Emerging Research Shows Cancer-Prevention Benefits of Contraceptives
November 1, 2025 8 minutes read
By Melinda Young
Executive Summary
Contraceptives, including the emergency contraceptive ulipristal acetate (UPA), have the potential to help patients with breast cancer, sickle cell disease, and even brain cancer.
- Selective progesterone receptor modulators (SPRMs) can decrease molecular markers of carcinogens in people who carry a mutation that increases the risk of breast and ovarian cancer. UPA and mifepristone are both SPRMs.
- UPA also can reduce fibroids in the uterus and was used extensively in Europe for that purpose until a few patients developed dangerous liver disease while using the treatment.
- Other conditions for which UPA shows promise as a treatment are premenstrual syndrome, adenomyosis, infertility, and heavy menstrual bleeding.
The ovarian cancer prevention strategy of opportunistic salpingectomy is well documented in recent research literature. But there are many additional ways contraception may help prevent cancer and be a treatment for other medical issues. One of these involves emerging evidence of ulipristal acetate (UPA), a prescription emergency contraceptive also called Ella, Logilia, Esmya, and Fibristal, and its potential for preventing breast cancer. There is evidence that UPA also can be used to treat painful uterine growths and excessive bleeding.1-4
“UPA isn’t marketed for ongoing contraception in the U.S. right now; in studies where they have given it to animals daily — that’s where we saw benefits for preventing cancer, and breast cancer prevention is the biggest,” says Ashley Ebersole, MD, MS, an assistant professor of pediatrics in the division of adolescent medicine at Nationwide Children’s Hospital in Columbus, OH. Ebersole also is in the department of pediatrics at The Ohio State University College of Medicine.
UPA, in combination with cancer-fighting drugs like temozolomide, has potential for helping patients with central nervous system (CNS) brain cancer malignancies and sickle cell disease as well, Ebersole says.1 Ulipristal acetate and the abortion drug mifepristone both are selective progesterone receptor modulators (SPRMs) that are used for their antiprogestogen effect in gynecology.1
SPRMs appear to decrease molecular markers of carcinogenesis in people who carry the BRCA1 mutation, which increases one’s risk of developing cancer — especially breast and ovarian cancer. They block progesterone action and are called antiprogestogens.1
Since there is early evidence that the hormone progesterone plays a role in breast cancer, then it is possible that agents like UPA and mifepristone, which modulate the progesterone receptor, could be helpful in preventing and treating breast cancer, new research suggests.1
UPAs also have been used to treat uterine fibroids caused by endometrial changes. Mifepristone, the other SPRM, is a potential treatment for glioblastoma multiforme (GBM), a brain malignancy. Mifepristone can block growth of GBM cells and sensitize to temozolomide in glioblastoma. Emerging research suggests UPA also is a potential treatment for brain cancer.1,5
There has been clinical evidence that giving people UPA for several months before they undergo surgery for fibroids in their uterus can make fibroids more manageable by shrinking them, says Abigail Liberty, MD, MSPH, an assistant professor in the division of complex family planning in the department of obstetrics and gynecology at the Oregon Health & Science University in Portland. “What was licensed for fibroid management was UPA 5 mg daily, and it was used in creative ways,” Liberty says.
“Some people were taking it forever, and others were taking it for a few months before surgery — so instead of a big surgery, they could have a small surgery, like laparoscopic,” she explains. “Taking out a 2 cm fibroid is much easier healing for the uterus than a 12 cm fibroid, and there’s less bleeding during surgery.” The use of UPA also decreased bleeding during surgery and resulted in better return-to-fertility outcomes for patients, she adds.
“The main benefit of UPA that we know about is reducing fibroids in the uterus, and that’s where the majority of research is,” Ebersole says. “There is a lot of science that says it helps surgical outcomes when used before surgery.”
SPRMs like UPA also could reduce abnormal or breakthrough bleeding in people who use an IUD or Nexplanon, Ebersole notes. “There has even been a copper IUD in development that will release UPA to mitigate the side effect,” Ebersole explains. “They gave patients 520 or 40 micrograms a day, and it would be marketed to people who don’t want a copper IUD because of bleeding and cramping.”
