Apomorphine is a non-selective D1/D2 receptor agonist with moderate efficacy and good tolerability in the treatment of mild ED (80). Apomorphine can be administered via subcutaneous injection or sublingually. However, studies have shows a lower efficacy for apomorphine compared to oral sildenafil (81,82). Apomorphine has a set role in the management of PD for non-motor symptoms, and has been reported to cause spontaneous erections and possible hypersexuality in PD men (83,84). Its role in the management of ED has been postulated for men with PD but should be considered as an alternative to sildenafil.
The observation that TRT enhances the efficacy of PDE5 inhibitors in hypogonadal men taking these therapies with suboptimal response to the PDE5 inhibitors alone has been reported.33 In addition, investigators have demonstrated that TRT in hypogonadal men can improve erectile function even without the benefit of PDE5 inhibitors.33 In addition, guidelines for managing ED in hypogonadal men by the European Association of Urology recommend controlling the man to a eugonadal state prior to initiation of PDE5 inhibitor therapy.36 Testosterone measurement consists of a serum specimen which should be ideally obtained in the morning because of the normal diurnal variation of testosterone which is at its peak in the morning. Since TRT is relatively safe, and men can potentially see an improvement in erectile function, it seems prudent to consider this issue when presented with a patient suffering from ED.
The availability of phosphodiesterase-5 (PDE5) inhibitors—sildenafil, vardenafil, tadalafil, and avanafil—has fundamentally altered the medical management of ED. In addition, direct-to-consumer marketing of these agents over the last 15 years has increased the general public’s awareness of ED as a medical condition with underlying causes and effective treatments.
The FDA recommends that men follow general precautions before taking a medication for ED. Men who are taking medications that contain nitrates, such as nitroglycerin, should NOT use these medications. Taking nitrates with one of these medications can lower blood pressure too much. In addition, men who take tadalafil or vardenfil should use alpha blockers with care and only as instructed by their physician, as they could result in hypotension (abnormally low blood pressure). Experts recommend that men have a complete medical history and physical examination to determine the cause of ED. Men should tell their doctor about all the medications they are taking, including over-the-counter medications.
Does drinking water improve erectile dysfunction? Erectile dysfunction or ED is a common concern for men. Everyday factors, such as hydration levels, may affect a person's ability to get or maintain an erection. Drinking water may, therefore, help some men with ED. In this article, learn about the link between hydration and ED, and other factors that can cause ED. Read now
Penile erection is managed by two mechanisms: the reflex erection, which is achieved by directly touching the penile shaft, and the psychogenic erection, which is achieved by erotic or emotional stimuli. The former uses the peripheral nerves and the lower parts of the spinal cord, whereas the latter uses the limbic system of the brain. In both cases, an intact neural system is required for a successful and complete erection. Stimulation of the penile shaft by the nervous system leads to the secretion of nitric oxide (NO), which causes the relaxation of smooth muscles of corpora cavernosa (the main erectile tissue of penis), and subsequently penile erection. Additionally, adequate levels of testosterone (produced by the testes) and an intact pituitary gland are required for the development of a healthy erectile system. As can be understood from the mechanisms of a normal erection, impotence may develop due to hormonal deficiency, disorders of the neural system, lack of adequate penile blood supply or psychological problems. Spinal cord injury causes sexual dysfunction including ED. Restriction of blood flow can arise from impaired endothelial function due to the usual causes associated with coronary artery disease, but can also be caused by prolonged exposure to bright light.
Induction of erection occurs after stimulation of the cavernous and pelvic nerve plexus. Conversely, stimulation of the sympathetic trunk leads to detumescence. The reflex erectile response requires that the sacral reflex arc remain intact. Tactile and sensory signals are received by the somatic sensory pathways and integrate with parasympathetic nuclei within the sacral spinal cord (S2-4) leading to induction of erection via cholinergic signaling. These reflexogenic erections remain intact with upper motor neuron injuries. Psychogenic erections do not require that the sacral reflex arc remain intact. In a cat models, spinal cord removal below L4/L5 led to absence of a reflexogenic erection but stimulation of the medial preoptic area (MPOA) or placement near a female cat in heat led to erection (5,6). Psychogenic erections occur via induction of central pathways traveling from the brain through the sympathetic chain. Non-penile sensory pathways induced by sight, sound, touch and smell travel through the MPOA to the erection centers within the cord T11-L2, and S2-S4 to induce erections (7). When a sacral lower motor neuron injury is present in men, below T12 these types of erections are more likely to occur (8). Spinal cord lesions above T9 are not associated with psychogenic erections (9). Rigidity of erections is less with psychogenic erections because the thoracolumbar sympathetic outflow may contain a decreased concentration of neurons compared to the parasympathetic outflow from the sacral spinal cord.
