All NOS subtypes produce NO, but each may play a different biologic role in various tissues. nNOS and eNOS are considered constitutive forms because they share biochemical features: They are calcium-dependent, they require calmodulin and reduced nicotinamide adenine dinucleotide phosphate for catalytic activity, and they are competitively inhibited by arginine derivatives. nNOS is involved in the regulation of neurotransmission, and eNOS is involved in the regulation of blood flow.
Positron emission tomorgraphy (PET), and functional magnetic resonance imaging (fMRI) have led to a greater understanding to which center are activated during arousal. These imaging studies measure increases in cerebral blood flow or changes in cerebral activity on a real-time basis. Studies are performed when male subject are aroused by visual cues (usually sexual explicit photos or videos) and compared to images obtained during exposure to sexually neutral cues differences can be measured. Several studies have identified that the inferior frontal lobes, inferior temporal lobes and insular gyrus, and occipital lobes are involved with processing arousal cues, although each are likely to process different stimuli (20-23).
Chronic stress dumps adrenaline in your system multiple times a day. And that can lead to high blood pressure, heart disease, obesity, and diabetes. Chronic stress is like red-lining your car all day long. When you drive 100 mph all the time, something is going to break down. A high-stress environment can actually change the way your brain sends messages to your body. Dumping too much adrenaline into your bloodstream can affect blood flow and severely limit your ability to achieve and maintain an erection.
Other factors leading to erectile dysfunction are diabetes mellitus, which is a well-known cause of neuropathy).[2] ED is also related to generally poor physical health, poor dietary habits, obesity, and most specifically cardiovascular disease, such as coronary artery disease and peripheral vascular disease.[2] Screening for cardiovascular risk factors, such as smoking, dyslipidemia, hypertension, and alcoholism is helpful.[2]

The diagnosis of erectile dysfunction relies on the history. It is important to ensure that the problem is truly erectile dysfunction and not a different type of sexual dysfunction. The evaluation of erectile dysfunction focuses on identifying possible medical causes of the erectile dysfunction. Thus, the physician should conduct a full medical history (reviewing past medical and surgical history, medications, and social history) as well as physical examination. Thereafter, a more focused and thorough sexual, medical, and psychosocial history should be performed. Erectile dysfunction is a delicate topic, and a doctor should be sensitive and caring to make you comfortable about sharing these intimate details of your private life. Prior to your visit, you may also complete a validated ED questionnaire such as the IIEF-SHIM questionnaire.

The physical side effects of chemotherapy are usually temporary and resolve within one to two weeks after stopping the chemotherapy. However, chemotherapy agents, such as Ciplatin or Vincristine, may interfere with the nerves that control erection leading to possible impotence. Make sure you discuss potential side effects of cancer chemotherapy with your doctor or healthcare provider.


Many factors can contribute to sexual dysfunction in older men, including physical and psychological conditions, comorbidities and the medications used to treat them. Aspects of an ageing man’s lifestyle and behaviour and androgen deficiency, most often decreasing testosterone levels, may affect sexual function as well. A study of men between the ages of 30 and 79 years showed that 24% had testosterone levels below 300 ng/dL and 5.6% had symptomatic androgen deficiency.2
PDE5 inhibitors, the primary second-line therapy, have been the mainstay of ED treatment since the release of sildenafil (Viagra) in 1998, with the subsequent development of many others, and still more in the development stage. These medications do improve erectile quality for the majority of men, and they work by enhancing blood flow in the corpora cavernosa. These medications are generally used on demand and need to be taken about an hour before sexual intimacy. Tadalafil (Cialis) is longer acting and does come in a daily preparation potentially eliminating the ‘on-demand’ need. The daily dosing of tadalafil, 2.5–5 mg\day, has also been approved by the FDA for treatment of symptoms of BPH.41 PDE5 inhibitors are contraindicated in men taking nitrates, but otherwise PDE5 inhibitors are very safe and effective. When PDE5 inhibitors are coadministered with nitrates, pronounced systemic vasodilation and severe hypotension are possible. Many patients with ED are elderly and have the same risk factors as patients with CAD, so these drug combinations are commonly considered or encountered in clinical practice.42

