VOLUME 5; ISSUE 3 2026 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE This publication is intended for registered healthcare professionals only.
VOLUME 5; ISSUE 3 2026 Editor Prof Shingai Mutambirwa - Urologist MBChB, MMed (Urology) Medunsa Head of Urology - Sefako Makgatho Health Sciences University Chairman - The South African Urological Association Academic committee Chairman - Medical and Scientic Advisory Board of The Prostate Cancer Foundation Editorial Board Dr. Sheynaz Bassa - Clinical and Radiation Oncologist MBChB (Univ of Natal), FC Rad (Onc) SA Head of Department: Radiation Oncology Steve Biko Academic Hospital and The University of Pretoria Dr Jireh Serfontein - Medical Sexologist MBChB (Pret.), Dip HIV Management, MMed Sexual Health (Univ. Sydney) Clinical head: My Sexual Health Pretoria Andrew Oberholzer - Staff Writer Nat Dip Pod. Dip IMM CEO Prostate Cancer Foundation Editorial and Publishing Ofce Maria Philippou Randburg 2194 Enquiries 082 3355 444 Publisher Maria Philippou Andrew Oberholzer Disclaimer All rights reserved. No editorial matter published in Urology, Urooncology and Sexology Update may be reproduced in any form or language without written permission from the publishers. While every effort is made to ensure accurate reproduction, the Prostate Cancer Foundation, the authors, publishers and their employees or agents shall not be responsible or in any way liable for any errors, omissions or inaccuracies in the publication whether arising from negligence or for any consequences arising there from. The inclusion or exclusion of any product does not mean that the Prostate Cancer Foundation, the publisher or the editorial board advocates or rejects its use either generally or in any particular eld or elds. This publication is intended for registered healthcare professionals only. If you received this publication or a link to this publication in error, please do not directly or indirectly use, print, copy, forward, or disclose any part of this publication. Please delete the copy or link to the publication and notify the publisher. UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE CONTENTS 1 UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE Supported by: Awareness and prevalence of the symptoms of testosterone deciency: a cross-sectional survey of community-dwelling men in the UK The United States is Making Testosterone Replacement Therapy More Accessible for US Military personnel. What's new in prostate cancer treatment and how do we improve disease free survival in high-risk prostate cancer: Report back from the plenary session at ASCO 2026 A Tribute to Dr Prinitha Pillay known as Prini Optimal prostate-specic antigen cutoff linked to improved prostate cancer survival New Nasal Spray for Erectile Dysfunction Now Available in Australia and the USA Low-Intensity Shockwave Therapy for Erectile Dysfunction: What the Evidence Actually Shows 2 7 8 12 13 14 16
2 Awareness and prevalence of the symptoms of testosterone deficiency: a cross-sectional survey of community-dwelling men in the UK 1. Background and Aim Testosterone deciency (TD), also known as low testosterone or male hypogonadism, is a condition associated with symptoms that can affect sexual health, physical performance, energy levels and psychological well-being. The clinical diagnosis is based on symptoms and morning serum testosterone levels. Despite its potential impact on quality of life, testosterone deciency may remain undiagnosed because its symptoms are often non-specic and men may not recognise them as possible signs of a hormonal problem. The age-related physiological changes attributable to low testosterone has received renewed interest in the last few years with the availability of testosterone replacement therapy (TRT) and the publication of the TRAVERSE study which demonstrated the relative safety of treatments. The study aimed to investigate: • How common symptoms associated with testosterone deciency are among men in the UK. • How aware men are of the symptoms and available treatments. • How many men reporting symptoms have received a formal diagnosis. • What barriers prevent men from seeking medical advice or treatment. 2. Methodology The researchers conducted a cross-sectional online survey of men living in the UK. • Participants: 973 adult men. • Age range: 18–86 years. • Survey: A 54-question questionnaire covering symptoms, awareness of testosterone deciency, treatment options and barriers to accessing healthcare. • Assessment tool: The quantitative Androgen Deciency in the Aging Male questionnaire (qADAM), which evaluates symptoms associated with testosterone deciency. The researchers also examined whether age and other demographic characteristics were associated with a greater likelihood of reporting symptoms. Importantly, the study assessed self-reported symptoms and awareness. It did not establish the prevalence of biochemically conrmed testosterone deciency through blood testing. 3. Key Findings A. Symptoms were common, but formal diagnoses were uncommon The study found a substantial gap between the number of men reporting symptoms associated with testosterone deciency and the number who had received a diagnosis. Authors: Vivian N. Liu, David Roy Huang, Aos Alaa, Benedict Hayhoe and Austen El-Osta Journal: BMJ Open, published 10 July 2025.
