ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacoepidemiology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1630843
Recombinant Human Growth Hormone and Brain Neoplasm Association: A Pharmacovigilance and Mendelian Randomization Analysis Based on US FAERS, Japanese JADER, and Canadian CVARD
Provisionally accepted
- 1Women and Infants Hospital of Zhengzhou, Zhengzhou, China
- 2The Ninth People's Hospital of Zhengzhou, Zhengzhou, China
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Objective:This study aimed to analyze the statistical association between recombinant human growth hormone (rhGH) and brain neoplasm adverse events (AEs) by mining data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, the Japanese Adverse Drug Event Report (JADER) database, and the Canada Vigilance Adverse Reaction Online Database (CVARD). Furthermore, Mendelian randomization (MR) was utilized to evaluate the potential causal link between rhGH and brain neoplasm, thereby providing a reference for safe clinical medication use. Methods:Reports of brain neoplasm associated with rhGH originated from the FAERS database (Q1 2004 -Q4 2024), the JADER database (April 2004 -December 2024), and the CVARD database (January 1991 -December 2024). Disproportionality analysis methods, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Information Component (IC), were used to detect pharmacovigilance signals. Subsequently, a two-sample Mendelian randomization analysis was conducted, treating rhGH as the exposure and brain neoplasm as the outcome, to evaluate the causal relationship. Results:A total of 323 reports of rhGH-associated brain neoplasms AEs were identified (FAERS: n=282; JADER: n=14; CVARD: n=27). Brain neoplasm was detected as a positive signal in all three databases by all three signal detection methods, consistently classified as medium clinical priority. Multivariable logistic regression analysis demonstrated an independent association between age and the increased risk of rhGH-induced brain tumors. Specifically, age groups 18-45 years and 46-65 years showed significantly elevated risks [OR (95% CI): 3.71 (1.09-13.34), P=0.048; and 3.78 (1.02-14.62), P=0.049, respectively].. The two-sample MR analysis, using the Inverse Variance Weighted (IVW) method, yielded an OR of 1.415 (95% CI: 1.005, 1.991, P=0.046), suggestive of causal relationship between rhGH and brain neoplasms. Conclusion:Pharmacovigilance analysis revealed a significant statistical association between rhGH and brain neoplasms. Mendelian randomization analysis further suggested a causal relationship between them. These findings highlight the need to consider the potential risk of brain neoplasm adverse events during treatment with rhGH.
Keywords: Recombinant human growth hormone(rhGH), Brain neoplasm, FAERS, JADER, CVaRD, Mendelian randomization analysis(MR)
Received: 18 May 2025; Accepted: 17 Jul 2025.
Copyright: © 2025 Huang, Zhang, Li and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yinpeng Xu, The Ninth People's Hospital of Zhengzhou, Zhengzhou, China
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