Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, South Korea.
Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul, South Korea.
PLoS One. 2020 Oct 21;15(10):e0240870. doi: 10.1371/journal.pone.0240870. eCollection 2020.
The objective of this study was to evaluate predicting factors for supraphysiologic serum estradiol elevation during controlled ovarian stimulation (COS) with administration of letrozole and gonadotropins in patients with estrogen-dependent cancer. Use of aromatase inhibitors is recommended to prevent the potential effects of elevated serum estradiol levels and recurrence of tumor in patients with estrogen-dependent cancers during COS. Although previous studies reported that letrozole have shown an effective lowering of peak estrogen levels, a part of patients shows supraphysiologic levels of estrogen associated with ovarian stimulation despite the administration of letrozole. From January 2009 to December 2019, patients with estrogen-dependent cancer who underwent COS with antagonist protocol using a letrozole (5 mg/ day) to keep estrogen levels low were included in this study. Early monitoring serum estradiol was measured in all patients on the 4-6th day of stimulation. Subjects were classified into two groups according to the serum estradiol level on hCG triggering day, physiologic estradiol group (≤400 pg/mL) and supraphysiologic estradiol group (>400 pg/mL). A total of 96 COS cycles were retrospectively analyzed. Supraphysiologic level of serum estradiol was found in 21.9% of the patients. Mean age, AMH, duration of stimulation, total dose of gonadotropins administered were not different between the two groups. However, early monitoring serum estradiol level was significantly higher in the supraphysiologic estradiol group (67.1±47.9 vs. 115.6±78.1, p = 0.001) and was associated with the occurrence of supraphysiologic elevation of serum estradiol on hCG triggering day. Patients with early monitoring serum estradiol ≥84.5 pg/mL had an odds ratio of 5.376 [95% CI, 1.613-17.913] for supraphysiologic elevation of serum estradiol compared to those with early monitoring serum estradiol below 84.5 pg/mL. In conclusion, early monitoring serum estradiol is an independent predicting factor for supraphysiologic level of serum estradiol on hCG triggering day in the COS cycles using letrozole and gonadotropins.
本研究旨在评估在接受芳香化酶抑制剂（letrozole）和促性腺激素治疗的雌激素依赖性癌症患者中，控制性卵巢刺激（COS）期间血清雌二醇升高的预测因素。在接受芳香化酶抑制剂治疗的雌激素依赖性癌症患者中，推荐使用促性腺激素抑制素来预防潜在的血清雌二醇水平升高和肿瘤复发的影响。尽管之前的研究表明，letrozole 可以有效降低峰值雌二醇水平，但部分患者在接受 letrozole 治疗的情况下仍会出现与卵巢刺激相关的超生理水平雌二醇。本研究纳入了 2009 年 1 月至 2019 年 12 月期间接受拮抗剂方案（使用 letrozole 5mg/天以保持低雌激素水平）的雌激素依赖性癌症患者。所有患者在刺激的第 4-6 天进行早期监测血清雌二醇。根据 hCG 触发日的血清雌二醇水平，将受试者分为两组，即生理雌二醇组（≤400pg/mL）和超生理雌二醇组（>400pg/mL）。共回顾性分析了 96 个 COS 周期。发现 21.9%的患者存在血清雌二醇超生理水平。两组患者的平均年龄、AMH、刺激持续时间、使用的促性腺激素总剂量无差异。然而，超生理雌二醇组的早期监测血清雌二醇水平明显更高（67.1±47.9 vs. 115.6±78.1，p=0.001），且与 hCG 触发日血清雌二醇超生理升高有关。早期监测血清雌二醇≥84.5pg/mL 的患者发生血清雌二醇超生理升高的优势比为 5.376[95%CI，1.613-17.913]，而早期监测血清雌二醇<84.5pg/mL 的患者发生血清雌二醇超生理升高的优势比为 5.376[95%CI，1.613-17.913]。综上所述，在接受 letrozole 和促性腺激素治疗的 COS 周期中，早期监测血清雌二醇是 hCG 触发日血清雌二醇超生理水平的独立预测因素。