But use of SPRMs for non-cancer health issues had a setback around the time of the COVID-19 pandemic, when a very rare but also very serious potential side effect emerged. “What happened was they licensed this medicine in Europe and Canada, and it’s called Esmya,” Liberty says. “It was rolled out really big — hundreds of thousands of women were taking it.”
This resulted in five women having serious complications of liver toxicity. One woman died, and several had emergent liver transplants. According to the European Consortium for Emergency Contraception (ECEC), UPA treatment for fibroids was halted before its role in causing drug-induced liver injury was confirmed.2 “They pulled it from Europe and then in Canada. When this happened, they revoked the licensing, and it stopped all research into SPRMs, and I suspect it may have impacted any development of an SPRM IUD,” Liberty adds.
Researchers in the Netherlands recently published a paper that examines the hepatic safety considerations of the use of UPA for symptomatic uterine fibroids. Their conclusion was that “UPA had a unique place in the treatment of uterine fibroids.”6 The new research notes that the risk of severe drug-induced liver injury (DILI) is low, with an incidence rate of one in 200,000 for liver transplantation, and that this number is lower than with many other widely prescribed medications, where there is no recommended liver monitoring.6 By comparison, research shows that use of amoxicillin-clavulanate, an antibiotic, has resulted in drug-induced liver injury in 43 cases per 100,000.7
The authors of the UPA study say that the risk of severe hepatotoxic events is important, but a balanced approach to safety measures is needed, “particularly in light of the higher risks associated with alternative treatment options such as surgical intervention.”6
The paper suggests that the withdrawal of the drug’s marketing authorization in Europe and elsewhere was an overly cautious regulatory measure because of exceedingly rare DILI incidences, and there “is a need for an improved understanding of DILI mechanisms and causality assessments to aid in the development of more proportional regulatory responses, balancing patient safety and sustained access to effective innovative treatment.”6
UPA research is continuing, including studies that look at UPA and breast cancer — performed primarily in mice. There was a small study of women with increased familial risk of breast cancer who were given UPA for 12 weeks, and investigators discovered decreased proliferation of KI-67, a protein found in the nucleus of cancer cells, including breast cancer, and reduced tissue stiffness, so UPA was considered protective, Ebersole says.1 “We don’t know if it would rebound after 12 weeks,” she adds.
Other contraceptives can be treatment for polycystic ovary syndrome (PCOS) and reduce the risk of endometrial cancer, Ebersole notes. “The first-line contraceptives recommended for polycystic ovary syndrome are combined hormonal contraceptives because they can have other benefits,” she says.
Combined oral contraceptives, used for 12 months or longer, can reduce the risk of endometrial cancer by about 40%, according to 2025 edition of Contraceptive Technology.4 Longer durations of use appeared to have even greater cancer-prevention benefit, with a 72% decrease in patients who used combined oral contraceptives for 12 years or longer. Combined oral contraceptives also can be used as a treatment to prevent endometrial cancer.3
Research shows promise for the use of UPA to treat these additional conditions:
- Premenstrual syndrome: UPA appears to improve symptoms of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). UPA can improve lethargy, sense of fatigue, and lack of energy. It also may improve psychological symptoms of PMDD.2,8,9
- Adenomyosis: Treatment with UPA may temporarily relieve pain from adenomyosis, a condition in which the uterine lining grows into the muscular wall of the uterus and that leads to very heavy menstrual bleeding and pain. So far, the research has shown mixed results.2
- Infertility: For some patients with infertility issues that may lead them to in vitro fertilization, treatment with UPA could restore the physiologic shape of the uterus and help patients avoid surgery before in vitro fertilization, offering patients a pregnancy rate similar to people who do not have a problem with fibroids.2
- Heavy menstrual bleeding: Research found that UPA alone as three 12-week treatment cycles of 5 mg UPA daily, separated by four-week treatment-free intervals, is superior to the levonorgestrel IUD at inducing amenorrhea in study participants and could be a promising option for patients with heavy menstrual bleeding.2,10
Americans still have access to emergency contraception, but this could change, which is why it is important for researchers and clinicians to show the non-contraceptive benefits of the drug, Ebersole notes.
