A note on proposed etiologies about Post-Finasteride Syndrome
Men experiencing persistent side effects after stopping finasteride often face denial or misdiagnosis in the clinic, resulting in poor documentation of reported symptoms and other key clinical features.
Over time, this clinical blackspot has created a number of hypotheses about the etiology of Post-Finasteride Syndrome that are not coherent with what is occurring to patients, or findings from case-controlled study. These proposed etiologies frequently come about in online discussions between patients. Alarmingly, however, there have been an increasing number of hypotheses published by researchers in medical journals which do not demonstrate a clear grasp of the issue.
As patient advocates pushing for scientific discovery and greater recognition, this is deeply concerning. It is urgently important that any further scientific investigation demonstrates an appreciation of the complete clinical picture and the serious reality facing patients. Without doctors and scientists understanding the problem to be looked into, there cannot be useful progress.
The importance of plausible hypotheses
Hypotheses built on a misinformed clinical picture presents several practical risks to progressing scientific understanding in the foreseeable future.
Most notably, it risks basic science proceeding on a narrow or incorrect basis, which would compound the lack of meaningful scientific discovery over the previous two decades. Research which focuses on a narrow selection of reported symptoms is of little value, because it is extremely limited in the potential insights it could deliver for a disease that is unfortunately far more significant and systemic than what is often discussed.
Significant physiological symptoms including metabolic disorder, skin changes, autonomic problems, bone issues, atrophy of genital tissues and muscle, semen changes, post-orgasm exacerbation of symptoms, as well as broad cognitive symptoms are a few serious symptoms occurring frequently in the worst cases of PFS. Any hypothesis has to explain what is happening to patients experiencing these symptoms.
Research which ignores key features of the disease, such as worsening of symptoms after stopping finasteride, is also of little value. Such research would fail to explain how a key feature, experienced by more than 80% of patients who completed our clinical survey, is occurring, and how it interacts with a proposed disease etiology. This is extremely important, given "the crash" describes the onset or intensification of symptoms after withdrawal, and is therefore intrinsically tied to the driving pathomechanism.
Given the significant burden funding research which does demonstrate a clear grasp of the problem, there is another more practical challenge: Misguided scientific investigation will drain precious resources from an already-depleted community. It simply doesn’t make sense to fund research which is not grounded in clinical specifics or previous case-controlled findings. Doing so will only further delay understanding and extend the suffering of patients.
Online discussions
Discussions about proposed etiologies are often initiated by patients online. This occurs for a number of reasons:
Lack of effective treatment options and desperate need for symptomatic relief
Lack of faith in scientific discovery, or that treatment options will be available in a desirable timeframe
Lack of understanding of more plausible, albeit complex, hypotheses and case-controlled findings
Desire for quick fix treatments
We must be clear that these are not excuses for initiating, participating in or enabling the same circular discussions that have delayed scientific discovery for almost two decades. While these discussions may seem harmless, and provide an outlet for desperate patients, please be aware they are having a tangibly detrimental effect on meaningful progress.
Patients spend precious time and energy developing or discussing proposed etiologies with little grounding in the clinical reality. These ideas then spread broadly into the community and act as a distraction, particularly to new patients who frequently appear on online support forums looking for non-existent quick fixes. As a result, community cohesion towards practical objectives is poor.
This ingrained culture also diminishes the severity and complexity of the disease within the patient community, and the urgent need for action. Why should patients support scientific discovery, tell their story publicly, or report their symptoms, if PFS can be treated by some simple changes to diet and lifestyle? Alarmingly, it has a similar effect on outside observers, as evidenced by frequent and reductive characterisations that PFS is “persistent erectile dysfunction and depression”.
Suggested improvements
The disease as described to support some hypotheses, while a lot more pleasant, is not what we are dealing with personally or in our role managing the patient community.
We strongly suggest those interested in the disease read the literature on what patients report, and view our video series in which patients and their families characterise some of their symptoms. Some symptoms are hard to talk about, but the videos make the horrendous and broad impact of the disease very clear. We also suggest familiarising yourself with other key features of the disease frequently reported by patients.
Four key criteria
It is crucial that any proposed etiology or scientific investigation demonstrates an appreciation of the following:
The complete symptom profile being reported by PFS patients. We cannot simply ignore a collection of symptoms because of their incompatibility with a proposed etiology. They must be plausibly explained in their entirety.
The worsening experienced by patients after stopping finasteride, or other 5-alpha reductase inhibitors. This key clinical feature was reported by over 80% of patients who completed our clinical survey. In some cases, patients experience few or no on-drug side effects, only for severe and multi-systemic symptoms to onset after stopping finasteride. In some cases, physical decay can appear overnight. Given the commonality and peculiarity of this feature, it is essential to consider it in any hypotheses.
Susceptibility to further worsening after disruption of androgen signalling, which is sometimes permanent. Many patients report a worsening in symptoms after further disrupting androgen signalling, whether that be through therapeutic attempts or accidental consumption of a known anti-androgenic substance.
Existing case-controlled findings. Any proposed etiology must adequately consider previous case-controlled findings. Most importantly, this includes evidence of androgen receptor (AR) overexpression in PFS patients, which has now been demonstrated in androgen target tissue in two separate case-controlled studies, and specific changes in gene expression.
We ask patients to please remain vigilant and sceptical of any proposed explanations of PFS, and rigorously evaluate them using these criteria. This includes published literature and online patient discussions.
As a patient community we have a responsibility to ourselves and each other. Alongside supporting appropriate scientific research, we must constantly press for appropriate recognition of how this disease is affecting the health and lives of individuals - and how remarkably serious that can be for some.