Estrogen receptor-α immunoreactivity predicts symptom severity and pain recurrence in deep endometriosis

Objective: To determine the relationship between steroid receptor expression and pain symptoms in endometriosis. Design: Cross-sectional Setting: University Hospital Patient(s): Women with endometriosis (N = 92). Intervention(s): Tissue samples were obtained from patients with surgically diagnosed endometriosis. Main Outcome Measure(s): A tissue microarray (TMA) was generated from patients with endometriosis. Data were collected on the presence and severity of dysmenorrhea, deep dyspareunia, dyschezia, and nonmenstrual pain by use of a numerical rating scale (NRS) at the time of surgery and after 1 year. The intensity of receptor expression was evaluated through immunohistochemistry and measured according to an immunoreactive score (IRS). Clinical variables were correlated to IRS by multivariate logistic regression analysis. Results: Estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), androgen receptor (AR), and aromatase expression differed among study participants. ER-alpha expression was reduced by progestin therapy, whereas of expressions of PR, AR, and aromatase were unchanged. Higher ER-alpha expression increased the likelihood of moderate to severe dysmenorrhea and deep dyspareunia in women not receiving hormonal treatment. In women receiving progestin therapy, persistently higher ER-alpha expression was correlated with greater likelihood of deep dyspareunia, severe dyschezia, and endometriosis-associated pain persistence at 1 year. Conclusion(s): ER-alpha, PR, AR, and aromatase were all expressed in deep endometriosis. ER-alpha levels best correlated with severity of symptoms, which suggests that ER is a key driver of deep endometriosis. Progestin treatment was associated with a reduction of ER-alpha expression; however, failure of ER suppression by progestins was also a predictor of pain severity and recurrence at 1 year. ((C) 2020 by American Society for Reproductive Medicine.)