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4 The main nding is that symptoms associated with testosterone deciency were much more common than a formal diagnoses. However, the 49% gure represents men whose reported symptoms met the study's screening criteria, not men proven to have low testosterone levels. B. Older men were more likely to report symptoms Men aged over 50 were signicantly more likely to have symptom proles suggestive of testosterone deciency than men under 40. The odds were approximately 1.5–2 times higher in the older age groups, depending on the age group examined. Older men also reported more frequent problems with: • Libido and sexual function. • Energy levels. • Physical strength and endurance. • Sports performance. Interestingly, older men were also more likely to be unfamiliar with the symptoms and treatment options associated with low testosterone. These ndings suggest that increasing age may be associated with both a greater symptom burden and an ongoing need for better education about men's hormonal health. C. Awareness of testosterone deciency was limited Despite the frequency of reported symptoms, more than half of the respondents were unfamiliar with the signs and symptoms of testosterone deciency. Furthermore, 47% were unaware of treatment options such as testosterone replacement therapy. This lack of awareness may mean that some men do not recognise their symptoms as a potential reason to seek medical advice. The researchers also found that only 7% of respondents were satised with their access to resources relating to low testosterone in the UK. This nding highlights potential shortcomings in public education and access to information about men's hormonal health. D. Barriers to seeking medical advice The study identied several factors that prevented men from seeking medical advice or treatment. These ndings indicate that the challenge extends beyond identifying symptoms. Even when men experience symptoms that affect their quality of life, a lack of awareness, nancial concerns and social stigma may discourage them from seeking professional assessment. Finding Percentage Men with symptom proles suggestive of testosterone deciency 49% Men with low libido 31% Men reporting reduced erectile strength 27% Men reporting more than three symptoms associated with testosterone deciency 26% Men who had received a formal diagnosis of testosterone deciency Approximately 5% Men unfamiliar with the signs and symptoms of testosterone deciency 55% Men unfamiliar with treatment options such as testosterone replacement therapy (TRT) 47% Barrier Percentage of respondents Lack of awareness of symptoms 39% Financial costs 35% Stigma surrounding hormonal health 29% Lack of time 26% Source: Liu et al., BMJ Open, 2025.
5 The study also found that men reporting more severe symptom proles tended to demonstrate reduced health-seeking behaviour. 4. Strengths and Limitations Strengths • The study included a relatively large sample of 973 men. • It investigated symptom prevalence alongside awareness, diagnosis and barriers to healthcare. • It provides useful insight into potential gaps in men's hormonal health education and access to care. Limitations • Symptoms do not conrm testosterone deciency. Many symptoms associated with low testosterone can also occur with other medical conditions, including depression, obesity, sleep disorders and chronic illness. • No biochemical conrmation: The study did not establish the proportion of respondents with testosterone levels below the clinical reference range. • Online recruitment: Men without reliable internet access or those less inclined to participate in online surveys may have been underrepresented. • Self-reported data: Responses may have been affected by recall, personal perceptions or reluctance to disclose sensitive health information. • Cross-sectional design: The study provides a snapshot at one point in time and cannot establish cause-and-effect relationships. • Generalisation: The ndings may not represent all men in the UK or men in other countries. Consequently, the results should be interpreted as evidence of a potentially substantial burden of symptoms, rather than proof that nearly half of men have testosterone deciency. 5. Implications for Men's Health The study has several important implications. First, education is essential. Men need better information about the potential symptoms of testosterone deciency and when to seek medical advice. Second, symptoms should not be dismissed. Persistent problems with libido, erectile function, energy or physical performance warrant appropriate clinical assessment, although they do not necessarily indicate low testosterone. Third, diagnosis needs to be distinguished from screening. A symptom questionnaire can identify men who may benet from further investigation, but it cannot independently diagnose testosterone deciency. Clinical assessment and appropriately performed testosterone blood tests are necessary. Fourth, access to healthcare matters. The nancial and social barriers identied by the study suggest that improving awareness alone may not be sufcient. Men also need practical access to appropriate assessment and treatment. Finally, the study highlights the importance of distinguishing genuine testosterone deciency from symptoms caused by other conditions. This is particularly important when considering testosterone replacement therapy, which should be prescribed when clinically indicated rather than solely on the basis of symptoms. 6. Overall Conclusion The study by Liu and colleagues identies a substantial gap between symptoms associated with testosterone deciency and formal diagnosis among men living in the UK. Almost half of the respondents reported symptom proles suggestive of testosterone deciency, yet only approximately 5% reported having received a formal diagnosis. More than half were unfamiliar with the symptoms, while nancial costs, stigma and lack of awareness were common barriers to seeking medical advice.
6 The ndings support the need for better education, improved access to healthcare and more appropriate investigation of men experiencing persistent symptoms. However, the study does not demonstrate that 49% of UK men have low testosterone. Instead, it highlights the potential scale of unmet need and the importance of identifying those whose symptoms warrant proper clinical evaluation. The central message is that men's hormonal health may be under-recognised, but effective diagnosis requires more than symptom recognition: it requires appropriate clinical assessment and biochemical conrmation. Reference Liu VN, Huang DR, Alaa A, Hayhoe B, El-Osta A. Awareness and prevalence of the symptoms of testosterone deciency: a cross-sectional survey of community-dwelling men in the UK. BMJ Open. 2025;15:e094145.
