Abstract
Purpose of Review
This study aimed to review recent evidence on conservative non-surgical options for erectile dysfunction (ED) in men. A narrative review of the literature was performed. A comprehensive search in the MEDLINE, Embase, and Cochrane databases was done. Papers in English language, published from May 2017 until May 2022, were included. Papers reporting basic research or animal research were excluded, as long as reviews or meta-analyses. Congress reports, clinical cases, or clinical trials protocols with no results were also excluded.
Recent Findings
We found a multitude of different treatment modalities for ED. We must take into account the type of patient, their comorbidities, the origin of their ED, and its severity in order to reproduce effective results using these therapies. Some of the treatments show good results with a good level of evidence (new IPDE5 formulations, intracavernous injections, shock wave therapy, hormonal theraphy, psycho-sexual theraphy). However, others (some new molecules, stem cell theraphy, platelet-rich plasma injections, oxygenation-based therapy, nutraceuticals), although some of them present promising results, require randomized studies with a larger number of patients and a longer follow-up time to be able to establish firm recommendations.
Summary
Regarding the conservative treatment of erectile dysfunction, in recent years, some therapies have been consolidated as effective and safe for certain types of patients. On the other hand, other treatment modalities, although promising, still lack the evidence and the necessary follow-up to be recommended in daily practice.
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Introduction
Erectile dysfunction (ED) is defined as the persistent inability to achieve and maintain an erection hard enough to permit satisfactory sexual intercourse [1]. According to the five-item International Index of Erectile Function questionnaire (IIEF-5) score, ED severity is classified on severe (score 1–7), moderate (8–11), mild-moderate (12–16), mild (17–21), and no ED (22–25) [2].
ED has become a major health concern even in younger men, causing a significant impact on men’s quality of life [3]. Its prevalence varies on the different series published, but it is constantly high. In the Boston area, 52% of men between 40 and 70 years old were shown to suffer some grade of ED, according to the Massachusetts Male Aging Study (MMAS) [4]. Generally, ED can be considered as a natural part of aging, and its prevalence increases with age, ranging from 12% in those men < 59 years, 22% in men 60–69 years, and 30% in men > 69 years old, as per a population-based study of US health professionals [5]. In a cross-sectional real-life study performed among men asking for their first medical help for new-onset ED, 25% of patients were younger than 40 years old, with almost 50% of the younger men complaining of severe ED [6]. It is expected that by the end of 2025, the number of ED cases can rise to as high as 322 million across the world [7].
Treatment of ED has evolved along the years, with the introduction of sildenafil, the first 5-phosphodiesterase inhibitor (5-PDEi), as a major milestone in the late 1990s [8]. Since then, clinical practice guidelines have established different algorithms and recommendations, usually proposing therapeutic lines depending on the invasiveness of the treatments [9]. But recently, the European Association of Urology Guidelines on Sexual and Reproductive Health have proposed some changes in this paradigm [10]. Thereby, some treatments are no longer considered second-line options, and they can be offered to patients according to their preferences and their clinical situation, like intracavernous injections (ICI) or topical or intraurethral alprostadil. Also, some treatments previously considered experimental have recently been included in clinical practice guidelines according to their growing scientific evidence, like shockwave therapy. In the present paper, we aimed to comprehensively review the evidence on non-surgical treatments for ED of the last 5 years (2017–2022), focusing on the new developments.
Methods
Search Strategy
A non-systematic review of the literature was carried out using the MeSH terms “erectile dysfunction/drug therapy” or “erectile dysfunction/therapy,” or using free language terms, erectile dysfunction and treatment or therap*, from May 2017 to May 2022. Language was limited to English. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations [11] were used to guide reporting of the study. The search was initially carried out in the electronic database PubMed and identified a total of 1871 articles. The search was then limited separately to articles published in EMBASE and Cochrane (1512 publications). Both searches were subsequently compared, duplicates eliminated, and a final total of 2729 articles identified for review.
Eligibility Criteria
Only original papers of clinical prospective and retrospective studies assessing the outcomes of different conservative (non-surgical) therapies for ED in men > 18 years old were included for revision. Therefore, papers reporting basic research or animal research were excluded, as long as reviews or meta-analyses. Congress reports, clinical cases, or clinical trials protocols with no results were also excluded. Papers reporting the results of rehabilitation therapy for ED after radical pelvic surgery were not considered for revision.
