madman
Super Moderator
The Italian Society of Andrology and Sexual Medicine (SIAMS), along with ten other Italian Scientific Societies, guidelines on the diagnosis and management of erectile dysfunction (2023)
G. Corona · D. Cucinotta · G. Di Lorenzo · A. Ferlin · V. A. Giagulli · L. Gnessi · A. M. Isidori· M. I. Maiorino · P. Miserendino · A. Murrone · R. Pivonello · V. Rochira · G. M. Sangiorgi · G. Stagno · C. Foresta · A. Lenzi · M. Maggi · E. A. Jannini
Abstract
Purpose
Erectile dysfunction (ED) is one of the most prevalent male sexual dysfunctions. ED has been in the past mistakenly considered a purely psycho-sexological symptom by patients and doctors. However, an ever-growing body of evidence supporting the role of several organic factors in the pathophysiological mechanisms underlying ED has been recognized.
Methods The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving several other National Societies to provide an updated guideline on the diagnosis and management of ED. Derived recommendations were based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system.
Results Several evidence-based statements were released providing the necessary up-to-date guidance in the context of ED with organic and psychosexual comorbidities. Many of them were related to incorrect lifestyle habits suggesting how to associate pharmacotherapies and counseling, in a couple-centered approach. Having oral therapy with phosphodiesterase type 5 inhibitors as the gold standard along with several other medical and surgical therapies, new therapeutic or controversial options were also discussed.
Conclusions
These are the first guidelines based on a multidisciplinary approach that involves the most important Societies related to the field of sexual medicine. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving the couple's sexual satisfaction and overall general health.
Introduction
After the loss of the penis bone or baculum, during evolution [1, 2], male erectile function shifted from a voluntary, osteo-muscular action, as in the very large majority of mammals, primates included [3], to a psycho-neuro-endocrine and vascular reaction, where the cortical voluntary control, if any, appears to be much more negative than positive [4]. The lack of the baculum and its striated muscular machinery is not the unique peculiarity of the human erection (and of the consequent erectile dysfunction, ED); the vessels feeding the high oxygen need of the corpora cavernosa are, in fact, characterized by a very small diameter, much smaller than the coronaries, vessels considered to be at high risk for atherosclerotic degeneration due to the particular geometry [5, 6].
Because of the loss of the baculum, ED may have evolved as a marker of poor phenotypic quality and erectile function in humans appears to be large, if not totally, will-independent, while it is, at the same time, strictly age and lifestyle-dependent [6, 7]. Incorrect behavioral choices are in fact able to affect the ability both to obtain and to maintain an erection in the presence of proper erotic stimuli (which roughly corresponds to the National Institutes of Health’s definition of ED) [8]. Interestingly, the main reasons for having ED, i.e. smoking, physical inactivity, poor eating habits and disorders, and abuse of alcohol and substances, are also the main causes of the four plus one classical non-communicable chronic diseases (NCDs: cardiovascular, metabolic, respiratory and oncological diseases, plus neuropsychiatric diseases, recently added to the list) [6, 9].
Taking into consideration all these findings, it would be easy to consider ED as the perfect (early) biomarker of NCDs, as largely demonstrated by epidemiological studies [6, 7]. In particular, erectile function could be considered as the classical ‘canary in the coal mine’, thanks to its particular ability to occur earlier, as a consequence of lifestyle mistakes, with respect to the other NCDs [10]. Since the interdisciplinary field of study on NCDs, which looks at the systems of the human body as part of an integrated whole—incorporating biochemical, physiological, and environmental interactions—has been named Systems Medicine [11], a new paradigm, named Systems Sexology, which increases and ameliorates the complexity of the traditional bio-psycho-social model [12], seems to be the best approach to ED that results from the complex interactions within the male human body in light of a patient's genomics, behavior and environment [6, 7]
In the majority of cases, ED appears, in fact, as a medical symptom (vascular, endocrine, neurologic, and iatrogenic, frequently with mixed risk factors), more rarely surgical in nature, but with almost unavoidable psychological and relational comorbidity. For these reasons, diagnosis, management, and follow-up of the patients and of the couples with ED appear relatively complex and deserving of a renewed effort to implement already published guidelines. This is the aim of these new guidelines of the Italian Society of Andrology and Sexual Medicine (SIAMS) in collaboration with ten other National Societies. While several important guidelines on ED have been produced by other national or continental urological Scientific Societies, this is, to our knowledge, the first one “multicultural” in nature, being produced by a number of different scientific backgrounds, but all interested and involved in the management of ED from various perspectives.
Epidemiology and risk factors
Evidence supporting that a specific ED case is due to a single and unique etiological factor is scarce and not supported by common clinical practice. For this reason, in defining the well-known pathophysiological mechanisms related to ED, we discourage the use of the term “etiologies”. The expression to be “Risk Factors” is preferred, also considering that there are frequently multiple factors in the same patient (see also Table 1).
Epidemiology
Recommendation #1. We recommend considering erectile dysfunction as a common male disorder whose incidence and prevalence are strongly associated with age and health status (1 ØØØØ).
*Evidence
*Remarks
Risk factors
Several systemic conditions as well as organic, relational, and intrapsychic factors can contribute to the development of ED (Table 1). Moreover, ED is frequently comorbid with other sexual dysfunctions, either in the patients and/or in the partner, which may amplify the erectile failure in subclinical forms (see below) into an overt ED.
Systemic risk factors
Recommendation #2. We recommend investigating the sexual function and ruling out erectile dysfunction in all patients with systemic diseases, especially in those with organ failure (Good clinical practice).
*Evidence and remarks
Cardiovascular and respiratory risk factors
Arterial hypertension
Recommendation #3. We recommend investigating erectile dysfunction in individuals with arterial hypertension since it is strongly associated with hypertension duration and severity (1ØØØØ), and it might be related to the use of some anti-hypertensive medications (1ØOOO).
