Estradiol therapy and breast cancer risk in perimenopausal and postmenopausal women: a systematic review and meta-analysis

Abstract

Objective: To investigate the association between estradiol therapy and incidence of breast cancer, taking into consideration of different types of combined progestogen, the duration of exposure and the type of regimen.

Method: A systematic review and meta-analysis.

Result: A total of 14 studies were included in our study. In estradiol-only therapy analysis, meta-analysis resulted a pooled OR =0.90, 95% CI (0.40, 2.02) from the RCTs and pooled OR = 1.11, 95% CI (0.98, 1.27) from observational studies. However, in the analysis of estradiol-progestogen therapy, the risk of breast cancer varies according to the type of progestogen and the duration with more than five years (OR = 2.43, 95% CI (1.79, 3.29)) presented a higher risk than using less than five years (OR = 1.49, 95% CI (1.03, 2.15)).

Conclusions: Estradiol-only therapy carries no risk for breast cancer, while the breast cancer risk varies according to the type of progestogen. Estradiol therapy combined with medroxyprogesterone, norethisterone and levonorgestrel related to an increased risk of breast cancer, estradiol therapy combined with dydrogesterone and progesterone carries no risk. The breast cancer risk rise progressively by prolonged use, furthermore, comparing to sequential therapy, continuous therapy carries a higher risk.

Chinese abstract

目的: 研究雌二醇治疗与乳腺癌发病率之间的关系, 考虑不同类型的联合孕激素, 暴露持续时间和方案类型。

方法: 系统综述和Meta分析。

结果: 共有14项研究纳入我们的研究。对单纯雌二醇治疗进行分析, Meta分析产生了来自RCT的合并OR =0.90,95％CI (0.40,2.02) 和来自观察性研究的合并OR =1.11,95％CI (0.98,1.27) 。 然而, 雌孕激素序贯治疗分析显示, 乳腺癌的风险根据孕激素的类型而不同, 并且与治疗时间在五年以下的患者相比治疗的持续时间超过五年 (OR =2.43,95％CI (1.79,3.29) ) 的患者表现出更高的乳腺癌风险 (OR =1.49,95％CI (1.03,2.15) ) 。

结论: 单纯雌二醇的治疗无发生乳腺癌的风险, 而乳腺癌的发生风险因孕激素的类型而异。 雌二醇治疗联合甲状腺激素, 炔诺酮和左炔诺孕酮增加乳腺癌的患病风险, 雌二醇治疗与地屈孕酮和孕酮联合治疗无发生乳腺癌的风险。用药的时间的延长也会增加乳腺癌的发生风险, 此外与序贯治疗相比, 连续治疗具有更高的风险。

Keywords:

• Breast cancer
• estradiol
• estrogen progestogen therapy
• hormone replacement therapy
• menopause

Disclosure of interest

All authors declare no potential conflicts of interest. This study was supported by grants from the National Natural Science Foundation of China (Grant No. 0040215401138). We are grateful to all the contributions of all the authors.