7 The United States is Making Testosterone Replacement Therapy More Accessible for US Military personnel. In June this year, US Defence Secretary, Pete Hegseth announced that the military would be launching a new screening program for "testosterone deciency" among troops, calling it necessary to allow them to operate at their "absolute best." This after a study published in JAMA showed that 20% of male soldiers younger than 30 years had testosterone levels less than the threshold established by the American Urological Association of 10 nmol /L Testosterone screenings will be included in annual health checks. These are required for service members 30 year and older. Younger troops under 30 can volunteer to be tested. Hegseth said receiving testosterone replacement therapy would be voluntary. The move comes as The Health Secretary, Robert F. Kennedy Jr. and other Trump administration ofcials are moving to make it easier for doctors to prescribe testosterone. Kennedy Jr. is a prominent advocate for expanding access to testosterone replacement therapy and personally uses testosterone as part of his anti-aging and wellness program. The Food and Drug Administration is also advocating for men to have easier access to testosterone replacement therapies. Proposed changes to current labelling would: • Remove the limitation of use stating that the safety and effectiveness of testosterone replacement therapy in men with agerelated hypogonadism have not been established. • Update information related to prostate cancer risk. • Revise warnings regarding benign prostatic hyperplasia, also known as enlarged prostate. “During Men's Health Month, we are putting science back at the center of men's healthcare,” said HHS Secretary Robert F. Kennedy, Jr. “By updating testosterone therapy labels to reect current evidence, we are giving patients and physicians clearer information, supporting informed medical decisions, and improving care for millions of American men.” References 1 HHS Announces Requested Updates to Testosterone Therapy Product Labels June 18, 2026. Available at: https://www.hhs.gov/pressroom/fda-requests-updates-testosteronetherapy-labeling.html. Accessed on 18 October 2026. 2 Routine testosterone screening of US troops may require extensive follow-on care, study nds. Patricai Kime. Available at: https://www.militarytimes.com/news/yourmilitary/2026/10/15/routine-testosteronescreening-of-us-troops-may-require-extensivefollow-on-care-study-nds/. Accessed on 18 October 2026.
8 What's new in prostate cancer treatment and how do we improve disease free survival in high-risk prostate cancer: Report back from the plenary session at ASCO 2026 ASCO 2026: Perioperative (Neoadjuvant and Adjuvant) Apalutamide + ADT Versus Placebo + ADT with Radical Prostatectomy in High-Risk Localized or Locally Advanced Prostate Cancer: Final Analysis of the PROTEUS Phase 3 Study. High-Risk Relapse Rates: While overall post-prostatectomy BCR (Biochemical recurrence) across all risk groups is about 20% to 40%, patients with high-risk features have much higher relapse rates. Specialized cohort studies on high-risk localized disease report biochemical recurrence-free survival rates of roughly 65% to 70% at 5–10 years (meaning a 30% to 35%+ relapse rate). Although there is improvement in surgical techniques including robotic assistance, which have ensured improvement in mortality and morbidity, prostate cancer is a systemic illness, and the disease is often microscopically more advanced than predicted by PSA levels, MRI, and PSMA-PET ndings. ASCO is the largest oncology conference in the world. Groundbreaking and practice changing results are kept for the plenary session. This year ASCO did not disappoint, and the nal results of the phase 3 PROTEUS trial were presented. Many trials have failed to establish a benet with perioperative systemic therapy in tandem with radical prostatectomy (RP) in high-risk localized prostate cancer, this phase 3 trial delivered a breakthrough. However, there are positive phase 2 trials such as the ARNEO study, which recruited around the same time as PROTEUS: Conducted from 2019 to 2021 and presented at the European Association of Urology Annual Congress in 2022. It included a propensity score analysis emphasising the difference in relapse rate and the decreased necessity of future therapies. The Apa-RP study (NCT04523207) produced similar results, published in 2024. There are several other phase II trials alluding to the improved relapse free survival, inclusive of patients' quality of life and sexual function questionnaires. The trials were small but produced promising results. Dr Daleen Geldenhuys MBBCh (WITS), FCP (SA), Certificate Medical Oncology (SA) Dr Daleen Geldenhuys is a community oncologist working at Life Flora Clinic and Johannesburg Surgical Hospital. Both hospitals have multidisciplinary meetings with various specialities represented.
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10 PROTEUS: Standard of care at the present time is surgery alone. The trial compared androgen deprivation (ADT) with GNRH analogue injections as a control arm. ADT is not standard of care, but the trialists believed patients would not agree to a trial where they may not receive any therapy at all except for the prostatectomy, therefore the control arm had to offer treatment other than just observation. The trial design: patients were randomised into 2 groups, one group receiving ADT and apalutamide (oral androgen receptor pathway inhibitor) for 6 months prior to surgery/neo adjuvant therapy versus ADT alone, followed by surgery and then completing another 6 months with the same protocol in the adjuvant setting. The number of patients enrolled in the trial was 2 109. They were stratied by Gleason score, nodal status, and geographic region before being randomly assigned to either group. It accrued from 18 countries making the population of the study diverse. The trial was designed to answer 2 questions: The dual primary end points were: 1: Pathological complete response/minimal residual disease (PCR/MRD) - dened as a pathological stage of ypT2 or lower, with a tumor size of ≤5 mm in the greatest dimension at the time of surgery. 2: Metastasis-free survival (MFS), as assessed with conventional imaging or prostate-specic membrane antigen positron-emission tomography. (PSMA-PET) By pairing pCR/MRD with MFS as dual primary endpoints, the trial was designed to assess both early tumour response at surgery and whether that response translated into meaningful long-term benet. Secondary end points included event-free survival (EFS), rst subsequent treatment, and distant metastasis (assessed in time-to-event analyses), as well as safety. First endpoint: 8.9% of patients had no detectable cancer and another 30.6% had a tumour smaller than ypT2 (pathology stage less than ypT2 such as ypT0 or ypT1). This is almost 40% in total, indicating that after androgen deprivation therapy, the tumour has either completely disappeared or is microscopic, with no cancer found in the surgical specimen. Second endpoint: The 5-year Median metastasis-free survival rate was 78.2% in the combination arm and 73.5% in the control arm (ADT alone), compared to an average of 50% with surgery alone.
