Suicidal risk associated with finasteride versus dutasteride among men treated for benign prostatic hyperplasia: nationwide cohort study

Laanani, Moussa; Weill, Alain; Jollant, Fabrice; Zureik, Mahmoud; Dray‐Spira, R.

doi:10.1038/s41598-023-32356-3

Cited by 4 publications

(2 citation statements)

References 72 publications

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“…Alarmingly, former finasteride users had a marked increase in suicidal thoughts (44%) compared to nonusers (3%), 54 which may be particularly relevant for a subset of patients with a history of mood disorders. 57 Fewer studies have explored the relationship between anxiety and finasteride usage, but self-reports indicate a comparable number of patients experiencing anxiety (73%) as depression (74%). 58 Preclinical studies have demonstrated that treating rodents with finasteride increases depressive and anxiety phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Witnessed trauma exposure induces fear in mice through a reduction in endogenous neurosteroid synthesis

Evans‐Strong,

Walton,

Blandino

et al. 2024

J Neuroendocrinology

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Neurosteroids have been implicated in the pathophysiology of post‐traumatic stress disorder (PTSD). Allopregnanolone is reduced in subsets of individuals with PTSD and has been explored as a novel treatment strategy. Both direct trauma exposure and witnessed trauma are risk factors for PTSD; however, the role of neurosteroids in the behavioral outcomes of these unique experiences has not been explored. Here, we investigate whether observational fear is associated with a reduced capacity for endogenous neurosteroidogenesis and the relationship with behavioral outcomes. We demonstrated that mice directly subjected to a threat (foot shocks) and those witnessing the threat have decreased plasma levels of allopregnanolone. The expression of a key enzyme involved in endogenous neurosteroid synthesis, 5α‐reductase type 2, is decreased in the basolateral amygdala, which is a major emotional processing hub implicated in PTSD. We demonstrated that genetic knockdown or pharmacological inhibition of 5α‐reductase type 2 exaggerates the behavioral expression of fear in response to witnessed trauma, whereas oral treatment with an exogenous, synthetic neuroactive steroid gamma‐aminobutyric acid‐A receptor positive allosteric modulator with molecular pharmacology similar to allopregnanolone (SGE‐516 [tool compound]) decreased the behavioral response to observational fear. These data implicate impaired endogenous neurosteroidogenesis in the pathophysiology of threat exposure, both direct and witnessed. Further, these data suggest that treatment with exogenous 5α‐reduced neurosteroids or targeting endogenous neurosteroidogenesis may be beneficial for the treatment of individuals with PTSD, whether resulting from direct or witnessed trauma.

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Section: Discussionmentioning

confidence: 99%

Witnessed trauma exposure induces fear in mice through a reduction in endogenous neurosteroid synthesis

Evans‐Strong,

Walton,

Blandino

et al. 2024

J Neuroendocrinology

View full text Add to dashboard Cite

show abstract

“…Several studies have demonstrated an association between finasteride use and the incidence of depression (Altomare & Capella, 2002;Irwig, 2012;Rahimi-Ardabili, Pourandarjani, Habibollahi, & Mualeki, 2006;Welk et al, 2017) (for review see (Hirshburg et al, 2016)). Alarmingly, former finasteride users had a marked increase in suicidal thoughts (44%) compared to non-users (3%) (Irwig, 2012) which may be particularly relevant for a subset of patients with a history of mood disorders (Laanani, Weill, Jollant, Zureik, & Dray-Spira, 2023). Fewer studies have explored the relationship between anxiety and finasteride usage but self-reports indicate a comparable number of patients experiencing anxiety (73%) as depression (74%) (Walf, Kaurejo, & Frye, 2018).…”

Section: Endogenous Neurosteroids and Affective Tonementioning

confidence: 99%

Witnessed trauma exposure induces fear in mice through a reduction in endogenous neurosteroid synthesis