*Evidence
*Remarks
Cardiovascular diseases
Recommendation #4. We recommend checking for symptoms of coronary artery disease in all patients with erectile dysfunction at each visit and evaluating the cardiovascular risk profile using cardiovascular algorithms such as SCORE2 or SCORE2-OP (Systematic Coronary Risk Estimation 2 and Systematic Coronary Risk Estimation 2-Older Persons) (1 ØØØØ).
*Evidence
*Remarks
Chronic obstructive pulmonary disease and sleep apnea
Recommendation #5. We suggest investigating erectile dysfunction in all patients with chronic obstructive pulmonary disease and obstructive sleep apnea (2 ØØØΟ).
*Evidence and remarks
Metabolic risk factors
Obesity
Recommendation #6. We recommend investigating sexual function in all male patients with obesity (1 ØØØØ)
*Evidence
Diabetes mellitus
Recommendation #7. We recommend investigating erectile dysfunction in all patients with diabetes mellitus since it is strongly associated with diabetes duration, metabolic control, and the coexistence of other diabetic complications (1 ØØØØ).
*Evidence
*Remarks
Dyslipidemia and gout
Recommendation #8. We recommend investigating erectile dysfunction in all patients with dyslipidemia (1 ØØØØ) and gout (1 ØOOO).
Dyslipidemia
It is well known that dyslipidemia is clearly associated with MACE, [64]. Considering that ED is another well-known risk factor for MACE [6], associations between the two conditions have been thoroughly investigated
*Evidence
*Remarks
Gout
The association between gout, the most common crystal arthropathy, and sexual dysfunction has often been investigated by studies in recent decades. Awareness of this association is frequently lacking and the pathogenetic mechanisms have only partially been identified.
*Evidence
*Remarks
Hormonal disorders
Recommendation #9. We recommend investigating sexual function in male patients with low testosterone. (1ØØØØ).
Recommendation #10. We
suggest considering the investigation of sexual function in other endocrine conditions such as thyroid, adrenal, and pituitary diseases (2 ØOOO).
*Evidence
*Remarks
Neurological disorders
Recommendation #11. We suggest investigating erectile function in all patients with central and peripheral neurological diseases potentially affecting male sexual response (2 ØØOO).
*Evidence
Urological disorders
Lower urinary tract symptoms
Recommendation #12. We recommend screening patients with erectile dysfunction with the International Prostatic Symptom Score and patients with benign prostate obstruction with the International Index of Erectile Function (1 ØØØO).
*Evidence
*Remarks
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)
Recommendation #13. We suggest investigating erectile dysfunction in all patients with CP/CPPS (2 ØØOO).
*Evidence
Peyronie’s disease (PD)
Recommendation #14. We suggest ruling out erectile dysfunction in all patients with Peyronie’s disease (2 ØOOO).
*Evidence
Toxicological and iatrogenic risk factors
Substances/drugs abuse
Recommendation #15. We recommend considering the use of psychotropic drugs (e.g.: opioids, amphetamine, methamphetamine, and, to some extent, cannabis) as a possible risk factor for erectile dysfunction (1ØØOO).
Recommendation #16. We suggest specifically investigating the presence of long-term use of illicit psychotropic drugs in patients with inadequate response to treatment of erectile dysfunction (2ØØOO).
*Evidence and remarks
Iatrogenic medical
Recommendation #17. All patients treated with anti-androgenic drugs must be informed about possible negative effects on erectile function (Good Clinical Practice).
Recommendation #18. We recommend investigating erectile function in all men treated with most antidepressants or antipsychotic medications (1ØØØØ).
Recommendation #19. We suggest investigating sexual function in young patients with a history of previous treatment with drugs affecting the serotoninergic pathway or the conversion of testosterone to dihydrotestosterone (2ØOOO). Recommendation #20. We suggest against using beta-blockers as a first-line therapy in patients with de-novo-diagnosed arterial hypertension if no specific cardiological indications are present (2ØOO).
*Evidence
*Remarks
Iatrogenic surgical
Recommendation #21. We recommend investigating sexual function in all patients treated with pelvic surgery for malignancies (1ØØØØ).
*Evidence and remarks
Psychiatric, psychological, and relational risk factors
Psychiatric disorders
Recommendation #22. We recommend considering psychiatric disorders (such as schizophrenia, bipolar disorders, and post-traumatic stress disorder) as risk factors for erectile dysfunction (1ØØØO).
Recommendation #23. We recommend considering anxiety and depression as independent predictors of erectile dysfunction and its severity. (1ØØOO).
*Evidence
*Remarks
Intrapsychic and relational risk factors
Recommendation #24. We recommend considering intrapsychic factors as major risk factors for developing and maintaining erectile dysfunction (1 ØØOO).
Recommendation #25. We recommend considering relational and marital factors as major risk factors for developing and maintaining erectile dysfunction (1 ØØOO).
Recommendation #26. We recommend considering nonorganic and organic risk factors always jointly and in their entirety (Good Clinical Practice).
*Evidence
Sexual risk factors
Hypoactive sexual desire
Recommendation #27. We recommend investigating sexual desire in subjects with erectile dysfunction because the two conditions are often comorbid (1 ØOOO).
*Evidence
*Remarks
Premature ejaculation
Recommendation #28. We suggest, in patients with loss of control of erection and ejaculation, addressing the erectile function before any therapeutical attempt to improve the ejaculatory control (2 ØØØO).
*Evidence
*Remarks
Partner sexual disorders and “couple pause”
Recommendation #29. We recommend considering the partner and her/his sexual dysfunctions as direct or indirect risk factors for erectile dysfunction (Good Clinical Practice).
*Evidence
*Remarks
Sexual orientation
Recommendation #30. We suggest non-judgmentally exploring patients’ sexual orientation (and gender identity) and personal perceived attitudes towards it when managing their erectile dysfunction (2 ØØOO).
*Evidence
*Remarks
Infertility
Recommendation #31. We suggest investigating the presence of erectile dysfunction in the workup of couple infertility, particularly when undergoing assisted reproduction techniques (Good Clinical Practice).
