Long-term follow-up of the effect of oral dienogest and dienogest/ethinylestradiol treatment on cell-free DNA levels in patients with deep endometriosis.

Background: Endometriosis is currently considered a systemic inflammatory disease and different non-invasive inflammatory markers, such as cell-free DNA (cfDNA), have recently been evaluated. Hormonal treatments are frequently prescribed as first-line treatments to improve symptoms, reduce lesions and improve the quality of life of patients with endometriosis. The most frequently used hormonal treatments are estroprogestins and progestins due to their effectiveness and well-tolerated clinical profile. However, the impact these hormonal treatments may have on these markers has yet to be determined. The aim of this study was to assess whether cfDNA levels are modified under the two main first-line hormonal treatments in patients with deep endometriosis (DE).

Methods: Ninety patients diagnosed with DE were analyzed in this prospective, observational study. Forty-five received daily oral treatment with dienogest 2 mg, and 45 with 2 mg dienogest/30 μg ethinylestradiol. Plasma cfDNA levels were evaluated by fluorescent assay prior to initiation of treatment and at 6 and 12 months of treatment.

Results: An increase in cfDNA levels was observed during the follow-up at 6 and 12 months. However, these higher levels were only statistically significant at 12 months of treatment. The increase of cfDNA levels was similar with both treatments.

Conclusion: Higher cfDNA levels were observed in DE patients at 12 months of oral hormonal treatment showing similar results with dienogest or dienogest/ethinylestradiol. This increase could be explained by apoptosis of the endometriosis foci due to the treatment.