Several pathways have been described to explain how information travels from the hypothalamus to the sacral autonomic centers. One pathway travels from the dorsomedial hypothalamus through the dorsal and central gray matter, descends to the locus ceruleus, and projects ventrally in the mesencephalic reticular formation. Input from the brain is conveyed through the dorsal spinal columns to the thoracolumbar and sacral autonomic nuclei.

Ultrasound with Doppler imaging (ultrasound plus evaluation of blood flow in the arteries and veins) can provide additional information about blood flow of the penis and may help in the evaluation of patients prior to surgical intervention. This study is typically performed after the injection of a chemical that causes the arteries to open up, a vasodilator (prostaglandin E1), into the corpora cavernosa in order to cause dilation of blood vessels and promote blood flow into the penis. The rate of blood flow into the penis can be measured along with an evaluation of problems with compression of the veins.
ED is defined as the inability to achieve a full erection or the inability to maintain an erection adequate for sexual intimacy. Other types of sexual dysfunction such as premature ejaculation and low libido may occur; however, the most common and disruptive problem in men is ED. Although most men will experience periodic episodes of ED, these episodes tend to become more frequent with advancing age.

Vascular damage may result from radiation therapy to the pelvis and prostate in the treatment of prostate cancer. [36] Both the blood vessels and the nerves to the penis may be affected. Radiation damage to the crura of the penis, which are highly susceptible to radiation damage, can induce ED. Data indicate that 50% of men undergoing radiation therapy lose erectile function within 5 years after completing therapy; fortunately, some respond to one of the PDE5 inhibitors.
When lifestyle changes alone don’t work, drug therapy (Viagra®, Cialis®, Levitra®, etc.) is normally the next step. Most of these medications work similarly to enhance a natural chemical in your body that relaxes the muscles in your penis. The goal of this medication is to increase your response to sexual stimulation by increasing the blood flow in your penis allowing you to get an erection.22
Erections are initiated and maintained via integration of afferent inputs in the supra sacral regions of the central nervous system. Regions of the brain cited to have key roles in the integration of signals include the medial amygdala, MPOA, periaqueductal gray matter, paraventricular nucleus (PVN), and ventral tegmentum among others (16). Studies in animal models, particularly in rats, have been paramount in identifying these key areas of signal integration and control. Electrostimulation of the MPOA, PVN and hippocampus lead to erection and lesions in these areas may prevent erection (17). Marson et al. injected labeled pseudorabies virus into rat corpora cavernosa and traced them to neurons in the spinal cord, brain stem and hypothalamus (18). Stimulation of the rat dorsal nerve led to increased firing in the MPOA not found elsewhere (19). Axonal tracing in animals have shows direct projections from the hypothalamus to the lumbosacral autonomic erection centers. Oxytocin and vasopressin have been identified as central neurotransmitters within the hypothalamic nuclei and may have a role in penile erection (17). These signaling studies identifying key areas of erectile response integration may explain how ED is associated with cerebrovascular accident (CVA), Parkinson’s, epilepsy and MS.
Monitoring erections that occur during sleep (nocturnal penile tumescence) can help you and your doctor to understand if the erectile dysfunction is due to psychological or physical causes. The nocturnal penile tumescence test is a study to evaluate erections at night. Normally men have three to five erections per eight hours of sleep. The test can be performed at home or in a sleep lab. The most accurate way to perform the test involves a special device that is connected to two rings. The rings are placed around the penis, one at the tip of the penis and the other at the bottom (base) of the penis. The device records how many erections occur, how long they last, and how rigid they are. The test is limited in that it does not assess the ability to penetrate.
The role of the endothelium in ED has been noted for a number of years and the overlapping of ED and other conditions, especially coronary heart disease, CVD, affecting endothelial function/dysfunction, is clearly present. The endothelial cell is now known to affect vascular tone and impact the process of atherosclerosis, and impacting ED, CVD and peripheral vascular disease.16
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.
An alprostadil cream that patients apply into the tip of the penis (the urethral meatus, the opening that urine passes through) is currently available in the UK and Europe. It is currently under review by the U.S. Food and Drug Administration (FDA). After application of the cream, an erection occurs within five to 30 minutes, and the erection lasts one to two hours in men who respond to the cream. Doctors recommend that one use the cream for a maximum frequency of two to three times per week and no more frequent than once every 24 hours. It has essentially the same contraindications and side effects as the other formulations of alprostadil. The cream may cause vaginal burning in roughly 4% of partners. Men should not use alprostadil cream for sexual intercourse with women of childbearing potential unless a condom is used. Researchers have performed controlled trial studies to evaluate the safety and effectiveness of this drug. Overall, 52% of men reported improvement in their erections compared to 20% of men receiving placebo. A later analysis demonstrated that 36% of men using the alprostadil cream had a clinically relevant improvement in vaginal penetration ability and 31% clinically relevant improvement in ability to have successful intercourse to ejaculation.

MUSE should not be used in men with a history of urethral stricture (narrowing of the tube in the penis that urine and semen pass through), inflammation or infection of the glans (tip) of the penis (balanitis), severe hypospadias (a condition where the opening of the urethra is not at the tip of the penis, rather on the underside of the penis), penile curvature (abnormal bend to the penis), and urethritis (inflammation/infection of the urethra).