Evans-Strong

Walton

Roper

et al. 2023

Preprint

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Neurosteroids have been implicated in the pathophysiology of post-traumatic stress disorder (PTSD). Allopregnanolone is reduced in subsets of individuals with PTSD and has been explored as a novel treatment strategy. Both direct trauma exposure and witnessed trauma are risk factors for PTSD; however, the role of neurosteroids in the behavioral outcomes of these unique experiences has not been explored. Here we investigate whether observational fear is associated with a reduced capacity for endogenous neurosteroidogenesis and the relationship with behavioral outcomes. We demonstrate that both mice directly subjected to the threat (foot shocks) and those witnessing the threat have decreased plasma levels of allopregnanolone. The expression of a key enzyme involved in endogenous neurosteroid synthesis, 5α-reductase type 2, is decreased in the basolateral amygdala (BLA), which is a major emotional processing hub implicated in PTSD. We demonstrate that knockdown of 5α-reductase type 2 exaggerates the behavioral expression of fear in response to witnessed trauma, whereas treatment with an exogenous, synthetic neuroactive steroid GABAA receptor PAM with molecular pharmacology similar to allopregnanolone (SGE-516 [tool compound]) decreases the behavioral response to observational fear. These data implicate impaired endogenous neurosteroidogenesis in the pathophysiology of threat exposure, both direct and witnessed. Further, these data suggest that treatment with exogenous 5α-reduced neurosteroids or targeting endogenous neurosteroidogenesis may be beneficial for the treatment of individuals with PTSD, whether resulting from direct or witnessed trauma.

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Multidimensional assessment of adverse events of finasteride: a real-world pharmacovigilance analysis based on FDA Adverse Event Reporting System (FAERS) from 2004 to April 2024

Zhong,

Yang,

Wei

et al. 2024

Preprint

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Background Finasteride is commonly utilized in clinical practice for treating androgenetic alopecia, but real-world data regarding the long-term safety of its adverse events remains incomplete, necessitating ongoing supplementation. This study aims to evaluate the adverse events (AEs) associated with finasteride use, based on data from the US Food and Drug Administration Adverse Event Reporting System (FAERS), to contribute to its safety assessment. Methods We reviewed adverse event reports associated with finasteride from the FAERS database, covering the period from the first quarter of 2004 to the first quarter of 2024. We assessed the safety of finasteride medication and AEs using four proportional disproportionality analyses: reported odds ratio, proportionate reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPN), and Multi-Item Gamma Poisson Shrinkage (MGPS). These methods were used to evaluate the of finasteride medication and AEs. whether there is a significant association between finasteride drug use and AEs. To investigate potential safety issues related to drug use, we further analyzed the similarities and differences in the onset time and AEs by gender, as well as the similarities and differences in AEs by age. Results Among the 11,557 adverse event reports where finasteride was the primary suspected drug, most patients affected were male (86.04%), with a significant proportion being the young adult aged 18-45 years (27.22%). We categorized 73 adverse events (AEs) into 7 different system organ categories (SOCs), which included common AEs like erectile dysfunction and sexual dysfunction. Notably, Peyronie's disease and post 5α reductase inhibitor syndrome were AEs not listed in the drug insert. We identified 102 AEs for men and 7 for women. Depression and anxiety were notable AEs for both male and female. Additionally, we examined 17 adverse events (AEs) in patients under 18 years old, 157 in patients aged 18 to 65 years, and 133 in patients aged 65 years and older. Each age group exhibited unique AEs, although erectile dysfunction, decreased libido, depression, suicidal ideation, psychotic disorder, and attention disturbance were common AEs observed across different age brackets. Ultimately, the median onset time for all instances was 61 days. The onset was mainly within one month after initiation of finasteride and it is noteworthy that the second highest number of cases involved adverse drug reactions persisted beyond one year of treatment. Conclusion The results of our study uncovered both known and novel AEs associated with finasteride medication. Some of these AEs were identical to the specification, and some of them signaled AEs that were not demonstrated in the specification. In addition, some AEs showed variations based on gender and age in our study. Consequently, our findings offer valuable insights for future research on the safety of finasteride medication and are anticipated to enhance its safe use in clinical practice.

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Suicidal risk associated with finasteride versus dutasteride among men treated for benign prostatic hyperplasia: nationwide cohort study

Cited by 4 publications

References 72 publications

Witnessed trauma exposure induces fear in mice through a reduction in endogenous neurosteroid synthesis

Witnessed trauma exposure induces fear in mice through a reduction in endogenous neurosteroid synthesis

Witnessed trauma exposure induces fear in mice through a reduction in endogenous neurosteroid synthesis

Multidimensional assessment of adverse events of finasteride: a real-world pharmacovigilance analysis based on FDA Adverse Event Reporting System (FAERS) from 2004 to April 2024

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