The average time to clinical diagnosis of endometriosis for women is 9 years, leaving them to suffer for nearly a decade before they are eligible for treatment.

Definitive diagnosis of the disease is difficult, and until recently, has relied on laparoscopic surgery. Now, with novel clinical recommendations, advanced diagnostic tools, and research into inflammation and immune responses, there is the promise that women with endometriosis will find relief sooner, without surgery, according to experts.

New Recommendations

Endometriosis is a chronic inflammatory disorder that can develop when endometrial cells escape the uterus and cause lesions to form outside of it, leading to chronic pelvic inflammation. This can result in pain, infertility, and decreased quality of life. The World Health Organization estimates that worldwide 190 million women of reproductive age — nearly 11% of all women — are affected by endometriosis.

Earlier this year, the American College of Obstetricians & Gynecologists (ACOG) released updated clinical guidance, including comprehensive recommendations for the diagnosis of endometriosis. The first-line recommendation replaces laparoscopy for obtaining a clinical diagnosis with “a symptom-based assessment, physical examination, or both.” This recommendation is listed as strongly recommended but with low-quality evidence.

“In the past, the gold standard was surgery,” Hugh Taylor, MD, told Medscape Medical News. Taylor is chair in the Department of Obstetrics, Gynecology, and Reproductive Sciences at Yale School of Medicine in New Haven, Connecticut. “When surgery confirms it over 90% of the time, there is no reason to wait until somebody is in enough pain that they want the surgery to start treatment.”

To that end, Steven J. Fleischman, MD, MBA, ACOG president, said in a statement that the goal of the new guidance is to speed diagnosis so that endometriosis sufferers can more quickly access treatment and other resources, such as patient education and support groups. “Endometriosis pain can be incredibly burdensome for women and girls, and we know that on top of that pain, many patients experience understandable frustration due to delays in care and limited management options offered to them,” he said.

In addition, the clinical practice guideline also highlights the need for further research into the pathogenesis and pathophysiology of endometriosis to facilitate the development and validation of noninvasive methods that can accurately diagnose endometriosis without the need for surgery, according to Catherine Witkop, MD, PhD, MPH, Uniformed Services University of the Health Sciences, Bethesda, Maryland, the author of the guidance.

Emerging Diagnostics

Another recommendation from ACOG is to avoid “the use of blood, urine, endometrial, or other biomarkers to diagnose endometriosis,” saying that they have low-quality evidence. There are some advances on the biomarker front, however. In France, for example, a microRNA saliva test for endometriosis has shown high levels of specificity and sensitivity.

At the Paris Women’s Health Conference held in April last year, Medscape Medical News reported the salivary microRNA signature achieved an overall accuracy of 96.6%, with a sensitivity of 97.3%, a specificity of 94.1%, a positive predictive value of 98.2%, and a negative predictive value of 91.3%.

The presented study showed that when an endometriosis diagnosis was confirmed surgically, “the rates of misclassification, underestimation, and overestimation were 4.6%, 2.4%, and 2.2%, respectively, for the salivary miRNA [microRNA] signature compared with 27.2%, 15.1%, and 12.2%, respectively, for imaging using transvaginal ultrasound, MRI, or both,” Medscape Medical News reported.

The saliva study’s lead author, Sofiane Bendifallah, MD, PhD, American Hospital of Paris, Paris, France, told Medscape Medical News that salivary microRNA could help with earlier identification of endometriosis. “In essence, the goal is better timing and better targeting,” he said.

To assess the clinical utility of the saliva test, the Endobest trial, funded by the French national health authority, is underway across more than 100 designated endometriosis centers in France. The study’s two endpoints are whether the test will reduce the number of planned and actual laparoscopies and whether it leads to a change in case management in women without a prior indication for laparoscopy.