*Evidence
*Remarks
Diagnosis
The aim of the diagnosis of ED is to (i) identify the severity of the symptom (subclinical, mild, moderate, severe), (ii) identify the comorbidity with other sexual dysfunctions (e.g. hypoactive sexual disorder, ejaculatory disturbances), (iii) find as many risk factors as possible ascertaining their impact on the single case of ED. Hence, the diagnosis is never aiming to exclude etiologies, but, on the contrary, to include the risk factors resulting from careful general and sexual anamnesis, focused physical examination, psychometric, laboratory, and instrumental tools evaluating their “specific weight” in the pathogenesis and care of ED.
Psychogenic vs. organic diagnosis of erectile dysfunction
Recommendation #32. We recommend against the use of the redundant and stigmatizing term «psychogenic» for patients with non-organic, or idiopathic, erectile dysfunction. (Expert opinion).
Recommendation #33. We recommend against the “exclusion diagnosis”, as it is not evidence-based, of erectile dysfunction. (Good clinical practice).
*Evidence
*Remarks
Diagnosis of subclinical erectile dysfunction
Recommendation #34. We suggest considering subclinical erectile dysfunction as a taxonomic entity deserving of clinical attention (Expert Opinion).
*Evidence
*Remarks
Self‑reported questionnaires and structured interviews
Recommendation #35. We suggest using validated questionnaires and structured interviews to support medical and sexological history during erectile dysfunction assessment and/or follow-up (2ØØOO).
*Evidence
*Remarks
Self‑reported questionnaires and structured interviews
Recommendation #35. We suggest using validated questionnaires and structured interviews to support medical and sexological history during erectile dysfunction assessment and/or follow-up (2ØØOO).
*Evidence
*Remarks
Physical examination
Recommendation #36. We recommend a focused genital-urinary and physical examination including penis, testis, and prostate evaluation, at least at the patient’s first visit, in addition to the mandatory general physical examination (1ØØØØ).
*Evidence
*Remarks
Metabolic and hormonal evaluation
Recommendation #37. We recommend routine laboratory tests including fasting glucose, glycated hemoglobin and triglycerides, and total and HDL cholesterol, in all patients affected by erectile dysfunction (1 ØØØØ).
Recommendation #38. We recommend routine hormonal parameters including luteinizing hormone, follicle-stimulating hormone, total testosterone, sex hormone binding globulin, and albumin (for calculated free testosterone determination) in all patients affected by ED (1 ØØØØ).
Recommendation #39. We suggest considering prolactin and thyroid stimulation hormone evaluation in the presence of other sexual comorbidities such as reduced sexual desire or ejaculatory dysfunctions (2 ØOOO).
*Evidence
*Remarks
Instrumental evaluation
Recommendation #40. We suggest performing Penile Color Doppler Ultrasound, at least in flaccid conditions, in all men with erectile dysfunction (2ØØØO).
Recommendation #41. We suggest performing Nocturnal Penile Tumescence and Rigidity (NPTR) test or other instrumental examinations only in selected patients (2ØOOO).
*Evidence
*Remarks
Cardiological assessment
Recommendation #42. We suggest that coronary artery calcium score (if permitted by local expertise and availability), could be considered as a further diagnostic test in men with calculated risks around decision thresholds (low-to-intermediate CVD risk profile), in order to relocate them to different risk groups (2ØOOO).
*Evidence
*Remarks
Psychological assessment
Recommendation #43. We suggest educational, psychological, psycho-sexological, and marital assessment in all patients with ED (Good clinical practice).
*Evidence and remarks
Psychiatric assessment
Recommendation #44. We recommend investigating anxiety and depressive symptoms, through standardized self-reported assessment, in men with erectile dysfunction, due to high incidences of these disorders (1 ØØØØ).
Recommendation #45. We suggest using as screening tools “General Anxiety Disorder-7” and “Patient Health Questionnaire-9”, for anxiety and depression, respectively (2ØØOO).
*Evidence
*Remarks
Therapy
Etiological (or causal) therapies
All the therapies directly addressing the causes or that act as risk factors of ED are to be considered etiological. Therapies addressing lifestyle (diet, smoking cessation, physical activity, etc.), and hormonal therapies for endocrine diseases, are to be considered typical etiological therapies. Etiological therapies may be sufficient in curing ED or they may need the support of symptomatic therapy (see below) [156].
Diet
Recommendation #46. We recommend the assumption of healthy diets to reduce the risk of ED (1ØØOO).
Recommendation #47. We recommend the use of Mediterranean dietary patterns to prevent the development or reduce the progression of ED in men with diabetes, obesity, or metabolic syndrome (1ØØØO)
*Evidence
*Remarks
Physical exercise
Recommendation #48. We recommend physical activity in all subjects with ED, particularly in overweight or obese subjects. (1ØØOO).
*Evidence and remarks
Bariatric surgery
Recommendation #49. We suggest bariatric surgery to decrease erectile dysfunction in morbidly obese men (2 ØØØO).
*Evidence
Smoking and drug cessation
Recommendation #50. We recommend quitting smoke as a major therapeutical strategy to improve general and sexual health and erectile function (1ØØØØ).
Recommendation #51. We recommend quitting abuse of alcohol and illegal psychotropic substances as major therapeutical strategies to improve general and sexual health, including erectile function (1ØØØØ).
Recommendation #52. We suggest discussing with the physician the prescription of drugs with the lowest impact on sexual function (2ØØOO)
*Evidence and remarks
Hypogonadism
Recommendation #53. We recommend treating hypogonadal ED patients with testosterone, with the best results obtained in patients with overt hypogonadism (i.e. total T<8 nmol/L) (1 ØØØØ).
*Evidence
*Remarks
Other associated endocrine diseases
Recommendation #54. We recommend treating erectile dysfunction in patients with severe hyperprolactinemia to improve sexual desire, testosterone levels, and erectile function (1ØØØO).
Recommendation #55. We suggest treating patients with hypo-hyperthyroidism (2ØØOO) or hypocortisolism (2ØOOO) with their specific therapy to also improve erectile function.
*Evidence
*Remarks
Psychoanalysis
Recommendation #56. We suggest considering psychoanalysis as a therapeutical option in selected patients in whom other therapeutic approaches for erectile dysfunction have failed (Expert opinion).
