Nicola Pluchino1, Ramanaiah Mamillapalli2, Jean-Marie Wenger3, Lauriane Ramyead3, Panagiotis Drakopoulos4, Jean-Christophe Tille5, Hugh S Taylor6. 1. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA; Division of Obstetrics and Gynecology, University Hospital of Geneva, Switzerland. 2. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA. Electronic address: ramana.mamillapalli@yale.edu. 3. Division of Obstetrics and Gynecology, University Hospital of Geneva, Switzerland. 4. Center for Reproductive Medicine, Universitair Ziekenhuis Brussel, Brussels, Belgium. 5. Division of Pathology, University Hospital of Geneva, Switzerland. 6. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA.
Abstract
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.
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.
Authors: Antonio Mercorio; Pierluigi Giampaolino; Andrea Romano; Patrick Dällenbach; Nicola Pluchino Journal: Front Endocrinol (Lausanne) Date: 2022-09-20 Impact factor: 6.055