Ulipristal acetate
In placebo-controlled trials of women with fibroids, daily ulipristal controlled bleeding in about 90% against 19% on placebo, shrank fibroids and raised hemoglobin, and matched leuprolide with fewer hot flashes. Serious liver injury, with five liver transplants reported, led the EU to restrict it, and it is no longer authorized there. US approval is for emergency contraception.
Add to Bio HackChecked 2026-11-13
- Status
- Prescription drug in the US, where the label covers one 30 mg tablet (ella) for emergency contraception after unprotected sex or contraceptive failure. The US label does not include fibroids. In the EU, the 5 mg daily tablet for fibroids (Esmya) was restricted in 2021 after serious liver injury, and its EU authorization was withdrawn in July 2024 at the company's request for commercial reasons.
- Also called
- ulipristal, ulipristal acetate, UPA, Esmya, ella, ellaOne, selective progesterone receptor modulator, SPRM
- Taken for
- fibroids, heavy bleeding from fibroids, shrinking fibroids, anemia before fibroid surgery, avoiding fibroid surgery, emergency contraception, morning-after pill
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Shown to help6
- StrongShown to control fibroid bleeding in about 91% of women against 19% on placebo, with amenorrhea in 47% to 82% against 2% to 6%, over 12 to 13 weeks.Very common
- ModerateShown to control fibroid bleeding in 90% to 98% of women, as often as leuprolide injections at 89%, with moderate to severe hot flashes in 10% to 11% against 40%.
- ModerateShown to shrink fibroids against placebo, a median 21% and 12% on 5 mg and 10 mg against a 3% rise, though less than GnRH agonists shrank the uterus.
- ModerateShown to raise hemoglobin before fibroid surgery by about 0.9 g/dL more than placebo, in women taking SPRMs including ulipristal.
- ModerateShown to improve fibroid symptom severity by about 20 points and quality of life by about 23 points on a 100-point scale, against placebo.
- ModerateShown to lower pregnancies after unprotected sex compared with levonorgestrel emergency pills, 1.8% against 2.6% within 72 hours in the largest trial.
Reported risks6
- ModerateAfter the emergency dose, 18% reported headache and 12% nausea, as often as on levonorgestrel. In fibroid trials, headache and breast tenderness did not differ from placebo.Very common
- LimitedAfter the emergency dose, 19% had their next period more than 7 days late and 7% more than 7 days early, with cycles about 2.5 days longer on average.Very common
- LimitedCase reports: serious liver injury occurred on the daily fibroid dose, with five liver transplants reported in Europe. One review estimated severe injury at 13.5 per 100,000 users.Rare
- ModerateShown to cause benign changes in the uterine lining more often than placebo or leuprolide. In one trial the changes had resolved 6 months after treatment ended.How often is not known
- LimitedEMA restricted the 5 mg fibroid tablet to premenopausal women for whom surgery, including embolization, is not appropriate or has failed. Its EU authorization was later withdrawn.How often is not known
- LimitedThe ella label states progestin contraceptives may weaken its effect and that it may weaken them, and that CYP3A4 inducers such as rifampin lower its levels.How often is not known
What people take it for, and what was found
Shown to help6
Heavy bleeding with fibroids, against placebo
Shown to control fibroid bleeding in about 91% of women against 19% on placebo, with amenorrhea in 47% to 82% against 2% to 6%, over 12 to 13 weeks.
Compared with placebo [1][2][3][4]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In anemic women with heavy bleeding, 13 weeks of ulipristal controlled bleeding (a PBAC score under 75) in 91% on 5 mg and 92% on 10 mg against 19% on placebo, with amenorrhea in 73% and 82% against 6% [1]. In a US trial, amenorrhea occurred in 47.2% on 5 mg and 58.3% on 10 mg against 1.8% on placebo [2]. Pooled across SPRM trials, amenorrhea rose from 29 per 1,000 on placebo to 237 to 961 per 1,000 (OR 82.50, 95% CI 37.01 to 183.90, 7 RCTs, 590 women) and patient-reported blood loss fell (SMD -1.11) [3]. A second meta-analysis found amenorrhea against placebo with RR 24.54 (95% CI 10.82 to 55.64, 5 RCTs, 882 participants) [4].