When sexually stimulated/aroused, the nerves supplying the penis release a chemical, nitric oxide (NO). Nitric oxide is important because it stimulates the production of a chemical called cyclic guanosine monophosphate (cGMP). cGMP causes the muscle in arteries of the penis to relax and increase blood flow into the penis. NO is broken down in the body by phosphodiesterase enzymes. PDE5 inhibitors thus prevent the breakdown of NO and thus promote increased blood flow into the penis.


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. [37] On the other hand, bicycling for less than 3 hours per week may be somewhat protective against ED. [37] Some of the newer bicycle seats have been designed to diminish pressure on the perineum. [37, 38]
Neurogenic ED remains difficult to diagnose and treat effectively. It is important to realize that many men with neurologic disorders may have ED related to disease related factors separate from the insult to the neuro-erectile pathway. These disease related factors must be addressed prior or simultaneously with pharmacologic and/or surgical therapy to effectively treat their SD. As awareness of the complexities of normal sexual function increase so will the recognition of SD in this population. This movement will lead to improved quality of life in men with neurologic disorders, as proven by the strong link between sexual function and quality of life.
SD in MS can be classified into three categories. Primary SD is due directly due to MS-related neurological deficits, secondary SD is related to physical impairments and symptoms or drugs used for MS treatment, and tertiary SD is due to the psychological, social and cultural problems attributed to MS (38). These classifications are important, and underscore the importance of addressing all the issues leading to SD not just the neurologic impairment.
As men age they require more stimulation up front to get and maintain an erection firm enough for sex.  Engaging in some foreplay either on you or on your partner is a great way to get your arousal levels up and get an erection that is firm enough for sex.  Many men begin to rush the process of sex once they experience ED.  They worry that they will lose their erection so they rush rather than go slow understanding that rushing will only make the problem worse.

As is true in so many medical conditions, lifestyle modifications, considered first-line therapy, can have a salutary effect in ED management, and men should be encouraged to make the necessary changes to the benefit of their sexual function and to their overall health as well. Despite the benefits of behaviour modification, men presenting with ED want the physician to help with measures that can have an immediate impact.
Look, ED can have many causes. Most of the time, it’s physiological. But there are also lots of psychological reasons why someone may experience ED. Treating ED isn’t all about medication. Dealing with some of these psychological issues can help you battle ED, too. I’m talking about depression, anxiety, loss of desire, sense of inadequacy, guilt, fatigue, anger, relationship dysfunction. Working through these types of psychological challenges can help you achieve the happy, healthy manhood you deserve.
Before taking any medication for erectile dysfunction, including over-the-counter supplements and herbal remedies, get your doctor's OK. Medications for erectile dysfunction do not work in all men and might be less effective in certain conditions, such as after prostate surgery or if you have diabetes. Some medications might also be dangerous if you:
The idea of using low-energy shock waves to treat erectile dysfunction comes from studies that show that these types of shocks help heart blood vessels regrow, a process called revascularization. Shock wave therapy may also work on the penis, and there have been some promising results, but it’s not currently an approved ED treatment. "It’s similar to the type of shock waves used to break up kidney stones, and it may cause revascularization,” says Bennett. “However, there are not yet any good controlled studies to recommend it to patients."

