Progesterone Receptor Status Predicts Response to Progestin Therapy in Endometriosis
Open accessAbstract
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.
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PRs may be present but biologically inactive, or absent, leading to progesterone resistance and no decrease in lesion size with OCP or progestogen therapy.
“PRs may be present, but biologically inactive. On the other hand, PRs may well be absent, leading to progesterone resistance and no decrease in lesion size with OCP or progestogen therapy [58].”
From Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review (2021) · cites this paper as [58]
The risk of venous or arterial thrombosis with OCPs is not negligible.
“the risk of venous or arterial thrombosis is not negligible [54,55,56,57,58,59,60,61,62,63,64,65,66,67].”
From Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review (2021) · cites this paper as [58]
Low PR levels were observed in subjects who failed to respond to progestin-based therapies.
“in this study, low PR levels were observed in subjects who failed to respond.”
From Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review (2021) · cites this paper as [58]
Endometriotic stromal cells are poorly differentiated with deficient PRs and fail to send physiological paracrine signals to adjacent epithelial cells, explaining the absence of response in more than 30% of women treated with progestins.
“endometriotic stromal cells are poorly differentiated with deficient PRs and fail to send physiological paracrine signals to adjacent epithelial cells, explaining the absence of response in more than 30% of women treated with progestins [58,84].”
From Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review (2021) · cites this paper as [58]
PR status is strongly associated with a response to progestin-based therapies (including combined OCPs).
“PR status is strongly associated with a response to progestin-based therapies (including combined OCPs).”
From Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review (2021) · cites this paper as [58]
Progesterone resistance is an explanation for why 33% of patients do not respond to OCPs and progestins, with this percentage climbing even higher in women with deep nodular endometriosis.
“In the present paper, we thoroughly scrutinized the concept of progesterone resistance as an explanation for why 33% of patients do not respond to OCPs and progestins, with this percentage climbing even higher in women with deep nodular endometriosis [46,47,56,58].”
From Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review (2021) · cites this paper as [58]
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- Authors
- Flores, V. A., Vanhie, A., Dang, T., & Taylor, H. S.
- Affiliations
- Yale University (US)
- Corresponding author
- Flores, Valerie A
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2018-10-23
- Volume
- 103
- Issue
- 12
- Pages
- 4561-4568
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC6226602
- OpenAlex
- W2898392298
- Cited by
- 118
- References
- 34
- Citations by year
- 2026: 21 · 2025: 7 · 2024: 25 · 2023: 15 · 2022: 17 · 2021: 15 · 2020: 11 · 2019: 7
- FWCI
- 8.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion)
- Funders
- National Institutes of Health (HD076422)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
- Keywords
- endometriosis, progesterone receptor, progestin therapy, treatment response prediction, predictive biomarkers, endometriotic lesions, H-score, precision medicine, hormone therapy
- MeSH terms
- Adult, Drug Resistance, Endometriosis, Endometrium, Female, Humans, Immunohistochemistry, Pain, Predictive Value of Tests, Progestins, Prognosis, Receptors, Progesterone, Retrospective Studies, Treatment Outcome, Patient Selection, Young Adult
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