- Population
- 242 women with fibroids, heavy bleeding and hemoglobin of 10.2 g/dL or less [1]; 157 premenopausal women aged 18 to 50 [2]; 14 RCTs of SPRMs with 1,215 women [3]; 6 RCTs with 1,121 participants [4].
- Sources
- [1], [2], [3], [4]
- Caveats
- The Cochrane review pooled several SPRMs (mifepristone, ulipristal and asoprisnil), not ulipristal alone [3]. The first trial was funded by PregLem [1].
Heavy bleeding with fibroids, against leuprolide
Shown to control fibroid bleeding in 90% to 98% of women, as often as leuprolide injections at 89%, with moderate to severe hot flashes in 10% to 11% against 40%.
Compared with leuprolide injections [3][5][6]
The numbers and sources
- Effect
- Over 13 weeks, bleeding was controlled in 90% on 5 mg and 98% on 10 mg ulipristal and 89% on monthly leuprolide 3.75 mg, meeting the trial's noninferiority margin. Median time to amenorrhea was 7 and 5 days against 21 days. Moderate to severe hot flashes affected 11% and 10% against 40% [5]. Fibroid symptom severity and quality of life did not differ from leuprolide (MD -3.70 and 1.06 points, 1 RCT, 281 women) [3]. Before surgery, bleeding reduction did not differ between ulipristal 5 mg and GnRH agonists (OR 0.71, 95% CI 0.30 to 1.68), and uterine volume fell 20% to 22% on ulipristal against 47% on GnRH agonists [6].
- Population
- 307 women with fibroids and heavy bleeding [5]; 281 women in the quality of life comparison [3]; women in trials before fibroid surgery [6].
- Sources
- [5], [3], [6]
- Caveats
- One main head-to-head trial, funded by PregLem [5].
Fibroid size
Shown to shrink fibroids against placebo, a median 21% and 12% on 5 mg and 10 mg against a 3% rise, though less than GnRH agonists shrank the uterus.
Compared with placebo [1][3][6]; GnRH agonists [6]
The numbers and sources
- Effect
- At 13 weeks, median total fibroid volume changed -21% on 5 mg, -12% on 10 mg and +3% on placebo [1]. SPRMs reduced uterine and fibroid volume against placebo in heterogeneous trials too varied to pool [3][6]. Uterine volume fell 47% on GnRH agonists against 20% and 22% on ulipristal 5 mg and 10 mg [6].
- Population
- 242 anemic women with fibroids [1]; RCTs of SPRMs [3]; women before fibroid surgery in 41 RCTs [6].
- Sources
- [1], [3], [6]
- Caveats
- The pooled results cover SPRMs as a class [3][6].
Hemoglobin before fibroid surgery
Shown to raise hemoglobin before fibroid surgery by about 0.9 g/dL more than placebo, in women taking SPRMs including ulipristal.
Compared with placebo [6]; GnRH agonists [6]
The numbers and sources
- Effect
- SPRMs raised preoperative hemoglobin by 0.93 g/dL against placebo (95% CI 0.52 to 1.34, 2 studies, 173 women, I² 0%, moderate certainty). Preoperative hemoglobin did not differ between GnRH agonists and other medicines including ulipristal (MD -0.02 g/dL, 95% CI -0.41 to 0.37, 242 women) [6].
- Population
- Premenopausal women before fibroid surgery in randomized trials [6].
- Sources
- [6]
- Caveats
- Two pooled trials, pooled across SPRMs. In one trial all women received iron [1].
Fibroid symptoms and quality of life
Shown to improve fibroid symptom severity by about 20 points and quality of life by about 23 points on a 100-point scale, against placebo.
The numbers and sources
- Effect
- On the Uterine Fibroid Symptom and Quality of Life scale, SPRMs improved symptom severity by 20.04 points (95% CI 13.46 to 26.63, 4 RCTs, 171 women) and health-related quality of life by 22.52 points (95% CI 12.87 to 32.17, 4 RCTs, 200 women) against placebo [3]. Both ulipristal doses improved quality of life against placebo in a US trial [2]. Pelvic pain results were too variable to draw conclusions [3].
- Population
- Premenopausal women with fibroids [2][3].
- Sources
- [3], [2]
- Caveats
- Moderate-quality evidence, with possible publication bias [3].
