Estrogen receptor-α immunoreactivity predicts symptom severity and pain recurrence in deep endometriosis
Nicola Pluchino1, Ramanaiah Mamillapalli2, Jean-Marie Wenger3
1Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA; Division of Obstetrics and Gynecology, University Hospital of Geneva, Switzerland.
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-α (ER-α), progesterone receptor (PR), androgen receptor (AR), and aromatase expression differed among study participants. ER-α expression was reduced by progestin therapy, whereas of expressions of PR, AR, and aromatase were unchanged. Higher ER-α 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-α expression was correlated with greater likelihood of deep dyspareunia, severe dyschezia, and endometriosis-associated pain persistence at 1 year.
Conclusion(S):
ER-α, PR, AR, and aromatase were all expressed in deep endometriosis. ER-α 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-α expression; however, failure of ER suppression by progestins was also a predictor of pain severity and recurrence at 1 year.
