An evaluation of the federal adverse events reporting system data on adverse efects of 5‑alpha reductase inhibitors
Harrell et al., 2020
“Analysis of FAERS data suggests adverse efects of 5ARIs are dose independent with greater likelihood of occurrence in younger patients, particularly in sexual and mental domains.”
Seeking to investigate the sexual, physical, and mental adverse effects attributed to PFS associated with exposure to 5alpha reductase inhibitors, FAERS adverse event records for finasteride and dutasteride between May 2002 to April 2019 were analysed.
Young men taking finasteride 1mg for treatment of hair loss were more likely to be using the drug without other medications.
Adverse event frequencies were higher across all symptom domains with 1mg dosages. The authors describe this as a unique example of higher doses of a medication being correlated with lower frequencies of adverse effects. Importantly, the average age of those taking finasteride 1 mg was 35 years - far lower than those taking finasteride 5 mg (63 years) or dutasteride 0.5 mg (67 years).
Physical, sexual, and psychological adverse events were recorded, including libido loss, erectile dysfunction, ejaculatory disorder, penile and testicular adverse effects, musculoskeletal problems, skin issues, metabolic changes, as well as problems with memory, cognition, psychological wellbeing and sleep. These occurred in higher combination in the younger low dose cohort.
The range and severity of adverse effects identified in the study extended far beyond the realm of those previously reported from long-term controlled studies.
While the authors stress FAERS data cannot determine causality, this large analysis clearly reveals a significantly higher frequency and number of reported ADRs from a younger cohort using a lower dose preparation.
PFSNetwork comment
Potential endocrine disruptors can act on hormone receptors directly or interfere with proteins mediating hormonal delivery to target tissues and cells. They may act at low doses, exhibit non-monotonic dose-response relationships, cause tissue specific effects and differing endpoints (Bergman et al., 2012). There is broad potential for pharmaco/toxicodynamic influences from EDCs including alteration of receptor expression and interruption of the critical and complex feedback mechanisms regulating the endocrine system (Lagarde et al., 2015).
In late adolescent rats, finasteride remarkably decreases the activity of the dopaminergic system, exploratory and motor behaviours through decreasing DHT production and consequently androgen receptor activation on dopamine neurons in the substantia nigra and ventral tegmental area.
Interestingly, this effect was not seen in older or younger rats (Li et al., 2017). The reported reduction in brain DHT of late adolescent rats had not been observed in younger rats in a previous study (Giatti et al., 2015), suggesting significant interruption in brain dopaminergic activity occurs when AR activation is inhibited during the time testosterone levels are at their natural peak (Li et al., 2017).
This spatiotemporal observation of age-related difference is of potential relevance to the prevalence of PFS in young adult men of fertile age.
— Excerpts from Post-Finasteride Syndrome as an Epigenetic Post-Androgen Deprivation Syndrome: A potential pathological link between Drug-Induced Androgen Receptor Overexpression and Polyglutamine Toxicity, 2019. Read more