11 The addition of apalutamide to ADT resulted in a signicant 18.7-month increase in median event-free survival, improving from 38.4 months with ADT alone to 57.1 months with the combination. This was largely driven by lower rates of biochemical failure (77% vs 80%) and locoregional recurrence with the inclusion of apalutamide. The combination also signicantly delayed the development of distant metastasis, with 83% of patients remaining metastasis free at 5 years compared with 76% in the ADT alone arm. One year of perioperative combination therapy spared patient from subsequent therapy for a median of 6.2 years vs 3.5 years with ADT alone. Recovery of testosterone levels after completion of the therapy, was around 80% at 8 months. The lead investigator, Dr Mary-Ellen Taplin who presented the trial at ASCO has stated: “These results have the potential to be practice changing and support perioperative apalutamide plus ADT as a new standard of care for patients with high-risk localized prostate cancer who are candidates for radical prostatectomy.” The discussant, Dr Declan Murphy agreed that he would be incorporating this regimen into his practice for high-risk localized prostate cancer. Quoting Dr Murphy: “All of this adds up to a much better patient journey.” Conclusion: PROTEUS is a landmark trial and will continue to deliver data over the coming months and years. The forthcoming PROTEUS updates will focus on patient-reported outcomes, biomarker analyses, and correlation of major pathologic response with MFS as well as a substudy that compares apalutamide, ADT, and surgery vs surgery alone. The future: We are looking forward to the results of the ATLAS study. A randomized, double-blind, placebo-controlled, phase 3 trial of apalutamide (ARN-509) in patients with highrisk localized or locally advanced prostate cancer receiving primary radiation therapy. This ongoing study is evaluating the efcacy and safety of adding apalutamide to GnRH analogues (ADT) and external bean radiation therapy (EBRT) vs ADT alone concurrent with radiation therapy (RT), in patients with high-risk localized or locally advanced prostate cancer. The trial will include 1 500 patients and will assess whether the addition of apalutamide, to a GnRH agonist will improve metastasis-free survival in high-risk patients treated with primary RT.
12 A Tribute to Dr Prinitha Pillay known as Prini It is with profound sadness that we remember Dr Prinitha Pillay, whose sudden passing has left an immeasurable void in the hearts of her patients, colleagues, and all who knew her. She was not only an exceptional oncologist but a true humanitarian—an incredible human being whose compassion and dedication dened her life's work. Dr Prinitha Pillay loved medicine deeply, but even more, she loved people. She never saw just the disease; she saw the person behind it—their fears, their hopes, their dignity. Her patients were never numbers or cases; they were lives she touched with empathy, wisdom, and unwavering care. Her legacy is one of healing, kindness, and humanity. She reminded us that medicine is not only about science but about the heart. In every consultation, every decision, and every moment of care, she brought light, courage, and comfort. Though her time with us was far too short, the impact she made will endure. We honour her memory by carrying forward her example: to treat every patient as a person, to serve with compassion, and to live with purpose. Dr Prinitha Pillay will forever be remembered not only as a brilliant physician but as a beacon of humanity.
13 Optimal prostate-specific antigen cutoff linked to improved prostate cancer survival A drop in prostate-specic antigen (PSA) levels is an indicator that is used to monitor treatment success for men with metastatic prostate cancer. A recent real-world study published by Freedland, S. J., et al. showed that reaching a PSA level below 0.2 ng/mL is an indicator of improved patient survival. Two commonly used measures are used to determine treatment success: • Absolute PSA level: Achieving a PSA nadir below 0.2 ng/mL. • Percentage PSA reduction: Achieving a reduction of at least 90% from the pretreatment PSA level. The researchers wanted to determine which measure was more strongly associated with overall survival and disease progression. Investigators analysed Veterans Health Administration data on 4,890 patients who received testosterone deprivation therapy with or without other treatments in 2018–2023 for metastatic hormone-sensitive prostate cancer. The primary outcomes were: • Overall survival (OS): The time until death. • Disease progression: A composite outcome that included PSA progression, initiation of a new anticancer treatment, development of castration resistance or death. Reference: Freedland SJ, Gao W, Touya M, et al. (2026). How low do you need to go? Association between various prostate-specic antigen response measures and clinical outcomes in metastatic castration-sensitive prostate cancer in the Veterans Health Administration data. Cancer. Cancer. 2026 Aug 15;132(16):e70494. Conclusion “These data show that we need to target a PSA below 0.2 ng/ml as our metric of success to optimize outcomes for our patients with metastatic prostate cancer." Stephen J. Freedland, MD, corresponding author, professor of Urology at Cedars-Sinai and Staff Physician at the Durham VA Medical Center Key ndings: • Over a median follow-up of approximately 2 years, 896 patients died. • Patients whose PSA levels dropped below 0.2 ng/mL within 9 months of starting treatment were 54% less likely to die than patients whose levels did not drop this low, whether their PSA levels also decreased by at least 90% or not. • Patients who had at least a 90% PSA decline but did not achieve a PSA of less than 0.2 ng/ml had no improvement in survival. The ndings suggest that patients who do not experience a PSA drop below 0.2 ng/mL could be candidates for more aggressive treatments. In addition, patients who received androgen deprivation therapy (ADT) plus an androgen deprivation therapy pathway inhibitor (ARPI) were more likely to reach a PSA below 0.2 ng/mL, demonstrating once again that ADT monotherapy is no longer standard of care.