In their extensive review, Bassil and coworkers summarise the benefits and risks, with benefits such as improvement of sexual function, bone density, muscle strength, cognition and overall improvement in quality of life. Among the risks that have been suggested include erythrocytosis, liver toxicity, worsening of sleep apnoea and cardiac function, possibly increasing symptoms of benign prostatic hyperplasia (BPH). They also note that although a possibility of stimulation of prostate cancer has been hypothesised, no scientific or clinical evidence exists to this possible risk.38
When sexually stimulated there is a release of a chemical, nitric oxide (NO) in the blood vessels of the corpus cavernosum. The NO stimulates the production of a compound called cGMP, which causes relaxation of the smooth muscle in the blood vessels supplying the corpus cavernosum. PDE 5 is an enzyme that breaks down cGMP. By inhibiting the breakdown of cGMP by PDE5, these medications allow cGMP to build up in the penis. cGMP causes muscles in the corpora cavernosa of the penis to relax. When the muscle is relaxed, more blood can flow into the penis and fill the spaces in the penis. As the penis fills with blood, the veins in the penis are compressed, and this results a hard erection. When the effect on PDE5 decreases, the cGMP levels go down and the muscle in the penis contracts, causing less blood to flow into the penis and allowing the veins to open up and drain blood out of the penis.
The dose of PDE5 inhibitor that you start with may vary with underlying medical conditions and medications that you are taking. Thus, it is important to review all medications (even over the counter medications) with your physician. Typically, one starts with a lower dose and increases as needed. Some medical conditions prevent going up to higher doses. You can review the drug prescribing information or consult with your doctor regarding the dose(s) that are appropriate for you.
The somatosensory pathways for erections originate in the penile skin, glans and urethra. Glans afferent sensory free nerve endings are 10-fold more than their corpuscular receptors, and are derived from Aδ and unmyelinated C fibers. The nerve endings coalesce to form the dorsal penile nerve along with other sensory nerve fibers. Through the pudendal nerve they enter the S2-4 nerve roots to terminate on spinal neurons and interneurons. The dorsal nerve is not purely somatic, however. Nerve bundles within the dorsal nerve contain nitric oxide (NO) synthase, found typically in autonomic nerves, and stimulation of the sympathetic chain can leak to evoked potentials from the dorsal nerve and vice versa (10-12).
The penis contains three cylinders, the two corpora cavernosa, which are on the top of the penis (see figure 1 below). These two cylinders are involved in erections. The third cylinder contains the urethra, the tube that the urine and ejaculate passes through, runs along the underside of the penis. The corpus spongiosum surrounds the urethra. Spongy tissue that has muscles, fibrous tissues, veins, and arteries within it makes up the corpora cavernosa. The inside of the corpora cavernosa is like a sponge, with potential spaces that can fill with blood and distend (known as sinusoids). A layer of tissue that is like Saran Wrap, called the tunica albuginea, surrounds the corpora. Veins located just under the tunica albuginea drain blood out of the penis.
Several medications can interfere with the chemical processing of PDE5i medications by the liver. These can include ketoconazole (an antifungal medication known by the brand name Nizoral), erythromycin (an antibiotic), and cimetidine (also known as Tagamet, for reducing stomach acid). A lower dose of PDE5i medications should be used if one is taking any of these medications.
Commercials for drugs to improve “low T,” or testosterone, the male hormone, are now vying for airtime, but they address desire, not performance. "Male hormone is not an approved treatment for erectile dysfunction," notes Bennett. "It may be used to increase desire in men who have low testosterone, but it doesn’t improve blood flow to an erection." A doctor can do a blood test to check you for low testosterone, but it is a rare cause of ED. Hormone therapy with injections, patches, or gels applied to the skin may improve mood and sex drive, but it likely won’t fix any mechanical issues. Also, testosterone drugs should not be used by men with prostate cancer. Side effects include acne, breast enlargement, prostate enlargement, and fluid retention.
The primary nerve fibers to the penis are from the dorsal nerve of the penis, a branch of the pudendal nerve. The cavernosal nerves are a part of the autonomic nervous system and incorporate both sympathetic and parasympathetic fibers. They travel posterolaterally along the prostate and enter the corpora cavernosa and corpus spongiosum to regulate blood flow during erection and detumescence. The dorsal somatic nerves are also branches of the pudendal nerves. They are primarily responsible for penile sensation. [10]
In the Massachusetts Male Aging Study (MMAS) among a community-based survey of men aged 40-70 years, 52% of the men reported some degree of erectile difficulty. Complete ED, defined as the total inability to obtain or maintain suitable erections during sexual stimulation, as well as the absence of nocturnal erections (normal erections [four to six/night], which occur during sleep), occurred in 10% of the men in the study. Lesser degrees of mild and moderate ED occurred in 17% and 25% of participants.
…have traditionally been classified as impotence (inability of a man to achieve or maintain penile erection) and frigidity (inability of a woman to achieve arousal or orgasm during sexual intercourse). Because these terms—impotence and frigidity—have developed pejorative and misleading connotations, they are no longer used as scientific classifications, having been…
The Food and Drug Administration (FDA) does not recommend alternative therapies to treat sexual dysfunction.[27] Many products are advertised as "herbal viagra" or "natural" sexual enhancement products, but no clinical trials or scientific studies support the effectiveness of these products for the treatment of ED, and synthetic chemical compounds similar to sildenafil have been found as adulterants in many of these products.[28][29][30][31][32] The FDA has warned consumers that any sexual enhancement product that claims to work as well as prescription products is likely to contain such a contaminant.[33]

Alprostadil should not be used in men with urethral stricture (scarring and narrowing of the tube that urine and the ejaculate pass through), balanitis (inflammation/infection of the glans [tip] of the penis, severe hypospadias (a condition where the opening of the urethra is not at the tip of the penis, rather on the underside of the penis), penile curvature (abnormal bend to the penis), and urethritis (inflammation/infection of the urethra).
Multiple combinations of intracavernosal therapy exist and the effectiveness of them varies based on patient characteristics and varying dosing strength (Table 1). Combination therapy have been extremely effective in the SCI population, and have several advantages including a reduction in cost per dose and side effects base on the lowered dose of each component (101,102). Effectiveness of combination therapy in the spinal cord population is well established, but no specific dose recommendations can be made based on the data (103-106). The use of combination therapy on other forms of neurogenic ED have not been well studied, but there use can be trialed as second-line therapy, or for populations were the side effects of PDE5i may preclude use such as in MSA due to hypotension.
If you’re experiencing psychological ED, you may benefit from talk therapy. Therapy can help you manage your mental health. You’ll likely work with your therapist over several sessions, and your therapist will address things like major stress or anxiety factors, feelings around sex, or subconscious conflicts that could be affecting your sexual well-being.
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