*Evidence and remarks
Symptomatic therapies
The symptomatic therapies of ED are those addressing the symptom, i.e., the chronic (clinical) or partial (subclinical) inability to obtain and/or maintain an erection, irrespective of the etiological or risk factor related to the sexual dysfunction. Note that, among a number of medical and surgical therapies, cognitive-behavioral and sexual therapies are to be considered symptomatic in nature. Typically, relapses are not rare after withdrawal from all these therapies. However, if the symptomatic therapies are supported by counseling and found successful and satisfactory by the patients and their partners, the possibility of producing a “positive memory” instead of a “prevision of failure” would increase the likelihood of a full recovery and, in some patients, a complete sexual rehabilitation.
Pharmacological therapies
Pharmacological therapies, such as Phosphodiesterase type 5 inhibitors (PDE5i), are to be considered the gold therapeutic standard after (which is the best choice) or together (with a motivational aim) with the lifestyle changes affecting erectile function. When the cause of ED is known, it appears also clinically sound to prescribe PDE5i after the failure of the corresponding etiological treatment (e.g. hypogonadism)
Oral therapy
Recommendation #57. We recommend using short- or long-acting PDE5i as first-line therapy for the treatment of ED (1ØØØØ).
Recommendation #58. We suggest preferring short-acting PDE5i in patients with high CV risk (2 ØØOO).
Recommendation #59. We recommend preferring long-acting PDE5i in patients with LUTS (1ØØØØ).
Recommendation #60. We suggest a combination of chronic and on-demand PDE5i in patients not responding to conventional therapy (Expert Opinion).
Recommendation #61. We recommend against the use of counterfeit PDE5i (Good clinical practice).
Recommendation #62. No sufficient evidence to recommend nutritional supplements is currently available.
*PDE5i evidence
*Remarks
Nutritional supplements
Evidence
Limited information derived from observational studies has suggested an association between reduced circulating levels of vitamin D and ED either in the general population [274, 275] or T2DM [276]. A similar observation has been reported for L-citrulline, beta-sitosterol, ginseng [275], and Tribulus Terrestris [274, 277]. Putative working mechanisms of action include stimulation of the nitric oxide pathway, anti-inflammatory effects, or T secretion enhancement. However, it should be noted that the available quality of the studies and the number of subjects included are too limited to draw any conclusions.
Topical therapy
Recommendation #63. We suggest topical or intraurethral alprostadil in men with erectile dysfunction in whom type 5 phosphodiesterase inhibitors are contraindicated or not tolerated or not effective and who prefer a less-invasive treatment (2 ØØOO).
*Evidence
*Remarks
Intracavernosal injection of vasoactive substances
Recommendation #64. We recommend intracavernosal therapy with alprostadil in men with erectile dysfunction in whom type 5 phosphodiesterase inhibitors are contraindicated or not tolerated or not effective due to organic reasons (1 ØØØØ).
*Evidence
*Remarks
Physical therapies
In patients not responsive to any pharmacological treatment, or when medications are contraindicated, according to their preferences, mechanical therapies, such as vacuum devices, prosthesis surgery, and shockwaves (discussed in another section of these Guidelines) can be prescribed. Furthermore, other newer therapies are expected in the future.
Devices
Recommendation #65. We suggest considering vacuum erection devices alone or as a combined therapy in men with erectile dysfunction in whom type 5 phosphodiesterase inhibitors and intracavernosal/transurethral therapies are contraindicated or not tolerated or not effective (2 ØØOO).
*Evidence
*Remarks
Surgical therapy
Recommendation #66. We recommend using penile prosthesis implantations in men with erectile dysfunction in whom all other therapies are not effective or contraindicated (1ØØØØ).
*Evidence
*Remarks
Counseling and psychotherapies
Recommendation #67. We suggest integrating psycho-sexological therapies with lifestyle changes, and medical, physical, and surgical therapies (2 ØØOO).
Recommendation #68. We recommend cognitive-behavioral approaches as the gold psychotherapeutic standard (1ØOOO).
*Evidence
*Remarks
Controversial issues/future directions
The last part of these Guidelines is a testimony to the fact that the field of sexual medicine in general, and that of ED in particular, is growing and continuously changing its landscape. Moreover, it appears clear that it must be fed and watered with more research and robust evidence, which are currently not enough in the topics here discussed.
Hemodynamic procedures and regeneration therapy
Recommendation #69. Due to limited available data, no clear recommendations on the use of stem cells or platelet-rich plasma as well as on penile mechanical hemodynamic revascularization procedure can be provided.
*Evidence
*Remarks
Shockwave
Recommendation #70. We suggest considering low-intensity shockwave therapy in patients with mild vasculogenic ED not responding to PDE5i (2ØOOO).
*Evidence
*Remarks
Diagnostic and therapeutic flow‑chart
Many attempts have been performed in the past 40 years to provide comprehensive and, at the same time, simple flow charts for both diagnostic and therapeutic purposes. Obviously, these simplifications of the medical act are proportional to the different expertise of the healthcare. The flowchart depicted in Fig. 1 is only apparently complex. It should be considered, in fact, that ED is indeed a complex symptom, deeply involving the general quality of life of the patient and of at least one other person. Since our knowledge of the pathophysiological mechanisms, the diagnostic tools, and the therapeutical options is continuously growing, the possible flow charts are growing in complexity. Our final flowchart aims to help the clinician make a therapeutic choice on the basis of scientific evidence, integrating as much as possible the various therapies available after a detailed diagnostic effort.
Conclusions
In a recent revision of the process of care model for the management of ED, it has been stated that its effective management could be achieved only through a combination of patient risk factor removal or modification and first-line therapies, such as PDE5i, always coupled with counseling and, in selected patients, with psychotherapy, addressing any patient comorbidities known to be associated with ED [197]. Hence, in the statements here presented, SIAMS and the scientific Societies involved stress the need for a careful and expert diagnostic work-up in light of Systems Sexology [7] for defining the treatment goals that must be individualized to restore sexual health and satisfaction to the patient and/or couple and to improve quality of life based on the expressed needs and desires of the patient.
