BACKGROUND: Uterine fibroids cause menorrhagia and adversely affect quality of life. Ulipristal acetate (UPA) can improve fibroid symptoms.
OBJECTIVES: To assess the effectiveness of UPA in women with symptomatic uterine fibroids.
SEARCH STRATEGY: We searched CENTRAL, MEDLINE, Embase, and CINHAL on December 31, 2018, using relevant search terms. Clinical trials registries were searched for ongoing trials and there were no language restrictions.
SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing UPA with placebo/no treatment/any pharmacological intervention for symptomatic uterine fibroids.
DATA COLLECTION AND ANALYSIS: Two authors independently screened trials, extracted data, and assessed the risk of bias in included studies. We used risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, plus their 95% confidence intervals (CIs).
MAIN RESULTS: We identified six RCTs (1121 participants). Five studies (882 participants) compared UPA with placebo. UPA significantly achieved amenorrhea (RR 24.54; 95% CI,10.82-55.64), reduced blood loss, and improved quality of life with insufficient evidence from RCTs for adverse events. There was insufficient evidence for improved outcomes when UPA was compared with leuprolide acetate.
CONCLUSION: Compared with placebo, oral UPA significantly induces amenorrhea, reduces heavy menses, and improves quality-of-life in women with uterine fibroids. This article is protected by copyright. All rights reserved.
BACKGROUND: Uterine fibroids are smooth muscle tumours arising from the uterus. These tumours, although benign, are commonly associated with abnormal uterine bleeding, bulk symptoms and reproductive dysfunction. The importance of progesterone in fibroid pathogenesis supports selective progesterone receptor modulators (SPRMs) as effective treatment. Both biochemical and clinical evidence suggests that SPRMs may reduce fibroid growth and ameliorate symptoms. SPRMs can cause unique histological changes to the endometrium that are not related to cancer, are not precancerous and have been found to be benign and reversible. This review summarises randomised trials conducted to evaluate the effectiveness of SPRMs as a class of medication for treatment of individuals with fibroids.
OBJECTIVES: To evaluate the effectiveness and safety of SPRMs for treatment of premenopausal women with uterine fibroids.
SEARCH METHODS: We searched the Specialised Register of the Cochrane Gynaecology and Fertility Group, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and clinical trials registries from database inception to May 2016. We handsearched the reference lists of relevant articles and contacted experts in the field to request additional data.
SELECTION CRITERIA: Included studies were randomised controlled trials (RCTs) of premenopausal women with fibroids who were treated for at least three months with a SPRM.
DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed all eligible studies identified by the search. We extracted data and assessed risk of bias independently using standard forms. We analysed data using mean differences (MDs) or standardised mean differences (SMDs) for continuous data and odds ratios (ORs) for dichotomous data. We performed meta-analyses using the random-effects model. Our primary outcome was change in fibroid-related symptoms.
MAIN RESULTS: We included in the review 14 RCTs with a total of 1215 study participants. We could not extract complete data from three studies. We included in the meta-analysis 11 studies involving 1021 study participants: 685 received SPRMs and 336 were given a control intervention (placebo or leuprolide). Investigators evaluated three SPRMs: mifepristone (five studies), ulipristal acetate (four studies) and asoprisnil (two studies). The primary outcome was change in fibroid-related symptoms (symptom severity, health-related quality of life, abnormal uterine bleeding, pelvic pain). Adverse event reporting in the included studies was limited to SPRM-associated endometrial changes. More than half (8/14) of these studies were at low risk of bias in all domains. The most common limitation of the other studies was poor reporting of methods. The main limitation for the overall quality of evidence was potential publication bias. SPRM versus placeboSPRM treatment resulted in improvements in fibroid symptom severity (MD -20.04 points, 95% confidence interval (CI) -26.63 to -13.46; four RCTs, 171 women, I2 = 0%; moderate-quality evidence) and health-related quality of life (MD 22.52 points, 95% CI 12.87 to 32.17; four RCTs, 200 women, I2 = 63%; moderate-quality evidence) on the Uterine Fibroid Symptom Quality of Life Scale (UFS-QoL, scale 0 to 100). Women treated with an SPRM showed reduced menstrual blood loss on patient-reported bleeding scales, although this effect was small (SMD -1.11, 95% CI -1.38 to -0.83; three RCTs, 310 women, I2 = 0%; moderate-quality evidence), along with higher rates of amenorrhoea (29 per 1000 in the placebo group vs 237 to 961 per 1000 in the SPRM group; OR 82.50, 95% CI 37.01 to 183.90; seven RCTs, 590 women, I2 = 0%; moderate-quality evidence), compared with those given placebo. We could draw no conclusions regarding changes in pelvic pain owing to variability in the estimates. With respect to adverse effects, SPRM-associated endometrial changes were more common after SPRM therapy than after placebo (OR 15.12, 95% CI 6.45 to 35.47; five RCTs, 405 women, I2 = 0%; low-quality evidence). SPRM