Progesterone Receptor Status Predicts Response to Progestin Therapy in Endometriosis

Abstract

Context Progestin-based therapy is the first-line treatment for managing endometriosis-associated pain. However, response to progestins is currently variable and unpredictable. Predictive markers for response to progestin-based therapy would allow for a personalized approach to endometriosis treatment. Objective We hypothesize that progesterone receptor (PR) levels in endometriotic lesions determine response to progestin-based therapy. Design Retrospective cohort study. Setting Academic center. Patients Fifty-two subjects with histologically confirmed endometriosis and a previous documented response to hormonal therapy were included. Interventions Immunohistochemistry was performed on sections of endometriotic lesions using a rabbit polyclonal IgG for detection of PR-A/B. Main Outcome Measures The Histo (H)-score was used for quantifying PR status. Response to progestin-based therapies was determined from review of the electronic medical record. Results H-score was higher in responders compared with nonresponders. Subjects were categorized into three groups: high (H-score > 80, n = 7), medium (H-score 6 to 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. Conclusion PR status is strongly associated with response to progestin-based therapy. Receptor status in endometriosis could be used to tailor hormonal-based regimens after surgery, and negate trialing progestin-based therapy to determine resistance. Ascertainment of PR status may allow for a novel, targeted, precision-based approach to treating endometriosis.

Progesterone and Estrogen Signaling in the Endometrium: What Goes Wrong in Endometriosis?

“…One potential molecular cause of P4 resistance is a loss or alteration of PGR expression, which has been documented in endometriotic lesions [121,122,123,124,125,126,127,128,129,130] and eutopic endometrium from women with endometriosis [124,130,145,146,147,148]. Further study has confirmed direct correlations between PGR loss with loss of P4-responsiveness in both lesions [149] and cells from the endometrium of women with endometriosis [150]. However, the contribution of PGR loss to the P4 resistance observed in endometriosis is controversial due to a few studies finding no significant difference in PGR levels in eutopic endometrium from women with endometriosis [123,151] or lesions [152].…”

Expression of Stromal Progesterone Receptor and Differential Methylation Patterns in the Endometrium May Correlate with Response to Progesterone Therapy in Endometrial Complex Atypical Hyperplasia

“…For example, ER-positive breast cancers, as determined by ER expression in the tumor, are treated with tamoxifen, a selective ER modulator that blocks the effects of estrogen-induced proliferation [ 41 ]. Additionally, PR status is being explored as a potential biomarker of response to progestin-based therapy in endometriosis [ 42 ]. However, the significance of hormone receptor expression for progestin therapy in patients diagnosed with endometrial hyperplasia or adenocarcinoma is inconclusive.…”

Aromatase CYP19A1, progesterone receptor PGR and estrogen receptor ESR1 gene expression in biopsy specimens of endometrioid heterotopia and endometrial tissue by reverse transcription PCR

“…рецепторы эстрогенов и прогестерона играют определяющую роль в действии стероидных гормонов на клеткимишени. резистентность очагов эндометриоза к действию гормональных препаратов может быть объяснена сниженной или измененной чувствительностью рецепторов стероидных гормонов в эктопических очагах [16][17][18]. считается, что при эндометриозе высокие уровни эстрадиола и эстрогеновых рецепторов стимулируют пролиферацию эндометрия, изменяют нормальный характер генной экспрессии и снижают рецептивность эндометрия [17,19].…”