The Post-finasteride Syndrome: Clinical Manifestation of Drug-Induced Epigenetics Due to Endocrine Disruption
Traish, 2018
“It is disconcerting that many dermatologists with little or no formal training in endocrinology and neuroendocrinology are happily prescribing this drug without full understanding of the pathophysiology or the clinical ramifications.”
In an important literature review from a steroid biologist, Traish considered that the magnitude of post-finasteride syndrome is inadequately appreciated, and that strong biological rationale exists for enzyme inhibition with Finasteride resulting in neurological and sexual adverse effects.
PFS is noted to be a rare and heterogeneous disorder with varying degrees in the constellation of symptoms. The disease is recognised to be clinically challenging in that there are no known effective and available treatments, and the syndrome is indiscriminate in that it develops in men without any prior medical or psychiatric history, pre-existing sexual dysfunction, or any other apparent risk factors.
Traish considered loss of libido, ED, ejaculatory dysfunction, depression, suicidal ideation, anxiety, panic attacks, insomnia, and cognitive dysfunction to be the most clinically recognised symptoms. Persistent loss of libido and erectile dysfunction are recognised as “signs of something terribly amiss with physiological process”.
Traish addresses the disconcerting dismissal and obfuscation of the severity and importance of the condition. He reviews the important biological implications of 5alpha reductase inhibition. Animal and human studies are shown as providing considerable evidence for the potential mechanisms of finasteride induced adverse sexual side effects and neurological side effects. He notes evidence that the integrity of the penile vascular bed and peripheral vessels is critically dependent on the androgen milieu.
Traish hypothesises that finasteride-induced epigenetic changes, manifesting in observed AR upregulation, suggest that such epigenetic modifications may cause in the symptoms of PFS by attenuating or silencing appropriate androgen and neurotransmitter signaling.
He appropriately describes as “incomprehensible” to PFS patients the fact “that there are members of the medical community who wish to dismiss this rare yet real syndrome or have it go away.” He additionally notes the dismissal of suicides and persistent symptoms as distressing. Traish suggests this, along with the lack of effort to improve care for afflicted patients, has “translated into loss of credibility and confidence by patients in their doctors and huge loss of faith in the medical community at large”.
“Many patients are frustrated by the perception in the medical community that such condition does not exist and they are labeled to suffer from psychological disorder, rather than an organic disorder, attributed to a biochemical imbalance due to enzyme inhibition of a key biochemical pathway in steroid and neurosteroid biosynthesis and metabolism.”
Traish concludes it is imperative that the scientific and medical communities do not dismiss this syndrome or stereotype patients affected with a serious and debilitating disorder. He urges investigation of the pathophysiology as well as efforts by the medical profession to expand awareness amongst physicians and patients.