14 New Nasal Spray for Erectile Dysfunction Now Available in Australia and the USA Before the launch of sildenal (Viagra), treatments for erectile dysfunction (ED) were limited. Vacuum pump devices were an option, and for a short period a urethral suppository containing alprostadil was available (MUSE). Intracavernosal injections were the most effective treatment option available but were understandably not particularly appealing to the majority of most men who feared having to self-inject medication into the penis. The availability the rst oral medication to treat ED (a phosphodiesterase type 5 inhibitor - PDE5I) took the world by storm and millions of men benetted from a convenient and simple option to treat their ED. However, PDE5 inhibitors take a bit of time to work, which means that spontaneity sometimes has to take a back seat, and planning is required for sexual encounters. So it's not surprising that a fast-acting PDE5 inhibitor would be an appealing option for those “unplanned encounters.” A nasal formulation was developed containing the PDE5 inhibitor vardenal (an established oral treatment originally co-developed by Bayer, GlaxoSmithKline, and Schering-Plough and approved as an oral tablet (Levitra) in August 2003). A comparative study was published in the Journal of Sexual medicine in June 2023. The study showed that the nasal formulation reached peak concentration in 10 minutes vs 58 minutes for the oral formulation. That's a one third reduction in waiting time! Australian biotech rm LTR Pharma scaled up commercialization of the formulation under the development name SDS-089 (branded as Spontan® in Australia and Roxus® in the United States). Human bioequivalence clinical trials for this commercial product kicked off in February 2024, and it ofcially entered the U.S. consumer market via prescription in October 2026. The new formulation is available through a compound pharmacy and has not undergone FDA review or approval.
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16 Low-Intensity Shockwave Therapy for Erectile Dysfunction: What the Evidence Actually Shows Abstract Background: Erectile dysfunction (ED) is highly prevalent and rises with age. Phosphodiesterase type 5 inhibitors (PDE5i) remain effective but symptomatic, which has created interest in restorative therapies that target the underlying vascular pathology. Low-intensity extracorporeal shockwave therapy (Li-ESWT) is the most clinically advanced of these. Objective: To summarise the current evidence on Li-ESWT for ED, covering its proposed mechanism, efcacy, patient selection, safety and guideline status, and to clarify where the evidence is strong and where caution is warranted. Methods: Narrative review of randomised controlled trials, meta-analyses and current clinical practice guidelines. Findings: Meta-analyses consistently show statistically signicant but modest improvements in the International Index of Erectile Function and the Erection Hardness Score in men with mild-tomoderate vasculogenic ED, with the clearest benet in milder disease and in PDE5i poor responders; combining it with a daily PDE5i improves outcomes. The 2025 Cochrane review rated overall certainty low and cautioned that the effect may fall below the minimal clinically important difference. The positive evidence comes almost entirely from focused-energy devices. Data in neurogenic and post-prostatectomy ED remain immature. The safety prole is favourable, with only mild, transient adverse effects. Conclusion: Focused Li-ESWT is a reasonable, well-tolerated, non-invasive option for selected men with mild-to-moderate vasculogenic ED, particularly PDE5i poor responders, but it is not a rst-line therapy, its durability is uncertain, and protocol standardisation with longer, independently funded trials is needed. Cecilia Raath Physiotherapist BPhysT (Honours), University of Pretoria Postgraduate Certicate, Orthopaedic Manipulative Therapy (OMT/NMS) Postgraduate Certicate, Sport Physiotherapy (SPT) Postgraduate Certicate, Women's Health Physiotherapy (PWH) Cecilia has been a physiotherapist in private practice since 1999, specialising in the integration of neuromusculoskeletal (NMS) and pelvic health physiotherapy. She has been actively treating pelvic health patients since 2004, with a clinical approach that evaluates the pelvis as part of a three-dimensional, whole-body system — identifying and addressing the mechanical and orthopaedic drivers (previous sports injuries, minor trauma, habitual posture) that frequently underlie pelvic oor dysfunction and its co-morbidities. She treats both women's and men's health conditions, including pelvic pain, incontinence, sexual dysfunction, pregnancy-related pelvic girdle pain, and paediatric pelvic health. She is a partner at Raath & Spies Physiotherapists — Silver Lakes, Pretoria, a team member and supervisor at My Sexual Health (MSH) and is a senior lecturer for pre- and postgraduate physiotherapy programmes.
