This is the full text of Buntrock & Diehm (2026), introduced by Stefan Buntrock himself in this short video:
https://www.youtube.com/watch?v=AQyhCLMuc54

Challenging the paradigm: what is vasculogenic erectile dysfunction?

IJIR: Your Sexual Medicine Journal; https://doi.org/10.1038/s41443-026-01311-x

Received: 6 May 2026; Revised: 31 May 2026; Accepted: 18 June 2026

In 1982, Goldstein and colleagues introduced the term “vasculogenic impotence” to describe a specific haemodynamic event: insufficient arterial inflow into the corpora cavernosa during erection, caused by atherosclerotic obstruction of the pudendal-cavernosal arterial bed [1]. The definition was precise, mechanistically coherent, and diagnostically actionable. Over the subsequent four decades, however, the term evolved into an omnibus category encompassing virtually all organic erectile dysfunction (ED) of presumed vascular aetiology — conflating two fundamentally distinct pathophysiological entities that require different diagnostic approaches and different therapies.

The clinical consequences of this conflation are now visible in the largest interventional registry to date: across more than 1000 endovascular procedures for vasculogenic ED, arterial revascularisation yielded clinically meaningful improvement in 44% of all comers (including various comorbidities with additional impact on erectile function) at 30 months by International Index of Erectile Function-6 (IIEF-6) criteria, and subjective improvement in 61% — with substantially higher response rates when venous embolisation was added for mixed pathology [2].

The treatment succeeded where pathology was predominantly haemodynamic; it failed or required escalation where structural cavernous degeneration had advanced beyond haemodynamic correction. These findings are difficult to reconcile within a purely haemodynamic framework, as technically successful revascularisation does not consistently translate into functional recovery. This discrepancy strongly suggests that end-organ integrity, rather than arterial inflow alone, determines therapeutic outcome.

We propose a terminological and clinical reform. The term “vasculogenic ED” should be restricted to its original meaning: haemodynamic insufficiency during erection due to atherosclerotic obstruction. We simultaneously introduce a novel entity, Chronic Hypoperfusive Erectile Dysfunction (CHPED), defined as structural cavernous tissue degeneration resulting from sustained inadequate perfusion during the detumescent state. This distinction is not semantic: it identifies a mechanistically defined, clinically prevalent condition that current nomenclature renders invisible — with direct consequences for patient outcomes.

## The Haemodynamic Paradigm and Its Limits

The European Association of Urology (EAU) Guidelines operationalise vasculogenic ED through dynamic duplex ultrasonography: peak systolic velocity (PSV) below 30 cm/s indicates arterial insufficiency [3]. This haemodynamic model is the appropriate basis for identifying the classical vasculogenic entity; it is not, however, designed to capture the structural cavernous pathology that drives CHPED, and its predictive value for regenerative therapeutic outcomes is accordingly limited. Huang and Hsieh demonstrated that PSV, end-diastolic velocity, resistance index, and cavernous artery diameter did not differ significantly between sildenafil responders and non-responders; more than 75% of non-responders had adequate PSV [4]. Wespes and colleagues, in a morphometric study of 30 sildenafil non-responders, found that virtually all had cavernous smooth muscle content below 35% [5] — a structural threshold rather than a vascular one. The editorial comment on that paper introduced the concept of “penile end-organ disease” [5]: a concept that has never been developed into a formal framework.

The haemodynamic model captures one half of the pathophysiology. Azadzoi’s landmark 2006 review demonstrated that arterial insufficiency triggers “a cascade of ischaemic/hypoxic cytotoxic events” extending well beyond haemodynamics, involving cavernous endothelial loss, nitric oxide synthase (NOS) depletion, smooth muscle atrophy, TGF-β-mediated fibrosis, and progressive veno-occlusive failure [6]. He concluded explicitly that “a haemodynamic examination alone cannot precisely predict the degree of vasculogenic ED” [6]. This evidence was published twenty years ago. The nomenclature has not responded.

## The Detumescent State: The Missing Pathophysiological Context

The critical insight motivating CHPED is that the corpus cavernosum is a chronically hypoxic organ in its resting state. Padmanabhan and McCullough demonstrated using non-invasive tissue oximetry that flaccid corporal oxygen saturation averages approximately 45–52% — on the steep portion of the haemoglobin dissociation curve, where small reductions in oxygen partial pressure produce disproportionate tissue hypoxia [7]. Men with ED showed significantly lower flaccid corporal oxygen saturation than potent controls, independent of aetiology [7].

