Steroid Hormones and Genetic Drivers
The formation of endometrial polyps is rooted in the dysregulation of local estrogen and progesterone receptors. In the proliferative phase, polyps typically demonstrate elevated Bcl-2—a key anti-apoptotic protein—alongside decreased progesterone receptor (PR) sensitivity, preventing the terminal differentiation required for normal endometrial shedding.
Genetic studies have identified recurrent KRAS and NRAS mutations in nearly half of all polyp cases, signaling a monoclonal origin for many of these lesions. Furthermore, the upregulation of PROKR1 and specific genes within the Wnt signaling pathway suggests that polyps are not merely passive responders to systemic hormones but are active, self-regulating proliferative entities.
Contesting Post-Operative Prevention
Standard post-polypectomy care has long relied on the assumption that systemic hormonal therapy mitigates the risk of recurrence. However, recent evidence challenges the efficacy of short-term systemic hormonal regimens (such as COCs) in preventing regrowth, as they may not sufficiently alter the local endometrial milieu compared to the localized effect of an LNG-IUS.
The high reported prevalence of chronic endometritis (up to 92.6% in some cohorts) suggests that inflammation may be an underestimated driver of polyps. Future clinical paradigms must likely shift to integrate anti-inflammatory measures alongside traditional hormonal management to address the root cause of high recurrence rates.