G. Corona · D. Cucinotta · G. Di Lorenzo · A. Ferlin · V. A. Giagulli · L. Gnessi · A. M. Isidori· M. I. Maiorino · P. Miserendino · A. Murrone · R. Pivonello · V. Rochira · G. M. Sangiorgi · G. Stagno · C. Foresta · A. Lenzi · M. Maggi · E. A. Jannini
Abstract
Purpose
Erectile dysfunction (ED) is one of the most prevalent male sexual dysfunctions. ED has been in the past mistakenly considered a purely psycho-sexological symptom by patients and doctors. However, an ever-growing body of evidence supporting the role of several organic factors in the pathophysiological mechanisms underlying ED has been recognized.
Methods The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving several other National Societies to provide an updated guideline on the diagnosis and management of ED. Derived recommendations were based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system.
Results Several evidence-based statements were released providing the necessary up-to-date guidance in the context of ED with organic and psychosexual comorbidities. Many of them were related to incorrect lifestyle habits suggesting how to associate pharmacotherapies and counseling, in a couple-centered approach. Having oral therapy with phosphodiesterase type 5 inhibitors as the gold standard along with several other medical and surgical therapies, new therapeutic or controversial options were also discussed.
Conclusions
These are the first guidelines based on a multidisciplinary approach that involves the most important Societies related to the field of sexual medicine. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving the couple's sexual satisfaction and overall general health.
Introduction
After the loss of the penis bone or baculum, during evolution [1, 2], male erectile function shifted from a voluntary, osteo-muscular action, as in the very large majority of mammals, primates included [3], to a psycho-neuro-endocrine and vascular reaction, where the cortical voluntary control, if any, appears to be much more negative than positive [4]. The lack of the baculum and its striated muscular machinery is not the unique peculiarity of the human erection (and of the consequent erectile dysfunction, ED); the vessels feeding the high oxygen need of the corpora cavernosa are, in fact, characterized by a very small diameter, much smaller than the coronaries, vessels considered to be at high risk for atherosclerotic degeneration due to the particular geometry [5, 6].
Because of the loss of the baculum, ED may have evolved as a marker of poor phenotypic quality and erectile function in humans appears to be large, if not totally, will-independent, while it is, at the same time, strictly age and lifestyle-dependent [6, 7]. Incorrect behavioral choices are in fact able to affect the ability both to obtain and to maintain an erection in the presence of proper erotic stimuli (which roughly corresponds to the National Institutes of Health’s definition of ED) [8]. Interestingly, the main reasons for having ED, i.e. smoking, physical inactivity, poor eating habits and disorders, and abuse of alcohol and substances, are also the main causes of the four plus one classical non-communicable chronic diseases (NCDs: cardiovascular, metabolic, respiratory and oncological diseases, plus neuropsychiatric diseases, recently added to the list) [6, 9].
Taking into consideration all these findings, it would be easy to consider ED as the perfect (early) biomarker of NCDs, as largely demonstrated by epidemiological studies [6, 7]. In particular, erectile function could be considered as the classical ‘canary in the coal mine’, thanks to its particular ability to occur earlier, as a consequence of lifestyle mistakes, with respect to the other NCDs [10]. Since the interdisciplinary field of study on NCDs, which looks at the systems of the human body as part of an integrated whole—incorporating biochemical, physiological, and environmental interactions—has been named Systems Medicine [11], a new paradigm, named Systems Sexology, which increases and ameliorates the complexity of the traditional bio-psycho-social model [12], seems to be the best approach to ED that results from the complex interactions within the male human body in light of a patient's genomics, behavior and environment [6, 7]
In the majority of cases, ED appears, in fact, as a medical symptom (vascular, endocrine, neurologic, and iatrogenic, frequently with mixed risk factors), more rarely surgical in nature, but with almost unavoidable psychological and relational comorbidity. For these reasons, diagnosis, management, and follow-up of the patients and of the couples with ED appear relatively complex and deserving of a renewed effort to implement already published guidelines. This is the aim of these new guidelines of the Italian Society of Andrology and Sexual Medicine (SIAMS) in collaboration with ten other National Societies. While several important guidelines on ED have been produced by other national or continental urological Scientific Societies, this is, to our knowledge, the first one “multicultural” in nature, being produced by a number of different scientific backgrounds, but all interested and involved in the management of ED from various perspectives.
Epidemiology and risk factors
Evidence supporting that a specific ED case is due to a single and unique etiological factor is scarce and not supported by common clinical practice. For this reason, in defining the well-known pathophysiological mechanisms related to ED, we discourage the use of the term “etiologies”. The expression to be “Risk Factors” is preferred, also considering that there are frequently multiple factors in the same patient (see also Table 1).
Epidemiology
Recommendation #1. We recommend considering erectile dysfunction as a common male disorder whose incidence and prevalence are strongly associated with age and health status (1 ØØØØ).
*Evidence
*Remarks
Risk factors
Several systemic conditions as well as organic, relational, and intrapsychic factors can contribute to the development of ED (Table 1). Moreover, ED is frequently comorbid with other sexual dysfunctions, either in the patients and/or in the partner, which may amplify the erectile failure in subclinical forms (see below) into an overt ED.
Systemic risk factors
Recommendation #2. We recommend investigating the sexual function and ruling out erectile dysfunction in all patients with systemic diseases, especially in those with organ failure (Good clinical practice).
*Evidence and remarks
Cardiovascular and respiratory risk factors
Arterial hypertension
Recommendation #3. We recommend investigating erectile dysfunction in individuals with arterial hypertension since it is strongly associated with hypertension duration and severity (1ØØØØ), and it might be related to the use of some anti-hypertensive medications (1ØOOO).
*Evidence
*Remarks
Cardiovascular diseases
Recommendation #4. We recommend checking for symptoms of coronary artery disease in all patients with erectile dysfunction at each visit and evaluating the cardiovascular risk profile using cardiovascular algorithms such as SCORE2 or SCORE2-OP (Systematic Coronary Risk Estimation 2 and Systematic Coronary Risk Estimation 2-Older Persons) (1 ØØØØ).
