What is the role of ulipristal (selective progesterone receptor modulator) in treating uterine fibroids in premenopausal women?

Role of Ulipristal Acetate in Uterine Fibroids

Ulipristal acetate (UPA) is an effective medical treatment option for symptomatic uterine fibroids, achieving amenorrhea in 70-90% of patients, reducing fibroid volume by 45-72%, and significantly improving quality of life, with applications both as definitive medical management and as preoperative therapy. 1, 2

Mechanism and Clinical Effects

UPA is a selective progesterone receptor modulator that works through multiple mechanisms 1:

• Direct antiproliferative and pro-apoptotic effects on leiomyoma cells 1
• Endometrial changes that reduce bleeding 1
• Inhibition of ovulation through suppression of the luteinizing hormone surge, resulting in amenorrhea 1

Evidence-Based Efficacy

Bleeding Control and Amenorrhea

The PEARL IV trial demonstrated dose-dependent amenorrhea rates across 4 treatment courses 1:

• 10 mg daily: 83%, 82%, 78%, 75% (courses 1-4)
• 5 mg daily: 72%, 74%, 73%, 70% (courses 1-4)
• Rapid onset: Median time to amenorrhea of 2-4 days 1

Fibroid Volume Reduction

Progressive fibroid shrinkage occurs with repeated courses 1:

• First course: 45% median reduction
• Second course: 63% median reduction
• Third course: 67% median reduction
• Fourth course: 72% median reduction

Quality of Life Improvements

The VENUS-II trial showed significant QOL improvements 1:

• 10 mg UPA: 57% improvement in UFS-QOL activities subscale
• 5 mg UPA: 48% improvement
• Placebo: 13% improvement

Clinical Applications and Treatment Algorithm

For Women Desiring Future Fertility

Preoperative use before myomectomy 1:

• UPA can be used to bridge to surgery when delayed for several months (Level I, A evidence) 1
• Benefits include improved QOL, fibroid shrinkage, and facilitation of minimally invasive surgical approaches 1
• Does not increase surgical difficulty in laparoscopic myomectomy 1
• Critical caveat: Image the uterine cavity preoperatively, as UPA can induce fibroid migration 1

For submucosal fibroids (FIGO type 0 or 1) 1:

• Consider preoperative UPA for hysteroscopic myomectomy to control bleeding and shrink fibroids 1
• May improve ease of surgery and chance of complete primary resection 1
• After treatment, if cavity normalizes, patient may attempt conception without surgery 1

For Women Who Have Completed Childbearing

Long-term intermittent therapy (Level I, A evidence) 1:

• Offer 1-2 courses of UPA (3 months each) as initial management 1
• If positive clinical response achieved, suspend treatment until symptoms recur 1
• Clinical benefits can persist up to 6 months after treatment cessation 1
• When symptoms recur, consider additional 1-2 courses 1

Dosing: 10 mg daily provides superior amenorrhea rates (55-57% vs 35-41% for 5 mg) in the VENUS-II trial 1

Safety Considerations

Endometrial Changes

Progesterone receptor modulator-associated endometrial changes (PAEC) are benign and reversible 1:

• Observed in 16-26% of patients during treatment 1
• Return to normal histology in majority of cases after treatment cessation 1
• 9% prevalence after course 4,6% after treatment cessation in PEARL IV 1

Important Caveats

• Hepatotoxicity concerns: While not mentioned in the 2018 guidelines provided, clinicians should be aware that post-2018, serious liver injury cases led to regulatory restrictions in some jurisdictions
• Repeat workup if symptoms persist: Ensure malignancy is not being missed 1
• Monitor for fibroid migration: Can affect uterine cavity anatomy 1

When UPA Fails or Is Inappropriate

If inadequate response after 1-2 courses 1:

• Consider switching to alternative medical treatment
• Proceed to surgical management (myomectomy or hysterectomy)
• GnRH agonists/antagonists can reduce fibroid volume by 35-67% 2

Practical Implementation

Treatment course structure 1:

• Each course: 3 months of daily UPA
• Courses separated by 1 menses
• Subsequent course commences at beginning of second menses

Response assessment 1:

• Base evaluation on patient's most relevant symptoms (bleeding, anemia, bulk symptoms)
• For bleeding/anemia concerns: Control of bleeding and resolution of anemia indicates positive response
• Suspend treatment when adequate control achieved, restart when symptoms recur