Plougmann Gislinge Julie Isabelle, Rubeck Petersen Kresten, Borgquist Signe, Ravn Pernille
Department of Gynecology, Obstetrics and Fertility, Copenhagen University Hospital Herlev, Herlev, Denmark.
Department of Oncology, University of Aarhus Skejby Hospital, Aarhus, Denmark.
Climacteric. 2025 Jun 20:1-9. doi: 10.1080/13697137.2025.2509839.
Tamoxifen (TMX) is known to increase the risk of endometrial cancer (EC) in postmenopausal women, but data on the effects in premenopausal and perimenopausal women remain inconsistent and not well illuminated. This study aimed to evaluate whether TMX increases the risks of gynecological symptoms and EC in premenopausal and perimenopausal women receiving adjuvant therapy for estrogen receptor-positive breast cancer.
Systematic searches in PubMed, Cochrane and Web Of Science yielded 319 relevant articles, of which 38 were analyzed after excluding duplicates and non-qualifying studies. The Oxford Criteria were used to ensure consistent evaluation before final inclusion. No meta-analysis was conducted due to study heterogeneity.
Ten studies (two meta-analyses, one systematic review, four retrospective cohort studies, one retrospective comparative study, one prospective cohort study and one case-control study) were included. TMX was associated with an increased risk of EC in premenopausal and perimenopausal women (mean relative risk 2.25; standard deviation 0.9) compared to no treatment or treatment with raloxifene or aromatase inhibitors. Risk appeared in some studies to increase with treatment duration and persisted for ≥5 years post treatment. TMX also significantly increased the risk of gynecological symptoms, benign and premalignant endometrial pathology, intrauterine procedures and hysterectomy ( < 0.001).
TMX seems to increase EC risk and significantly increase the risk of gynecological symptoms in premenopausal and perimenopausal women, with risk persisting years following treatment cessation. Healthcare professionals should counsel these women on potential risks and emphasize prompt evaluation of gynecological symptoms.
已知他莫昔芬（TMX）会增加绝经后女性患子宫内膜癌（EC）的风险，但关于其对绝经前和围绝经期女性影响的数据仍不一致且未得到充分阐明。本研究旨在评估TMX是否会增加接受雌激素受体阳性乳腺癌辅助治疗的绝经前和围绝经期女性出现妇科症状和患EC的风险。
在PubMed、Cochrane和科学网进行系统检索，共获得319篇相关文章，排除重复和不合格研究后，对其中38篇进行分析。在最终纳入前，使用牛津标准确保评估的一致性。由于研究存在异质性，未进行荟萃分析。
纳入了10项研究（两项荟萃分析、一项系统评价、四项回顾性队列研究、一项回顾性比较研究、一项前瞻性队列研究和一项病例对照研究）。与未治疗或使用雷洛昔芬或芳香化酶抑制剂治疗相比，TMX与绝经前和围绝经期女性患EC的风险增加相关（平均相对风险2.25；标准差0.9）。在一些研究中，风险似乎随着治疗持续时间的增加而增加，并且在治疗后持续≥5年。TMX还显著增加了妇科症状、子宫内膜良性和癌前病变、宫内手术和子宫切除术的风险（<0.001）。
TMX似乎会增加绝经前和围绝经期女性患EC的风险，并显著增加妇科症状的风险，且在停药后数年风险仍持续存在。医疗保健专业人员应向这些女性咨询潜在风险，并强调对妇科症状进行及时评估。