Study Selection and Data Extraction
A total of 2729 papers were reviewed by two different experts in the field. After filtering for the previous inclusion/exclusion criteria, and excluding those not matching the search criteria in terms of date, language, and publication type, a total of 199 papers were finally considered for revision. The process of paper selection is represented in Fig. 1. Then, relevant data from these papers were extracted, considering the interventional type of treatment, type of ED, the number of patients included, the follow-up period, rate of success in correcting ED, the tool used to measure ED, adverse events, and satisfaction rate, if available. Each study was identified by the first author and year of publication.
Search flow diagram
Results
Psycho-sexual Therapy
A total of seven papers evaluating phyco-sexual interventions to treat DE were included, and their characteristics are resumed in Table 1.
Cognitive behavioral sexual therapy (CBST) is the most common intervention studied, with five out of the seven papers evaluating it. In four of them, only non-organic erectile dysfunction (NOED) patients were included, whereas in the remaining three, psycho-sexual therapy was studied in order to improve the results in any kind of ED. Six of the papers analyzed showed a significant and positive result of the psycho-sexual therapies in improving DE, according to the scores of the different questionnaires used. The study by Bossio et al. [17] found a positive but not significant effect of a mindfulness intervention in a small sample of 10 patients with NOED.
Hormonal Therapy
Six papers studied the effect of testosterone therapy (TT) to improve ED as a single therapy in hypogonadal men [19–24], with different formulations. All of them showed a benefit of the TT, according to the scores of the IIEF-EF or the IIEF-5. The remaining paper compared the results of TT alone or in combination with tadalafil 10 mg on alternate days [25], in a randomized, crossover study with 29 patients. It demonstrated higher satisfaction rates in the combination group.
5-PDE5i
Forty papers investigating the effects of PDE5is were identified. The results are resumed in Table 2.
Topical Drugs
Two papers analyzed the use of topical alprostadil to treat ED. In one of them [66], 71 patients were randomized to receive 300 μg of alprostadil over the glans, as the standard administration route, or within the urethral meatus, as an alternative administration route. The results showed that the alternative administration route achieved better results in terms of IIEF-5 score (+ 3.8 vs + 6.3, p < 0.001), and positive response to sex encounter profile (SEP)-2 (10 vs 27, p < 0.001), with no differences in the profile safety. The paper by Garrido-Abad et al. [67] evaluated the efficacy of topical alprostadil alone or in combination with maximum doses of PDE5i in patients non-responding to PDE5i alone. Those in the combination group presented higher IIEF-5 scores after the treatment (12.4 vs 17.1, p < 0.001), whereas those in the alprostadil alone group showed no significant improvement (12.2 vs 12.7, p = 0.148).
A randomized, placebo-controlled trial by Ralph et al. [68] assessed the efficacy of a novel topical gel containing 0.2% of glyceryl trinitrate (GNT), and is currently under investigation to become an agent to treat ED. It is supposed to have a fast absorption, minutes-length erection, and satisfactory safety profile. Treated patients showed a slight but significant higher score in the IIEF-EF comparing with those receiving placebo (19.6 vs 18.5, p = 0.0132), with a greater increase in the mild ED group (23.1 vs 21.3, p < 0.001).
Shockwave Therapy
A number of 29 papers analyzing the results of different regimes of shockwave therapy in the management of ED were identified. Their results are resumed in Table 3.
Stem Cells
A total of 10 papers evaluating the utility of stem cells for ED were found. Great heterogenicity was found in respect to the type of stem cell used: in four [114–117], they used bone marrow cells, whereas in the other six, they used mesenchymal stem cells [118–123]. Additionally, other paper studied the effect of stem cell-derived bioactive molecules to restore erectile function (EF) [124]. In all of them, ED is evaluated according to IIEF-5, and in half of them, they also include an assessment of penile hemodynamics with a color Doppler ultrasound. The number of patients included is low in all of them (5-40), 8 papers being pilot phase I studies. Only one [119] is a randomized single-blinded clinical trial, in which 20 diabetic, PDE5i non-responder patients were administered either intracavernosal autologous mesenchymal stem cells or placebo. In the treatment group, mean IIEF-5 score was 7.2 ± 2.1, 9.2 ± 3.4, and 10.6 ± 4.7 before, 3 months, and 6 months after the injection, respectively (p = 0.01). This follow-up time is common in most of the studies, with the exception of the one by Yiou et al. [117], with a mean follow-up of 62.1 ± 11.7 months, in which a slow decline on EF was observed after the improvement in the first year. This trend was also observed in other papers with lower follow-up times [120, 122].