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18 Introduction Erectile dysfunction (ED) affects a large and growing proportion of adult men, with prevalence rising steeply from middle age. For four decades treatment has been dominated by on-demand pharmacology, chiey phosphodiesterase type 5 inhibitors (PDE5i), which are effective and safe but symptomatic: they potentiate an erection when taken, without altering the underlying vascular pathology. This leaves two persistent gaps. A meaningful minority of men respond poorly to or cannot tolerate oral therapy, and even successful users are managing a condition rather than modifying it. Low-intensity extracorporeal shockwave therapy (Li-ESWT) is the most clinically advanced of the interventions proposed to ll that gap. Adapted from the high-energy shockwave technology of urological lithotripsy but delivered at a fraction of the energy, it is intended to be restorative: to improve cavernosal blood ow by stimulating tissue regeneration rather than transiently relaxing smooth muscle. After more than a decade of randomised trials, the therapy sits in an unusual position. The mechanism is plausible, the measured effect is reproducible but modest, and guidelines cannot yet agree on how to classify it. This review summarises what the evidence shows, where it is strong, and where caution is required. Proposed mechanism of action The rationale for Li-ESWT is regenerative. Acoustic energy applied to the corpora cavernosa is thought to act through mechanotransduction, the conversion of mechanical shear stress into biological signalling, which triggers a cascade that promotes vascular repair. A systematic scoping review of 59 pre-clinical studies concluded that the therapy improves erectile function through several convergent pathways: stimulation of cellular mechanosensors, upregulation of angiogenic mediators such as vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), neovascularisation and improved cavernosal microcirculation, recruitment of endothelial and mesenchymal progenitor cells, peripheral nerve regeneration, and reduction of local [1] inammation . The appeal is that, unlike a PDE5i, the intervention aims to remodel the vascular substrate of erection. The caveat is that the magnitude and consistency of these effects vary considerably with device type, energy ux density and treatment protocol, and no single denitive mechanism has been conrmed in humans. The biology supports clinical benet but does not prove it. Proposed mechanism of action of low-intensity focused shockwave therapy in erectile tissue STAGE 1 Focused acoustic shockwaves Applied to the corpora cavernosa STAGE 2 Mechanotransduction Shear stress on vascular endothelium activates cellular mechanosensors STAGE 3 Molecular signalling Up-regulation of VEGF, eNOS and other angiogenic mediators STAGE 4 Tissue regeneration Neovascularisation, progenitor cell recruitment, nerve regeneration, ↓ inammation OUTCOME Improved cavernosal blood ow & erectile function Figure 1. Proposed mechanism of action of low-intensity focused shockwave therapy in erectile tissue. Schematic representation. The strength and consistency of these effects vary with device type, energy ux density and protocol, so single mechanisms are likely oversimplied in humans. Original gure. Synthesised from Sokolakis et al., J Sex Med 2020.
19 The clinical evidence base The rst sham-controlled randomised trial showed that focused Li-ESWT produced a measurable physiological improvement in erectile function, establishing proof of [2] concept . A series of meta-analyses has since broadly conrmed a statistically signicant, if modest, treatment effect in men with vasculogenic ED: • A meta-analysis of seven randomised controlled trials (602 men) found a mean improvement in the Erectile Function domain of the International Index of Erectile Function (IIEF-EF) of 6.40 points with active treatment versus 1.65 with [3] sham . • A larger synthesis of 14 studies (833 men) in European Urology reported a pooled IIEF improvement of about 2 points and a signicant Erection Hardness Score (EHS) response, with benet most evident in mild-to-moderate disease and sustained [4] for at least three months . • A meta-analysis of nine studies (637 men) found an IIEF improvement of around 2.5 points and suggested that lower energy ux density combined with a higher pulse count (in the region of 3,000 pulses per session) was associated with better [5] outcomes . • A meta-analysis of 16 RCTs (1,064 men) reported IIEF improvements of roughly 3 points sustained to six months and found that men with a baseline EHS of 2 or below were about ve times more likely to improve to a functionally meaningful EHS of 3 or above with Li-ESWT than with sham (odds ratio 5.07; 95% CI 1.78 to 14.44). The same analysis suggested an energy density near 0.09 mJ/mm² with 1,500 to 2,000 pulses, and a more pronounced [6] effect in moderate ED . • A systematic review and meta-analysis of randomised trials similarly concluded that the therapy produces a clinically relevant improvement in appropriately selected men [7], and the most recent update (12 RCTs, 882 men) continues to report signicant gains in IIEF-EF and EHS versus [8] sham . These consistent positive signals must, however, be weighed against the most rigorous recent appraisal. The 2025 Cochrane review judged the overall certainty of evidence to be low, cautioned that the true effect size may fall below the minimal clinically important difference, and emphasised that the literature is limited by substantial heterogeneity in devices and protocols and [9] by industry involvement in several trials . A fair reading is therefore not that Li-ESWT is proven, but that it probably produces a real, modest and possibly time-limited improvement in mildto-moderate vasculogenic ED. That is strong enough to justify clinical use in selected men, but not strong enough to