Considerations on implementation of the newest treatment for symptomatic uterine fibroids: Oral GnRH antagonists.

Novel gonadotrophin releasing hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add-back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix and linzagolix have assessed treatment efficacy for fibroid-related heavy menstrual blood loss in comparison to placebo. Marketing authorization has been granted by several agencies including those in Europe, the United Kingdom and the United States. While the registration trials report a robust effect on the reduction of heavy menstrual blood loss and improvement in quality of life scores, reticence is advised before widespread prescription. In this review, we demonstrate limitations in the trial data, namely a lack of generalizability due to the restricted study population, the lack of transparency in the distribution of disease-level characteristics limiting the predictability of treatment success in the real-world diverse population, and the absence of any comparison to current alternative treatment methods. Importantly, no clinically meaningful volume reductions were found with GnRH antagonist combination preparations, and long-term safety data, particularly concerning modest but stable bone mineral density decline, need further addressing. Symptoms related to uterine fibroids adversely affect many women's quality of life and effective medical treatments are lacking. However, despite the urgent need for conservative treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness and cost-effectiveness in a representative population and are compared with alternative treatment methods before introduction into mainstream clinical practice.

Uterine artery embolization vs hysterectomy in the treatment of symptomatic uterine fibroids: 10-year outcomes from the randomized EMMY trial.

BACKGROUND: Since 1995 uterine artery embolization has been described as an alternative for hysterectomy in patients with symptomatic fibroids. Many studies including several randomized controlled trials established uterine artery embolization as a valuable treatment. These randomized controlled trials reported outcomes in terms of health-related quality of life, clinical outcomes, efficacy, and cost-effectiveness after 1, 2, and 5 years of follow-up. OBJECTIVE: The purpose of this study was to compare clinical outcome and health-related quality of life 10 years after uterine artery embolization or hysterectomy in the treatment of heavy menstrual bleeding caused by uterine fibroids in a randomized controlled trial. STUDY DESIGN: In all, 28 Dutch hospitals recruited patients with symptomatic uterine fibroids who were eligible for hysterectomy. Patients were 1:1 randomly assigned to uterine artery embolization or hysterectomy. The outcomes assessed at 10 years postintervention were reintervention rates, health-related quality of life, and patient satisfaction, which were obtained through validated questionnaires. Study outcomes were analyzed according to original treatment assignment (intention to treat). RESULTS: A total of 177 patients were randomized from 2002 through 2004. Eventually 81 uterine artery embolization and 75 hysterectomy patients underwent the allocated treatment shortly after randomization. The remaining patients withdrew from the trial. The 10-year questionnaire was mailed when the last included patient had been treated 10 years earlier. The mean duration of follow-up was 133 months (SD 8.58) accompanied by a mean age of 57 years (SD 4.53). Questionnaires were received from 131 of 156 patients (84%). Ten years after treatment, 5 patients underwent secondary hysterectomy resulting in a total of 28 of 81 (35%) (24/77 [31%] after successful uterine artery embolization). Secondary hysterectomies were performed for persisting symptoms in all cases but 1 (for prolapse). After the initial treatment health-related quality of life improved significantly. After 10 years, generic health-related quality of life remained stable, without differences between both groups. The urogenital distress inventory and the defecation distress inventory showed a decrease in both groups, probably related to increasing age, without significant differences between study arms. Satisfaction in both groups remained comparable. The majority of patients declared being (very) satisfied about the received treatment: 78% of the uterine artery embolization group vs 87% in the hysterectomy group. CONCLUSION: In about two thirds of uterine artery embolization-treated patients with symptomatic uterine fibroids a hysterectomy can be avoided. Health-related quality of life 10 years after uterine artery embolization or hysterectomy remained comparably stable. Uterine artery embolization is a well-documented and less invasive alternative to hysterectomy for symptomatic uterine fibroids on which eligible patients should be counseled.

Uterine artery embolization vs hysterectomy in the treatment of symptomatic uterine fibroids: 5-year outcome from the randomized EMMY trial.

OBJECTIVE: The purpose of this study was to compare clinical outcome and health related quality of life (HRQOL) 5 years after uterine artery embolization (UAE) or hysterectomy in the treatment of menorrhagia caused by uterine fibroids. STUDY DESIGN: Patients with symptomatic uterine fibroids who were eligible for hysterectomy were assigned randomly 1:1 to hysterectomy or UAE. Endpoints after 5 years were reintervention rates, menorrhagia, and HRQOL measures that were assessed by validated questionnaires. RESULTS: Patients were assigned randomly to UAE (n = 88) or hysterectomy (n = 89). Five years after treatment 23 of 81 UAE patients (28.4%) had undergone a hysterectomy because of insufficient improvement of complaints (24.7% after successful UAE). HRQOL measures improved significantly and remained stable until the 5-year follow-up evaluation, with no differences between the groups. UAE had a positive effect both on urinary and defecation function. CONCLUSION: UAE is a well-established alternative to hysterectomy about which patients should be counseled.