Phytotherapy/Nutraceuticals
Twenty-six papers investigating the effect in DE of different phytotherapy or nutraceutical agents have been identified. Nineteen studies analyzed the effect of as many substances in mild ED or special-to-treat patients [125–142]. Most of them showed a positive effect of these substances as a single therapy or, most commonly, as a concomitant treatment added to a standard oral therapy.
Three papers investigated the utility of l-arginine for patients with ED. Gallo et al. [143] demonstrated that the combination of l-arginine and oral daily tadalafil 5 mg was superior to both therapies alone (IIEF-EF: + 7.1 vs + 3.1 vs + 6, respectively, p < 0.0001). Similar results were reported by Abu El-Hamd et al. [144] (SHIM: + 13.69 vs + 10.33 vs 12.27, p < 0.0001), who also found that treatment with l-arginine, tadalafil, or its combination conducted to a significative increase in testosterone levels in all patients, in contrast to placebo (+ 2.37 vs + 9.04 vs + 11.23 nmol/L for l-arginine, tadalafil, and combination groups, respectively; p < 0.0001). In a recent study, Menafra et al. [145] showed that supplementation with high doses of l-arginine alone for 3 months conducted to an increase in the score of the IIEF-6 (+ 4, p < 0.0001) and in the peak systolic volume (PSV) (+ 4.6 cm/s, p < 0.0001) in contrast to placebo.
Tribulus terrestris is a plant originating from Bulgaria that is considered to be an herbal steroid. Its effect in ED in hypogonadal men has been investigated by GamalEl Din et al. [146], where they found an improvement in IIEF-5 score (+ 5.4, p < 0.0001) and in the testosterone levels (+ 0.58 nmol/L, p < 0.0001), compared to placebo. Kamenov et al. [147] conducted a RCT in a cohort of 180 patients with mild or moderate ED who were treated with Tribulus or placebo. After 12 weeks, they found a significant difference in IIEF scores for the treatment group (+ 4.75 vs 1.97, p < 0.0001).
The response to vitamin D supplementation in patients with ED and deficiency of this element has been studied in two papers, both comparing the effect of regular tadalafil intake only or in combination with vitamin D. Demirci et al. [148] found better scores in IIEF-EF in the combination group after 3 months (+ 13 vs + 8, p = 0.01), similarly to Ali et al. [149] that found a higher improvement in IIEF-5 scores in the combination group compared to tadalafil only (+ 8.44 vs + 5.72, p = 0.012).
Platelet-Rich Plasma Injections
Intracavernosal therapy with platelet-rich plasma (PRP) was assessed in 6 papers in the last years. Their results are presented in Table 4.
Effect of Previously Known Molecules on ED
The effect of different established drugs for other indications has been studied in several papers, including mirabegron, aspirin, bupropion, cabergoline, and levotiroxin.
Mirabegron is a selective β3 adrenergic receptor agonist that is supposed to cause relaxation of the vascular smooth muscle cells of the corpora cavernosa [156]. Its effect on ED has been studied in two recent articles. In the first, a pilot study by Karakus et al. [157], 20 patients with DE and lower urinary tract symptoms (LUTS) were administered mirabegron for 12 weeks. After this period, 38.5% of the patients improved the IIEF-5 score ≥ 4 points, whereas in 61.5 there was no variation. These results were widely studied in a RCT by Elbaz et al. [158], in which 55 patients with ED and LUTS were randomized to receive mirabegron and doxazosin (treatment group) or tolterodine and doxazosin (control) for 12 weeks. The found a significant difference in IIEF score improvement between both groups (+ 15 vs + 3, p < 0.05).
Aspirin has also been evaluated as a potential treatment for ED, given its antiplatelet action. In a paper by Bayraktar and Albayrak [159], 184 patients with vasculogenic ED were randomized to take aspirin 100 mg daily for 6 weeks or placebo. They found significant differences in IIEF-EF (+ 7.2 vs + 2, p < 0.0001), and in the SEP 2 and 3. The same group published later the results of a study in which 336 patients were randomized to take aspirin 100 mg daily, tadalafil 5 mg daily, both drugs, or placebo for 6 weeks [160]. They found similar improvements in IIEF-EF scores in all treatment groups, with a weaker increment in the placebo group (+ 7.2, + 7.3, + 7.5, p < 0.0001 vs + 2.0, p = 0.0204).