displace established rst-line therapy. Patient selection: who is most likely to benet The evidence points consistently to one prole: men with mild-to-moderate vasculogenic ED. Benet is least convincing in severe disease and in ED of predominantly neurogenic or psychogenic origin. A second, clinically valuable group is PDE5i poor responders. One of the most frequently cited rationales for the therapy is its potential to "convert non-responders to responders": to improve cavernosal haemodynamics enough that a previously ineffective oral agent begins to work. Real-world cohorts of PDE5i-refractory men support a meaningful response in a proportion of patients. The signal that combination therapy outperforms monotherapy is among the more practically useful recent ndings. A severitystratied protocol has been proposed: for example, a shorter Li-ESWT course plus daily low-dose tadalal for mild disease, and a longer course with daily tadalal in partial responders with more severe disease. This rests on evidence that pairing shockwave with a daily PDE5i yields better outcomes than either [10] alone . Special populations Diabetic and vasculogenic-comorbid ED. Men with diabetes and cardiovascular disease represent the most therapeutically resistant vasculogenic subgroups. Emerging randomised data suggest Li-ESWT retains efcacy and safety even when ED is attributable to these conditions, which is
20 encouraging given how poorly this group often responds to oral therapy. Post-radical-prostatectomy ED. This is the weakest part of the evidence base and warrants explicit caution. ED after radical prostatectomy is predominantly neurogenic, arising from cavernous nerve injury, rather than the vasculogenic mechanism that the bulk of the literature addresses. The rst randomised trial of Li-ESWT for penile rehabilitation after prostatectomy did not reach its primary endpoint of a clinically signicant IIEF [11] difference , and pooled analyses suggest any benet appears at three to four months and does not reliably persist. The 2025 Cochrane review excluded prostatectomy patients altogether. In this population, Li-ESWT should be regarded as a biologically rational but unproven adjunct within a broader penile- [12] rehabilitation strategy , not as an established treatment. Safety and tolerability Li-ESWT is consistently well tolerated. Across the randomised literature, adverse events are minimal and typically limited to mild, transient discomfort or occasional petechiae, with no serious treatment-related events reported. Treatment has also been shown to be safe in men receiving antiplatelet or anticoagulant therapy, with no signicant bleeding events [13] observed . The principal contraindications are a malignancy within the treatment eld, severe coagulopathy and local active infection. This favourable safety prole is one of the therapy's genuine strengths: even where the efcacy ceiling is modest, the risk of harm is low. Protocols and the standardisation problem The single greatest methodological weakness across the evidence base is the absence of a standardised protocol. Trials differ widely in device type, energy ux density, number of pulses per session, total number of sessions, treatment frequency, anatomical application to the shaft and crura, and duration of followup. This heterogeneity complicates direct comparison between studies and is a major reason the pooled certainty of evidence remains low. Notably, the positive trial evidence derives almost entirely from focusedenergy devices, which deliver energy to a focal zone at depth within the corpora cavernosa rather than dissipating it at the surface (Figure 2); clinicians adopting the therapy should align their protocols with those used in the trials that demonstrated benet, and should document baseline and follow-up validated outcome measures (IIEF-EF and EHS) to track individual response. Figure 2. Focused low-intensity shockwave therapy delivered to the penis (transverse cross-section, approximately to scale). The focused beam converges to a focal zone within the corpus cavernosum, the erectile target, which lies approximately 1 cm beneath the surface. Original schematic, not for diagnostic use. Proportions approximate; depth values are indicative and device/energy-dependent. The focused beam converges to a focal zone within the corpus cavernosum — the erectile target sits only ~1 cm beneath the surface, and focal depth is adjustable, so focused devices deliver a therapeutic dose at depth rather than only at the skin. Skin / dartos / Buck's fascia ≈ 1 cm to corpus Urethra Corpus spongiosum Tunica albuginea Cavernosal (deep) artery Corpus cavernosum paired erectile bodies — primary target Median septum Dorsal neurovascular bundle deep dorsal vein, dorsal arteries & nerves Focused low-intensity shockwave therapy: penetration to the erectile target Transverse cross-section of the penis (approximately to scale; accid diameter ≈ 3 cm) Focused applicator Focused pressure prole Steep spike, high peak
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22 Guideline status Major guidelines take the same cautious but open posture, and they diverge: • The European Association of Urology accepts that Li-ESWT may be used in men with mild organic (vasculogenic) ED, or as an option in poor responders to PDE5 inhibitors, but assigns a weak strength of [14] recommendation . • The American Urological Association classies Li-ESWT as investigational for ED, a conditional recommendation graded C, which reects low to very low [15] condence in the evidence . No major guideline positions the therapy as rst-line. A clinician citing “the guidelines” should be specic about which body and which recommendation strength they mean. Limitations and future directions Three gaps dene the research agenda. First, durability: several datasets show benet fading by 9 to 12 months, and re-treatment intervals are undened. Second, standardisation: