Background Preclinical studies have suggested that antidepressant drugs may possess antineoplastic properties. In a nationwide case–control study, we examined the association between use of antidepressants and endometrial-cancer risk with a particular focus on selective serotonin reuptake inhibitors (SSRIs). Methods From the Danish Cancer Registry, we identified all women with a histologically verified diagnosis of endometrial cancer between 2000 and 2016, and, for each woman, 15 age-matched controls. We obtained information on use of SSRIs, tricyclic antidepressants (TCAs) and other antidepressants based on records of filled prescriptions from the National Prescription Register. Using conditional logistic regression, we calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between use of antidepressants and endometrial-cancer risk compared with non-use. In active comparator analyses, SSRI use was compared with TCA use. Results The study population comprised 8164 cases and 122 432 controls. Compared with non-use, SSRI use was associated with an OR of 0.88 (95% CI 0.82–0.96) for endometrial cancer, whereas the association with TCA use was close to unity (OR 1.05, 95% CI 0.90–1.22). Use of other antidepressants yielded an OR of 0.86 (95% CI 0.71–1.03). We observed no apparent trends in associations according to cumulative amount. The inverse association with SSRI use persisted when compared with TCA use (OR 0.81, 95% CI 0.66–0.99). Conclusions Use of SSRIs was associated with a decreased risk of endometrial cancer, whereas no inverse association appeared with use of TCAs. The antineoplastic potential of SSRIs should be investigated in future studies.

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使用抗抑郁药和子宫内膜癌风险：一项全国性巢式病例对照研究

背景 临床前研究表明，抗抑郁药可能具有抗肿瘤特性。在一项全国性病例对照研究中，我们检查了使用抗抑郁药与子宫内膜癌风险之间的关联，特别关注选择性血清素再摄取抑制剂 (SSRI)。方法 从丹麦癌症登记处，我们确定了 2000 年至 2016 年间经组织学验证诊断为子宫内膜癌的所有女性，并且为每位女性确定了 15 名年龄匹配的对照。我们根据国家处方登记处的处方记录获得了有关使用 SSRI、三环类抗抑郁药 (TCA) 和其他抗抑郁药的信息。使用条件逻辑回归，我们计算了与不使用抗抑郁药相比，使用抗抑郁药与子宫内膜癌风险之间关联的调整优势比 (OR) 和 95% 置信区间 (CI)。在主动比较分析中，将 SSRI 的使用与 TCA 的使用进行了比较。结果研究人群包括8164例病例和122432例对照。与不使用相比，使用 SSRI 与子宫内膜癌的 OR 为 0.88（95% CI 0.82-0.96）相关，而与使用 TCA 的相关性接近一致（OR 1.05, 95% CI 0.90-1.22）。使用其他抗抑郁药的 OR 为 0.86 (95% CI 0.71–1.03)。根据累积量，我们没有观察到明显的关联趋势。与使用 TCA 相比，与使用 SSRI 的负相关仍然存在（OR 0.81，95% CI 0.66–0.99）。结论 SSRIs 的使用与子宫内膜癌风险降低相关，而使用 TCA 没有出现反向关联。SSRIs 的抗肿瘤潜力应在未来的研究中进行调查。