Main messages

• On the one hand, ulipristal acetate increases the probability of amenorrhea, slightly improves quality of life, and increases the risk of reduced menstruation flow. On the other hand, it increases the risk of adverse effects in patients with symptomatic uterine fibroids.
• Ulipristal acetate reduces the size of fibroids; however, the certainty of the evidence is low.
• Regarding the risk of adverse effects, it is recommended to monitor liver function before, during, and after using ulipristal acetate.

What is the evidence
See evidence matrix in Epistemonikos later

We identified nine systematic reviews [1],[4],[5],[6],[7],[8],[9],[10],[11] including 11 studies overall[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22] of which five were randomized trials [12],[13],[14],[15],[16],[17].

What types of patients were included*

All trials included patients with uterine fibroids, which were defined as the presence of at least one fibroid diagnosed by ultrasound [12],[15],[16], or magnetic resonance [13]. One trial did not define the imaging technique for the diagnosis of uterine fibroids [12].

Of these patients, the age range was 18 to 50 years [12],[15],[16],[17], only one trial considered ages 33 to 50 years [13].

What types of interventions were included*

All trials used ulipristal as an intervention and were compared with placebo. Three trials [12],[15],[16] used the drug at doses of 5 and 10 milligrams. Only one trial [13] considered doses of 10 and 20 milligrams.

What types of outcomes were measured

All the clinical trials reported multiple outcomes, which were as follows:

• Amenorrhoea
• Quality of life 
• Adverse effects
• Reduction in menstruation 
• Fibroid size

Follow-up ranged from 12 [15],[16] to 13 weeks [12]. Only one trial had a follow-up of 90 and 110 days [13].

• This evidence applies to women of childbearing age, considered between 18 and 50 years of age, who present at least one symptomatic uterine myoma diagnosed by ultrasound or magnetic resonance imaging.
• Postmenopausal women who use drugs such as corticosteroids, progestins, or agents that alter ovarian or liver function are excluded, as well as a history of previous gynecological surgery or suspicion of malignant disease.

• The outcomes included in the summary of findings table are those considered critical for decision-making, according to the opinion of the authors of this summary, and in general, coincide with the systematic reviews identified.
• The outcome “myoma size” was included in the results summary table because it is a relevant outcome for clinical experts, even though it is a surrogate outcome. The reduction of the size of the myoma facilitates the management, surgical technique and reduces the intraoperative bleeding rates.
• The authors consider relevant outcomes for decision-making are hepatotoxicity and pregnancy rates, which were not reported in the systematic reviews.

• The benefit/risk ratio of ulipristal acetate is positive in terms of clinical improvement. It presents a high level of certainty of the evidence regarding the reduction of menstruation and amenorrhea, in addition to improving the quality of life, despite presenting a slight increase in adverse effects.
• On the other hand, regarding the reduction in the size of the fibroids, we consider that it is relevant as it could facilitate surgery; however, it is not possible to make an adequate balance of risks and benefits on the use of ulipristal in this outcome, because the certainty of the evidence is low.
• No information was reported regarding the pregnancy rate and hepatotoxicity after the use of ulipristal, which we consider to be relevant outcomes when using this drug; this balance may not be entirely favorable concerning these aspects.

• None of the included studies performed a resource analysis; however, ulipristal acetate has a high economic cost: Nevertheless, it provides benefits in terms of symptomatic relief with decreased menstrual bleeding, thus improving the quality of life. Likewise, it must be considered that it is not free of adverse effects. Its cost-effectiveness must be evaluated directly in each patient.
• The economic cost of ulipristal acetate is around 200 to 600 USD per month for a treatment that varies between 3 and 6 months. On the other hand, myomectomy ranges from 1,400 to 2,300 USD according to private health institutions adjusted to the FONASA code of Chile [23]; however, these prices can vary significantly depending on the medical center.

• Among medical treatments, ulipristal acetate is accepted among physicians as an alternative for surgery to manage the symptoms produced by uterine fibroids in the face of the failure of other first-line medical treatments such as contraceptives and non-steroidal anti-inflammatory drugs.
• Regarding patient opinion, although this treatment reduces bleeding, they could eventually reject it due to hepatotoxicity and its high economic cost.

• The conclusions of this summary are consistent with the identified systematic reviews.
• The National Institute for Health Care and Excellence (NICE) guidelines [24] recommend ulipristal acetate 5 mg as a treatment option for women with symptomatic fibroids with a diameter of 3 cm or greater for the management of heavy menstrual bleeding.
• The Food and Drug Administration (FDA) [25] initially rejected the use of ulipristal acetate as a treatment for uterine fibroids due to its hepatotoxicity; therefore, the European Pharmacovigilance Risk Assessment Committee (PRAC) [26] initiated an investigation that concluded that ulipristal might have contributed to the development of some cases of severe liver injury. Consequently, new measures such as monitoring of liver function and contraindication in women with an underlying liver disorder were generated.
• The Spanish Society of Gynecology and Obstetrics (SEGO) [27] reports that ulipristal acetate 5 mg has a favorable safety and tolerability profile and is the only treatment indicated for the intermittent repeat treatment of uterine fibroids. In addition, they state that it is useful for women of childbearing age who want to preserve their uterus, preserve fertility, improve their quality of life, achieve pregnancy, and delay or avoid surgery. Also, the drug has been shown to rapidly control and reduce uterine bleeding and fibroids volume, improving pain and quality of life for women with this condition.

• Given the certainty of the evidence, the probability that future research changes the conclusions of this summary is low in relation to increased amenorrhea, reduced menstruation, quality of life, and adverse events; however, there is still uncertainty in relation to other relevant outcomes.
• The International Prospective Register of Systematic Reviews (PROSPERO) identified three ongoing systematic reviews that include the use of ulipristal to treat uterine fibroids [28],[29],[30].
• In the International Clinical Trials Registry Platform of the World Health Organization, we identified two ongoing studies on the use of ulipristal in uterine fibroids [31],[32].