Pharmacologically induced syndromes: a growing concern

Post-finasteride syndrome (PFS)

A comprehensive review by Leliefeld et al. [1] explores the evolving landscape of PFS, underscoring the persistent sexual, physical, and psychological symptoms observed long after finasteride cessation. The evidence suggests a multifactorial etiology including androgen receptor polymorphisms and gut microbiota alterations [2]. The message in this issue for PFS is clear: clinicians prescribing 5-alpha reductase inhibitors must be fully transparent about these potential risks and approach emerging symptoms with legitimacy, not skepticism [1, 3,4,5].

Beyond the well-known sexual and mood-related effects, recent pharmacovigilance data suggest a potential association between finasteride and Peyronie’s-like features, including penile curvature. A disproportionality analysis found significantly elevated Proportional Reporting Ratios (PRRs) for this outcome in both the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and European Medicines Agency (EMA) databases [6]. While causality remains unproven, these findings highlight the need to consider structural complications as part of the PFS spectrum. Other drug-associated syndromes, such as post-SSRI and post-retinoid sexual dysfunction, are also emerging in the literature, although less well characterized. These conditions highlight the broader impact of pharmacologic agents on sexual function and deserve further clinical attention [7].

Ejaculatory disorders: dysfunctions in timing and aftermath

Post-orgasmic illness syndrome (POIS)

POIS is an underrecognized but debilitating condition marked by flu-like symptoms following ejaculation [8]. While its pathophysiology remains unclear, proposed mechanisms include autonomic dysregulation, immune responses, and psychological factors [9, 10]. A global survey of sexual medicine experts highlighted widespread clinical uncertainty: over 65% of respondents believed available information was insufficient, and treatment practices varied significantly [8]. Psychotherapy, antihistamines, and SSRIs are commonly attempted, though reported success rates remain low. This lack of consensus and poor therapeutic outcomes underscore the urgent need for clinical guidelines and further research [9, 10].

Delayed ejaculation (DE)

The challenge with DE lies in its multifactorial etiology and poor standardization. The special issue includes an up-to-date exploration of DE and reinforces that what often seems like a benign complaint may mask underlying psychosexual, endocrine, or neurological dysfunctions [11]. One study reveals a significant increase in the prevalence and incidence of DE from 2013 to 2019, yet pharmacological treatment rates remain low despite growing clinical need [12]. Additionally, a recent analysis found that most publicly accessible YouTube content on DE is of low educational quality, highlighting a gap in reliable online patient information and the need for academic engagement in public education [13]. DE deserves the same structured work-up as premature ejaculation or erectile dysfunction.

Sleep-linked dysfunctions: disorders that wake men up

Sleep-related painful erections (SRPEs)

These REM-associated painful events disrupt sleep and mimic priapism without causing structural damage [14]. Findings in this issue suggest a pelvic floor etiology in some cases and potential autonomic dysregulation in others [14]. Baclofen and PDE5 inhibitors have shown promise, but awareness remains low. Urologists should ask about nocturnal symptoms more often [15].

Vascular dysregulation and sexual emergencies

Although typically viewed as an acute urological emergency, priapism—particularly stuttering or recurrent forms—can evolve into a chronic and psychologically distressing disorder. Real-world data from a large cross-sectional analysis show that 4% of men receiving intracavernosal injections (ICI) develop priapism, most within three days, with risk factors including younger age, psychiatric comorbidities, and sickle cell disease [16]. In pediatric populations, up to 95% of cases are ischemic, often related to Sickle Cell Disease (SCD), and delayed treatment may result in irreversible erectile damage [17]. Despite its frequency and recurrence (up to 35% over five years), long-term management remains underutilized, and penile prosthesis implantation is rare. These findings underscore the importance of age-appropriate classification, risk stratification, and timely intervention to prevent corporal fibrosis and preserve erectile function. Priapism is not just an acute episode—it can be a gateway to lifelong sexual health challenges.

Others of unclear or mixed origin

Hard flaccid syndrome (HFS)

Among conditions with no clear structural abnormality but significant functional impact, Hard Flaccid Syndrome (HFS) has recently drawn considerable attention. First brought to the literature by our own group in 2019 [18], HFS is now recognized globally as a distinct syndrome characterized by a semi-rigid penis in the flaccid state, sensory changes, and pelvic pain [19,20,21]. Studies included in this issue validate the neuromuscular and vascular basis of the syndrome [22]. Treatment remains multidisciplinary: pelvic floor therapy, psychological support, and in select cases, pharmacologic agents such as PDE5 inhibitors [23, 24].

MNGIE syndrome and anejaculation

This mitochondrial disorder, typically presenting with gastrointestinal and neurological features, has now been linked to sexual dysfunction in male patients [25]. Although rare, its inclusion here illustrates how systemic diseases can manifest with subtle yet meaningful sexual consequences such as anejaculation, which are often overlooked.

Conclusion: a call to recognition, research, and respect

This special issue does not claim to have solved the mysteries of rare sexual disorders. Rather, it invites the reader to listen more carefully to patient experiences, to challenge dogmatic thinking, and to embrace diagnostic uncertainty when necessary. Many of these conditions will not be found in classical textbooks, yet they are very real in our clinics. As clinicians, we must avoid reductionist frameworks that label these disorders as either purely psychogenic or entirely organic. The truth, as always, lies in between — and the path forward lies in humility, curiosity, and collaboration. We hope this collection will serve as both a reference and a catalyst, empowering physicians to take these disorders seriously and inspiring researchers to fill the many knowledge gaps that remain.