Erectile dysfunction (ED) is caused by microvascular or macrovascular insufficiency in the majority of patients. Recent studies have shown that hyperbaric oxygen therapy (HBOT) can induce angiogenesis in different body organs. The effect of HBOT on the non-surgery-related ED has not been investigated yet. The aim of the study “Hyperbaric oxygen can induce angiogenesis and recover erectile function” was to evaluate the effects of HBOT on sexual function and penile vascular bed in non-surgical ED patients. It is a prospective analysis of patients suffering from chronic ED treated with 40 daily HBOT sessions. Clinical efficacy was assessed using the International Index of Erectile Function questionnaire (IIEF) and a global efficacy question (GEQ). The effect on the penile vascular bed was evaluated by perfusion MRI.
Thirty men (mean age of 59.2 ± 1.4) suffering from ED for 4.2 ± 0.6 years completed the protocol. HBOT significantly improved all IIEF domains by 15–88% (p < 0.01). Erectile function improved by 88% (p < 0.0001) and 80% of the patients reported positive outcomes according to the GEQ. Angiogenesis was indicated by perfusion MRI that showed a significant increase by 153.3 ± 43.2% of K-trans values in the corpus cavernous (p < 0.0001). 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 cases of ED.
The normal erection is a complex event resulting from the coordinated function of psychological, neurological, hormonal, and vascular systems. Penile blood flow disruption due to inadequate vascular perfusion is present in at least 60% of the erectile dysfunction (ED) patients. The first-line therapy used for ED relies on the vasodilatation effect of phosphodiesterase-5 inhibitors (PDE5Is). However, since the vasodilatation effect of PDE5Is is transient and dependent on the presence of adequate blood vessels within the corpora cavernosa (CC), there is a need for a treatment modality that intervenes with the baseline pathology and induces generation of new blood vessels (angiogenesis). Hyperbaric oxygen therapy (HBOT) has been shown to induce angiogenesis in different tissues experiencing compromised blood perfusion such as the brain and non-healing wounds.
The effect of HBOT on penile angiogenesis has not been investigated yet. HBOT incorporates the inhalation of 100% oxygen at pressures exceeding 1 atmosphere absolute (ATA), thus increasing the amount of oxygen dissolved in the body tissues. One of the most interesting mechanisms induced by HBOT is angiogenesis mediated by the release of omnipotent stem cells capable of differentiating into endothelial cells. HBOT also boosts the release of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1alpha (HIF-1alpha), crucial mediators for the angiogenesis process. In addition, the improved oxygenation by HBOT creates the necessary environment needed for stem cell proliferation. Pre-clinical and clinical studies have demonstrated that HBOT can induce angiogenesis even in tissues with low regenerative potential such as the brain. Two studies, on both humans and animals, suggested a possible therapeutic effect of HBOT on ED related to surgical injuries. In the clinical study, which included a cohort of 12 men suffering from ED after posterior urethral reconstruction surgery, HBOT significantly improved erectile function .
The aim of the current study was to evaluate the effects of HBOT on sexual function and penile microvasculature in non-surgical ED patients.
A prospective analysis of men, age 18 years or older, with a clinical diagnosis of erectile dysfunction, of more than six months duration. The study was approved by the institutional review board, and all participants gave written informed consent prior to their inclusion. The study was registered in the US National Institute of Health Clinical Trails registry (NCT02619383). Exclusion criteria included penile anatomical defects, any active or history of malignancy including prostate cancer, spinal cord injury, any major psychiatric disorder uncontrolled with treatment, claustrophobia, chronic lung disease, or chronic middle ear or sinus diseases. Participants were allowed to continue with PDE5I medication if it was chronically used for more than 6 months prior to their inclusion.
The treatment comprised 40 daily hyperbaric sessions, 5 days a week. Each session consisted of 90 min of exposure to 100% oxygen at 2 ATA with 5 min air breaks every 30 min.
Between June 2013 to May 2015, 42 men suffering from ED were screened. Two did not fulfill inclusion criteria and 3 were excluded due to contraindications (2 middle ear diseases, 1 active malignancy). HBOT was applied for 37 patients. Seven patients did not complete 40 hyperbaric sessions (6 due to barotrauma, 1 claustrophobia). Accordingly, 30 men completed the study and were included in the final analysis. The mean age was 59.2 ± 1.4 years and the mean duration of symptoms prior to inclusion was 4.2 ± 0.6 years. All 30 patients reported having previous experience with PDE5Is; 46.7% continued using PDE5Is while in the study.
HBOT improved the mean scores of IIEF questions assessing the frequency of penetration (3.0 ± 0.2 post-HBOT vs. 1.9 ± 0.2 pre-HBOT, p < 0.001) and maintenance of erections after penetration (3.4 ± 0.2 post-HBOT vs. 1.7 ± 0.2 pre-HBOT, p < 0.001). The percent increase from the base line was 58% for question 3 and 100% for question 4. Penetration and maintenance of erections improved to a response level of 4 or 5 (“success most times”) in 50% of men who were at level 0 or 1 (“no attempts or almost never successful”) before treatment, and in 50% and 70% of men who were at level 2 and 3 (“success at half or less than half the times”), respectively, prior to the treatment. HBOT increased the mean scores for the erectile function domain by 10.4 ± 1.2 (90%) (p < 0.001).
After HBOT, 63% of the men had none to mild erectile dysfunction (total of questions 1, 2, 3, 4, 5, and 15 was within 19-30). The mean scores for the orgasmic-function, intercourse-satisfaction, and overall satisfaction domains were significantly improved by 29–59% after HBOT (p < 0.001). After HBOT, 24 of the 30 men (80%) reported improved erections (global efficacy question). Age, duration of symptoms, BMI, the presence of diabetes mellitus, hypertension, dyslipidemia, ischemic heart disease, history of smoking, and concurrent use of PDE5Is did not affect any of the above-mentioned outcome measures (p > 0.1).
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.
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 an unsatisfactory response to PDE5Is. Further studies are needed to evaluate the subgroups of men who can benefit the most from this treatment.
Amir Hadanny; Erez Lang; Laurian Copel; Oshra Meir; Yair Bechor; Gregory Fishlev; Jacob Bergan; Amnon Zisman y Shai Efrati. 2018. Hyperbaric oxygen can induce angiogenesis and recover erectile function.
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