Level 1: Likely reliable evidence
Uterine fibroids can cause pain and heavy bleeding and are a common indication for hysterectomy, but little evidence exists to guide fibroid management (AHRQ Research Report, March 2011). The gonadotropin-releasing hormone agonist leuprolide acetate has been shown to reduce uterine volume and fibroid size prior to surgery (Cochrane Database Syst Rev. 2001;2:CD000547), but it may also increase the incidence of hot flushes and reduce bone mineral density.
Two recent trials, PEARL I and PEARL II, evaluated the efficacy of ulipristal acetate (Ella), a selective progesterone receptor modulator, in women planning to have surgery for symptomatic fibroids.
In the PEARL I trial, 242 women (mean age 42 years) with excessive uterine bleeding were randomized to ulipristal acetate (5 mg vs. 10 mg orally once daily) vs. placebo for up to 13 weeks (N Engl J Med. 2012;366:409-420). All women received iron supplementation and were eligible to have fibroid surgery after the end of the treatment period. Excessive uterine bleeding was defined as a score >100 on the pictorial blood-loss assessment chart (PBAC) (0 to >500 scale with higher score indicating greater bleeding).
At 13 weeks, uterine bleeding was controlled (defined as PBAC score <75) in 91% of women taking ulipristal 5 mg, in 92% taking ulipristal 10 mg, and in 19% taking placebo (p <0.001, NNT 2 for each ulipristal dose vs. placebo). Amenorrhea rates (PBAC <2) were 73% for ulipristal 5 mg, 82% for ulipristal 10 mg, and 6% for placebo (p <0.001, NNT 2 for each ulipristal dose vs. placebo). Both ulipristal doses were associated with reduced discomfort (p <0.001). There were no significant differences in surgical rates or in adverse events. The most common adverse events reported in the ulipristal groups were headache and breast pain.
The PEARL II trial compared the same two daily doses of oral ulipristal for 13 weeks vs. three monthly intramuscular injections of leuprolide acetate 3.75 mg in 301 women (mean age 40 years) with symptomatic fibroids (N Engl J Med. 2012;366:409-420). Women received supplemental iron at the discretion of the treating clinician and were eligible for surgery after treatment. Rates of controlled uterine bleeding were non-significantly higher for ulipristal: 90% for ulipristal 5 mg, 94% for ulipristal 10 mg, and 86% for leuprolide (not significant) in an intention-to-treat analysis.
The 10-mg ulipristal dose was associated with significantly greater bleeding control vs. leuprolide in a per-protocol analysis (p=0.03, NNT 12). Incidence of hot flushes was significantly lower in both ulipristal groups (11% for ulipristal 5 mg, 10% for ulipristal 10 mg, 40% for leuprolide, p<0.001, NNT 4 for each ulipristal dose vs. leuprolide). There were no significant differences in pain reduction, surgical rates, or severe adverse events. Leuprolide was associated with significantly greater reduction in uterine volume.
Neither trial was designed to address differences in surgical rates or in surgical outcomes after treatment. Ulipristal is currently available only in a 30-mg tablet.
Alan Ehrlich, MD, is a deputy editor for DynaMed, Ipswich, Mass., and assistant clinical professor in Family Medicine, University of Massachusetts Medical School in Worcester. DynaMed is a database that provides evidence-based information on more than 3,000 clinical topics and is updated daily through systematic surveillance covering more than 500 journals. The most important evidence identified is summarized here.