Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS database
Background and purpose: Testosterone is an essential sex hormone in maintaining masculine characteristics, which is prescribed for male hypogonadism as testosterone replacement treatment (TRT). Herein, we investigated long-standing controversies about the association between TRT and major adverse ca...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1182113/full |
| _version_ | 1797782377139798016 |
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| author | Hui Zhao Jun-Min Li Zi-Ran Li Qian Zhang Ming-Kang Zhong Ming-Ming Yan Xiao-Yan Qiu |
| author_facet | Hui Zhao Jun-Min Li Zi-Ran Li Qian Zhang Ming-Kang Zhong Ming-Ming Yan Xiao-Yan Qiu |
| author_sort | Hui Zhao |
| collection | DOAJ |
| description | Background and purpose: Testosterone is an essential sex hormone in maintaining masculine characteristics, which is prescribed for male hypogonadism as testosterone replacement treatment (TRT). Herein, we investigated long-standing controversies about the association between TRT and major adverse cardiovascular events (MACEs), based on real world adverse event (AE) reports, registered in the Food and Drug Administration Adverse Event Reporting System (FAERS).Methods: Publicly available FAERS data from 1 January 2004 to 31 December 2022 were retrieved from the Food and Drug Administration (FDA) website. The data mining protocol including the reporting odds ratio (ROR) and the Bayesian confidence propagation neural network (BCPNN) was applied to analyze overreporting caused by risk factors and MACEs, including TRT, morbidities, and ages. The ROR and the BCPNN were also applied to investigate the annually developing trend of pharmacovigilance (PV) signals in the real world, retrospectively.Results: A total of 3,057 cases referring to MACEs, with a median age of 57 years old (yo), were identified from 28,921 cases of testosterone users. MACEs related to PV signals have emerged since 2014, including cardiac death, non-fatal myocardial infarction, and non-fatal stroke. Myocardial infarction (MI) (ROR: 9.46; IC025: 3.08), acute myocardial infarction (AMI) (ROR: 16.20; IC025: 3.72), ischemic cardiomyopathy (ROR: 11.63; IC025: 2.20), and cardiomyopathy (ROR: 5.98; IC025: 1.96) were the most significant signals generated, and weaker signals included cardiac failure acute (ROR: 4.01; IC025: 0.71), cardiac arrest (ROR: 1.88; IC025: 0.56), and ventricular fibrillation (VF) (ROR: 2.38; IC025: 0.38). The time-to-onset (TTO) of MACEs was calculated with a median of 246 days for AMI.Conclusion: For myocardial infarction and cardiomyopathy, TRT statistically tended to increase the risk of MACEs, while for cardiac arrhythmia, cardiac failure, and stroke, TRT demonstrated beneficial effects among the population with morbidities, such as testosterone deficiency (TD), diabetes mellitus (DM), and hypertension. MACEs were rare but led to serious outcomes including significant increase in death and disability. Since 2018, and before 2014, reports referring to TRT associated with MACEs were relatively scarce, which indicated that there might be a considerable number of cases that went unrecorded, due to neglection. Health workers and testosterone users might pay more attention to testosterone-induced MACEs. |
| first_indexed | 2024-03-13T00:10:07Z |
| format | Article |
| id | doaj.art-dedd46f3612c41d7895fcb9c0bd29965 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-13T00:10:07Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-dedd46f3612c41d7895fcb9c0bd299652023-07-12T13:09:42ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-07-011410.3389/fphar.2023.11821131182113Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS databaseHui Zhao0Jun-Min Li1Zi-Ran Li2Qian Zhang3Ming-Kang Zhong4Ming-Ming Yan5Xiao-Yan Qiu6Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, ChinaSchool of Pharmacy, Fudan University, Shanghai, ChinaDepartment of Pharmacy, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Pharmacy, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Pharmacy, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Pharmacy, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Pharmacy, Huashan Hospital, Fudan University, Shanghai, ChinaBackground and purpose: Testosterone is an essential sex hormone in maintaining masculine characteristics, which is prescribed for male hypogonadism as testosterone replacement treatment (TRT). Herein, we investigated long-standing controversies about the association between TRT and major adverse cardiovascular events (MACEs), based on real world adverse event (AE) reports, registered in the Food and Drug Administration Adverse Event Reporting System (FAERS).Methods: Publicly available FAERS data from 1 January 2004 to 31 December 2022 were retrieved from the Food and Drug Administration (FDA) website. The data mining protocol including the reporting odds ratio (ROR) and the Bayesian confidence propagation neural network (BCPNN) was applied to analyze overreporting caused by risk factors and MACEs, including TRT, morbidities, and ages. The ROR and the BCPNN were also applied to investigate the annually developing trend of pharmacovigilance (PV) signals in the real world, retrospectively.Results: A total of 3,057 cases referring to MACEs, with a median age of 57 years old (yo), were identified from 28,921 cases of testosterone users. MACEs related to PV signals have emerged since 2014, including cardiac death, non-fatal myocardial infarction, and non-fatal stroke. Myocardial infarction (MI) (ROR: 9.46; IC025: 3.08), acute myocardial infarction (AMI) (ROR: 16.20; IC025: 3.72), ischemic cardiomyopathy (ROR: 11.63; IC025: 2.20), and cardiomyopathy (ROR: 5.98; IC025: 1.96) were the most significant signals generated, and weaker signals included cardiac failure acute (ROR: 4.01; IC025: 0.71), cardiac arrest (ROR: 1.88; IC025: 0.56), and ventricular fibrillation (VF) (ROR: 2.38; IC025: 0.38). The time-to-onset (TTO) of MACEs was calculated with a median of 246 days for AMI.Conclusion: For myocardial infarction and cardiomyopathy, TRT statistically tended to increase the risk of MACEs, while for cardiac arrhythmia, cardiac failure, and stroke, TRT demonstrated beneficial effects among the population with morbidities, such as testosterone deficiency (TD), diabetes mellitus (DM), and hypertension. MACEs were rare but led to serious outcomes including significant increase in death and disability. Since 2018, and before 2014, reports referring to TRT associated with MACEs were relatively scarce, which indicated that there might be a considerable number of cases that went unrecorded, due to neglection. Health workers and testosterone users might pay more attention to testosterone-induced MACEs.https://www.frontiersin.org/articles/10.3389/fphar.2023.1182113/fullpharmacovigilancetestosterone treatmentTTmajor adverse cardiovascular eventsMACEFAERS |
| spellingShingle | Hui Zhao Jun-Min Li Zi-Ran Li Qian Zhang Ming-Kang Zhong Ming-Ming Yan Xiao-Yan Qiu Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS database Frontiers in Pharmacology pharmacovigilance testosterone treatment TT major adverse cardiovascular events MACE FAERS |
| title | Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS database |
| title_full | Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS database |
| title_fullStr | Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS database |
| title_full_unstemmed | Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS database |
| title_short | Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS database |
| title_sort | major adverse cardiovascular events associated with testosterone treatment a pharmacovigilance study of the faers database |
| topic | pharmacovigilance testosterone treatment TT major adverse cardiovascular events MACE FAERS |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1182113/full |
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