Emergency contraception (ella)
Shown to lower pregnancies after unprotected sex compared with levonorgestrel emergency pills, 1.8% against 2.6% within 72 hours in the largest trial.
Compared with levonorgestrel emergency contraception [7][8]
The numbers and sources
- Effect
- Pooled, ulipristal was linked to fewer pregnancies than levonorgestrel (RR 0.59, 95% CI 0.35 to 0.99, 2 RCTs, 3,448 women) [7]. In the larger trial, pregnancies occurred in 1.8% on ulipristal and 2.6% on levonorgestrel when taken within 72 hours (OR 0.68, 95% CI 0.35 to 1.31). Between 72 and 120 hours, all 3 pregnancies were in the levonorgestrel group [8]. In women with BMI over 30, the pregnancy rate on ulipristal was 3.1%, not significantly below the 4.5% expected without emergency contraception [9].
- Population
- 2,221 women with regular cycles seeking emergency contraception within 5 days [8]; 115 emergency contraception trials with 60,479 women, 2 of them for this comparison [7]; women in the label trials [9].
- Sources
- [7], [8], [9]
- Caveats
- The single trial on its own did not reach significance [8]. This is a single 30 mg dose, not the 5 mg daily fibroid dose.
Mixed results1
Pregnancy after ulipristal for fibroids
Case reports: of 71 pregnancies after ulipristal for fibroids, 50 ended in live births and 19 in miscarriage, with no comparison group.
Compared with no comparison group in the case series [10]
The numbers and sources
- Effect
- A systematic review found 24 pregnancies after ulipristal (19 live births, 6 miscarriages), and a case series added 47 (31 live births, 13 miscarriages, 1 fetal death, 2 terminations, 1 ongoing). Of the 71, 44 had myomectomy after ulipristal. Five women who did not have surgery had delivery complications related to their fibroids [10].
- Population
- 71 pregnancies from 6 case reports, 1 retrospective series and a multicenter chart review [10].
- Sources
- [10]
- Caveats
- No comparison group, so these counts cannot show whether ulipristal changed the chance of pregnancy or miscarriage.
Doses studied
The fibroid trials used 5 mg or 10 mg by mouth once daily for 12 to 13 weeks [1][2][5]. The EU fibroid product was 5 mg daily, used for up to 3 months before surgery or in repeated courses with breaks in women who could not have surgery [11]. Emergency contraception uses one 30 mg tablet within 120 hours of unprotected sex [9].
Risks
Reported risks6
Common side effects
After the emergency dose, 18% reported headache and 12% nausea, as often as on levonorgestrel. In fibroid trials, headache and breast tenderness did not differ from placebo.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In the 13-week placebo-controlled trial, headache and breast tenderness were the most common adverse events and did not occur significantly more often than on placebo [1]. In a US fibroid trial, hypertension, raised creatine phosphokinase and hot flushes each affected 5% or more in a ulipristal group [2]. After a single 30 mg dose, headache affected 18%, abdominal pain 12%, nausea 12%, period pain 9%, fatigue 6% and dizziness 5% [9]. Headache rates matched levonorgestrel (19.3% and 18.9%) [8].
- Population
- 242 women [1] and 157 women [2] in fibroid trials; women in the emergency contraception trials [8][9].
- Sources
- [1], [2], [9], [8]
- Caveats
- The emergency contraception rates come from trials without a placebo arm [9].
Change in timing of the next period (ella)
After the emergency dose, 19% had their next period more than 7 days late and 7% more than 7 days early, with cycles about 2.5 days longer on average.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In clinical trials, cycle length rose a mean 2.5 days and returned to normal the next cycle. Seven percent reported menses more than 7 days early and 19% more than 7 days late [9]. Ulipristal users were more likely than levonorgestrel users to have periods return after the expected date [7].
- Population
- Women in the emergency contraception trials [7][9].
- Sources
- [9], [7]
- Caveats
- Single-arm label data for the percentages [9].
Serious liver injury
Case reports: serious liver injury occurred on the daily fibroid dose, with five liver transplants reported in Europe. One review estimated severe injury at 13.5 per 100,000 users.
The numbers and sources
- How common
- Rare: fewer than 1 in 1,000 people.
