Characteristics of Men Who Report Persistent Sexual Symptoms After Finasteride Use for Hair Loss
Basaria et al., 2016
“we observed enormous variation in the duration of finasteride exposure before the onset of symptoms. Some patients reported the development of symptoms after ingesting just a few doses of finasteride, whereas others developed symptoms after months or years of finasteride use.”
In an assessment of 24 PFS patients, Basaria et al. found no significant sequence variations in AR, SRD5A1 or SRD5A2. Depression scores were significantly higher in PFS patients via BDI, Hamilton Depression inventory and PHQ-9. PHQ-9 scoring was not significantly related to either the duration of finasteride use or the time since discontinuation of the drug. No hormonal correlate able to account for the pathological presentation was identified.
Two fMRI measurements suggested neurobiological abnormalities in PFS patients. fMRI of PFS patients’ brains in response to erotic stimuli was conducted. Worsening IIEF scores correlated to increased activity in the neural areas the authors deemed to correspond with sexual arousal, while activity in brain regions they associated with higher level cognitive and motivational networks decreased concomitantly, revealing a dissociation in activity that was considered a possible marker of neural changes following use of finasteride. Blood-oxygen dependent activity in brain areas implicated in major depression were also identified in PFS patients with correlation to BDI scores pertaining to negative affect .
The authors did not identify a notable sequence variation in AR, SRD5A1, or SRD5A2, nor notable evidence of persistent inhibition of 5AR, or changes in AR-dependent gene expression alteration in back skin. They note the possibility of variations in other genes, the gene expression levels in other tissues, and the possibility that finasteride may exert epigenetic effects which may account for persistent symptoms.
The reported findings from the limited gene expression assay of back skin in this study contrasts with the finding of significant AR overexpression in prepuce tissue by Di Loreto et al., and the recently reported tissue-specific observation of methylation of the gene promotor of SRD5A2 in CSF by Melcangi et al. We therefore consider it critical that symptomatically relevant, androgen-dependent tissue should be used in future investigations of the plausible epigenetic impact of PFS.
Of interest, although the paper stated that “we did not find evidence of…significant alterations in expression of AR-dependent genes in the skin”, a statement in the study’s supplementary appendix reads: “While the DESeq analysis determined there were statistically significant differences in a few of the androgen-regulated genes, the hierarchical clustering analysis revealed that the symptomatic and non-symptomatic subjects did not share the immediate cluster”.
