Unravelling Post-Finasteride Syndrome

Figure 1. Illustration of the horseshoe pattern of male hair loss, showing frontal and vertex thinning while the occipital area remains intact. Created in BioRender.com, 2025

This process is driven by 5α-reductase (5α-R), an enzyme that converts testosterone into DHT within cells (Azzouni et al. 2012). Blocking that enzyme, then, seems like a logical solution, and that’s precisely what the drug Finasteride was designed to do.

Understanding Finasteride and How It Changed Hair Loss Therapy

Approved in 1997 for AGA, Finasteride soon gained popularity as one of only two drugs on the market to treat hair thinning (Devjani et al. 2023). Finasteride acts as an inhibitor of type II and III 5α-reductase enzymes, the enzymes responsible for the conversion of testosterone (T) to dihydrotestosterone (DHT), cutting DHT serum levels by approximately 65–70% (Nemane et al. 2019). With less DHT around, hair follicles are spared from miniaturization and growth resumes.

Figure 2. Mechanism of Action of Finasteride and Its Effects on AGA. Created using Canva.com (2025)

When the Cure Becomes the Problem: Post-Finasteride Syndrome

Despite Finasteride’s success in the treatment of hair loss, in recent years, a growing body of clinical reports and patient testimonies has highlighted a concerning pattern: a subset of men experiencing persistent sexual, physical, and psychological symptoms that continue long after discontinuation of the medication. The condition? Post-Finasteride Syndrome (PFS) (Diviccaro et al. 2020). A summarisation of these symptoms is detailed in Figure 3 (Traish, 2020).

Figure 3. A breakdown of the Psychological, Sexual, and Physical Symptoms associated with Post Finasteride Syndrome. Created in BioRender.com (2025)

Despite controversy surrounding the legitimacy of post-finasteride syndrome, the reduced quality of life experienced by those experiencing the persistent symptoms after Finasteride usage warrants further research (Chiriacò et al. 2016).

So what could be causing these lingering symptoms?

The Missing Link: Neurosteroids and Their Role in the Brain

Finasteride’s action isn’t limited to the scalp. The same 5α-reductase enzyme that it blocks in hair follicles is also active in the brain, where it helps produce neurosteroids such as allopregnanolone. Allopregnanolone is a key regulator of GABAA receptors, which play a role in mood disorders (Traish, 2020).

By blocking 5α-reductase, Finasteride also decreases allopregnanolone levels. Studies indicate that low levels of this neurosteroid are associated with depression, anxiety, and post-traumatic stress disorder (PTSD) (Eser et al. 2006). It offers a potential biological explanation for the psychological symptoms observed in some PFS patients.

Figure 4.  Impact of Finasteride treatment on the production of allopregnanolone. Created using Canva.com (2025).

Novel Therapeutics: Restoring Balance Through Neurosteroids

One of the most promising directions in treating the neurological effects of Post-Finasteride Syndrome (PFS) lies not in reversing scalp hormone loss, but in rebalancing the brain.

A possible solution is to restimulate GABAA receptors with a synthetically derived form of allopregnanolone.

A leading candidate is Brexanolone, a synthetic analogue of allopregnanolone, the brain’s natural calming neurosteroid (Cornett et al. 2021). Approved by the FDA in 2019 for postpartum depression, Brexanolone works by enhancing GABA_A receptor activity, the same system responsible for relaxation and mood regulation (Cornett et al. 2021).

Its rapid onset, often producing relief within days, has made it an exciting breakthrough (Kanes et al. 2017). But could this exact mechanism offer hope to men with persistent neurological and psychological symptoms after Finasteride use?

Synthetic Allopregnanolone Treatment: Why Brexanolone is setting the standard?

Finasteride’s inhibition of the enzyme 5α-reductase not only lowers dihydrotestosterone (DHT), it also disrupts the synthesis of other neurosteroids, including allopregnanolone (Eser et al. 2006). Low levels of this compound have been linked to anxiety, depression, and cognitive fog (Eser et al. 2006; Traish, 2020).

However, using natural allopregnanolone directly as a drug isn’t practical: it’s poorly soluble in water, breaks down quickly, and can cause sedation at high doses. That’s why researchers created synthetic analogues like Brexanolone, molecules that imitate the brain’s natural neurosteroids but are more soluble, stable, and controllable. (Belelli et al. 2022). A treatment like this, in conjunction with Finasteride, could restore this lost neurochemical balance without reigniting DHT-related hair loss.

To achieve this, analytical techniques such as mass spectrometry, nuclear magnetic resonance (NMR), and high-performance liquid chromatography (HPLC) are used to confirm the structure, purity, and function of the compounds (Rustichelli et al. 2013).

Formulation chemistry can also be used to overcome solubility issues, improve bioavailability, and ensure ease of administration and safety during intravenous infusion. Allopregnanolone can be dissolved in a carrier molecule, such as sulfobutylether-β-cyclodextrin (SBECD), to reap these benefits. This is how Brexanolone is formulated for use (Kanes et al. 2017; Sarabia-Vallejo et al. 2023).

These innovations transformed a molecule that proved challenging to work with into a deliverable, measurable, and effective medicine.

Restoring Balance: A Neurosteroid Approach to Post-Finasteride Syndrome

To test whether this therapy could help men with PFS, a double-blind, placebo-controlled trial could be designed, enrolling 80 men aged 18–55 who continue to experience symptoms such as depression, anxiety, and low motivation after discontinuing Finasteride.

Participants would receive a 60-hour IV infusion of an allopregnanolone analogue, modified for stability and solubility with sulfobutylether-β-cyclodextrin (SBECD), or placebo, in a hospital setting, where vital signs and mood changes could be closely monitored (Cornett et al. 2021).

Before and after treatment, researchers would collect blood and cerebrospinal fluid (CSF) samples to measure allopregnanolone levels and inflammatory markers using liquid chromatography–mass spectrometry (LC–MS/MS) (Rustichelli et al. 2013).

They would also assess depressive symptoms using the Montgomery–Åsberg Depression Rating Scale (MADRS) (Montgomery and Åsberg 1979).

Figure 5. Proposed results after treatment with Allopregnanolone. Created in Biorender.com (2025)

Beyond the Scalp: Why It Matters

If future neurosteroid-based treatments can reverse PFS symptoms, it would represent a significant leap in neuroendocrinology, offering proof that hormonal balance and mental health are deeply interconnected.

For patients, it could mean not just symptom relief, but the restoration of a sense of normalcy and confidence lost after treatment.

Perhaps the most remarkable aspect is that this approach targets brain chemistry rather than DHT levels.

That means patients can treat neurological side effects without losing the hair-growth benefits that Finasteride provides —a genuine win-win for both body and mind.

The Bigger Picture

Androgenetic alopecia might begin on the scalp, but its story runs far deeper, into the brain, hormones, and mental health.

Finasteride remains a cornerstone in combating hair loss, yet as science uncovers its broader effects, researchers are recognizing that proper recovery means treating the whole person.

By blending modern analytical chemistry, neurobiology, and clinical innovation, neurosteroid-based treatments, such as allopregnanolone analogues like Brexanolone, could redefine how we think about the intersection between hormones and the mind.

Every discovery, even those born from side effects, brings medicine one step closer to understanding and restoring balance.