The present study shows for the first time that penile angiogenesis and improved erectile function can be induced by HBOT in men suffering from chronic non-surgical ED. The improvement in sexual performance was significant in all IIEF domains and was most noticeable in both erectile function and the global efficacy question responses. Penile angiogenesis was demonstrated by perfusion MRI analysis.

Vascular integrity, including appropriate vascular dilatation and increased blood flow to the cavernous sinusoidal system, is a key component of the physiology of penile erections. Endothelial dysfunction, atherosclerosis and microvascular diseases disrupt the penile blood flow and accordingly vascular etiology is the leading cause of ED. Because of the small diameter of penile arteries (1–2 mm), compared with other arteries (such as coronary arteries), the same level of endothelial dysfunction and atherosclerosis may lead to a clinically more significant reduction of blood flow to the penis culminating in ED. Consequently, ED can be the earliest symptom of cardiovascular disease.

Angiogenesis is the sprouting of new blood vessels using vasculogenic stem cells which differentiate into endothelial cells, as well as other supporting structures. The use of stem cells and/or angiogenic growth factors for erectile dysfunction has been suggested previously. Several pre-clinical studies have shown beneficial effects using intracavernosal injections of bone marrow stem cells, as well as VEGF in different rat models. Both mobilization of vasculogenic stem cells and induction of angiogenic factors release (such as VEGF and HIF-1alpha) can be induced by repetitive HBOT sessions. Recent studies in patients suffering chronic neurological impairments stemming from stroke, traumatic brain injury and anoxic brain injury have shown that HBOT neuro-therapeutic effects are mediated by brain angiogenesis.

One of the known differentiation characteristics of newly formed blood vessels is their relatively high leakage compared to normal blood vessels. The high leakage of these newly formed blood vessels has been exploited to demonstrate angiogenesis using DCE-MRI. In the present study, by use of DCE-MRI and demonstration of higher K-trans values after HBOT, it was clearly demonstrated that angiogenesis was induced in the penis CC. The demonstrated penile angiogenesis may be one of the underlying physiological mechanisms responsible for the beneficial clinical effect of HBOT on erectile and sexual functions.

When compared to PDE5I or other ED treatments, HBOT holds the promise of unique new intervention modality with several advantages and disadvantages. Starting with the advantages, the induction of angiogenesis by HBOT is aiming for resolution of the basic vascular pathology instead of short-term symptomatic relief. PDE5I or other penile injections/interventions require pre-planning and preparation prior to sexual intercourse. When compared to PDE5I, HBOT enables regaining the ability to have spontaneous or unplanned intercourse. Second, diabetic patients had similar efficacy with HBOT, unlike the lower efficacy seen with PDE5I. The third and most important advantage relates to the high potency of HBOT even in men in whom PDE5Is have no beneficial effect, compared to at least 30% of patients who do not regain erectile function using PDE5Is. In the current study population, ED persisted 4.2 ± 0.6 years prior to inclusion and all men used PDE5Is prior to inclusion without gaining satisfactory erectile function. HBOT carries two main disadvantages. First, while PDE5Is or intracavernosal injections have immediate effect, in HBOT, as in other regenerative therapies, the beneficial effect can be recognized only after a series of sessions. Second, HBOT sessions require considerable time and dedication (40 daily treatments, 90 min each).

HBOT is considered to be a safe method of treatment in general, in other vascular related pathologies and was found to be safe also for ED patients. In general, the main adverse effects include middle ear or sinus barotraumas which are usually mild and temporary, with complete resolution after several days. In the current study, the six patients who stopped HBOT due to barotrauma could have continued the treatment with no additional risk if they so wanted.

Our study has several limitations. The first is related to the relatively small number of patients. However, the clear statistical significant effect (a two-way pairwise method analysis) has considerable power (100%) even in a small group of patients. Second, our study lacks an appropriate control/placebo group. Nevertheless, one should not expect any significant improvement in IIEF questionnaires within 3 months in men suffering from ED for several years. In addition, the improvement in penile perfusion was clearly noticeable in objective analysis of perfusion MRI. The correlation between the clinical and the objective penile perfusion MRI findings give further strength to study results. Third, HBOT is a rather costly therapy compared to the accepted medications.

This is the first study evaluating the effect of HBOT on this population suffering from chronic non-surgical ED. Additional, studies are necessary in order to evaluate which subgroups of patients can benefit the most from this treatment, and the optimal HBOT protocol needed for those patients.

HBOT can induce penile angiogenesis and improve erectile function in men suffering from ED. HBOT reverses the basic common pathophysiology, atherosclerosis and decreased penile perfusion, responsible for most of ED cases. The treatment can be considered even years after the onset of erectile dysfunction and in men with unsatisfactory response to PDE5Is. Further studies are needed to evaluate the subgroups of men who can benefit the most from this treatment.

Source: https://www.nature.com/articles/s41443-018-0023-9