Dataset Information

Route-specific association of progestin therapy and concurrent metformin use in obese women with complex atypical hyperplasia.

ABSTRACT:

Introduction

Previous studies have suggested that metformin use may enhance the therapeutic effect of progestin therapy for endometrial hyperplasia or malignancy. However, it is not known how the impact of concurrent metformin may be altered by route of progestin therapy, either locally via an intrauterine device or systemically. This study examined the effectiveness of concurrent metformin use and progestin therapy for women with complex atypical hyperplasia stratified by progestin route (systemic vs local).

Methods

This single-institution retrospective study examined consecutive women with complex atypical hyperplasia who received progestin therapy from 2003 to 2018. Time-dependent analyses for complete response rate were performed comparing concurrent metformin users versus non-users in the oral progestin group and in the levonorgestrel-releasing intrauterine device group.

Results

Across the study cohort (n=245), there were 137 (55.9%) women who responded to progestin therapy. In the oral progestin group (n=176), the median age and body mass index were 36 years and 37.7 kg/m², respectively. 36 (20.5%) of women on oral progestins also took metformin. After controlling for diabetes status, women taking both oral progestins and metformin had a complete response rate similar to those not taking metformin (6 month cumulative rates, 23.1% vs 27.8%, adjusted hazard ratio (aHR) 0.71, 95% confidence interval (95% CI) 0.36 to 1.41). In the levonorgestrel-releasing intrauterine device group (n=69), the median age and body mass index were 35 years and 39.9 kg/m², respectively. There were 15 (21.7%) women who took metformin in addition to the levonorgestrel-releasing intrauterine device. After controlling for diabetes status, women who had the levonorgestrel-releasing intrauterine device and took metformin had a significantly higher complete response rate compared with those not taking metformin (6 month cumulative rates, 86.7% vs 58.9%, aHR 2.31, 95% CI 1.09 to 4.89).

Conclusion

In a predominantly obese population, concurrent metformin may possibly offer treatment benefit when used with the levonorgestrel-releasing intrauterine device.

SUBMITTER: Matsuo K

PROVIDER: S-EPMC7521080 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThough 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.ObjectiveWe 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.MethodsThis 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.ResultsA total of 245 women with complex atypical hyperplasia received progestin therapy (levonorgestrel-releasing intrauterine device n = 69 and systemic therapy n = 176). The mean age and body mass index were 36.9 years and 40.0 kg/m2, respectively. In the patient-level analysis, women who received the levonorgestrel-releasing intrauterine device had higher rates of complete response (78.7% vs 46.7%; adjusted hazard ratio, 3.32; 95% confidence interval, 2.39-4.62) and a lower likelihood of progression to cancer (4.5% vs 15.7%; adjusted hazard ratio, 0.28; 95% confidence interval, 0.11-0.73) compared to those who received systemic therapy. In particular, women with class III obesity derived a higher relative benefit from levonorgestrel-releasing intrauterine device therapy in achieving complete response compared to systemic therapy: class III obesity, adjusted hazard ratio 4.72, 95% confidence interval 2.83-7.89; class I-II obesity, adjusted hazard ratio 1.83, 95% confidence interval 1.09-3.09; and nonobese, adjusted hazard ratio 1.26, 95% confidence interval 0.40-3.95. In the cohort-level analysis, the obesity rate increased during the study period (77.8% to 88.2%, 13.4% relative increase, P = .033) and levonorgestrel-releasing intrauterine device use significantly increased after 2007 (6.3% to 82.7%, 13.2-fold increase, P < .001), both concomitant with a higher proportion of women achieving complete response (32.9% to 81.4%, 2.5-fold increase, P = .005).ConclusionOur study suggests that local therapy with the levonorgestrel-releasing intrauterine device may be more effective than systemic therapy for women with complex atypical hyperplasia who opt for nonsurgical treatment, particularly in morbidly obese women. Shifts in treatment paradigm during the study period toward increased levonorgestrel-releasing intrauterine device use also led to improved complete response rates despite increasing rates of obesity.

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