Happy Fact Friday! Each week we pick one new endometriosis or adenomyosis study and translate it into plain English. This week’s find: a study in the peer-reviewed journal iScience from teams at UCSF, Emory, and Stanford[1] used a computer-driven approach to scan thousands of existing drugs for ones that might counteract the biology of endometriosis. Their top two candidates, simvastatin (a common cholesterol drug) and primaquine (an antimalarial), were then tested in an animal model and checked against real patient health records. Here’s what they found, and what it does and doesn’t mean for you.

If you live with endometriosis, treatment options have barely changed in decades. Endometriosis is a condition where tissue similar to the uterine lining (the endometrium) grows outside the uterus, most often on the ovaries, peritoneum, and bowel. Because it still responds to hormonal cycles, it can bleed, inflame surrounding tissue, and cause fibrosis (tough scar tissue), driving painful periods, chronic pelvic pain, pain during sex, and often infertility.^[2]

Endometriosis affects roughly 10% of women of reproductive age, likely an undercount since diagnosis usually requires surgery.^[1][2][3] It’s also costly: the study estimates nearly $70 billion a year in the US,^[1] a figure consistent with other research showing its healthcare and productivity costs rival other major chronic diseases.^[4][5]

Current treatment is largely limited to hormonal therapies and NSAIDs,^[2] which often bring partial or temporary relief. Surgery can help, but symptoms frequently return. Developing an entirely new drug is slow and expensive, which is exactly why “drug repurposing,” finding new uses for old drugs, is such an appealing shortcut.^[1]

This research moved through three stages: computer analysis, lab animals, then real patient data.

Earlier work by this team compared gene activity in endometrial tissue from people with and without the disease against a public database (the Connectivity Map) recording how thousands of existing drugs affect gene expression, looking for drugs that reverse the disease’s pattern. That analysis flagged 299 candidates, topped by the NSAID fenoprofen, later shown to ease pain in an animal model.^[6] For this study, the team investigated two more top candidates: simvastatin and primaquine.^[1]

Researchers did not study rats with endometriosis. They surgically transplanted a small piece of each rat’s own uterine tissue elsewhere in the abdomen, creating tissue that behaves somewhat like ectopic endometrial tissue: hormone-responsive and associated with pain-like behavior. Rats then received four weeks of simvastatin, primaquine, or placebo, with pain measured through a well-established “vaginal distension” test, and RNA sequencing to check whether the drugs reversed disease-linked gene activity, not just masked pain.^[1]

The team examined de-identified records from roughly 9.8 million patients across six University of California health systems, comparing women prescribed simvastatin for cholesterol (with no prior endometriosis diagnosis) to a matched group never prescribed it. Too few patients were on primaquine for a similar analysis.^[1]

Results were consistent across all three stages.

In rats, both drugs reduced pain-related behavior after four weeks of treatment. Simvastatin performed about as well as ibuprofen and fenoprofen, the study’s positive controls; primaquine helped, but less consistently.^[1]

RNA sequencing added weight: all four drugs measurably reversed disease-linked gene activity in the uterus, though the effect was weaker in the transplanted lesion tissue itself, possibly because dense, fibrous, poorly vascularised lesions are harder for drugs to penetrate.^[1]

Then the real-world data: 2.9% of simvastatin-prescribed women went on to be diagnosed with endometriosis, versus 3.8% to 4.1% of matched women never prescribed it, a roughly 25% lower relative risk (RR 0.75, 95% CI 0.58 to 0.97).^[1] This is an association, not proof of prevention, but a striking echo of the lab findings.

It isn’t a new idea either: lab studies show statins like simvastatin slow endometrial stromal cell growth and invasiveness,^[7] and a small earlier trial of 60 women found simvastatin worked about as well as a GnRH agonist (a standard hormonal treatment) at reducing pain after surgery.^[8] Other repurposed drugs, including antimalarials, have shown similar early promise in mouse models.^[9][10]

This is early, hypothesis-generating science, not a treatment you can ask your doctor for tomorrow, but it matters for a few reasons.

It shows new treatment leads don’t have to start from scratch. Simvastatin is cheap, widely available, and has decades of safety data. If larger trials confirm it eases endometriosis pain, it could become an additional, non-hormonal option, especially valuable for people who can’t tolerate hormonal therapies.

