Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, California.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, California; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
Am J Obstet Gynecol. 2020 Jul;223(1):103.e1-103.e13. doi: 10.1016/j.ajog.2019.12.273. Epub 2020 Jan 21.
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.
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.
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.
A 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/m, 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).
Our 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.
尽管子宫切除术仍然是复杂性非典型增生的标准治疗方法，但希望生育或手术条件差的患者可能会选择孕激素治疗。然而，与全身治疗相比，左炔诺孕酮释放宫内节育器在复杂性非典型增生治疗中的效果尚未得到很好的研究。
我们旨在研究局部孕激素治疗（左炔诺孕酮释放宫内节育器）与全身孕激素治疗在复杂性非典型增生妇女中的治疗反应差异。
这项单机构回顾性研究检查了 2003 年至 2018 年期间接受孕激素治疗的复杂性非典型增生妇女。通过随后的活检评估治疗反应。通过时间依赖性分析比较了左炔诺孕酮释放宫内节育器和全身治疗的完全缓解和进展为癌症的情况。使用倾向评分逆概率治疗加权模型创建了一个加权队列，该队列基于治疗类型有所不同，但在其他特征方面相似。进行了交互项分析，以检查身体形态对治疗反应的影响，并进行了中断时间序列分析，以评估治疗模式的变化是否与随时间推移的结果相关。
共有 245 名复杂性非典型增生患者接受了孕激素治疗（左炔诺孕酮释放宫内节育器 n=69 和全身治疗 n=176）。平均年龄和体重指数分别为 36.9 岁和 40.0 kg/m。在患者水平分析中，接受左炔诺孕酮释放宫内节育器的患者完全缓解率更高（78.7%比 46.7%；调整后的危险比，3.32；95%置信区间，2.39-4.62），进展为癌症的可能性更低（4.5%比 15.7%；调整后的危险比，0.28；95%置信区间，0.11-0.73）与接受全身治疗的患者相比。特别是，III 类肥胖的女性通过左炔诺孕酮释放宫内节育器治疗获得完全缓解的相对获益高于全身治疗：III 类肥胖，调整后的危险比 4.72，95%置信区间 2.83-7.89；I 类- II 类肥胖，调整后的危险比 1.83，95%置信区间 1.09-3.09；非肥胖，调整后的危险比 1.26，95%置信区间 0.40-3.95。在队列水平分析中，研究期间肥胖率增加（77.8%至 88.2%，相对增加 13.4%，P=0.033），左炔诺孕酮释放宫内节育器的使用率显著增加（6.3%至 82.7%，13.2 倍增加，P<0.001），同时完全缓解的女性比例也更高（32.9%至 81.4%，增加 2.5 倍，P=0.005）。
我们的研究表明，对于选择非手术治疗的复杂性非典型增生患者，局部孕激素治疗（左炔诺孕酮释放宫内节育器）可能比全身治疗更有效，尤其是对于病态肥胖的女性。研究期间治疗模式向增加左炔诺孕酮释放宫内节育器使用的转变也导致了完全缓解率的提高，尽管肥胖率有所增加。
