Ulipristal acetate for uterine fibroid-related symptoms

2015 ◽  
Vol 51 (11) ◽  
pp. 661 ◽  
Keyword(s):  
Uterine Fibroid ◽  
Ulipristal Acetate

scholarly journals The Selective Progesterone Receptor Modulator Ulipristal Acetate Inhibits the Activity of the Glucocorticoid Receptor

2019 ◽  
Vol 105 (3) ◽  
pp. 716-734 ◽  
Author(s):  
Benjamin Small ◽  
Charles E F Millard ◽  
Edwina P Kisanga ◽  
Andreanna Burman ◽  
Anika Anam ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Uterine Fibroid ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Ex Vivo ◽  
Therapeutic Option ◽  
The Body ◽  
Dependent Manner ◽  
Ulipristal Acetate

Abstract Context The selective progesterone modulator ulipristal acetate (ulipristal) offers a much-needed therapeutic option for the clinical management of uterine fibroids. Although ulipristal initially passed safety evaluations in Europe, postmarketing analysis identified cases of hepatic injury and failure, leading to restrictions on the long-term use of ulipristal. One of the factors potentially contributing to significant side effects with the selective progesterone modulators is cross-reactivity with other steroid receptors. Objective To determine whether ulipristal can alter the activity of the endogenous glucocorticoid receptor (GR) in relevant cell types. Design Immortalized human uterine fibroid cells (UtLM) and hepatocytes (HepG2) were treated with the synthetic glucocorticoid dexamethasone and/or ulipristal. Primary uterine fibroid tissue was isolated from patients undergoing elective gynecological surgery and treated ex vivo with dexamethasone and/or ulipristal. In vivo ulipristal exposure was performed in C57Bl/6 mice to measure the effect on basal gene expression in target tissues throughout the body. Results Dexamethasone induced the expression of established glucocorticoid-target genes period 1 (PER1), FK506 binding protein 51 (FKBP5), and glucocorticoid-induced leucine zipper (GILZ) in UtLM and HepG2 cells, whereas cotreatment with ulipristal blocked the transcriptional response to glucocorticoids in a dose-dependent manner. Ulipristal inhibited glucocorticoid-mediated phosphorylation, nuclear translocation, and DNA interactions of GR. Glucocorticoid stimulation of PER1, FKBP5, and GILZ was abolished by cotreatment with ulipristal in primary uterine fibroid tissue. The expression of glucocorticoid-responsive genes was decreased in the lung, liver, and uterus of mice exposed to 2 mg/kg ulipristal. Interestingly, transcript levels of Fkbp5 and Gilz were increased in the hippocampus and pituitary. Conclusions These studies demonstrate that ulipristal inhibits endogenous glucocorticoid signaling in human fibroid and liver cells, which is an important consideration for its use as a long-term therapeutic agent.

scholarly journals A-Kinase Anchoring Protein 13 (AKAP13) Augments Progesterone Signaling in Uterine Fibroid Cells

2018 ◽  
Vol 104 (3) ◽  
pp. 970-980 ◽  
Author(s):  
Sinnie Sin Man Ng ◽  
Soledad Jorge ◽  
Minnie Malik ◽  
Joy Britten ◽  
Szu-Chi Su ◽  
...  
Keyword(s):  
Uterine Fibroid ◽  
Binding Assays ◽  
Glutathione S Transferase ◽  
Uterine Leiomyomata ◽  
Ulipristal Acetate ◽  
Mechanical Signaling ◽  
Anchoring Protein ◽  
Altered Response ◽  
Luciferase Reporters ◽  
Insight Into

Abstract Context Uterine leiomyomata (fibroids) are prevalent sex hormone‒dependent tumors with an altered response to mechanical stress. Ulipristal acetate, a selective progesterone receptor (PR) modulator, significantly reduces fibroid size in patients. However, PR signaling in fibroids and its relationship to mechanical signaling are incompletely understood. Objective Our prior studies revealed that A-kinase anchoring protein 13 (AKAP13) was overexpressed in fibroids and contributed to altered mechanotransduction in fibroids. Because AKAP13 augmented nuclear receptor signaling in other tissues, we sought to determine whether AKAP13 might influence PR signaling in fibroids. Methods and Results Fibroid samples from patients treated with ulipristal acetate or placebo were examined for AKAP13 expression by using immunohistochemistry. In immortalized uterine fibroid cell lines and COS-7 cells, we observed that AKAP13 increased ligand-dependent PR activation of luciferase reporters and endogenous progesterone-responsive genes for PR-B but not PR-A. Inhibition of ERK reduced activation of PR-dependent signaling by AKAP13, but inhibition of p38 MAPK had no effect. In addition, glutathione S-transferase‒binding assays revealed that AKAP13 was bound to PR-B through its carboxyl terminus. Conclusion These data suggest an intersection of mechanical signaling and PR signaling involving AKAP13 through ERK. Further elucidation of the integration of mechanical and hormonal signaling pathways in fibroids may provide insight into fibroid development and suggest new therapeutic strategies for treatment.

Potential synergism between ulipristal acetate and vitamin D3 in uterine fibroid pharmacotherapy – 2 case studies

2019 ◽  
Vol 35 (6) ◽  
pp. 473-477 ◽  
Author(s):  
Michał Ciebiera ◽  
Błażej Męczekalski ◽  
Krzysztof Łukaszuk ◽  
Grzegorz Jakiel
Keyword(s):  
Case Studies ◽  
Vitamin D3 ◽  
Uterine Fibroid ◽  
Ulipristal Acetate

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

2018 ◽  
Vol 37 (9) ◽  
pp. 2215-2223 ◽  
Author(s):  
Silvia Baggio ◽  
Paola Pomini ◽  
Fabiana Galeone ◽  
Francesca Presti ◽  
Lorenza Santi ◽  
...  
Keyword(s):  
Uterine Fibroid ◽  
Ulipristal Acetate

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

2020 ◽  
Vol 12 (3-4) ◽  
pp. 170-175 ◽  
Author(s):  
Ana R Costa ◽  
Ana P Carvalho ◽  
Diana R Martins ◽  
Maria J Carvalho ◽  
Pedro T Silva ◽  
...  
Keyword(s):  
Birth Outcomes ◽  
Uterine Fibroid ◽  
Descriptive Analysis ◽  
Uterine Fibroids ◽  
Case Series ◽  
Excessive Bleeding ◽  
Ulipristal Acetate ◽  
Pregnancy And Birth Outcomes ◽  
Interval Surgery ◽  
Pregnancy And Birth

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.

scholarly journals Ulipristal Acetate Efficacy in a Patient with Symptomatic Fibroid and Concomitant Pulmonary Embolism

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
S. von Wunster ◽  
P. D’Oria ◽  
L. Colonna ◽  
G. Patelli
Keyword(s):  
Pulmonary Embolism ◽  
Adverse Events ◽  
Uterine Fibroid ◽  
Uterine Fibroids ◽  
Effective Drug ◽  
Bleeding Control ◽  
Ulipristal Acetate ◽  
Threatening Condition ◽  
Life Threatening ◽  
Fibroid Volume

Ulipristal acetate (UPA) is an effective drug for the treatment of symptomatic uterine fibroids. The drug is highly effective in controlling bleeding control and in the recovery of anemia. Here, we report the case of a woman with severe menorrhagia due to a uterine fibroid and with concomitant pulmonary embolism, a serious life-threatening condition. UPA was shown to be effective in reducing fibroid volume and controlling symptoms, without worsening the underlying embolic disease. No adverse events were observed, and the patient has completely recovered.

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