Epigenetic Markers May Predict Progesterone Resistance in Endometriosis

Investigators at Yale School of Medicine reported that blood-based DNA methylation patterns might help distinguish subgroups of endometriosis patients who are unlikely to benefit from progesterone-based birth control, with the signal potentially being predictive of progesterone resistance.

The work is presented as an effort to move beyond trial-and-error use of progesterone-based birth control by using epigenetic markers measured in circulating white blood cells. The article focuses on cohort characteristics, the methylation differences observed, and possible downstream uses if the findings are confirmed.

Methylation profiling was performed on white blood cells collected from 31 women with endometriosis, including 21 characterized as having progesterone-resistant disease. Investigators reportedly compared progesterone “responders” with “nonresponders” and identified more than 1,400 genes that were differentially methylated between the two groups. The report also highlights three genes (MMP20, NRXN1, and RNA5-8SN5) that were described as possible predictors of progesterone resistance in the studied cohort.

From the broader set of differentially methylated loci, the article emphasizes MMP20, NRXN1, and RNA5-8SN5 as leading candidates. As described in the report, higher methylation rates in these genes were associated with progesterone-resistant endometriosis and were characterized as possible predictors of resistance in the studied group. The story adds that these genes were not thought to be directly connected to progesterone signaling or receptors, while relaying the investigators’ view that they could relate to inflammatory biology.

The investigators suggest that, if confirmed in further studies, a blood-based test could be used to identify patients who are resistant to progesterone-based birth control and shorten time spent on ineffective trials.