MicroRNA Test in Adolescents

Taylor is a coauthor of a study published earlier this year examining microRNA in the serum of adolescents. The work builds on Taylor and his colleagues’ previous research, which identified biomarkers for endometriosis in adult women. The more recent study, a prospective clinical trial, enrolled participants aged 13-26 years with pelvic pain, who were undergoing gynecologic surgery between 2019 and 2024. Total RNA was extracted from the study group’s respective serum samples and evaluated for microRNA.

The investigators found that levels of four microRNA’s indicative of endometriosis were significantly elevated in participants, leading the investigators to conclude, “Our findings present a unique signature of microRNA found in the serum of adolescents with endometriosis. This finding may be useful as a noninvasive biomarker to diagnose early disease in adolescents,” he said.

Although microRNA technology is not yet widely available on the market, Taylor said that the study “moved the needle” in the field by identifying markers in a younger population in whom “the disease first manifests.”

Treating Inflammation

Endometriosis and autoimmune diseases have inflammation in common, according to a study that found autoimmune diseases occur in women with endometriosis at rates up to 80% higher than in those without it. Another group of researchers suggest that endometriosis itself is an autoimmune disease.

Inflammation, along with hormones, is what drive endometriosis, according to Taylor. Rising estrogen levels occurring each menstrual cycle promote the growth of the lesions, yet progesterone does not seem to help shrink them. The lesions then become places of chronic, low-grade inflammation, irritating the nerves, creating pain, and allowing inflammatory mediators to travel through the whole body, the bowels and bladder, in particular, according to Taylor.

Now, research is focused on altering the inflammatory response and the immune response. “That’s where the future lies,” Taylor said. “We’ll be treating the inflammation, which propagates the disease and causes the pain and causes the damage and the scarring.”

In this vein, there’s been much research into controlling proinflammatory macrophages as a treatment for endometriosis. It’s been a generation since a review of the literature established that endometriotic lesions are exacerbated when macrophages are recruited to the inflammatory environment of the lesions. The macrophages then secrete cytokines, growth factors, and other proinflammatory mediators. The result is angiogenesis, tissue remodeling, and resistance to immune clearance, creating a chronic disease.

Taylor said there is a test drug that does stop the macrophages, but “it’s still just made it through animal trials, it hasn’t started human trials yet,” he said. “We’re still a way off in getting these immune therapies into women.”

The Immune Paradox

“There is an endometriosis immune paradox,” said Taylor. Why the immune system doesn’t seem to heal the lesions is still unknown. “Endometriosis knows how to protect itself from the immune system,” he said.

Researchers at the University of Cincinnati, led by Katherine Burns, PhD, published work in 2018 showing in a mouse model that it is an immune response that actually causes the endometrial lesions to begin with. Burns is an associate professor in the Division of Environmental & Molecular Toxicology, Environmental & Public Health Sciences in the College of Medicine at the University of Cincinnati in Cincinnati.

The lesions are driven by estrogen after the initial immune response. In a follow-up study, Burns and colleagues used samples of menstrual effluent to study neutrophils (the white blood cells that initiate an immune response) in women with and without endometriosis.

Burns told Medscape Medical News that the findings, published in 2025, “indicate that neutrophils are signaling incorrectly in endometriosis and may not be clearing debris as they should be doing.” Morphological changes in white blood cells in menstrual effluent may be a noninvasive endometriosis diagnostic tool for women, she said.

The historic issue in endometriosis research, according to Burns, is lack of funding across all women’s health specialties. In the meantime, she said researchers are teaming up to leverage what resources there are to “the best of our ability.”

In the meantime, she suggests that women with endometriosis consume a diet that helps keep stools soft to help with the “frozen pelvis” that presents due to endometrial lesions and fibrosis. She also recommends sufferers try pelvic physical therapy with a certified pelvic therapist. Lastly, Burns recommends to those with the disease to “Give yourself grace.”

Burns reported having a patent pending for a noninvasive diagnostic, being on the Scientific Advisory Board for Endometriosis Foundation, and being an associate editor for Biology of Reproduction. Fleischman, Taylor, Witkop, and Bendifallah reported no relevant conflicts of interest.