Intrauterine Progestin Therapy as a New Approach to Premalignant Endometrial Polyps: A Prospective Observational Study

Abstract

Background/Aim: Endometrial hyperplastic polyps (EHP) may progress to endometrial carcinoma (EC) if left untreated. We aimed to prospectively investigate the efficacy of the low-dose levonorgestrel intrauterine system (LNG-IUS) as therapy for EHP with malignant potential. Patients and Methods: In total, 37 women with EHP underwent therapy with LNG-IUS containing 13.5 mg levonorgestrel for six months or 4-10 weeks depending on whether the EHP was characterized (by D-score analysis) as low-to medium-risk (n=33) or high-risk (n=4) of coexistent or future EC. Therapy response was defined as complete clearance of hyperplastic glands in post-therapy endometrial biopsy. Results: All women with low-to medium-risk EHP obtained therapy response, whereas only 1 out of 4 with highrisk EHP responded to therapy. None of the women were diagnosed with EC during the study and no serious adverse events occurred. Conclusion: Low-dose LNG-IUS represents a promising therapy for selected women with EHP. Endometrial polyps (EP) frequently occur in pre, peri and postmenopausal women and may be diagnosed in 20-30% of patients with abnormal uterine bleeding (1). Although most EP are benign, a systematic review has reported premalignant (hyperplastic) and malignant changes to be present in 0.2-23.8% and 0-12.9% of the cases, respectively (2).

Data on RT-qPCR assay of nuclear progesterone receptors (nPR), membrane progesterone receptors (mPR) and progesterone receptor membrane components (PGRMC) from human uterine endometrial tissue and cancer cells of the Uterine Cervix

“…All endometrial tissue specimens (baseline and post therapy biopsies) were conserved in RNAlater stabilization solution (Ambion RNAlater™, ThermoFisher Scientific, Whatham, MA, USA, code AM7021) and immediately frozen and kept at-18 °C until further analysis. Details of the clinical investigations are reported earlier [ 3 , 4 ] .…”

“…The current data were a second gain of two clinical investigations [ 3 , 4 ] . The investigations were approved by the Regional Committees for Medical and Health Research Ethics (2015/381) and by the Norwegian Medicines Agency (EUDRACT nr 2015–000612- 17).…”

“…We conducted new investigations of endometrial hyperplasia, now with 6 months low dose levonorgestrel IUS treatment. Again, the growth disturbances were reversed with normalization of the endometrium [ 3 , 4 ]. In the context of these studies, RT-qPCR analyses of the endometrium were performed before and after treatment, to determine expression of nuclear progesterone receptors (nPRA+ B and nPRB), membrane progesterone receptors (mPR, α-, β- and γ-subtypes) and progesterone receptor membrane components (PGRMC1and PGRMC2).…”