*Evidence
*Remarks
Chronic obstructive pulmonary disease and sleep apnea
Recommendation #5. We suggest investigating erectile dysfunction in all patients with chronic obstructive pulmonary disease and obstructive sleep apnea (2 ØØØΟ).
*Evidence and remarks
Metabolic risk factors
Obesity
Recommendation #6. We recommend investigating sexual function in all male patients with obesity (1 ØØØØ)
*Evidence
Diabetes mellitus
Recommendation #7. We recommend investigating erectile dysfunction in all patients with diabetes mellitus since it is strongly associated with diabetes duration, metabolic control, and the coexistence of other diabetic complications (1 ØØØØ).
*Evidence
*Remarks
Dyslipidemia and gout
Recommendation #8. We recommend investigating erectile dysfunction in all patients with dyslipidemia (1 ØØØØ) and gout (1 ØOOO).
Dyslipidemia
It is well known that dyslipidemia is clearly associated with MACE, [64]. Considering that ED is another well-known risk factor for MACE [6], associations between the two conditions have been thoroughly investigated
*Evidence
*Remarks
Gout
The association between gout, the most common crystal arthropathy, and sexual dysfunction has often been investigated by studies in recent decades. Awareness of this association is frequently lacking and the pathogenetic mechanisms have only partially been identified.
*Evidence
*Remarks
Hormonal disorders
Recommendation #9. We recommend investigating sexual function in male patients with low testosterone. (1ØØØØ).
Recommendation #10. We
suggest considering the investigation of sexual function in other endocrine conditions such as thyroid, adrenal, and pituitary diseases (2 ØOOO).
*Evidence
*Remarks
Neurological disorders
Recommendation #11. We suggest investigating erectile function in all patients with central and peripheral neurological diseases potentially affecting male sexual response (2 ØØOO).
*Evidence
Urological disorders
Lower urinary tract symptoms
Recommendation #12. We recommend screening patients with erectile dysfunction with the International Prostatic Symptom Score and patients with benign prostate obstruction with the International Index of Erectile Function (1 ØØØO).
*Evidence
*Remarks
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)
Recommendation #13. We suggest investigating erectile dysfunction in all patients with CP/CPPS (2 ØØOO).
*Evidence
Peyronie’s disease (PD)
Recommendation #14. We suggest ruling out erectile dysfunction in all patients with Peyronie’s disease (2 ØOOO).
*Evidence
Toxicological and iatrogenic risk factors
Substances/drugs abuse
Recommendation #15. We recommend considering the use of psychotropic drugs (e.g.: opioids, amphetamine, methamphetamine, and, to some extent, cannabis) as a possible risk factor for erectile dysfunction (1ØØOO).
Recommendation #16. We suggest specifically investigating the presence of long-term use of illicit psychotropic drugs in patients with inadequate response to treatment of erectile dysfunction (2ØØOO).
*Evidence and remarks
Iatrogenic medical
Recommendation #17. All patients treated with anti-androgenic drugs must be informed about possible negative effects on erectile function (Good Clinical Practice).
Recommendation #18. We recommend investigating erectile function in all men treated with most antidepressants or antipsychotic medications (1ØØØØ).
Recommendation #19. We suggest investigating sexual function in young patients with a history of previous treatment with drugs affecting the serotoninergic pathway or the conversion of testosterone to dihydrotestosterone (2ØOOO). Recommendation #20. We suggest against using beta-blockers as a first-line therapy in patients with de-novo-diagnosed arterial hypertension if no specific cardiological indications are present (2ØOO).
*Evidence
*Remarks
Iatrogenic surgical
Recommendation #21. We recommend investigating sexual function in all patients treated with pelvic surgery for malignancies (1ØØØØ).
*Evidence and remarks
Psychiatric, psychological, and relational risk factors
Psychiatric disorders
Recommendation #22. We recommend considering psychiatric disorders (such as schizophrenia, bipolar disorders, and post-traumatic stress disorder) as risk factors for erectile dysfunction (1ØØØO).
Recommendation #23. We recommend considering anxiety and depression as independent predictors of erectile dysfunction and its severity. (1ØØOO).
*Evidence
*Remarks
Intrapsychic and relational risk factors
Recommendation #24. We recommend considering intrapsychic factors as major risk factors for developing and maintaining erectile dysfunction (1 ØØOO).
Recommendation #25. We recommend considering relational and marital factors as major risk factors for developing and maintaining erectile dysfunction (1 ØØOO).
Recommendation #26. We recommend considering nonorganic and organic risk factors always jointly and in their entirety (Good Clinical Practice).
*Evidence
Sexual risk factors
Hypoactive sexual desire
Recommendation #27. We recommend investigating sexual desire in subjects with erectile dysfunction because the two conditions are often comorbid (1 ØOOO).
*Evidence
*Remarks
Premature ejaculation
Recommendation #28. We suggest, in patients with loss of control of erection and ejaculation, addressing the erectile function before any therapeutical attempt to improve the ejaculatory control (2 ØØØO).
*Evidence
*Remarks
Partner sexual disorders and “couple pause”
Recommendation #29. We recommend considering the partner and her/his sexual dysfunctions as direct or indirect risk factors for erectile dysfunction (Good Clinical Practice).
*Evidence
*Remarks
Sexual orientation
Recommendation #30. We suggest non-judgmentally exploring patients’ sexual orientation (and gender identity) and personal perceived attitudes towards it when managing their erectile dysfunction (2 ØØOO).
*Evidence
*Remarks
Infertility
Recommendation #31. We suggest investigating the presence of erectile dysfunction in the workup of couple infertility, particularly when undergoing assisted reproduction techniques (Good Clinical Practice).
