Ulipristal Acetate: A New Treatment for Symptomatic Uterine Fibroids?

BACKGROUND AND PURPOSE: 

  • Ulipristal Acetate is an oral selective progesterone receptor modulator 
    • 5-10 mg per day can decrease bleeding and the size of leiomyomas 
    • Studies were in performed in non-diverse populations and may not be generalizable to the US population  
  • Simon et al. (Obstetrics & Gynecology, 2018) examined efficacy and tolerability of ulipristal acetate for the treatment of symptomatic uterine leiomyomas 

METHODS: 

  • This was a phase 3, multicenter, randomized, doubleblind, double-dummy, placebo-controlled, parallel group study  
  • Participants: premenopausal women, 18-50 years with  
    • Abnormal uterine bleeding 
    • One or more discrete leiomyomas 
    • Uterine size ≤20 weeks  
  • Patients were assigned to the following groups 
    • 5 mg ulipristal 
    • 10 mg ulipristal 
    • Placebo once daily  
  • Medications were taken for 12 weeks, followed by 12-week drug-free follow-up 
  • Amenorrhea was defined as no bleeding for the last 35 consecutive days of treatment 
  • Primary outcomes  
    • Proportion of patients who achieved amenorrhea (spotting permitted) during the last 35 consecutive days of treatment  
    • Time to amenorrhea during treatment 
  • Secondary outcomes  
    • Proportion of patients who achieved amenorrhea by day 11 and did not report bleeding (spotting permitted) for the duration of treatment  
    • Change from baseline to end of treatment on the Revised Activities subscale of the Uterine Fibroid Symptom and Health-Related Quality of Life questionnaire  
    • Questionnaire included questions pertaining to physical and social activites 

RESULTS: 

  • 157 patients were randomized 
    • Demographics were similar between groups 
  • Amenorrhea was achieved significantly greater number of individual in ulipristal groups (p<0.001) 
    • 5 mg ulipristal: 47.2% (97.5%, CI 31.6–63.2)   
    • 10 mg ulipristal 58.3% (97.5% CI 41.2–74.1)  
    • Placebo: 1.8% (97.5% CI 0.0–10.9)  
  • Time to amenorrhea was shorter for both ulipristal doses compared with placebo (P<.001), and both doses of ulipristal resulted in improved quality of life compared with placebo (P<.001) 
  • Improvement in anemia was seen at the end of treatment for patients treated with both ulipristal dose regimens 
  • Ulipristal also improved health-related quality of life (both physical and social activities)  
  • Common (≥5% in either ulipristal group) adverse events  
    • Hypertension 
    • Elevated blood CPK 
    • Hot flushes 

CONCLUSION: 

  • The study population was diverse with a high proportion of obese women, which is more reflective of the US population than previous studies  
  • A dose of 5 mg and 10 mg of Ulipristal was superior to placebo in rate of a time to amenorrhea in women with symptomatic uterine leiomyomas 
  • Ulipristal is generally well tolerated 
  • Not yet FDA approved – awaiting more safety data following reports of adverse events (liver damage) in Europe

Learn More – Primary Sources:  

Ulipristal Acetate for Treatment of Symptomatic Uterine Leiomyomas: A Randomized Controlled Trial 

Are Fibroids Associated with Miscarriage?

BACKGROUND AND PURPOSE:

  • Data is conflicting as to whether uterine leiomyomas are associated with miscarriage
    • Studies often include women who are obtaining fertility treatment
  • Sundermann et al. (Obstet Gynecol, 2017) examined the associated risk of spontaneous abortion and uterine leiomyomas in the general population

METHODS:

  • Systematic review and meta-analysis
  • Inclusion: Studies reporting risk of spontaneous abortion among pregnant women with  leiomyomas vs pregnant women without leiomyomas
  • Exclusion: Studies that only included women seeking care for recurrent miscarriage, infertility, or assisted reproductive technologies
  • Data was extracted and reviewed by two authors independently
  • Primary outcome: Spontaneous abortion (definition varied across studies) among recognized pregnancies

RESULTS:

  • 9 studies were included in the systematic analysis and 5 studies were used for the meta-analysis
  • Pooled data for the meta-analysis included 21,829 women
  • In the leiomyoma group, 11.5% has spontaneous abortion compared to 8.0% in the non-leiomyoma group
  • Uterine leiomyomas were not associated with an increased risk of spontaneous abortion
    • Relative risk 1.16, 95% CI 0.80–1.52
    • Significant association was still absent even after adjusting for confounders

CONCLUSION:

  • The presence of leiomyomas was not associated with increased risk of spontaneous abortion
  • Prior studies showing an association did not always adjust for confounders
  • This is the first association review that focused on a general risk population

Learn More – Primary Sources:

Leiomyomas in Pregnancy and Spontaneous Abortion: A Systematic Review and Meta-analysis