It also reinforces that endometriosis involves identifiable, reversible molecular changes, not just “worse period pain,” with several affected genes and pathways shared between the rat model and human tissue.^[1]

For adenomyosis, where endometrial-like tissue grows into the uterine wall itself, this study doesn’t apply directly, but it’s part of a broader wave of research bringing more sophisticated tools to uterine and pelvic pain conditions generally.

As with any single study, there are real limits, and the researchers are upfront about them.^[1]

READ BEFORE YOU GET TOO EXCITED

• The pain and gene-expression results come from transplanted rat tissue, not from rats with endometriosis, so they’re suggestive, not conclusive, for humans.
• The real-world data shows association, not prevention: these women took simvastatin for cholesterol, not endometriosis, and retrospective records can’t rule out every confounding factor.
• Only one dose was tested, with no dose-response data, so the ideal human dose is unknown.
• Effects on lesion tissue were weaker than on the uterus, suggesting drugs may struggle to reach lesions in sufficient amounts.
• No large human trials of primaquine exist, and simvastatin’s human evidence rests on this data plus one small, 60-patient trial.

In short: promising groundwork, not a finished answer. Human clinical trials are the necessary next step before simvastatin or primaquine could be recommended for endometriosis.

• Researchers used computational drug repurposing to flag simvastatin and primaquine as candidates. ^[1]
• In rats, both eased pain; simvastatin matched ibuprofen’s effect. ^[1]
• Both reversed disease-linked gene activity, mainly in uterine tissue. ^[1]
• Women prescribed simvastatin had a roughly 25% lower observed rate of endometriosis diagnosis in real-world records. ^[1]
• This is early research. Larger human trials are needed before any treatment conclusions.

Endometriosis research is finally attracting the investment and cross-institution collaboration it deserves, and repurposing existing, affordable drugs could shorten the road from promising idea to accessible treatment. It’s one encouraging step in the search for better pain management options.

1. Oskotsky TT, Tang X, Arthurs E, et al. A transcriptomics-based computational drug repurposing pipeline identifies simvastatin and primaquine as therapeutics for endometriosis. iScience. 2026;29(9):117153. doi:10.1016/j.isci.2026.117153
2. As-Sanie S, Mackenzie SC, Morrison L, Schrepf A, Zondervan KT, Horne AW, Missmer SA. Endometriosis: A Review. JAMA. 2025;334(1):64-78. doi:10.1001/jama.2025.2975
3. Shafrir AL, Farland LV, Shah DK, Harris HR, Kvaskoff M, Zondervan K, Missmer SA. Risk for and consequences of endometriosis: a critical epidemiologic review. Best Pract Res Clin Obstet Gynaecol. 2018;51:1-15. doi:10.1016/j.bpobgyn.2018.06.001
4. Simoens S, Dunselman G, Dirksen C, et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod. 2012;27(5):1292-1299. doi:10.1093/humrep/des073
5. Soliman AM, Surrey ES, Bonafede M, Nelson JK, Vora JB, Agarwal SK. Health care utilization and costs associated with endometriosis among women with Medicaid insurance. J Manag Care Spec Pharm. 2019;25(5):566-572. doi:10.18553/jmcp.2019.25.5.566
6. Oskotsky TT, Bhoja A, Bunis D, et al. Identifying therapeutic candidates for endometriosis through a transcriptomics-based drug repositioning approach. iScience. 2024;27(4):109388. doi:10.1016/j.isci.2024.109388
7. Sokalska A, Hawkins AB, Yamaguchi T, Duleba AJ. Lipophilic statins inhibit growth and reduce invasiveness of human endometrial stromal cells. J Assist Reprod Genet. 2018;36(3):535-541. doi:10.1007/s10815-018-1352-9
8. Almassinokiani F, Mehdizadeh A, Sariri E, et al. Effects of simvastatin in prevention of pain recurrences after surgery for endometriosis. Med Sci Monit. 2013;19:534-539. doi:10.12659/MSM.883967
9. Ruiz A, Rockfield S, Taran N, et al. Effect of hydroxychloroquine and characterization of autophagy in a mouse model of endometriosis. Cell Death Dis. 2016;7(1):e2059. doi:10.1038/cddis.2015.361
10. Matsuzaki S, Pouly JL, Canis M. In vitro and in vivo effects of MK2206 and chloroquine combination therapy on endometriosis: autophagy may be required for regrowth of endometriosis. Br J Pharmacol. 2018;175(10):1637-1653. doi:10.1111/bph.14170