- Effect
- In 2018 the European Medicines Agency reviewed serious liver injury, including four cases that led to liver transplant, among about 765,000 women treated, and judged a role for Esmya possible in 8 serious cases [11]. A US FDA review of postmarketing reports found 9 serious non-US cases, 5 with liver transplant or death judged probably caused by ulipristal [12]. A 2025 review counted five transplant cases across the 2018 and 2020 European reviews, a transplant reporting rate of about 0.52 per 100,000 users, and estimated severe drug-induced liver injury at 13.5 per 100,000 [13]. In a Korean cohort of 11,445 matched women per group, mild liver disease was slightly more common on ulipristal than on GnRH agonists (RR 1.094), while severe and toxic liver disease did not differ and no transplants occurred [14].
- Population
- Spontaneous reports to EMA and FDA [11][12]; regulator documents reviewed in [13]; 20,926 Korean women on ulipristal and 17,207 on GnRH agonists before matching [14].
- Sources
- [11], [12], [13], [14]
- Caveats
- Spontaneous reports cannot prove cause, and the rate is an estimate from exposure figures [13]. The 2025 review's authors argue the regulatory measures were overly cautious for the size of the risk [13]. The EMA states no concern about liver injury has been raised with the single-dose emergency contraceptive [15].
EU restriction and withdrawal
EMA restricted the 5 mg fibroid tablet to premenopausal women for whom surgery, including embolization, is not appropriate or has failed. Its EU authorization was later withdrawn.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- In 2018, the EMA added a contraindication in liver disease, liver tests before, during and after treatment, and a patient card [11]. On 12 November 2020, its human medicines committee advised restricting the 5 mg medicines to premenopausal women for whom surgical procedures, including uterine fibroid embolization, are not appropriate or have not worked, and not for symptom control while awaiting surgery. The European Commission's binding decision followed on 11 January 2021 [15]. On 18 July 2024, the European Commission withdrew Esmya's EU marketing authorization at the request of the holder, which stopped marketing for commercial reasons [16].
- Population
- Regulatory actions in the European Union [11][15][16].
- Sources
- [11], [15], [16]
- Caveats
- The withdrawal was requested by the company and was not a regulator's safety ruling [16].
Benign changes in the uterine lining
Shown to cause benign changes in the uterine lining more often than placebo or leuprolide. In one trial the changes had resolved 6 months after treatment ended.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- SPRM-associated endometrial changes were more common than on placebo (OR 15.12, 95% CI 6.45 to 35.47, 5 RCTs, 405 women) and than on leuprolide (OR 10.45, 95% CI 5.38 to 20.33). The reviewers describe these changes as benign, not cancer and not precancerous [3]. In the placebo-controlled trial, the changes had resolved by 6 months after the end of treatment [1].
- Population
- Women with fibroids in randomized trials [1][3].
- Sources
- [3], [1]
- Caveats
- Low-quality evidence for the comparison with placebo, and the trials ran for 3 months [3].
Interactions with hormonal contraception and liver enzyme drugs
The ella label states progestin contraceptives may weaken its effect and that it may weaken them, and that CYP3A4 inducers such as rifampin lower its levels.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- The label states progestin-containing contraceptives may impair ella's ability to delay ovulation, that ella may affect the progestin in hormonal contraceptives, and that its directions are to start hormonal contraception no sooner than 5 days after ella, with a barrier method until the next period. Rifampin, a CYP3A4 inducer, lowered ulipristal levels significantly, and CYP3A4 inhibitors such as itraconazole or ketoconazole raise them [9]. A 2025 review notes one transplant case in a woman also using raspberry leaf, a CYP3A4 inhibitor [13].
- Population
- Pharmacokinetic studies and label statements [9]; case review [13].
- Sources
- [9], [13]
- Caveats
- Drug level studies, not outcome trials.
Checked, no increase found1
Use in pregnancy
The ella label contraindicates use in known or suspected pregnancy and states postmarketing studies found no signal of pregnancy complications after exposure.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Ella is not indicated to end an existing pregnancy, and the label advises evaluation for ectopic pregnancy in women who become pregnant or have lower abdominal pain after use. Postmarketing studies found no signal of concern for pregnancy complications [9]. In the fibroid case series, 5 pregnancies began during ulipristal use, with 3 live births, 1 miscarriage and 1 termination [10].
