Immunohistochemical Evaluation of Androgen Receptor and Nerve Structure Density in Human Prepuce from Patients with Persistent Sexual Side Effects after Finasteride Use for Androgenetic Alopecia
Di Loreto et al., 2014
“An intriguing observation of our study was that the ratio of AR positive stromal cells (%) to serum total or free testosterone was 2-fold higher in former finasteride users than controls. This finding could indicate the presence in former finasteride users of an augmented regulatory feedback loop that normally serves to modulate hormonal responses.”
In a retrospective control matched study, expression of the androgen receptor and nerve density in multiple cell lines of prepuce tissue in PFS patients aged 29–43 years experiencing persistent sexual symptoms for over 6 months was evaluated. The most notable finding was significant and persistent androgen receptor overexpression.
Patients had used finasteride for an average of 32 months and were an average of 56 months after cessation at the point of study. All patients remained symptomatic. PFS patients self-reported symptoms including loss of penile sensation, erectile dysfunction, pain in the penis, scrotum or testes, penile tissue changes, reduced penile dimensions, and reduced volume of ejaculate.
PFS cases experienced sexual dysfunction at point of interview per Arizona Sexual Experience Scale (22.5±2.78). PFS patients were additionally asked to complete the ASEX survey considering themselves before use of finasteride and these pre-finasteride scores indicated no pre-existing sexual dysfunction (7.6±1.92).
Immunohistochemistry revealed a significantly higher percentage of nuclear AR-positive epithelial cells in all cases (mean±SD, 80.6±8.63%) than in controls (mean±SD, 65.0±19.1%), P = 0.043. Stromal cells in all cases showed a significantly greater expression of AR in the nuclei compared to controls (mean±SD, 40.0±15.1% in cases versus 23.4±8.68% in controls), P = 0.023. Percentage of AR positive vessel smooth muscle cells did not differ significantly between the 2 groups. Averagely, AR positive cells in the 3 tissues was higher in cases than in controls.
Histological evaluation of nerve density revealed similarity with controls.
Providing the first report of significant objective molecular level differences in PFS patients, Di Loreto et al. speculate that the permanent effects could be due to mechanisms of ageing prematurely induced by artificially reduced androgen levels with finasteride. They conclude a better understanding of the molecular events may inform possible therapies for these severe effects in young men of fertile age.
Further information
Although unreported in the manuscript, La Marra, co-author of the study, further elaborated on the data in a thesis centering on the investigation. They reported positive correlations between the increase of AR levels in the epithelial and stromal cells and the decrease in ability/frequency to perform sexually per the AMS, the increase of AR in the vessels cells and the intensification of ASEX sexual dysfunction and physical exhaustion, and the increase of AR in the epithelial cells and the worsening of muscular weakness and feeling “burnt out” per AMS. La Marra noted that exogenous androgens do little to improve – and sometimes worsen – PFS symptoms, concluding that investigations should centre on epigenetic alterations relevant to the changed sensitivity of the AR.
