Progestin therapy for obese women with complex atypical hyperplasia: levonorgestrel-releasing intrauterine device vs systemic therapy

Abstract

BACKGROUND: Though hysterectomy remains the standard treatment for complex atypical hyperplasia, patients who desire fertility or who are poor surgical candidates may opt for progestin therapy. However, the effectiveness of the levonorgestrel-releasing intrauterine device compared to systemic therapy in the treatment of complex atypical hyperplasia has not been well studied. OBJECTIVE: We sought to examine differences in treatment response between local progestin therapy with the levonorgestrel-releasing intrauterine device and systemic progestin therapy in women with complex atypical hyperplasia. METHODS: This single-institution retrospective study examined women with complex atypical hyperplasia who received progestin therapy between 2003 and 2018. Treatment response was assessed by histopathology on subsequent biopsies. Time-dependent analyses of complete response and progression to cancer were performed comparing the levonorgestrel-releasing intrauterine device and systemic therapy. A propensity score inverse probability of treatment weighting model was used to create a weighted cohort that differed based on treatment type but was similar with respect to other characteristics. An interaction-term analysis was performed to examine the impact of body habitus on treatment response, and an interrupted time-series analysis was employed to assess if changes in treatment patterns correlated with outcomes over time. RESULTS: A total of 245 women with complex atypical hyperplasia received progestin therapy (levonorgestrel-releasing intrauterine device n ¼ 69 and systemic therapy n ¼ 176). The mean age and body mass index were 36.9 years and 40.0 kg/m 2 , respectively. In the patient-level analysis, women who received the levonorgestrel-releasing intrauterine

The anticancer effects of Levonorgestrel on human esophageal squamous carcinoma cells

“…At present, levonorgestrel intrauterine system (LNG-IUS) a T-shaped intrauterine devices with a steroid reservoir containing levonorgestrel. The LNG, especially LNG-IUS, often used for contraception, control of menstrual disorders, treatment of endometriosis, and so on [11][12][13][14][20][21]. Recently, more and more studies suggested that LNG or LNG-IUS play important roles in cancer, but the effect of LNG or LNG-IUS on cancers still has a dispute.…”

“…Recently, more and more studies suggested that LNG or LNG-IUS play important roles in cancer, but the effect of LNG or LNG-IUS on cancers still has a dispute. Many researchers declared that LNG-IUS or LNG-IUS have a protective effect against endometrial malignant transformation [8,[11][12][13][14], but was associated with a higher than expected incidence of breast cancer [8][9]23]; and they also found LNG-IUS was associated with a lower incidence of endometrial, ovarian, pancreatic, and lung cancers [8]. While some researchers reported that LNG or LNG-IUS associated with a decreased risk of ovarian and endometrial cancer, without increased risk of breast cancer [7, 10, and 15].…”

“…Former studies showed that LNG or LNG-IUS was associated with endometrial, breast, ovarian, pancreatic, and lung cancers [7][8][9]. And it is amazing that many studies reported that LNG or LNG-IUS have different role in cancer occurrence, development and therapy, especially in breast and endometrial cancers [8][9][10][11][12][13][14][15][16][17]. However, little was known about the role of LNG on ESCC.…”

For obese postmenopausal women, what options may decrease endometrial cancer risk?

“…In a Cochrane systematic review and meta-analysis, the 52-mg LNG-IUD was reported to be somewhat more effective in resolving endometrial hyperplasia than cyclic oral progestins (89% vs 72%, respectively). 15 Other studies have also reported that the 52 mg LNG-IUD was more effective than oral progestin therapy for women with complex atypical endometrial hyperplasia. 16 There are no large randomized clinical trials of progestin therapy on prevention for future development of endometrial cancer in obese postmenopausal women who have a normal endometrial histology.…”

Fibroblast Growth Factor Receptor 2 Isoforms Detected via Novel RNA ISH as Predictive Biomarkers for Progestin Therapy in Atypical Hyperplasia and Low-Grade Endometrial Cancer

“…Progestin regimens frequently used include oral medroxyprogesterone acetate (MPA), megestrol acetate (MA) or a levonorgestrel releasing intrauterine device (LNG-IUD)/Mirena ® [ 6 ]. LNG-IUD has been used increasingly and is considered preferable as compared to oral progestin due to better tolerance (fewer side effects) and increased compliance [ 7 , 8 ]. The reported response rates for LNG-IUD therapy are ~80% for AH and ~60% for EEC [ 8 , 9 ], however reported relapse rates are high (22–41%) [ 10 , 11 , 12 ].…”