseline (n= 9, n= 8 and n=11 for placebo, UPA 10 mg and UPA 20 mg respectively). At the end of treatment 22% of the placebo group, 38% of the 10 mg group and 27% of the 20 mg group had normal uterine cavities. When the 10 mg and 20 mg groups were combined, 32% of the patients had normal uterine cavities post treatment. The results did not reach statistical significance. Conclusion: If future larger, randomized trials demonstrate a benefit, UPA may offer an alternative to surgical therapy for women requiring normalization of the uterine cavity.