versus leuprolide acetateIn comparing SPRM versus other treatments, two RCTs evaluated SPRM versus leuprolide acetate. One RCT reported primary outcomes. No evidence suggested a difference between SPRM and leuprolide groups for improvement in quality of life, as measured by UFS-QoL fibroid symptom severity scores (MD -3.70 points, 95% CI -9.85 to 2.45; one RCT, 281 women; moderate-quality evidence) and health-related quality of life scores (MD 1.06 points, 95% CI -5.73 to 7.85; one RCT, 281 women; moderate-quality evidence). It was unclear whether results showed a difference between SPRM and leuprolide groups for reduction in menstrual blood loss based on the pictorial blood loss assessment chart (PBAC), as confidence intervals were wide (MD 6 points, 95% CI -40.95 to 50.95; one RCT, 281 women; low-quality evidence), or for rates of amenorrhoea (804 per 1000 in the placebo group vs 732 to 933 per 1000 in the SPRM group; OR 1.14, 95% CI 0.60 to 2.16; one RCT, 280 women; moderate-quality evidence). No evidence revealed differences between groups in pelvic pain scores based on the McGill Pain Questionnaire (scale 0 to 45) (MD -0.01 points, 95% CI -2.14 to 2.12; 281 women; moderate-quality evidence). With respect to adverse effects, SPRM-associated endometrial changes were more common after SPRM therapy than after leuprolide treatment (OR 10.45, 95% CI 5.38 to 20.33; 301 women; moderate-quality evidence).
AUTHORS' CONCLUSIONS: Short-term use of SPRMs resulted in improved quality of life, reduced menstrual bleeding and higher rates of amenorrhoea than were seen with placebo. Thus, SPRMs may provide effective treatment for women with symptomatic fibroids. Evidence derived from one RCT showed no difference between leuprolide acetate and SPRM with respect to improved quality of life and bleeding symptoms. Evidence was insufficient to show whether effectiveness was different between SPRMs and leuprolide. Investigators more frequently observed SPRM-associated endometrial changes in women treated with SPRMs than in those treated with placebo or leuprolide acetate. As noted above, SPRM-associated endometrial changes are benign, are not related to cancer and are not precancerous. Reporting bias may impact the conclusion of this meta-analysis. Well-designed RCTs comparing SPRMs versus other treatments are needed.
OBJECTIVES: We assessed the evidence about management of uterine fibroids. Specifically, we sought to determine effectiveness of interventions, risks of harm, and whether individual or fibroid characteristics influence outcomes.
DATA SOURCES: We searched MEDLINE® via PubMed® and Embase® to identify publications, as well as reviewed the reference lists of included studies.
METHODS: We included studies published in English from January 1985 to September 2016. We identified randomized clinical trials to assess outcomes and harms of interventions. We used data from trials in a meta-analysis to estimate probability and timing of subsequent interventions for fibroids based on initial type of intervention. To describe risk of unrecognized leiomyosarcoma, we included studies that allowed calculation of prevalence of leiomyosarcoma discovered at the time of surgery for masses believed to be fibroids. We also identified publications that indicated operative approaches to removal of leiomyosarcoma tissue and built models to estimate survival. We extracted data, assessed risk of bias, and rated the strength of evidence for informing care.
RESULTS: Of 97 included randomized trials, 43 studies assessed medications, 28 assessed procedures, and 37 assessed surgeries. Gonadotropin-releasing hormone (GnRH) agonists, mifepristone, and ulipristal reduced fibroid size and improved fibroid-related symptoms, including bleeding and quality of life (moderate strength of evidence [SOE] except quality of life for GnRH agonist [low SOE]). Several other medications have promise but are not supported by sufficient evidence. Uterine artery embolization (UAE) (high SOE) as well as high intensity focused ultrasound (low SOE) are effective for decreasing fibroid size/volume. Few other outcomes are well investigated for high intensity focused ultrasound. UAE studies reported improved outcomes for bleeding (moderate SOE), and quality of life (moderate SOE). Myomectomy and hysterectomy improved q uality of life (both low SOE). Few well-conducted trials directly compared different treatment options. No studies were designed to evaluate expectant management, and evidence is insufficient to guide clinical care. Subsequent intervention ranged from 0 to 44 percent in studies that followed women after initial fibroid treatment. At 2-year followup, subsequent intervention rates were lowest for initial medical management and higher for UAE and myomectomy, especially among younger women. No individual characteristics of women or their fibroids were definitely associated with likelihood of intervention benefits or patient satisfaction. These findings were limited by the number and size of available studies. Using data from 160 studies, we estimated that among 10,000 women having surgery for presumed fibroids, between 0 and 13 will have a leiomyosarcoma detected. Of the surgical approaches, the 5-year survival after leiomyosarcoma diagnosis was 30 percent with power morcellation (95% Bayesian credible interval [BCI]: 13% to 61%), 59 percent with scalpel morcellation (BCI: 33% to 84%), and 60 percent with intact removal (BCI: 24% to 98%).
