The persitence of male sexual side effects (hypogonadism) after discontinuation of finasteride is a serious problem for a significant subset of men who use the drug. I had previously written about whether the propensity of finasteride to cause lasting hypogonadism could be due to the development of partial androgen resistance and whether this relates to the number of CAG repeats in exon 1 of their androgen receptor genes.
Recently, a patient of mine brought to my attention a research paper from Csoka, et al.(J Sex Med 2008;5:227-233) titled "Persistent Sexual Dysfunction after Discontinuation of Selective Serotonin Reuptake Inhibitors". They added 3 well-characterized case reports to the half dozen or so that were already in the literature and cited studies probing underlying mechanisms for the problem. Their fourth proposed mechanism relates to a growing field that has caught my attention in a big way, the field of epigenetics. They note that antidepressants can cause complex changes in the expression of genes. They cite animal research that has linked SSRI treatment during youth to permanantly decreased sexual behavior that persits into adulthood and that has explored underlying mechanisms for this including brain epigenetic changes at the molecular level.
Epigenetics is a field that concerns the complex web of proteins that surround our DNA. These proteins include histones, which help package and unpackage our genes to either turn on or turn off their function. "Acetylation" and "methylation" are chemical reactions that alter the histone's function, which in turn alters the expression of our genes. Within this emerging field may lie a new mechanism by which a drug can cause persistent changes in gene expression that can influence sexual behavior.
This brings up the idea that there is a common epigenetic mechanism that may apply generally to medications that cause persistent sexual dysfunction. It may be the case with finasteride that a common epigenetic effect interacts with a less common variant in the androgen receptor gene CAG repeat profile to cause its syndrome of crippling persistent post-finasteride hypogonadism.
Human research in this area has yet to be done, but holds promise for new therapies to treat this troublesome side effect of finasteride and other widely used medications.