Bupropion is an antidepressant with a dual reuptake inhibitor of dopamine and norepinephrine mechanism, and it has been hypothesized to have a benefit on DE. Ghoreishi et al. [161] studied its effects on a cohort of 40 patients with chronic kidney disease, who were randomized to treatment or placebo. After a 10-week period, changes in the IIEF were higher in the treatment than in the control group (+ 2.75 vs + 0.35, p < 0.005). Similarly, Yee et al. [162] studied the effect of bupropion against placebo on a randomized cohort of 80 male patients on methadone with ED for 6 weeks. Significant changes in the IIEF score (+ 8.37, p = 0.02) and in the total plasma testosterone level (+ 4.03 nmol/L, p = 0.01) were observed.
The effect of adding cabergoline to daily tadalafil was compared to daily tadalafil alone in a group of 580 patients diagnosed with psychogenic ED in a paper by Mohammad et al. [163]. They found that 92.7% of the patients in the combination group improved the EF, in contrast with a 53.6% of the patients in the tadalafil group (p < 0.05). Cannarella et al. [164] found that levothyroxine improved arterial ED in patients with subclinical hypothyroidism, according to IIEF-5 score (20.2 in the treatment group, no changes in the control group, p < 0.05). Also, a subanalysis of a systolic blood pressure intervention trial [165] found that an intensive treatment of high systolic blood pressure (goal of < 120 mmHg), in contrast to a standard treatment (goal of < 140 mmHg), had very small impact on ED, according to IIEF-5.
ICI of Vaso-active Agents
A total of six papers analyzing the effect of different types of intracavernosal botulinum toxin injections were evaluated, and the results are resumed in Table 5.
Besides, other ICI were studied in three more papers. Taşkapu et al. [172] demonstrated that adding clomiphene citrate to alprostadil 10 or 20 μg in late-onset hypogonadism men offered great results in ED scores (IIEF-EF + 11.07, EHS + 1.52, p < 0.001). Bernie et al. [173] compared a classical empirical approach algorithm of ICI to a new, risk-based approach, not observing significant differences in multiple domains of sexual function. A retrospective study by Bearelly et al. [174] showed that a cohort of 105 patients treated with different ICI combinations presented good response to their ED after a mean duration of therapy of 8.4 years, according to the IIEF-EF scores (+ 11.8, p < 0.05).
Oxygenation-Based Therapies
The effect on ED of both continuous positive airway pressure (CPAP) and hyperbaric oxygen therapy (HBOT) has been investigated. The results for these therapies are resumed in Table 6.
Other Physical Therapies
Finally, four articles were classified under the epigraph of “other physical therapies.” Two papers referred to the effect of electrostimulation (ES) in the management of ED. The first [183] was a RCT that compared a group of 15 young patients (39.17 ± 6.21) who received ES with another 15 who were proposed to aerobic exercise. After 6 weeks, the ES group presented a better score in the IIEF-5 compared to the exercise group (20.83 vs 14.33, p = 0.001). Similarly, the second paper [184] compared ES against a control group in a cohort of 22 patients, finding better significative (p < 0.05) scores in the IIEF-5 and EHS for the treatment group.
One paper [185] presented the results of a novel therapy of low-intensity pulsed ultrasound (LIPUS) in treating mild to moderate ED. A total of 120 patients were randomized to LIPUS [80] or sham treatment. They defined success as an improvement in the IIEF-5 ≥ 2 points, being the response after the complete therapy of 71.01% of patients in the LIPUS arm compared to 17.65% in the sham group (p < 0.05).
Finally, Juho et al. [186] presented a study in which they evaluated the efficacy of a far-infrarred textile on the underwear of 30 patients with vasculogenic ED, who were randomized to wear the assessed underwear or a regular one. Although an improvement on the IIEF-5 score, the PSV, and the end diastolic flow was observed, it did not reach statistical significance.