CONCLUSION: A range of interventions are effective for reducing fibroid size and improving symptoms. Some medications and procedures also improve quality of life. Few studies directly compare interventions. The risk of encountering a leiomyosarcoma at the time of fibroid surgery is low, and the method of fibroid removal may influence survival. Evidence to guide choice of intervention is likely best when applied in the context of individual patient needs and preferences.
BACKGROUND: Uterine fibroids are common, often symptomatic and a third of women need repeated time off work. Consequently 25% to 50% of women with fibroids receive surgical treatment, namely myomectomy or hysterectomy. Hysterectomy is the definitive treatment as fibroids are hormone dependent and frequently recurrent. Medical treatment aims to control symptoms in order to replace or delay surgery. This may improve the outcome of surgery and prevent recurrence.
PURPOSE: To determine whether any medical treatment can be recommended in the treatment of women with fibroids about to undergo surgery and in those for whom surgery is not planned based on currently available evidence.
STUDY SELECTION: Two authors independently identified randomised controlled trials (RCT) of all pharmacological treatments aimed at the treatment of fibroids from a list of references obtained by formal search of MEDLINE, EMBASE, Cochrane library, Science Citation Index, and ClinicalTrials.gov until December 2013.
DATA EXTRACTION: Two authors independently extracted data from identified studies.
DATA SYNTHESIS: A Bayesian network meta-analysis was performed following the National Institute for Health and Care Excellence-Decision Support Unit guidelines. Odds ratios, rate ratios, or mean differences with 95% credible intervals (CrI) were calculated.
RESULTS AND LIMITATIONS: A total of 75 RCT met the inclusion criteria, 47 of which were included in the network meta-analysis. The overall quality of evidence was very low. The network meta-analysis showed differing results for different outcomes.
CONCLUSIONS: There is currently insufficient evidence to recommend any medical treatment in the management of fibroids. Certain treatments have future promise however further, well designed RCTs are needed.
Ulipristal acetate (UA), a selective progesterone modulator, has been approved for short-term therapy for symptomatic fibroids. We decided to undertake a systematic review of the best available evidence and draw a more definitive conclusion regarding the efficacy of UA for the management of uterine fibroids. The outcomes included symptomatic relief, quality of life-related parameters, reduction in fibroid size, side effects and recurrence rate. We included four randomised controlled trials which consisted of three trials which compared UA with placebo, and one trial compared it with gonadotropin-releasing hormone analogues for symptomatic relief. The three trials comparing UA with placebo reported significant improvement in symptoms related to excessive uterine bleeding as evidenced by the attainment of amenorrhea or reduction in pictorial blood assessment chart. However, due to the heterogeneity of the available data, a meta-analysis was possible only for one the outcomes - attainment of amenorrhea which indicated improvement in symptoms [57.88 (19.81-169.16); p < 0.00001]. The improved quality of life parameters and reduction in fibroid size was noted in the UA group. With regards to adverse events, even though the three included studies reported increased non-physiological endometrial-related changes following UA, these changes reverted back to normal within 6 months. Short-term use of UA seems to be an effective and safe method of treating uterine fibroids.
Uterine fibroids cause menorrhagia and adversely affect quality of life. Ulipristal acetate (UPA) can improve fibroid symptoms.
OBJECTIVES:
To assess the effectiveness of UPA in women with symptomatic uterine fibroids.
SEARCH STRATEGY:
We searched CENTRAL, MEDLINE, Embase, and CINHAL on December 31, 2018, using relevant search terms. Clinical trials registries were searched for ongoing trials and there were no language restrictions.
SELECTION CRITERIA:
We included randomized controlled trials (RCTs) comparing UPA with placebo/no treatment/any pharmacological intervention for symptomatic uterine fibroids.
DATA COLLECTION AND ANALYSIS:
Two authors independently screened trials, extracted data, and assessed the risk of bias in included studies. We used risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, plus their 95% confidence intervals (CIs).
MAIN RESULTS:
We identified six RCTs (1121 participants). Five studies (882 participants) compared UPA with placebo. UPA significantly achieved amenorrhea (RR 24.54; 95% CI,10.82-55.64), reduced blood loss, and improved quality of life with insufficient evidence from RCTs for adverse events. There was insufficient evidence for improved outcomes when UPA was compared with leuprolide acetate.
CONCLUSION:
Compared with placebo, oral UPA significantly induces amenorrhea, reduces heavy menses, and improves quality-of-life in women with uterine fibroids. This article is protected by copyright. All rights reserved.
