Post-finasteride syndrome: what is it, where does it come from, and what can we do about it?

Figure 1. Depicting the pathway that testosterone takes in human cells. Finasteride intercedes the pathway that leads to hair loss, but it also shuts that pathway down completely. Figure composed using the Biorender software.

Finasteride is commonly administered for both aesthetic hair loss and for more persistent conditions, such as androgenetic alopecia. Whie impressive, it seemingly causes a major problem – after extended periods of use, typically 3 to 5 months, finasteride patients are seen to suffer from a variety of adverse side effects (figure 2) (Pereira and Coelho).

The primary focus of this article will be on a single case of a patient suffering from what has come to be called post-finasteride syndrome (PFS). Specifically, the patient is a 28-year-old male who has been seeing mental and physical complications as a result of PFS. Our outcomes for this case are thus:

1. PRIMARY OUTCOME: a measurable change in the patient’s hormone levels indicating an improvement in his condition.

2. SECONDARY OUTCOME: improvements in the patient’s quality of life (QoL), sleep quality, sexual function, among others.

What are the key elements of the problem?

At its core, PFS manifests in patients mostly as a variety of different psychological symptoms. Whether or not it is a disease or simply a medical condition is hotly debated, but the symptoms are more widely agreed (figure 2).

Figure 2. A graphical representation of some of the symptoms of PFS. Patients suffering from PFS tend to present with relatively uniform symptoms, and these are only a few. Based on Pereira and Coelho, 2020. Figure composed using the Biorender software.

Clearly any treatment that wishes to affect a positive primary and secondary outcome for this patient will need to work on addressing the root cause of these symptoms, given the variety However, there is one other issue faced by PFS research.

The key issue: is PFS real?

On the surface, the evidence appears compelling. 3-5 months after taking a chemical which acts on hormones in order to treat hair loss in men, debilitating symptoms are observed in the systems that those hormones are also commonly involved in.

However, studies performed on PFS and its symptoms frequently suffer from issues of small sample sizes and are reliant on patients providing information about themselves, which can frequently be overexaggerated or altered by that patient’s self-perception (Cilio et al.). In general the quality of studies done on PFS counterintuitively work to undermine the condition’s status, despite the fact that patients present with relatively uniform symptoms (Trueb et al.).

In particular with the case of PFS, there’s also a novel element complicating the problems that PFS raise – the prevalence of the internet and its role in diagnosing patients. When this young male patient began to suffer from side effects impacting their sexuality, it is likely that they sought out guidance and information online than in-person, which can lead to relying on the sometimes unfounded and exaggerated advice and experiences of their peers rather than the opinion of a trained medical professional (Cilio et al.).

Along with this, PFS also poses challenges to those working in a clinical environment. If this patient consults a medical practitioner with respect to their condition, it’s likely that they will be diagnosed with depression or another more common mental health disorder first, which leaves the root cause unaddressed.

This is further compounded by the fact that in clinical trials for finasteride products, adverse side effects commonly attributed to PFS are also seen occurring in placebo populations, which raises further doubts about the actual occurrence of these symptoms (Cilio et al.). It may even be likely that patients here are suffering from the “nocebo” phenomenon (figure 3), which further obscures the clinical reality of PFS and makes discerning fact from fiction difficult (Mondaini et al.).

Figure 3. A graphical explanation of the nocebo effect. In certain cases there appears to be a self-fulfilling element to certain side effects manifesting in patients. Figure composed using Biorender software.

Proposing a novel treatment for PFS

There are two broad pathways which can be taken to help in treating PFS. Firstly, a novel chemical could be produced to treat the condition indirectly (there are no evidence-based direct treatments available for PFS). Given that the compound which causes male hair loss, DHT, accumulates in hair follicles, perhaps for the primary outcome a more targeted approach is necessary, such as through the development of a hair cream or shampoo which destroys existing DHT instead of negating the pathway. Finasteride is administered as a tablet, leaving its effects broad and unspecified.

For the secondary outcome, away from directly treating PFS, perhaps a change in approach with regard to diagnosis and study is required. As previously mentioned, clinical studies on PFS often lack academic rigour which could be solved, but even prior to administering PFS perhaps clinicians should take a more holistic approach to assessing patients. Patients with a previous history of mental health difficulties, for instance, could potentially suffer for receiving it in treatment.

Conclusion

In short, so little is solidly understood about PFS that suggesting methods of treating it is difficult but studying it remains paramount given that the risks it poses and the harm it causes are real to those who suffer from it. Going forward, a change in approach may be needed to better assess the clinical realities of the disorder, and novel treatments can then follow.