TY - JOUR
T1 - The Possible Role of Prescribing Medications, Including Central Nervous System Drugs, in Contributing to Male-Factor Infertility (MFI): Assessment of the Food and Drug Administration (FDA) Pharmacovigilance Database
AU - Baldini, Sara
AU - Khattak, Ahmed
AU - Capogrosso, Paolo
AU - Antonini, Gabriele
AU - Dehò, Federico
AU - Schifano, Fabrizio
AU - Schifano, Nicolò
N1 - © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/
PY - 2023/12/31
Y1 - 2023/12/31
N2 - Background: A wide range of medications may have a possible role in the development of male-factor infertility (MFI), including various antineoplastic agents, testosterone/anabolic steroids, immunosuppressive drugs/immunomodulators, glucocorticosteroids, non-steroidal an-ti-inflammatory drugs, opiates, antiandrogenic drugs/5-alpha-reductase inhibitors, various antibi-otics, antidepressants, antipsychotics, antiepileptic agents and others. We aimed at investigating this issue from a pharmacovigilance-based perspective. Methods: The Food and Drug Administra-tion (FDA) Adverse Event Reporting System (FAERS) database was queried to identify the drugs associated the most with MFI individual reports. Only those drugs being associated with more than 10 MFI reports were considered for the disproportionality analysis. Proportional Reporting Ratios (PRRs) and their confidence intervals were computed for all the drugs identified in this way in January 2023. Secondary, ‘unmasking’, dataset analyses were carried out as well. Results: Out of the whole database, 955 MFI reports were identified, 408 (42.7%) of which were associated with 20 medications ,which had more than 10 reports each. Within this group, finasteride, testosterone, valproate, diethylstilbestrol, mechloretamine, verapamil, lovastatin and nifedipine showed signif-icant levels of actual disproportionate reporting. Out of these, and before unmasking, the highest PRR values were identified for finasteride, diethylstilbestrol and mechloretamine, respectively, with values of 16.0 (12.7–20.3), 14.3 (9.1–22.4) and 58.7 (36.3–95.9). Conclusions: A variety of several medications, a number of which were already supposed to be potentially linked with MFI based on the existing evidence, were associated with significant PRR levels for MFI in this analysis. A number of agents which were previously hypothesized to be associated with MFI were not represented in this analysis, suggesting that drug-induced MFI is likely under-reported to regulatory agencies. Reproductive medicine specialists should put more effort into the detection and reporting of these adverse drug reactions.
AB - Background: A wide range of medications may have a possible role in the development of male-factor infertility (MFI), including various antineoplastic agents, testosterone/anabolic steroids, immunosuppressive drugs/immunomodulators, glucocorticosteroids, non-steroidal an-ti-inflammatory drugs, opiates, antiandrogenic drugs/5-alpha-reductase inhibitors, various antibi-otics, antidepressants, antipsychotics, antiepileptic agents and others. We aimed at investigating this issue from a pharmacovigilance-based perspective. Methods: The Food and Drug Administra-tion (FDA) Adverse Event Reporting System (FAERS) database was queried to identify the drugs associated the most with MFI individual reports. Only those drugs being associated with more than 10 MFI reports were considered for the disproportionality analysis. Proportional Reporting Ratios (PRRs) and their confidence intervals were computed for all the drugs identified in this way in January 2023. Secondary, ‘unmasking’, dataset analyses were carried out as well. Results: Out of the whole database, 955 MFI reports were identified, 408 (42.7%) of which were associated with 20 medications ,which had more than 10 reports each. Within this group, finasteride, testosterone, valproate, diethylstilbestrol, mechloretamine, verapamil, lovastatin and nifedipine showed signif-icant levels of actual disproportionate reporting. Out of these, and before unmasking, the highest PRR values were identified for finasteride, diethylstilbestrol and mechloretamine, respectively, with values of 16.0 (12.7–20.3), 14.3 (9.1–22.4) and 58.7 (36.3–95.9). Conclusions: A variety of several medications, a number of which were already supposed to be potentially linked with MFI based on the existing evidence, were associated with significant PRR levels for MFI in this analysis. A number of agents which were previously hypothesized to be associated with MFI were not represented in this analysis, suggesting that drug-induced MFI is likely under-reported to regulatory agencies. Reproductive medicine specialists should put more effort into the detection and reporting of these adverse drug reactions.
KW - pharmacovigilance
KW - male-factor infertility
KW - adverse drug reaction
KW - finasteride
KW - testosterone
UR - http://www.scopus.com/inward/record.url?scp=85180486411&partnerID=8YFLogxK
U2 - 10.3390/brainsci13121652
DO - 10.3390/brainsci13121652
M3 - Article
SN - 2076-3425
VL - 13
SP - 1
EP - 14
JO - Brain Sciences
JF - Brain Sciences
IS - 12
M1 - 1652
ER -