Hugh Taylor, MD, on how blood-based epigenetic profiling could inform personalized endometriosis care

A blood-based epigenetic biomarker may help guide first-line treatment decisions in endometriosis, reducing reliance on trial-and-error approaches, according to Hugh Taylor, MD, chair, Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, and his recent study published in Biomarker Research.

“I think this paper tries to really optimize medical therapy for endometriosis. It's really an attempt at precision medicine for endometriosis,” Taylor said while on location at the 2026 American College of Obstetricians & Gynecologists (ACOG) Annual Clinical & Scientific Meeting. “We know the first-line therapy for endometriosis is an oral contraceptive pill, and it's the progestin in the oral contraceptive pill that prevents the growth of endometriosis and is often effective. But about a third of the time, it fails.”

Progestin resistance remains a major barrier to effective management, often prolonging symptom burden. “They are progestin resistant, and we've done a lot of research in the laboratory to show that this progestin resistance comes from either the progesterone receptor being expressed at a very low level. There's no progesterone receptor to respond to that progestin, or it's dysfunctional in some ways,” Taylor explained.

A prospective study published in Biomarker Research supports this concept, identifying distinct DNA methylation patterns associated with treatment response. Investigators reported 1439 differentially methylated genes between responders and nonresponders and developed a 3-gene signature—MMP20, NRXN1, and RNA5-8SN5—that predicted response with high accuracy (ROC AUC = 0.952; bootstrap AUC = 0.907; 95% CI: 0.80-0.957; permutation P < .001).

A potential move to first-line precision therapy for endometriosis

Taylor emphasized that identifying nonresponders before initiating therapy could significantly alter care pathways.

“But knowing that ahead of time, we could avoid treating a patient with an ineffective medication that just delays their definitively getting to, or delays their time to, the correct, proper treatment,” he said. “If we could do a test beforehand that gets them to the right drug the first time, we could really expedite them getting to that time when they're pain-free and getting their life back.”

Current practice often involves multiple cycles of ineffective hormonal therapy before escalation. “Unfortunately, we delay things because we try an oral contraceptive, and sometimes when that doesn't work, we just switch to another one,” Taylor said. “They may try a few different pills before they move on to another therapy.”

Efforts to identify biomarkers have shifted toward noninvasive approaches. “We've been able for some time to tell if the progesterone receptor is absent in a surgical specimen, but that's too late. They've already failed medical therapy [and are] going on to surgery,” Taylor noted. “We wanted to develop a blood test.”

He added that epigenetic profiling may provide that opportunity. “So again, we can get a simple blood test that will tell us whether a birth control pill is the right or wrong place to start for our patients,” Taylor said. “We can get them onto an effective therapy the first time, rather than a trial-and-error approach to treating their endometriosis. Personalized precision medicine for endometriosis.”

Reference

Cevik EC, Mamillapalli R, Sferruzza G, Mamillapalli P, Taylor HS. Epigenetic biomarkers of progestin-resistance in endometriosis. Biomark Res. 2026;14(1):32. doi:10.1186/s40364-026-00907-1