Epigenetic Effects of Finasteride on Human Leydig Cells

Abstract

Finasteride is a synthetic 4‐azasteroid, used in the treatment of both androgenetic alopecia and benign prostatic hyperplasia. In some men, its use is associated with persistent erectile dysfunction, ejaculatory dysfunction, loss of libido, altered sperm counts and infertility ‐ even after cessation of the drug. This condition has been termed “Post‐finasteride Syndrome” (PFS). We want to understand the underlying biochemical mechanisms that govern the development of this condition. Therefore in this experiment we tested the effects of exposure of finasteride on human Leydig cells, the main hormone‐producing cell of the testis, to identify epigenetic changes in the cells that could be at least partially responsible for PFS. We cultured human Leydig cells in the presence of 0.5 μM finasteride for 14 days and performed whole‐genome DNA methylation analysis using the NimbleGen Human DNA Methylation 3×720K Promoter Plus CpG Island Array and Ingenuity Pathway Analysis. Here we describe initial identification of specific genes and pathways involved that may ultimately lead to treatments to reverse PFS.Support or Funding InformationNIH/NIA (IR25AG047843‐01) to ABC