- Population
- Postmarketing studies summarized in the label [9]; 5 pregnancies conceived during use [10].
- Sources
- [9], [10]
- Caveats
- Observational postmarketing data. Five pregnancies cannot give a rate.
Claims tested and not found
- That the endometrial changes from ulipristal are precancerous. The Cochrane review describes SPRM-associated endometrial changes as benign, not related to cancer and not precancerous [3], and in a 13-week trial they had resolved by 6 months after treatment [1].
- That ulipristal controls fibroid bleeding less well than leuprolide. In a head-to-head trial, both doses met the noninferiority margin against leuprolide for bleeding control [5].
Related
Sources
- Donnez J, Tatarchuk TF, Bouchard P, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. New England Journal of Medicine. 2012. https://doi.org/10.1056/nejmoa1103182
- Simon JA, Catherino W, Segars JH, et al. Ulipristal Acetate for Treatment of Symptomatic Uterine Leiomyomas: A Randomized Controlled Trial. Obstetrics & Gynecology. 2018. https://doi.org/10.1097/aog.0000000000002462
- Murji A, Whitaker L, Chow TL, et al. Selective progesterone receptor modulators (SPRMs) for uterine fibroids. Cochrane Database of Systematic Reviews. 2017. https://doi.org/10.1002/14651858.cd010770.pub2
- Ghonim M, Magdy R, Sabbour M, et al. A systematic review and meta-analysis of ulipristal acetate for symptomatic uterine fibroids. International Journal of Gynecology & Obstetrics. 2019. https://doi.org/10.1002/ijgo.12868
- Donnez J, Tomaszewski J, Vázquez F, et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids. New England Journal of Medicine. 2012. https://doi.org/10.1056/nejmoa1103180
- Puscasiu L, Vollenhoven B, Nagels HE, et al. Preoperative medical therapy before surgery for uterine fibroids. Cochrane Database of Systematic Reviews. 2025. https://doi.org/10.1002/14651858.cd000547.pub3
- Shen J, Che Y, Showell E, et al. Interventions for emergency contraception. Cochrane Database of Systematic Reviews. 2019. https://doi.org/10.1002/14651858.cd001324.pub6
- Glasier AF, Cameron ST, Fine PM, et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis. The Lancet. 2010. https://doi.org/10.1016/s0140-6736(10)60101-8
- US Food and Drug Administration label. ELLA (ulipristal acetate) tablet, for oral use. DailyMed. 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2bf93d23-cddd-4613-9066-5b5fa090404b
- De Gasperis-Brigante C, Singh SS, Vilos G, et al. Pregnancy Outcomes Following Ulipristal Acetate for Uterine Fibroids: A Systematic Review. Journal of Obstetrics and Gynaecology Canada. 2018. https://doi.org/10.1016/j.jogc.2018.05.020
- European Medicines Agency. Esmya: new measures to minimise risk of rare but serious liver injury (Article 20 referral). 2018. https://www.ema.europa.eu/en/medicines/human/referrals/esmya
- Kang S, Brinker A, Jones SC, et al. An Evaluation of Postmarketing Reports of Serious Idiosyncratic Liver Injury Associated with Ulipristal Acetate for the Treatment of Uterine Fibroids. Drug Safety. 2020. https://doi.org/10.1007/s40264-020-00960-1
- Semmler A, de Lange ME, Drenth JPH, et al. Hepatic Safety Considerations in the Use of Ulipristal Acetate for Symptomatic Uterine Fibroids. Therapeutics and Clinical Risk Management. 2025. https://doi.org/10.2147/tcrm.s273358
- Yoon EL, Yuk JS. Use of Ulipristal Acetate and Risk of Liver Disease: A Nationwide Cohort Study. The Journal of Clinical Endocrinology & Metabolism. 2021. https://doi.org/10.1210/clinem/dgab081
- European Medicines Agency. Ulipristal acetate for uterine fibroids: EMA recommends restricting use (Article 31 referral, ulipristal acetate 5 mg medicinal products). 2021. https://www.ema.europa.eu/en/medicines/human/referrals/ulipristal-acetate-5mg-medicinal-products
- European Medicines Agency. Esmya (ulipristal acetate): withdrawal of the marketing authorisation in the European Union. 2024. https://www.ema.europa.eu/en/medicines/human/EPAR/esmya