Women with endometriosis have a distinct pattern of androgens in their blood that sets them apart from women without the disease, based on a recent case-control study.

These findings could lead to a noninvasive test for a condition that often takes years to diagnose and typically requires surgical confirmation, according to senior author Douglas Gibson, PhD, of the University of Edinburgh, Edinburgh, Scotland.

The results pointed to “a distinct hormone profile associated with endometriosis that is not seen in healthy controls,” Gibson told Medscape Medical News. Differences in androgens, including a class of adrenal androgens called 11-oxygenated androgens, “are a key feature of this condition,” he said, and could shape new diagnostic and therapeutic strategies.

The study was published in the European Journal of Endocrinology.

A Long Road to Diagnosis

On average, it takes 4-11 years from symptom onset for a woman with endometriosis to be diagnosed, said Katie Cameron, MD, a reproductive endocrinologist at Johns Hopkins University School of Medicine, Baltimore, who was not involved in the study.

During that time, “their symptoms may worsen and their quality of life declines,” she told Medscape Medical News, noting that a definitive diagnosis usually requires laparoscopic surgery.

Research has long centered on estrogen as the main driver of endometriosis, and the role of androgens has been comparatively overlooked, according to the study.

The investigators set out to test whether a broader panel of these hormones, especially the adrenal 11-oxygenated androgens, could help identify women with the disease.

Study Design

The investigators measured a panel of classic and 11-oxygenated androgens in stored blood samples from 159 women with surgically confirmed endometriosis and 57 women without the disease.

Hormone levels were analyzed to determine whether they could separate patients from control individuals. A simplified model was then tested on a blinded portion of the same group rather than an independent population.

A Distinct Androgen Profile

Women with endometriosis had higher blood levels of several androgens, including testosterone, than women without the disease. The strongest marker was 11-ketotestosterone, an 11-oxygenated androgen that was elevated in patients regardless of disease stage.

Incorporating all androgen markers, the model discriminated between groups with an area under the curve of 0.99, while a simplified version still correctly identified more than 95% of patients in a blinded subset of the study’s own cohort.

The investigators concluded that these findings reframed endometriosis as an “androgen-dependent” disorder, while positioning 11-oxygenated androgens as candidate biomarkers.

In contrast with this conclusion, a previous study by Marija Gjorgoska and colleagues reached the opposite conclusion, linking higher androgen levels with lower endometriosis risk.

When asked about those findings, Gibson attributed the discrepancy to the different approaches; the Gjorgoska analysis predicted lifelong hormone exposure from genetics, he said, whereas his team directly measured hormone levels in women with established disease.

“More work is needed to fully understand how these studies show different findings,” Gibson said.

Blood Test Needs to Clear More Hurdles

A reliable, noninvasive test “would significantly change how well we are able to care for these patients,” Cameron said.

Still, she cautioned that the findings represent an early step, not a diagnostic test ready for real-world usage, noting that the data came from a “single study site in a largely European population.”

Before routine usage can be considered, the test needs to be validated in larger and more diverse patient populations that include different ages, ethnic backgrounds, menstrual cycle phases, and concurrent hormone treatments, Cameron said.

Such a test would also have to distinguish endometriosis from other conditions that cause chronic pelvic pain, rather than simply separating patients from healthy volunteers.

“Many prior studies of somewhat promising biomarkers for endometriosis have fallen short at this step,” Cameron noted.

Time to Revisit Danazol?

According to Gibson, the new findings also support reconsideration of danazol, an older androgen-based drug that remains an approved treatment for endometriosis but is now rarely used because of adverse effects such as unwanted hair growth, acne, weight gain, and voice changes.

Although danazol is itself an androgen, the investigators proposed that it may work not by adding androgens but by suppressing the body’s own production of adrenal androgens, including the 11-oxygenated androgens the study linked to the disease.

Testing new ways to deliver the drug, such as vaginally, might reduce those unwanted effects, Gibson suggested, although clinical trials would be needed before such approaches could reach clinical practice.

Cameron agreed that danazol’s problem is tolerability rather than efficacy, adding that drugs designed to block 11-oxygenated androgens might one day offer a more targeted option, although “that is a long way away.”

For now, both Gibson and Cameron saw the new data as a reason to keep investigating an understudied disease.

“All high-quality research for endometriosis is important research,” Cameron said. “This is such an understudied and underfunded area that has an enormous impact on quality of life.”

The study was funded by the Wellcome Trust and the Medical Research Council. Gibson and two coauthors are listed as co-inventors on a UK patent application related to the work. Cameron reported having no relevant financial relationships.