*Evidence
*Remarks
Diagnosis
The aim of the diagnosis of ED is to (i) identify the severity of the symptom (subclinical, mild, moderate, severe), (ii) identify the comorbidity with other sexual dysfunctions (e.g. hypoactive sexual disorder, ejaculatory disturbances), (iii) find as many risk factors as possible ascertaining their impact on the single case of ED. Hence, the diagnosis is never aiming to exclude etiologies, but, on the contrary, to include the risk factors resulting from careful general and sexual anamnesis, focused physical examination, psychometric, laboratory, and instrumental tools evaluating their “specific weight” in the pathogenesis and care of ED.
Psychogenic vs. organic diagnosis of erectile dysfunction
Recommendation #32. We recommend against the use of the redundant and stigmatizing term «psychogenic» for patients with non-organic, or idiopathic, erectile dysfunction. (Expert opinion).
Recommendation #33. We recommend against the “exclusion diagnosis”, as it is not evidence-based, of erectile dysfunction. (Good clinical practice).
*Evidence
*Remarks
Diagnosis of subclinical erectile dysfunction
Recommendation #34. We suggest considering subclinical erectile dysfunction as a taxonomic entity deserving of clinical attention (Expert Opinion).
*Evidence
*Remarks
Self‑reported questionnaires and structured interviews
Recommendation #35. We suggest using validated questionnaires and structured interviews to support medical and sexological history during erectile dysfunction assessment and/or follow-up (2ØØOO).
*Evidence
*Remarks
Self‑reported questionnaires and structured interviews
Recommendation #35. We suggest using validated questionnaires and structured interviews to support medical and sexological history during erectile dysfunction assessment and/or follow-up (2ØØOO).
*Evidence
*Remarks
Physical examination
Recommendation #36. We recommend a focused genital-urinary and physical examination including penis, testis, and prostate evaluation, at least at the patient’s first visit, in addition to the mandatory general physical examination (1ØØØØ).
*Evidence
*Remarks
Metabolic and hormonal evaluation
Recommendation #37. We recommend routine laboratory tests including fasting glucose, glycated hemoglobin and triglycerides, and total and HDL cholesterol, in all patients affected by erectile dysfunction (1 ØØØØ).
Recommendation #38. We recommend routine hormonal parameters including luteinizing hormone, follicle-stimulating hormone, total testosterone, sex hormone binding globulin, and albumin (for calculated free testosterone determination) in all patients affected by ED (1 ØØØØ).
Recommendation #39. We suggest considering prolactin and thyroid stimulation hormone evaluation in the presence of other sexual comorbidities such as reduced sexual desire or ejaculatory dysfunctions (2 ØOOO).
*Evidence
*Remarks
Instrumental evaluation
Recommendation #40. We suggest performing Penile Color Doppler Ultrasound, at least in flaccid conditions, in all men with erectile dysfunction (2ØØØO).
Recommendation #41. We suggest performing Nocturnal Penile Tumescence and Rigidity (NPTR) test or other instrumental examinations only in selected patients (2ØOOO).
*Evidence
*Remarks
Cardiological assessment
Recommendation #42. We suggest that coronary artery calcium score (if permitted by local expertise and availability), could be considered as a further diagnostic test in men with calculated risks around decision thresholds (low-to-intermediate CVD risk profile), in order to relocate them to different risk groups (2ØOOO).
*Evidence
*Remarks
Psychological assessment
Recommendation #43. We suggest educational, psychological, psycho-sexological, and marital assessment in all patients with ED (Good clinical practice).
*Evidence and remarks
Psychiatric assessment
Recommendation #44. We recommend investigating anxiety and depressive symptoms, through standardized self-reported assessment, in men with erectile dysfunction, due to high incidences of these disorders (1 ØØØØ).
Recommendation #45. We suggest using as screening tools “General Anxiety Disorder-7” and “Patient Health Questionnaire-9”, for anxiety and depression, respectively (2ØØOO).
*Evidence
*Remarks
Therapy
Etiological (or causal) therapies
All the therapies directly addressing the causes or that act as risk factors of ED are to be considered etiological. Therapies addressing lifestyle (diet, smoking cessation, physical activity, etc.), and hormonal therapies for endocrine diseases, are to be considered typical etiological therapies. Etiological therapies may be sufficient in curing ED or they may need the support of symptomatic therapy (see below) [156].
Diet
Recommendation #46. We recommend the assumption of healthy diets to reduce the risk of ED (1ØØOO).
Recommendation #47. We recommend the use of Mediterranean dietary patterns to prevent the development or reduce the progression of ED in men with diabetes, obesity, or metabolic syndrome (1ØØØO)
*Evidence
*Remarks
Physical exercise
Recommendation #48. We recommend physical activity in all subjects with ED, particularly in overweight or obese subjects. (1ØØOO).
*Evidence and remarks
Bariatric surgery
Recommendation #49. We suggest bariatric surgery to decrease erectile dysfunction in morbidly obese men (2 ØØØO).
*Evidence
Smoking and drug cessation
Recommendation #50. We recommend quitting smoke as a major therapeutical strategy to improve general and sexual health and erectile function (1ØØØØ).
Recommendation #51. We recommend quitting abuse of alcohol and illegal psychotropic substances as major therapeutical strategies to improve general and sexual health, including erectile function (1ØØØØ).
Recommendation #52. We suggest discussing with the physician the prescription of drugs with the lowest impact on sexual function (2ØØOO)
*Evidence and remarks
Hypogonadism
Recommendation #53. We recommend treating hypogonadal ED patients with testosterone, with the best results obtained in patients with overt hypogonadism (i.e. total T<8 nmol/L) (1 ØØØØ).
*Evidence
*Remarks
Other associated endocrine diseases
Recommendation #54. We recommend treating erectile dysfunction in patients with severe hyperprolactinemia to improve sexual desire, testosterone levels, and erectile function (1ØØØO).
Recommendation #55. We suggest treating patients with hypo-hyperthyroidism (2ØØOO) or hypocortisolism (2ØOOO) with their specific therapy to also improve erectile function.
*Evidence
*Remarks
Psychoanalysis
Recommendation #56. We suggest considering psychoanalysis as a therapeutical option in selected patients in whom other therapeutic approaches for erectile dysfunction have failed (Expert opinion).
