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

PLoS One. 2014 Jun 24;9(6):e100237. doi: 10.1371/journal.pone.0100237. eCollection 2014.

Abstract

Finasteride is an inhibitor of 5-α-reductase used against male androgenetic alopecia (AGA). Reported side effects of finasteride comprise sexual dysfunction including erectile dysfunction, male infertility, and loss of libido. Recently these effects were described as persistent in some subjects. Molecular events inducing persistent adverse sexual symptoms are unexplored. This study was designed as a retrospective case-control study to assess if androgen receptor (AR) and nerve density in foreskin prepuce specimens were associated with persistent sexual side effects including loss of sensitivity in the genital area due to former finasteride use against AGA. Cases were 8 males (aged 29-43 years) reporting sexual side effects including loss of penis sensitivity over 6 months after discontinuation of finasteride who were interviewed and clinically visited. After informed consent they were invited to undergo a small excision of skin from prepuce. Controls were 11 otherwise healthy matched men (aged 23-49 years) who undergone circumcision for phimosis, and who never took finasteride or analogues. Differences in AR expression and nerve density in different portions of dermal prepuce were evaluated in the 2 groups. Density of nuclear AR in stromal and epithelial cells was higher in cases (mean 40.0%, and 80.6% of positive cells, respectively) than controls (mean 23.4%, and 65.0% of positive cells, respectively), P = 0.023 and P = 0.043, respectively. Conversely, percentage of vessel smooth muscle cells positive for AR and density of nerves were similar in the 2 groups. The ratio of AR positive stromal cells % to serum testosterone concentrations was 2-fold higher in cases than in controls (P = 0.001). Our findings revealed that modulation of local AR levels might be implicated in long-term side effects of finasteride use. This provides the first evidence of a molecular objective difference between patients with long-term adverse sexual effects after finasteride use versus drug untreated healthy controls in certain tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-alpha Reductase Inhibitors / administration & dosage
  • 5-alpha Reductase Inhibitors / adverse effects
  • 5-alpha Reductase Inhibitors / therapeutic use
  • Adult
  • Alopecia / drug therapy
  • Alopecia / metabolism*
  • Alopecia / pathology
  • Alopecia / physiopathology*
  • Case-Control Studies
  • Finasteride / administration & dosage
  • Finasteride / adverse effects*
  • Finasteride / therapeutic use
  • Foreskin / innervation*
  • Foreskin / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Receptors, Androgen / metabolism*
  • Retrospective Studies
  • Sexual Dysfunction, Physiological / chemically induced*
  • Testosterone / blood
  • Young Adult

Substances

  • 5-alpha Reductase Inhibitors
  • Receptors, Androgen
  • Testosterone
  • Finasteride

Grant support

Support was provided by University of Udine funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.