Economic evaluation of uterine artery embolization versus hysterectomy in the treatment of symptomatic uterine fibroids: results from the randomized EMMY trial.

PURPOSE: To investigate whether uterine artery embolization (UAE) is a cost-effective alternative to hysterectomy for patients with symptomatic uterine fibroids, the authors performed an economic evaluation alongside the multicenter randomized EMMY (EMbolization versus hysterectoMY) trial. MATERIALS AND METHODS: Between February 2002 and February 2004, 177 patients were randomized to undergo UAE (n = 88) or hysterectomy (n = 89) and followed up until 24 months after initial treatment allocation. Conditional on the equivalence of clinical outcome, a cost minimization analysis was performed according to the intention to treat principle. Costs included health care costs inside and outside the hospital as well as costs related to absence from work (societal perspective). Cumulative standardized costs were estimated as volumes multiplied with prices. The nonparametric bootstrap method was used to quantify differences in mean (95% confidence interval [CI]) costs between the strategies. RESULTS: In total, 81 patients underwent UAE and 75 underwent hysterectomy. In the UAE group, 19 patients (23%) underwent secondary hysterectomies. The mean total costs per patient in the UAE group were significantly lower than those in the hysterectomy group ($11,626 vs $18,563; mean difference, -$6,936 [-37%], 95% CI: -$9,548, $4,281). The direct medical in-hospital costs were significantly lower in the UAE group: $6,688 vs $8,313 (mean difference, -$1,624 [-20%], 95% CI: -$2,605, -$586). Direct medical out-of-hospital and direct nonmedical costs were low in both groups (mean cost difference, $156 in favor of hysterectomy). The costs related to absence from work differed significantly between the treatment strategies in favor of UAE (mean difference, -$5,453; 95% CI: -$7,718, -$3,107). The costs of absence from work accounted for 79% of the difference in total costs. CONCLUSIONS: The 24-month cumulative cost of UAE is lower than that of hysterectomy. From a societal economic perspective, UAE is the superior treatment strategy in women with symptomatic uterine fibroids.

Symptomatic uterine fibroids: treatment with uterine artery embolization or hysterectomy--results from the randomized clinical Embolisation versus Hysterectomy (EMMY) Trial.

PURPOSE: To prospectively evaluate health-related quality of life (HRQOL) outcomes for uterine artery embolization (UAE) and hysterectomy up to 24 months after the intervention in terms of mental and physical health, urinary and defecatory function, and overall patient satisfaction. MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained for the Embolisation versus Hysterectomy Trial. Women (n = 177) with uterine fibroids and heavy menstrual bleeding who were scheduled to undergo hysterectomy were randomly assigned to undergo UAE (n = 88) or hysterectomy (n = 89). HRQOL was measured six times during a 24-month follow-up period with the following validated questionnaires: Medical Outcome Study Short Form 36 (SF-36) mental component summary (MCS) and physical component summary (PCS), Health Utilities Index Mark 3, EuroQol 5D, urogenital distress inventory (UDI), incontinence impact questionnaire, and defecation distress inventory (DDI). Satisfaction was assessed with a seven-point Likert scale. Repeated measurement analysis was performed for between-group analysis. Paired t tests were performed for within-group analysis. Satisfaction was analyzed with the Fisher exact test. RESULTS: The SF-36 MCS and PCS, Health Utilities Index Mark 3, EuroQol 5D, and UDI scores were improved significantly in both groups at 6 months and afterward (P < .05). The DDI score was improved significantly in only the UAE group at 6 months and afterward (P < .05). No differences between groups were observed, with the exception of PCS scores at 6-week follow-up: Patients in the UAE group had significantly better scores than did patients in the hysterectomy group (P < .001). Improvement in PCS score at 24-month follow-up was significantly higher for patients who were employed at baseline (P = .035). At 24-month follow-up, patients in the hysterectomy group were significantly more satisfied than those in the UAE group (P = .02). CONCLUSION: Both UAE and hysterectomy improved HRQOL. No differences were observed between groups regarding HRQOL at 24-month follow-up. On the basis of HRQOL results, the authors determined that UAE is a good alternative to hysterectomy.