Researchers need to learn more about SPRMs — antiprogestogens — and their use in reducing breast cancer risk. SPRMs have fewer adverse effects than some cancer drugs, and they may be able to help as a nonsurgical cancer prevention strategy for people with mutations that put them at high risk.3
Liberty says she tells oncologists about the benefits of SPRMs, and she asks them to demand research into this medicine for their patients. “They have alternatives, but it used to be only tamoxifen,” Liberty notes.
“One clinical trial that was in Argentina gave mifepristone to people that already had cancer before a mastectomy; it was a short course of 10-14 days,” Liberty says. “The tumor and tissue around it looked more protective against cancer.”11
The study concluded that the use of mifepristone in patients with luminal breast cancer with high levels of progesterone receptor isoform A (PRA) or progesterone receptor isoform B (PRB) ratios warrant clinical evaluation for improving endocrine treatment responsiveness in these patients.11 This suggests that there could be a pre-surgery protocol using mifepristone for someone who has breast cancer, Liberty says.
Melinda Young has been a healthcare and medical writer for 30 years. She currently writes about contraceptive technology.
References
1. Ebersole AM, Liberty A, Edelman A, et al. Uses of ulipristal acetate beyond emergency contraception: A narrative review. Contraception. 2025;146:110862. [Online ahead of print].
2. Ebersole A. Uses of ulipristal acetate beyond emergency contraception. European Consortium for Emergency Contraception (ECEC) and American Society for Emergency Contraception (ASEC). March 2025. https://www.ec-ec.org/wp-content/uploads/2025/03/UPA-Indications-Beyond-EC_ASEC-ECEC_Mar25.pdf
3. Liberty A, Edelman A, Bernhardt SM. The emerging role of progesterone receptor modulators in breast physiology, cancer prevention and treatment. BMJ Sex Reprod Health. 2025; Apr 4:bmjsrh-2024-202662:1-9.
4. Cason P, Cwiak C, Edelman A, et al. Contraceptive Technology, 22nd Edition. Jones & Bartlett Learning;2025:372.
5. Altinoz MA, Yilmaz A, Taghizadehghalehjoughi A, et al. Ulipristal-temozolomide-hydroxyurea combination for glioblastoma: In-vitro studies. J Neurosurg Sci. 2024;68(4):1-14.
6. Semmler A, de Lange ME, Drenth JPH, et al. Hepatic safety considerations in the use of ulipristal acetate for symptomatic uterine fibroids. Ther Clin Risk Manag. 2025;21:367-382.
7. deLemos AS, Ghabril M, Rockey DC, et al. Amoxicillin-clavulanate-induced liver injury. Dig Dis Sci. 2016;61(8):2406-2416.
8. Chen BF, Powell MC, O’Beirne C. An observation study of the clinical evaluation of symptom relief and side effects associated with taking ulipristal acetate (esmya) including its effect on pre-menstrual syndrome. J Obstet Gynaecol. 2017;37(5):645-648.
9. Comasco E, Kallner HK, Bixo M, et al. Ulipristal acetate for treatment of premenstrual dysphoric disorder: A proof-of-concept randomized controlled trial. Am J Psychiatry. 2021;178(3):256-265.
10. Whitaker LHR, Middleton LJ, Daniels JP, et al. Ulipristal acetate versus levonorgestrel-releasing intrauterine system for heavy menstrual bleeding (UCON): A randomized controlled phase III trial. EClinicalMedicine. 2023;60:101995.
11. Elía A, Saldain L, Vanzulli SI, et al. Beneficial effects of mifepristone treatment in patients with breast cancer selected by the progesterone receptor isoform ratio: Results from the MIPRA trial. Clin Cancer Res. 2023;29(5):866-877.
Contraceptives have the potential to help patients with breast cancer, sickle cell disease, and even brain cancer.
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