Discussion
Studies related to psycho-sexual therapy are quite heterogeneous, most dealing with psychogenic ED in young patients. Cognitive behavioral therapy is the most studied treatment modality. Treatment combining cognitive-behavioral therapy and PDE5is achieves improvements in ED, as well as a significant reduction in anxiety and depression compared to PDE5is monotherapy [12•, 13, 16, 18]. A pilot study [17], with a reduced number of patients (n = 10) and no control group, studied the use of mindfulness-based group therapy in situational ED. No significant improvements in ED or overall satisfaction were appreciated. According to the analyzed data, it seems that psycho-sexual therapy, and specifically cognitive behavioral therapy (CBT), may be a useful treatment for the treatment of psychogenic ED in young patients, improving the effect of oral therapies in some cases and reducing anxiety and depression associated with the disease.
Hormone replacement therapy, both in monotherapy [19–24] and in combination with PDE5is [25], has shown significant benefits in the treatment of EF in patients with hypogonadism. This represents a reminder of the need of requesting testosterone levels in the study of patients with ED and offers hormonal treatment if needed.
With regard to classical oral treatments of 5-phosphodiesterase inhibitors, there have been no major developments in the last 5 years. In fact, we have only found in this review a single study on a new molecule: mirodenafil [26]. Sildenafil, vardenafil, tadalafil, and avanafil are still the most used PDE5is. Trials comparing the efficacy and safety of PDE5is are still lacking, with available data suggesting similar efficacy and safety profiles [27, 58]. Many publications report the effectiveness of daily tadalafil therapy, but there is still little published evidence comparing its efficacy versus on-demand use for the treatment of erectile dysfunction [56]. We found quite a few publications that study the recent new formulations: orodispersible tablets (ODT) [65], orodispersible films (ODF) [26, 33, 38, 61], and orally disintegrating strips [29]. These may be an advantage for patients who have difficulty swallowing tablets and for those who will benefit of a rapid onset of action, because of the more discreet route of administration which some patients may prefer.
The application of alprostadil inside the urethra has shown greater efficacy compared to classic topical administration with a similar safety profile [66, 67]. In addition, the combination therapy of alprostadil administered intraurethral together with 5-phosphodiesterase inhibitors [67] showed better results in the treatment of ED compared to inhibitors in monotherapy.
Regarding low-intensity shockwave therapy (Li-ESWT), there are very heterogeneous studies, even if they study the same treatment modality. This is due to several factors such as the diversity of treatment protocols (energy, type of focus, duration of sessions, number of sessions, etc.), the different devices used, the combination or not of other therapies, and the different evaluation methods. Due to this great heterogeneity regarding different energies and administration protocols, several articles strive to compare different treatment modalities [78, 81, 86, 87, 105]. The results proved to be comparable in the different evaluators’ treatment methods, without statistically significant differences. Li-ESWT is a clinically effective and safe treatment for erectile dysfunction regardless of generator type, source, emitted shock wave morphology, and treatment protocol [105, 107, 110, 113]. Most common inhibitor included in the Li-ESWT protocol is tadalafil [92, 93, 95, 104]. The preferred dose is 5 mg daily. Most of the studies showed a significant improvement in EF and penile rigidity, which was greater when the use of Li-ESWT was combined with PDEis, without reporting significant changes in its safety profile. Several publications [76, 104, 111] conclude that Li-ESWT is also effective in patients refractory to PDE5is, being able to directly improve their EF in some and make them respond to oral treatment in others. Results are better in younger patients, with ED of vascular origin, with fewer comorbidities, and with mild or moderate ED [107, 108, 111]. Long-term loss of efficacy has been reported, suggesting the need for follow-up and the possibility of repeating therapy [71•, 88, 107]. Li-ESWT appears to be an effective and safe method for the treatment of erectile dysfunction in diabetic patients [100, 101, 109]. Other studies demonstrated the efficacy and safety of Li-ESWT treating ED in patients with chronic pelvic pain syndrome [97], post-prostatectomy [99], pelvic fractures with urethral damage [104], and renal transplant patients [103].
The vast majority of available studies on stem cell therapy (SCT) had a small sample size, had no control group, and had other relevant methodological limitations. Due to the heterogeneity present in the studies regarding the type, the optimal dose, or the route of administration of SCT, the comparison of results is very difficult. Despite encouraging initial results in terms of efficacy and safety, these issues do not yet allow firm conclusions to be drawn.
