Erectile dysfunction (ED) refers to the consistent or recurrent inability to achieve or maintain a sufficient penile erection for satisfactory sexual intercourse. Based on its causes, ED can be classified into psychogenic, organic, and mixed types, with mixed ED being the most common. Organic ED can further be categorized into vascular (including arterial, venous, and mixed), neurogenic, endocrine, and anatomical types.
Epidemiology
More than half of men aged 40 to 70 experience varying degrees of ED, with over 10% being completely unable to achieve an erection. Risk factors associated with ED include:
- Advanced age.
- Physical conditions such as cardiovascular diseases, hypertension, diabetes, dyslipidemia, metabolic disorders, endocrine diseases, neurologic disorders, and urogenital diseases.
- Psychological and mental health factors.
- Medications and substances, including antihypertensives, antipsychotics, antidepressants, anti-androgen agents, and illicit drugs.
- Unhealthy lifestyle behaviors, such as smoking and excessive alcohol consumption.
- Pelvic trauma, surgeries, and other iatrogenic factors.
Over 80% of ED cases have an underlying organic cause.
Anatomical and Physiological Mechanisms of Penile Erection
Penile erection is a psychophysiological process involving a series of complex neurovascular activities. It results from an interplay between neuroendocrine regulation, hemodynamic changes, and psychological effects, and is divided into three phases: initiation, filling, and maintenance.
The cerebral cortex is the highest regulatory center for sexual physiological activities. Sexual stimuli received by the cerebral cortex are integrated in the hypothalamus and transmitted via the spinal cord and peripheral nerves to the cavernous nerves of the penis. This leads to relaxation of penile arteries and cavernosal smooth muscle, increased arterial blood flow, and engorgement of the penile cavernous sinuses. Venous outflow is concurrently restricted by compression of the subtunical venous plexus against the tunica albuginea, increasing intracavernosal pressure and resulting in penile rigidity and erection.
Erection subsides during ejaculation due to sympathetic nervous system activation, which causes arterial and cavernosal smooth muscle contraction, reduced arterial blood flow, and decreased intracavernosal pressure. As pressure decreases, there is less compression on subalbugineal venous structures, leading to increased venous outflow and penile detumescence.
The degree of erection depends on the balance between arterial inflow and venous outflow. Research indicates that the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway plays a central role during penile erection. Sexual stimulation promotes the release of NO from neurons and endothelial cells in the corpus cavernosum. NO activates guanylate cyclase (GC) in cavernosal smooth muscle cells, converting guanosine triphosphate (GTP) into cGMP. cGMP activates protein kinase G, reducing intracellular calcium levels and causing cavernosal smooth muscle relaxation, enabling blood inflow into the cavernous sinuses and resulting in erection.
Phosphodiesterase type 5 (PDE5) metabolizes cGMP into the inactive guanosine monophosphate (GMP), leading to elevated intracellular calcium levels, smooth muscle contraction, and penile detumescence. Other signaling pathways, including RhoA/Rho kinase, cyclic adenosine monophosphate (cAMP), calcium ion channels, hydrogen sulfide (H2S), tissue kallikrein 1, vasoactive intestinal peptide, calcitonin gene-related peptide, prostaglandins, relaxin, and endothelin, also participate in the regulation of cavernosal smooth muscle contraction and relaxation.
Diagnosis
A thorough evaluation of sexual history, past medical history, history of surgeries or trauma, drug history, lifestyle factors, psychological and social history, and physical examinations targeting the urogenital, endocrine, and neurovascular systems is crucial for the initial diagnosis of ED.
The International Index of Erectile Function (IIEF-5) questionnaire is used to assess five aspects of sexual activity over the past six months:
- Confidence in achieving and maintaining an erection.
- Frequency of successful vaginal penetration when stimulated.
- Ability to maintain an erection after penetration.
- Difficulty in maintaining an erection until completion of intercourse.
- Satisfaction during intercourse.
Responses are scored to determine the presence and severity of ED.
Other diagnostic tools include audiovisual sexual stimulation (AVSS) and nocturnal penile tumescence (NPT) testing, which are helpful in distinguishing psychogenic from organic ED. Further evaluations to identify organic causes may include hormonal assays, intracavernosal pharmacological stimulation tests, vascular studies (e.g., Doppler ultrasonography, cavernosometry, and cavernosography), and assessments of erectile nerve function (e.g., penile biothesiometry, bulbocavernosus reflex latency, and somatosensory evoked potentials from the dorsal nerve of the penis). These tests can help establish whether the cause is arterial, venous, neurogenic, or endocrine-related.
Treatment
Addressing Factors Contributing to ED
These include:
- Modifying unhealthy lifestyle behaviors and addressing social and psychological factors.
- Providing psychological counseling.
- Offering guidance on sexual techniques and sexual health education.
- Adjusting medications that may contribute to ED.
- Treating underlying organic conditions causing ED, such as testosterone replacement therapy for androgen deficiency.
Direct Treatments for ED
Sexual psychotherapy is applied as an intervention for psychological barriers related to ED.
Phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil and tadalafil, are commonly used and exhibit high clinical efficacy. These medications are contraindicated in individuals taking nitrate-based drugs due to the risk of severe hypotension.
Prostaglandin E1 (PGE1`) is a vasoactive agent for intracavernosal injection, with an effectiveness rate exceeding 80%. However, it is less commonly used because of its invasive nature, associated pain, risk of priapism, and the potential for local scarring of the penis with prolonged use. Vacuum erection devices function by creating negative pressure to draw blood into the penis, with a constriction ring applied at the penile base to restrict venous outflow and maintain erection. Disadvantages include operational complexity and side effects such as penile pain, numbness, bruising, and ejaculation difficulties. Low-energy extracorporeal shockwave therapy and low-intensity pulsed ultrasound have shown improvements in some cases of mild to moderate ED.
Surgical options include vascular surgery and penile prosthesis implantation, typically reserved for individuals with vascular-related ED or treatment-resistant cases of ED.