The physiological mechanism that counteracts this resting hypoxia is nocturnal penile tumescence (NPT): healthy men experience arterialisation of cavernous blood during approximately 60% of sleep time [7]. NPT is therefore a tissue protection mechanism against chronic cavernous hypoxia — a function frequently lost in ageing, diabetes mellitus, hypogonadism, and after radical pelvic surgery [8, 9]. The pathological consequences of NPT loss are well-documented in the post-prostatectomy literature: smooth muscle apoptosis, endothelial degeneration, collagen deposition, and progressive fibrosis [10]. The same cascade operates, at varying rates and through varying initiating mechanisms, across the broader ED population, driven in part by impaired nocturnal oxygenation and endothelial dysfunction [6, 8].

The detumescent state is not merely the absence of erection; it is actively maintained under sympathetic nervous system control. Corpus cavernosum electromyography (CC-EMG) confirms that the electrical complexes of the flaccid penis are sympathetically mediated, originating in cavernous smooth muscle and disappearing during erection [11]. Simultaneous EEG-CC-EMG recordings demonstrate that this sympathetic input is a direct output of central autonomic network activity, arriving at the corpus cavernosum within fractions of a second after stimulus onset at a pre-attentive level [12]. Chronically elevated central sympathetic tone — through psychosocial stress, depression, or Chronic Sympathetic Dysregulation (CSD) [13] — may contribute to a prolonged detumescent state, intensifying chronic cavernous hypoxia. This mechanism provides a structural explanation for the transition from psychosocial to organic ED: the entry pathway is central autonomic; the final common pathway is CHPED.

## Chronic Hypoperfusive Erectile Dysfunction: Definition and Entry Pathways

We define CHPED as a structural cavernous disorder resulting from sustained inadequate perfusion during the detumescent state, characterised by progressive endothelial dysfunction, smooth muscle atrophy, fibrosis, and impaired veno-occlusive mechanism. CHPED is independent of — though may coexist with — atherosclerotic arterial obstruction.

CHPED is conceptually analogous to heart failure in cardiology — a common final pathway into which mechanistically distinct entry routes converge on the same end-organ pathology. Major entry pathways include: (i) atherosclerotic angiopathy, reducing resting cavernous perfusion in addition to tumescence-phase inflow — the zone of overlap with classical vasculogenic ED; (ii) diabetes mellitus, through endothelial dysfunction, oxidative stress, and autonomic neuropathy — Condorelli and colleagues demonstrated that sildenafil non-responders among diabetic patients showed significantly higher endothelial apoptosis and longer ED duration than responders [14]; (iii) Chronic Sympathetic Dysregulation, through the CC-EMG mechanism described above [11–13]; (iv) hypogonadism, which causes cavernous smooth muscle apoptosis, fibrosis, and reduced NOS expression — structurally identical to ischaemic CHPED [15]; and (v) ageing, through endothelial senescence and progressive NPT reduction.

Veno-occlusive dysfunction, historically attributed to a primary “venous leak,” is in most cases a downstream structural consequence of smooth muscle depletion rather than an independent entity [6]. However, in selected patients with anatomically localised venous insufficiency and adequate preserved smooth muscle content — including carefully selected post-prostatectomy patients — targeted venous embolisation may hypothetically restore erectile function as an intermediate step between conservative therapy and prosthetic implantation [2].

## Therapeutic Implications

The therapeutic consequences of this distinction are immediate. Phosphodiesterase type 5 inhibitors (PDE5i) act by enhancing Nitric Oxide (NO)-mediated smooth muscle relaxation: they require intact NOS activity, adequate smooth muscle mass expressing PDE5, and haemodynamically competent arterial supply. In advanced CHPED, all three conditions are progressively compromised [6, 15]. This mechanistically explains why PDE5i non-response correlates with longer ED duration, diabetes, and advanced age — all CHPED progression markers [4, 14].

Low-intensity extracorporeal shockwave therapy (Li-ESWT) is uniquely positioned as a regenerative rather than haemodynamic intervention. Its mechanisms include VEGF-mediated neoangiogenesis, endothelial progenitor cell recruitment via SDF-1/CXCR-4 signalling, and Schwann cell-mediated neuroregeneration [16]. Critically, animal data suggest Li-ESWT’s pro-erectile effect operates independently of the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway — demonstrated by additive effects with sildenafil in diabetic rat models [17]. Li-ESWT does not augment haemodynamics; it repairs tissue. This distinction is mechanistically fundamental and clinically actionable.