*Evidence and remarks
Symptomatic therapies
The symptomatic therapies of ED are those addressing the symptom, i.e., the chronic (clinical) or partial (subclinical) inability to obtain and/or maintain an erection, irrespective of the etiological or risk factor related to the sexual dysfunction. Note that, among a number of medical and surgical therapies, cognitive-behavioral and sexual therapies are to be considered symptomatic in nature. Typically, relapses are not rare after withdrawal from all these therapies. However, if the symptomatic therapies are supported by counseling and found successful and satisfactory by the patients and their partners, the possibility of producing a “positive memory” instead of a “prevision of failure” would increase the likelihood of a full recovery and, in some patients, a complete sexual rehabilitation.
Pharmacological therapies
Pharmacological therapies, such as Phosphodiesterase type 5 inhibitors (PDE5i), are to be considered the gold therapeutic standard after (which is the best choice) or together (with a motivational aim) with the lifestyle changes affecting erectile function. When the cause of ED is known, it appears also clinically sound to prescribe PDE5i after the failure of the corresponding etiological treatment (e.g. hypogonadism)
Oral therapy
Recommendation #57. We recommend using short- or long-acting PDE5i as first-line therapy for the treatment of ED (1ØØØØ).
Recommendation #58. We suggest preferring short-acting PDE5i in patients with high CV risk (2 ØØOO).
Recommendation #59. We recommend preferring long-acting PDE5i in patients with LUTS (1ØØØØ).
Recommendation #60. We suggest a combination of chronic and on-demand PDE5i in patients not responding to conventional therapy (Expert Opinion).
Recommendation #61. We recommend against the use of counterfeit PDE5i (Good clinical practice).
Recommendation #62. No sufficient evidence to recommend nutritional supplements is currently available.
*PDE5i evidence
*Remarks
Nutritional supplements
Evidence
Limited information derived from observational studies has suggested an association between reduced circulating levels of vitamin D and ED either in the general population [274, 275] or T2DM [276]. A similar observation has been reported for L-citrulline, beta-sitosterol, ginseng [275], and Tribulus Terrestris [274, 277]. Putative working mechanisms of action include stimulation of the nitric oxide pathway, anti-inflammatory effects, or T secretion enhancement. However, it should be noted that the available quality of the studies and the number of subjects included are too limited to draw any conclusions.
Topical therapy
Recommendation #63. We suggest topical or intraurethral alprostadil in men with erectile dysfunction in whom type 5 phosphodiesterase inhibitors are contraindicated or not tolerated or not effective and who prefer a less-invasive treatment (2 ØØOO).
*Evidence
*Remarks
Intracavernosal injection of vasoactive substances
Recommendation #64. We recommend intracavernosal therapy with alprostadil in men with erectile dysfunction in whom type 5 phosphodiesterase inhibitors are contraindicated or not tolerated or not effective due to organic reasons (1 ØØØØ).
*Evidence
*Remarks
Physical therapies
In patients not responsive to any pharmacological treatment, or when medications are contraindicated, according to their preferences, mechanical therapies, such as vacuum devices, prosthesis surgery, and shockwaves (discussed in another section of these Guidelines) can be prescribed. Furthermore, other newer therapies are expected in the future.
Devices
Recommendation #65. We suggest considering vacuum erection devices alone or as a combined therapy in men with erectile dysfunction in whom type 5 phosphodiesterase inhibitors and intracavernosal/transurethral therapies are contraindicated or not tolerated or not effective (2 ØØOO).
*Evidence
*Remarks
Surgical therapy
Recommendation #66. We recommend using penile prosthesis implantations in men with erectile dysfunction in whom all other therapies are not effective or contraindicated (1ØØØØ).
*Evidence
*Remarks
Counseling and psychotherapies
Recommendation #67. We suggest integrating psycho-sexological therapies with lifestyle changes, and medical, physical, and surgical therapies (2 ØØOO).
Recommendation #68. We recommend cognitive-behavioral approaches as the gold psychotherapeutic standard (1ØOOO).
*Evidence
*Remarks
Controversial issues/future directions
The last part of these Guidelines is a testimony to the fact that the field of sexual medicine in general, and that of ED in particular, is growing and continuously changing its landscape. Moreover, it appears clear that it must be fed and watered with more research and robust evidence, which are currently not enough in the topics here discussed.
Hemodynamic procedures and regeneration therapy
Recommendation #69. Due to limited available data, no clear recommendations on the use of stem cells or platelet-rich plasma as well as on penile mechanical hemodynamic revascularization procedure can be provided.
*Evidence
*Remarks
Shockwave
Recommendation #70. We suggest considering low-intensity shockwave therapy in patients with mild vasculogenic ED not responding to PDE5i (2ØOOO).
*Evidence
*Remarks
Diagnostic and therapeutic flow‑chart
Many attempts have been performed in the past 40 years to provide comprehensive and, at the same time, simple flow charts for both diagnostic and therapeutic purposes. Obviously, these simplifications of the medical act are proportional to the different expertise of the healthcare. The flowchart depicted in Fig. 1 is only apparently complex. It should be considered, in fact, that ED is indeed a complex symptom, deeply involving the general quality of life of the patient and of at least one other person. Since our knowledge of the pathophysiological mechanisms, the diagnostic tools, and the therapeutical options is continuously growing, the possible flow charts are growing in complexity. Our final flowchart aims to help the clinician make a therapeutic choice on the basis of scientific evidence, integrating as much as possible the various therapies available after a detailed diagnostic effort.
Conclusions
In a recent revision of the process of care model for the management of ED, it has been stated that its effective management could be achieved only through a combination of patient risk factor removal or modification and first-line therapies, such as PDE5i, always coupled with counseling and, in selected patients, with psychotherapy, addressing any patient comorbidities known to be associated with ED [197]. Hence, in the statements here presented, SIAMS and the scientific Societies involved stress the need for a careful and expert diagnostic work-up in light of Systems Sexology [7] for defining the treatment goals that must be individualized to restore sexual health and satisfaction to the patient and/or couple and to improve quality of life based on the expressed needs and desires of the patient.