The use of nutraceuticals as a treatment for erectile dysfunction is controversial. Patients may perceive this type of therapy as more natural and safer. In addition, they can be obtained without a prescription and bought online and lack adequate health controls [187]. The use of nutraceuticals in erectile dysfunction has a very ancient history and has its roots in traditional Chinese medicine and Ayurvedic medicine [188]. Promising improvements in EF have recently been described with different nutraceuticals: l-arginine [143–145], Tribulus terrestris [146, 147], vitamin D [148, 149], panax ginseng [126], l-citrulline [127, 128], muira puama [133], and Ginkgo biloba [125]. However, the available studies on the subject are methodologically heterogeneous and generally of low quality, often reporting contradictory results, so recommendations on its use have not yet been established [9, 10].
We found 6 papers that analyze the effect of intracavernous injections PRP for the treatment of erectile dysfunction. Only one of the papers [153•] is a double-blind, randomized, placebo-controlled clinical trial. It is also the one that analyzes a greater number of patients (n = 60), obtaining a significant improvement in EF and patient satisfaction. Most studies [150, 151, 154, 155] reported statistically and clinically significant improvements in EF. In addition, smoking status, HbA1C, and severity of ED before treatment were strengthened as negative predictors of response to treatment [150, 154]. In general, no significant adverse effects were reported in any of the studies, the most frequent being mild pain at the injection site and mild penile bruising [151]. Therefore, analyzing the limited data available, it suggests that PRP can be used successfully for the treatment of ED. However, the available data is limited by its small sample size, short follow-up, and/or lack of controls. We also do not have standardized methods to prepare PRP or standardized treatment protocols.
In the last 5 years, the effect on EF of several drugs used for the treatment of other pathologies has been studied. Published papers include mirabegron [156, 157], aspirin [159, 160], bupropion [161, 162], cabergoline [163], and levothyroxine [164]. Most of the studies, although they analyzed different and special populations, found a significant difference in the improvement of ED. Only a few works did not find significant differences [160, 165]. It remains to be determined and it can be discussed whether the improvement in EF in some cases is due directly to the effect of the molecule or to the improvement of the underlying pathology of the patient (e.g., LUTS, hypothyroidism).
The use of intracavernous injections of botulinum toxin for the treatment of ED has recently been studied. We found three retrospective studies [166, 167, 171], and three double-blind randomized clinical trials [168, 169, 170•]. An improvement in the EF of patients was demonstrated, improving the results at high doses [168, 170•]. However, this therapy, although promising, still lacks long-term results, unlike the classic vaso-active drugs for the treatment of ED [174].
We have found five studies evaluating the effect of CPAP on EF [175, 176, 178–180]. In total, they include 318 patients with a follow-up time of between 3 and 12 months. Only one of the works is a clinical trial against placebo [180]. The correct use of CPAP improved both EF, sexual desire, general sexual satisfaction, self-esteem, relationship, and treatment, as well as drowsiness and quality of life. This improvement in EF was clinically significant in all but one study [176]. In addition, a trend of correlation between improvement in EF and hours of CPAP use was reported [175, 179].
Three papers have also been published [177, 181, 182] that evaluate the efficacy of hyperbaric therapy on EF. Significant improvements in IIEF and absence of adverse effects were reported. Unfortunately, all three are prospective pilot studies with a very short follow-up time (5-6 weeks). Innovatively, one of the works also demonstrates a significant improvement in angiogenesis measured by perfusion magnetic resonance imaging [182]. Therapies based on improving tissue oxygenation also seem promising therapies for the treatment of ED; however, the evidence is still scarce and long-term follow-up studies are lacking.
Conclusion
Numerous publications related to the conservative treatment of ED have been carried out. The significant rate of discontinuation of available therapies and the paucity of curative options prompted research on possible new treatments. In some cases, we must take into account the type of patient, their comorbidities, the origin of their ED, and its severity in order to reproduce effective results using these therapies. Some of these new treatments show good results with a good level of evidence (new PDE5i formulations, intracavernous injections, Li-ESWT, hormonal therapy). However, others (some new molecules, SCT, PRP, oxygenation-based therapies), although they present promising results, require better quality studies to establish firm recommendations.
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Alonso-Isa, M., García-Gómez, B., González-Ginel, I. et al. Conservative Non-surgical Options for Erectile Dysfunction. Curr Urol Rep 24, 75–104 (2023). https://doi.org/10.1007/s11934-022-01137-2
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DOI: https://doi.org/10.1007/s11934-022-01137-2