We therefore propose a mechanistically guided therapeutic cascade: classical vasculogenic ED (atherosclerotic obstruction, intact end-organ) → endovascular intervention [2]; early-to-intermediate CHPED (smooth muscle content >35%) → regenerative therapy (Li-ESWT, platelet-rich plasma (PRP)), risk factor treatment, hypogonadism correction; advanced CHPED (smooth muscle <35%, irreversible fibrosis) → venous embolisation in selected cases, prosthetic implantation at end-stage. Current standard of care reserves endovascular intervention for patients who have failed PDE5i therapy. If the CHPED framework is validated prospectively, this sequence may warrant reconsideration: early arterial revascularisation in patients with documented haemodynamic obstruction and preserved smooth muscle content could, in principle, prevent CHPED progression by restoring resting cavernous perfusion before irreversible fibrosis supervenes. This hypothesis requires prospective evaluation but is mechanistically coherent within the CHPED model. Precise staging prevents premature prosthetic escalation by identifying the actionable intermediate stage that current nomenclature obscures. Currently, therapeutic intervention in ED is typically initiated after the failure of PDE5i, reflecting a treatment paradigm focused on restoring erectile function at a symptomatic stage. Within the framework of CHPED, however, this approach may correspond to a relatively advanced phase of structural degeneration. This raises the question whether earlier, structure-preserving interventions could be beneficial before irreversible changes in cavernous tissue integrity occur, a concept that remains to be explored in future studies.

## Towards Operationalisation of CHPED

A legitimate challenge to any conceptual framework is operationalisability: can CHPED be identified clinically, without a biopsy? Four existing, validated approaches provide proxies for the key CHPED parameters. First, non-invasive tissue oximetry of the flaccid corpus cavernosum directly measures the chronic hypoxic state driving CHPED progression [7]. Padmanabhan and McCullough demonstrated that flaccid corporal oxygen saturation below 50% — the steepest portion of the haemoglobin dissociation curve — is significantly associated with ED severity and is independent of aetiology [7]. This instrument is FDA-approved, non-invasive, and clinically deployable. Second, the cavernous smooth muscle threshold of 35%, established by Wespes and colleagues as the morphometric boundary below which PDE5i therapy becomes mechanistically futile [5], provides a staging criterion for advanced CHPED. While biopsy remains the gold standard for direct quantification, shear wave elastography (SWE) of the flaccid corpus cavernosum offers a validated non-invasive alternative: tissue stiffness measured by SWE correlates inversely with smooth muscle cell content [18, 19], increases linearly with age and histological fibrosis [19], and distinguishes vasculogenic from non-vasculogenic ED subtypes with high sensitivity [20]. SWE therefore represents a clinically actionable proxy for cavernous structural integrity — and a candidate instrument for pre-interventional CHPED staging. Third, heart rate variability (HRV) assessment, as a validated marker of autonomic nervous system tone [13], offers a non-invasive means of identifying patients whose CHPED entry pathway is chronic sympathetic dysregulation. Together, these four parameters — flaccid penile oxygen saturation, cavernous tissue stiffness by SWE, smooth muscle content, and HRV — represent a preliminary, hypothesis-generating staging approach rather than a validated system. Prospective validation, including a pre-interventional SWE pilot study, is the immediate and necessary next step.

## Conclusion

The haemodynamic paradigm of vasculogenic ED has served urology well but has reached its explanatory limit. The structural cavernous pathology driving the majority of organic ED — and the therapeutic window for its regenerative treatment — is invisible within a framework defined by arterial flow velocity. The conceptual core of CHPED — and its most clinically actionable formulation — is the recognition that ED is, in its chronic structural form, a disease of the resting state. The detumescent state is not a passive absence of erection but an actively maintained, sympathetically driven condition under central nervous system control [11, 12]. Chronically elevated sympathetic tone — whether from cardiovascular risk, metabolic disease, or psychosocial stress — does not merely accompany ED: through the CC-EMG mechanism it may contribute to the deepening and prolongation of cavernous hypoxia, accelerating structural degeneration. This is the bridge between the psychosocial and the organic, between the central and the peripheral, between the reversible and the irreversible. It is also the mechanistic argument for early intervention: the CHPED window closes progressively, and regenerative therapy applied before irreversible fibrosis has the greatest chance of success. Restricting “vasculogenic ED” to its original haemodynamic meaning and introducing CHPED as a formally defined entity does not overturn existing knowledge: it completes it. The evidence base for this distinction has existed in the literature since the early 2000s [6]. What has been lacking is the conceptual synthesis and the clinical vocabulary to act on it. We offer both.

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