Progesterone receptor status as a predictor of response to progestins in endometriosis

Abstract

Progestin-based therapy is first-line in the management of endometriosis-associated pain. However, response to progestins is highly variable and currently unpredictable. A test that predicts response to progestin-based therapy would allow for a personalized approach to treating endometriosis. We hypothesize that progesterone receptor (PR) expression levels in endometriotic lesions regulates response to progestin-based therapy. Retrospective cohort study at a single academic center. Paraffin embedded endometriotic lesions were obtained from 52 subjects undergoing surgical evaluation. Twenty-one subjects had more than one lesion obtained at the time of surgery. Immunohistochemistry (IHC) was performed using a rabbit polyclonal IgG for detection of PR-A/B. The Histo (H)-score was used for quantifying PR status. Two investigators blinded to patient response independently scored IHC specimens. When multiple lesions were present, the highest H-score was used. Response to progestin-based therapies (including OCs) was determined from review of the electronic medical record. Student’s t-test, Receiver Operator Characteristics (ROC) curve analysis, and Chi-square test were used for statistical analysis. H-score was significantly higher in responders compared to non-responders (p<0.0001). Based on ROC curve analysis subjects were categorized into three groups: high (H-score > 80, n=7), medium (H-score 5-80, n=28) and low (H-score < 5, n=17) PR status. The threshold of PR >80 was associated with a 100% positive predictive value. The threshold of PR <5 was associated with a 94% negative predictive value. Response rates were: High PR= 100%, Medium PR= 21%, and Low PR= 6% (p<0.0001). Progesterone receptor status is strongly associated with response to progestin-based therapy. Receptor status in endometriosis could be used in a manner analogous to the use of ER/PR status in breast cancer for tailoring hormonal-based regimens. Such an individualized approach to endometriosis management would negate trialing progestin-based therapy to determine resistance. PR status may allow for a novel, targeted, precision approach to treating endometriosis.