An (Ir)reversible Affection of the Sexual Sphere: A Case Report

Introduction

Finasteride is a 5α-reductase inhibitor (5αRI) widely used in the treatment of benign prostatic hyperplasia and androgenetic alopecia (AGA). ¹ Its mechanism of action is based on inhibiting the conversion of testosterone to dihydrotestosterone (DHT), a potent androgen responsible for mediating the effects of testosterone in various target organs such as the prostate, skin, liver, and brain. ² Although its efficacy is well established, this drug has been associated with a wide range of adverse effects that may persist even after discontinuation. ³ These effects manifest as sexual alterations, including erectile dysfunction, decreased libido, reduced genital sensitivity and changes in ejaculatory quality, among others. Additionally, neuropsychiatric manifestations have been reported, including depression, anxiety, cognitive changes, and, in rare cases, suicidal ideation. ⁴ This constellation of symptoms, when persistent after discontinuation of the drug, is described in the literature as post-finasteride syndrome (PFS), a condition that has garnered increasing attention due to its debilitating, albeit rare, nature.

A homonymous foundation, headquartered in the United States, describes this syndrome as a set of ‘persistent sexual, neurological, physical, and mental adverse reactions in patients who have taken finasteride, a Type 2 5αRI used to treat hair loss and/or prostate hypertrophy’. However, there is still no formal definition, nor universally accepted diagnostic criteria, for this condition; none have even been proposed by any medical society. ⁴ This, in conjunction with the variability in clinical presentation and the limitations related to the subjectivity of patient reports, makes diagnosis particularly challenging.

Despite these challenges, the increasing number of reports, the significant impact on patients’ quality of life and the absence of an established treatment have motivated greater recognition of the problem and highlighted the need for further research.

This case report illustrates the occurrence of persistent sexual symptoms compatible with PFS in a young patient, detailing its implications for his quality of life and sexual health, as well as the clinical challenges they pose. This article was written in accordance with the CARE checklist (https://www.care-statement.org/checklist).

Case Description

A 26-year-old man, otherwise healthy and without relevant medical history, began treatment with finasteride 1 mg for AGA. The treatment was discontinued after six months due to the development of genital hypesthesia and reduced ejaculatory potency, accompanied by a significant loss of sexual pleasure. Subsequently, hair transplantation was chosen as an alternative treatment for AGA.

After discontinuation of the 5αRI and given the persistence of symptoms over a period of twelve months, the patient sought evaluation at his Family Health Unit in April 2024. During the appointment, a comprehensive anamnesis and physical examination were performed, ruling out possible physical, traumatic, psychological or relational causes, as well as lifestyle changes that could impact sexual health. The patient also denied any urinary or gastrointestinal tract disorders and musculoskeletal anomalies. Laboratory alterations were excluded as well, including elevated inflammatory markers or hormonal imbalances, and both pre- and post-treatment serum testosterone and DHT levels remained within normal parameters. Although a penile Doppler ultrasound was not requested to assess penile blood flow, it was considered unlikely that significant vascular alterations existed due to atherosclerosis, given the patient’s age and the absence of cardiovascular risk factors. It is also worth noting that, during this period, there was no use of any other medications, supplements, or potentially harmful or toxic substances.

The patient provided informed, free and clarified consent for this case report’s publication.

Discussion

Although acknowledged to be rare, the exact prevalence of PFS remains unknown, likely due to the absence of robust epidemiological studies and the difficulty in estimating this value. Currently, such estimates rely solely on subjective accounts associated with treatments using differing dosages and durations. ⁴ Nevertheless, a 2017 retrospective cohort involving 4284 men previously treated with finasteride at a dose below 1.25 mg (a dosage compatible with that used for AGA) calculated a prevalence of 0.79% for persistent sexual symptoms. ⁵ However, this estimate only encompasses sexual complaints and does not include symptoms from other systems, notably neuropsychiatric manifestations, which have also been described in association with PFS, despite their absence in this particular case.

The pathophysiology of this syndrome remains unclear. It is debated whether PFS may be precipitated by 5αRI treatment in patients with certain predisposed factors, rather than being a direct causal effect of the drug itself. ⁶ Nonetheless, literature suggests it may result from a complex combination of neurobiological, hormonal, and possibly genetic changes. One potential mechanism posited involves significant interference with neuroactive steroid levels, showing a decrease in tetrahydroprogesterone, isopregnanolone, and DHT and an increase in testosterone and 17β-estradiol in the cerebrospinal fluid, resulting in hormonal imbalances and signaling abnormalities. ⁷ Therefore, this drug appears to exert a direct influence on central nervous system activity. Additionally, animal studies have shown a transient decrease in hippocampal neurogenesis following finasteride administration, suggesting the drug may impact cognitive processes. ⁴ Growing evidence also highlights the relevance of epigenetic variants that could justify the onset and long-term persistence of symptoms. One of these studies described a methylation pattern of the SRD5A2 promoter (a regulator of the gene encoding Type 2 5α-reductase) in the cerebrospinal fluid of PFS patients, ⁷ suggesting that genetic factors may increase individual susceptibility to the syndrome. More recently, it has also been postulated that treatment with a 5αRI may induce a new form of androgen deficiency, with reduced peripheral DHT levels even with maintained serum testosterone. ⁸ Nevertheless, the evidence supporting these mechanisms remains preliminary and further studies are necessary to clarify the role and impact of these factors on the pathophysiology of PFS.

The persistence of symptoms after drug discontinuation is one of the most concerning aspects of this syndrome, raising troubling questions about the potentially permanent impact of this medication on an individual’s quality of life. Despite extensive studies and a well-known side-effect profile, reports of adverse effects persisting for at least three months after finasteride use have increased, especially among younger users.^9,10 Nonetheless, according to available evidence, symptom onset can occur regardless of dose, patient age or treatment duration, with reports of symptoms that have persisted for over 40 months post-discontinuation.^4,5 For clinicians, the challenge—compounded by the lack of defined diagnostic criteria and specific biomarkers for PFS—lies in identifying patients who are at greater risk or possess greater susceptibility to developing this problem. If treatment with finasteride is being considered, the potential risk of adverse effects must be carefully discussed with each patient before starting therapy, ensuring an informed decision and appropriate follow-up for early identification of potential complications. In this particular case, the patient denies having been informed by the dermatologist about the 5αRI adverse effect profile at the time of intervention, although alternative therapies, such as topical treatments, had been proposed. The patient chose treatment with finasteride after being told it could be more effective compared to topical options and less expensive than hair transplantation, which he ultimately opted for after discontinuing finasteride. When considering a 5αRI as a therapeutic proposal, possible factors increasing a patient’s susceptibility to adverse effects should also be weighed, and alternative treatments should be discussed in light of their risks and benefits. This proactive, patient-centered approach is essential to ensure the safety and efficacy of treatment, especially given a syndrome whose etiology and risk factors remain largely unclear.

Conclusion

In summary, PFS is a complex, albeit rare, entity with significant implications for patients’ quality of life. Its etiology and possible treatments are not clearly understood. A careful individual assessment, considering risks and benefits, should be undertaken by the physician before initiating this medication, along with the obtainment of the patient’s informed, free, and clarified consent. The ultimate goal is to achieve optimal therapeutic outcomes while minimizing the risk of PFS, thereby contributing to better care for patients affected by conditions for which finasteride is considered part of the therapeutic strategy.