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.
One of the first steps is to distinguish between physiological and psychological ED. Determining whether involuntary erections are present is important in eliminating the possibility of psychogenic causes for ED.[2] Obtaining full erections occasionally, such as nocturnal penile tumescence when asleep (that is, when the mind and psychological issues, if any, are less present), tends to suggest that the physical structures are functionally working.[19][20] Similarly, performance with manual stimulation, as well as any performance anxiety or acute situational ED, may indicate a psychogenic component to ED.[2]
This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. The NIDDK translates and disseminates research findings through its clearinghouses and education programs to increase knowledge and understanding about health and disease among patients, health professionals, and the public. Content produced by the NIDDK is carefully reviewed by NIDDK scientists and other experts.
The common PDE5 inhibitor drugs approved in the United States are sildenafil (Viagra), vardenafil (Levitra and Staxyn, the generic form), tadalafil (Cialis), or avanafil (Stendra). All of the currently approved PDE5 inhibitors work in the same way. They differ in the number of available doses, how quickly they work and last in your system, the dosing, and to some extent in the side effects. However, they generally share the same indications and contraindications. Currently, tadalafil is the only medication that patients can take on a daily basis and is approved for the treatment of both ED and BPH (benign enlargement of the prostate).

Normal erectile function depends on the release of NO and endothelial-dependent vasodilation of the penile arteries. The ‘artery size’ hypothesis, first described by Dr Montorsi, offers an explanation why men are more likely to develop ED before a myocardial infacrtion. It is believed that atherosclerosis affects all vascular beds equally but smaller arteries are more likely to become occluded than larger arteries.31 32 The penile arteries are 1–2 mm while the coronary arteries are 3–4 mm. Thus, the same degree of endothelial dysfunction and atherosclerosis is more likely to occlude blood flow in the penile arteries compared with the coronary arteries. The penile arteries therefore serve as a sensitive indicator for subsequent CVD. This theory is supported by the fact that ED occurs approximately 3 years prior to cardiac symptoms in virtually all patients with chronic coronary syndrome whereas patients with acute coronary syndrome have a much lower prevalence of sexual dysfunction.32
The sensitivity of the skin of the penis to detect vibrations (biothesiometry) can be used as a simple office nerve function screening test. This involves the use of a small vibrating test probe placed on the right and left side of the penile shaft as well as on the head of the penis. The strength of the vibrations is increased until you can feel the probe vibrating clearly. Although this test does not directly measure the erectile nerves, it serves as a reasonable screening for possible sensory loss and is simple to perform. More formal nerve conduction studies are only performed in selected cases.
Currently, there are no therapies that cure erectile dysfunction. However, a number of effective therapies are available that allow an individual to have an erection when desired. Depending on the cause of the erectile dysfunction, certain therapies may be more effective than others. Although there is limited data on lifestyle modification, intuitively, decreasing risk factors for erectile dysfunction may help prevent progression of disease.
Penile prostheses are very effective, and most patients who have a prosthesis placed are satisfied with the prosthesis. However, placement of a prosthesis causes scarring of the tissue within the corpora cavernosa, and if the prosthesis requires removal, other forms of therapy, except for the vacuum device, are often not effective. Thus, most physicians reserve placement of a prosthesis for men who have tried and failed or have contraindications to other therapies.

Male erectile problems often produce a significant emotional reaction based on the impact of erectile dysfunction on confidence, self-esteem, and morale in most men. This is described as a pattern of anxiety and stress that can further interfere with normal sexual function. Such "performance anxiety" needs to be recognized and addressed by a doctor.
ED may occur with or without other sexual dysfunction, including decreased libido (decreased interest in sexual activity), orgasmic dysfunction (troubles achieving an orgasm/climax), and ejaculatory dysfunction (problems with the fluid released during sex, including lack of ejaculation [anejaculation], small volume ejaculate, ejaculation that occurs too quickly [premature ejaculation], ejaculate that goes backward into the bladder [retrograde ejaculation] and pain with ejaculation).
Having erection trouble from time to time isn't necessarily a cause for concern. If erectile dysfunction is an ongoing issue, however, it can cause stress, affect your self-confidence and contribute to relationship problems. Problems getting or keeping an erection can also be a sign of an underlying health condition that needs treatment and a risk factor for heart disease.
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