until device and protocol parameters are harmonised, "shockwave therapy" in one trial cannot be assumed equivalent to another. Third, trial quality and independence: the eld needs betterpowered, longer, protocol-consistent and independently funded studies, particularly in the harder-to-treat neurogenic and postsurgical populations. Until these are addressed, conclusions should remain measured. Conclusion Low-intensity shockwave therapy has earned a dened, if limited, place in the management of erectile dysfunction. Its restorative rationale is biologically coherent, and the randomised evidence supports a real treatment effect in carefully selected men with mild-to-moderate vasculogenic ED, including some PDE5i poor responders, in whom combination with a daily PDE5i appears to improve outcomes. That effect is modest, of uncertain durability, and supported by evidence of low overall certainty. The therapy is well tolerated and low risk, which strengthens its case as an option for the informed patient, but it is not a cure and not a rst-line replacement for established therapy. Used selectively and described honestly, as vascular remodelling with nite, individual benet, Li-ESWT is a reasonable addition to the ED armamentarium. Oversold as a cure, it risks squandering the credibility of a promising approach. Declarations Conicts of interest: The author declares no conicts of interest. The author has no nancial relationship with, and has received no funding, equipment or support from, any manufacturer or distributor of shockwave therapy devices. Funding: This work received no specic funding. References 1. Sokolakis I, Dimitriadis F, Teo P, Hatzichristodoulou G, Hatzichristou D, Giuliano F. The basic science behind low-intensity extracorporeal shockwave therapy for erectile dysfunction: a systematic scoping review of pre-clinical studies. J Sex Med. 2019;16(2):168-194. https://doi.org/10.1016/j.jsxm.2018.12.016 2. Vardi Y, Appel B, Kilchevsky A, Gruenwald I. Does low-intensity extracorporeal shock wave therapy have a physiological effect on erectile function? Short-term results of a randomized, double-blind, sham controlled study. Eur Urol. 2012;61(1):149-156. https://doi.org/10.1016/j.eururo.2011.07.054 3. Clavijo RI, Kohn TP, Kohn JR, Ramasamy R. Effects of low-intensity extracorporeal shockwave therapy on erectile dysfunction: a systematic review and metaanalysis. J Sex Med. 2017;14(1):27-35. https://doi.org/10.1016/j.jsxm.2016.11.001 4. Lu Z, Lin G, Reed-Maldonado A, Wang C, Lee YC, Lue TF. Low-intensity extracorporeal shock wave treatment improves erectile function: a systematic review and meta-analysis. Eur Urol. 2017;71(2):223233. https://doi.org/10.1016/j.eururo.2016.05.050 5. Man L, Li G. Low-intensity extracorporeal shock wave therapy for erectile dysfunction: a systematic review and meta-analysis. Urology. 2018;119:97-103. https://doi.org/10.1016/j.urology.2017.09.011 6. Yao H, Wang X, Liu H, Sun F, Tang G, Bao X, et al. Systematic review and meta-analysis of 16 randomized controlled trials of clinical outcomes of low-intensity extracorporeal shock wave therapy in treating erectile dysfunction. Am J Mens Health.2022;16(2):15579883221087532. https://doi.org/10.1177/15579883221087532 7. Kalyvianakis D, Mykoniatis I, Pyrgidis N, Memmos E, Hatzichristou D. Clinical studies on low intensity extracorporeal shockwave therapy for erectile dysfunction: a systematic review and meta-analysis of randomised controlled trials. Int J Impot Res. 2019;31(3):177-194. https://doi.org/10.1038/s41443019-0117-z 8. Fatima M, et al. Efcacy of low-intensity extracorporeal shockwave therapy for erectile dysfunction: an updated systematic review and meta-analysis of randomised controlled trials. Future Sci OA. 2025.
23 https://doi.org/10.1080/20565623.2025.2511438 9. Ergun O, et al. Low-intensity shockwave therapy for erectile dysfunction. Cochrane Database Syst Rev. 2025. https://doi.org/10.1002/14651858.CD013166.pub3 10. Pyrgidis N, Kalyvianakis D, Mykoniatis I, Hatzichristou D. The recommended treatment protocol for lowintensity shockwave therapy based on the severity of erectile dysfunction. Int J Impot Res. 2024. https://doi.org/10.1038/s41443-024-00959-7 11. Baccaglini W, Pazeto CL, Corrêa Barros EA, et al. The role of the low-intensity extracorporeal shockwave therapy on penile rehabilitation after radical prostatectomy: a randomized clinical trial. J Sex Med. 2020;17(7):1264-1271. https://doi.org/10.1016/j.jsxm.2019.12.024 12. Feng D, Tang C, Liu S, Yang Y, Han P, Wei W. Current management strategy of treating patients with erectile dysfunction after radical prostatectomy: a systematic review and meta-analysis. Int J Impot Res. 2022;34(1):18-36. https://doi.org/10.1038/s41443-02000364-w 13. Kalyvianakis D, Memmos E, Mykoniatis I, Kapoteli P, Memmos D, Hatzichristou D. Low-intensity shockwave therapy for erectile dysfunction in patients on antiplatelet or anticoagulant therapy: a prospective study. J Sex Med. 2019;16(8):1284-1289. https://doi.org/10.1016/j.jsxm.2019.05.008 14. Salonia A, Capogrosso P, Boeri L, et al.; EAU Working Group on Male Sexual and Reproductive Health. European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2025 update on male hypogonadism, erectile dysfunction, premature ejaculation and Peyronie's disease. Eur Urol. 2025 (Epub ahead of print). https://uroweb.org/guidelines/sexual-andreproductive-health (Conrm volume, issue, pages and DOI on the EAU site before submission.) See also Schoofs E, Fode M, Capogrosso P, Albersen M; EAUYAU Men's Health Group. Current guideline recommendations and analysis of evidence quality on low-intensity shockwave therapy for erectile dysfunction. Int J Impot Res. 2019;31(3):209-217. 15. Burnett AL, Nehra A, Breau RH, et al. Erectile dysfunction: AUA guideline. J Urol. 2018;200(3):633641. https://doi.org/10.1016/j.juro.2018.05.004
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