Lifestyle choices that impair blood circulation can contribute to ED. Smoking, excessive drinking, and drug abuse may damage the blood vessels and reduce blood flow to the penis. Smoking makes men with atherosclerosis particularly vulnerable to ED. Being overweight and getting too little exercise also contribute to ED. Studies indicate that men who exercise regularly have a lower risk of ED.
Several pre-treatment factors have been described that may indicate success with PDE5i therapy. The presence of an upper motor neuron lesion up to T12 suggests a successful response, as well as requirement for a lower dosage of medication (62,68-71). Additionally, the presence of residual erections after injury or an incomplete SCI (ASI-A vs. ASIB-D) also improve the chance of PDE5i treatment success (59,67,68,71).
Risks associated with injection therapy including bleeding, pain with injection, penile pain, priapism, and corporal fibrosis (scarring inside of the corpora cavernosa). There is also concern that repetitive injections in the same area could cause scar tissue to build up in the tunica albuginea that could create penile curvature. Thus, doctors recommended that one alternate sides with injection and perform injections no more frequent than every other day.
Alprostadil (also known as prostaglandin E1 [PGE1]) is the prominent known smooth-muscle dilator of the corpus cavernosum. Its mechanism of action is believed to be the promotion of intracellular accumulation of cyclic adenosine monophosphate, thereby causing decreased intracellular accumulation of calcium and resulting smooth muscle relaxation. Alprostadil can be delivered to the erectile tissue either via an intraurethral suppository that is massaged and then absorbed across the corpus spongiosum of the urethra to the corpora cavernosa, or directly injected into the corpora cavernosa. When administered urethrally, doses are substantially higher than when directly injected (typical dosing is 500 mcg to 1 mg intraurethral compared with 2.5 mcg to 20 mcg intracavernosal).
Parasympathetic pathways originate from the intermediolateral cell columns of the 2nd, 3rd and 4th sacral spinal cord segments. Preganglionic fibers pass through the pelvic plexus where they coalesce with sympathetic fibers from the superior hypogastric plexus. The cavernous nerves that innervate the penis arise from the portion of the pelvic plexus. The pelvic plexus also contains nerves that innervate the rectum, bladder and urinary sphincter and the nerve projections can be damaged during radical excision of the bladder, prostate and rectum, leading to iatrogenic ED (4).
Move a muscle, but we're not talking about your biceps. A strong pelvic floor enhances rigidity during erections and helps keep blood from leaving the penis by pressing on a key vein. In a British trial, three months of twice-daily sets of Kegel exercises (which strengthen these muscles), combined with biofeedback and advice on lifestyle changes — quitting smoking, losing weight, limiting alcohol — worked far better than just advice on lifestyle changes.
The development of an erection is a complex event involving integration of psychologic, neurologic, endocrine, vascular, and local anatomic systems. Positron emission tomography scanning studies have suggested that sexual arousal is activated in higher cortical centers that then stimulate the medial preoptic and paraventricular nuclei of the hypothalamus.5 These signals ultimately descend through a complex neural network involving the parasympathetic nervous system and eventually activate parasympathetic nerves in the sacral area (S2 to S4).
Another study compared the response of surgically and medically castrated rabbits to vardenafil with that of control rabbits.  Castrated rabbits did not respond to vardenafil, whereas noncastrated rabbits did respond appropriately. This result suggests that a minimum amount of testosterone is necessary for PDE5 inhibitors to produce an erection.
Surgical intervention for a number of conditions may remove anatomical structures necessary to erection, damage nerves, or impair blood supply. Erectile dysfunction is a common complication of treatments for prostate cancer, including prostatectomy and destruction of the prostate by external beam radiation, although the prostate gland itself is not necessary to achieve an erection. As far as inguinal hernia surgery is concerned, in most cases, and in the absence of postoperative complications, the operative repair can lead to a recovery of the sexual life of people with preoperative sexual dysfunction, while, in most cases, it does not affect people with a preoperative normal sexual life.
Trauma to the pelvic blood vessels or nerves can also lead result in ED. Bicycle riding for long periods has been implicated as an etiologic factor; direct compression of the perineum by the bicycle seat may cause vascular and nerve injury.  On the other hand, bicycling for less than 3 hours per week may be somewhat protective against ED.  Some of the newer bicycle seats have been designed to diminish pressure on the perineum. [37, 38]
In comparison, 37% of men who had received external radiotherapy as their primary therapy reported the ability to attain functional erections suitable for intercourse, along with 43% of men who had received brachytherapy as primary treatment. Pretreatment sexual health-related quality of life score, age, serum prostate-specific antigen (PSA) level, race or ethnicity, body mass index, and intended treatment details were associated with functional erections 2 years after treatment. 
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For best results, men with ED take these pills about an hour or two before having sex. The drugs require normal nerve function to the penis. PDE5 inhibitors improve on normal erectile responses helping blood flow into the penis. Use these drugs as directed. About 7 out of 10 men do well and have better erections. Response rates are lower for Diabetics and cancer patients.