Kristensen Anna Kjær, Frandsen Clarissa Lima Brown, Møller Maria, Nøhr Bugge, Hjalgrim Henrik, Viuff Jakob Hansen, Hargreave Marie, Kjær Susanne Krüger, Jensen Allan
Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen, Denmark.
Department of Obstetrics and Gynecology, The Fertility Clinic, Copenhagen University Hospital, Herlev, Denmark.
Cancer Causes Control. 2025 Jun 2. doi: 10.1007/s10552-025-02017-z.
To investigate the association between fertility drug use and non-Hodgkin lymphoma.
This cohort study utilized data from the extensive Danish Infertility Cohort, comprising 148,036 women with fertility problems residing in Denmark between January 1, 1995 and December 31, 2017. The study cohort was linked to national registers to gather information on fertility drug use, cancer diagnoses, covariates, and emigration and vital status. Cox proportional hazard models were employed to calculate hazard ratios (HRs) and 95% confidence intervals for non-Hodgkin lymphoma (overall and for histologic subtypes), with adjustments for potential confounders.
Over a median follow-up of 11.3 years, 115 women were diagnosed with non-Hodgkin lymphoma. After adjustment for potential confounders, overall non-Hodgkin lymphoma rates were decreased following treatment with all specific types of fertility drugs analyzed being clomiphene citrate (HR 0.74; 95% CI 0.43-1.26), gonadotropins (HR 0.67; 95% CI 0.39-1.16), hCG (HR 0.69; 95% CI 0.41-1.17), GnRH receptor modulators (HR 0.58; 95% CI 0.33-1.03), and progesterone (HR 0.69; 95% CI 0.39-1.21). However, none of these associations were statistically significant implying that the results should be interpreted with great caution. Similar trends were seen for B-cell lymphomas. For most fertility drugs, we observed a tendency toward lower associations within the first 10 years after start of drug use.
The findings of this study do not indicate any strong associations between the use of fertility drugs and the risk of non-Hodgkin lymphoma. However, the relatively young age of the cohort at the end of follow-up underscores the need for an extended follow-up period to evaluate the long-term risk of non-Hodgkin lymphoma in women who have used fertility drugs.
研究使用促生育药物与非霍奇金淋巴瘤之间的关联。
这项队列研究利用了丹麦不孕症队列的大量数据，该队列包括1995年1月1日至2017年12月31日期间居住在丹麦的148,036名有生育问题的女性。研究队列与国家登记处相链接，以收集有关促生育药物使用、癌症诊断、协变量以及移民和生命状态的信息。采用Cox比例风险模型计算非霍奇金淋巴瘤（总体及组织学亚型）的风险比（HR）和95%置信区间，并对潜在混杂因素进行调整。
在中位随访11.3年期间，115名女性被诊断为非霍奇金淋巴瘤。在对潜在混杂因素进行调整后，使用所有分析的特定类型促生育药物（枸橼酸氯米芬（HR 0.74；95% CI 0.43 - 1.26）、促性腺激素（HR 0.67；95% CI 0.39 - 1.16）、人绒毛膜促性腺激素（HR 0.69；95% CI 0.41 - 1.17）、促性腺激素释放激素受体调节剂（HR 0.58；95% CI 0.33 - 1.03）和孕激素（HR 0.69；95% CI 0.39 - 1.21））治疗后，总体非霍奇金淋巴瘤发病率均有所下降。然而，这些关联均无统计学意义，这意味着对结果的解释应极为谨慎。B细胞淋巴瘤也观察到类似趋势。对于大多数促生育药物，我们发现在开始用药后的前10年内关联有降低的趋势。
本研究结果并未表明使用促生育药物与非霍奇金淋巴瘤风险之间存在任何强关联。然而，随访结束时队列相对年轻的年龄突出表明需要延长随访期，以评估使用促生育药物的女性患非霍奇金淋巴瘤的长期风险。
