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.


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.

While pills for ED are convenient, some men sustain stronger erections by injecting medication directly into the penis. Drugs approved for this purpose work by widening the blood vessels, causing the penis to become engorged with blood. Another option is inserting a medicated pellet into the urethra. The pellet can trigger an erection within 10 minutes.
Hypogonadism may be suggested by the patient's general appearance. If testosterone deficiency antedates puberty, as in Klinefelter's syndrome, eunuchoid proportions—defined as an arm span 5 cm or more in excess of height, or a sole-to-pubis length exceeding crown-to-pubis length by more than 2 cm—may be present. In postpubertal males whose testosterone levels are markedly depressed, the secondary sexual characteristics may become atrophic. Testicles less than 4 cm in length or a prostate gland that is smaller than expected may be the only clues on physical examination to a pituitary tumor with secondary hypogonadism.
Cardiovascular diseases: The most common cause of cardiovascular diseases in the United States is atherosclerosis, the narrowing and hardening of arteries that reduces blood flow. Atherosclerosis (a type of vascular disease) typically affects arteries throughout the body; hypertension, high blood cholesterol levels, cigarette smoking, and diabetes mellitus aggravate atherosclerosis. Hardening of the arteries to the penis and pelvic organs, atherosclerosis, causes insufficient blood flow into the penis. There is a close correlation between the severity of atherosclerosis in the coronary arteries and erectile dysfunction. For example, men with more severe coronary artery atherosclerosis (hardening of the arteries in the heart) also tend to have more erectile dysfunction than men with mild or no coronary artery atherosclerosis. Some doctors suggest that men with new onset erectile dysfunction undergo evaluation for silent coronary artery diseases (advanced coronary artery atherosclerosis that has not yet caused angina or heart attacks).
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.
The following products are considered to be alternative treatments or natural remedies for Erectile Dysfunction. Their efficacy may not have been scientifically tested to the same degree as the drugs listed in the table above. However there may be historical, cultural or anecdotal evidence linking their use to the treatment of Erectile Dysfunction.
The association between low testosterone and ED is not entirely clear. Although these 2 processes certainly overlap in some instances, they are distinct entities. Some 2-21% of men have both hypogonadism and ED; however, it is unclear to what degree treating the former will improve erectile function. [17] About 35-40% of men with low testosterone see an improvement in their erections with testosterone replacement; however, almost 65% of these men see no improvement. [15]

Constriction of the trabecular smooth muscle and helicine arteries induced by sympathetic innervation makes the penis flaccid, with blood pressure in the cavernosal sinuses of the penis near venous pressure. Acetylcholine is thought to decrease sympathetic tone. This may be important in a permissive sense for adequate trabecular smooth muscle relaxation and consequent effective action of other mediators in achieving sufficient inflow of blood into the lacunar spaces. When the trabecular smooth muscle relaxes and helicine arteries dilate in response to parasympathetic stimulation and decreased sympathetic tone, increased blood flow fills the cavernous spaces, increasing the pressure within these spaces so that the penis becomes erect. As the venules are compressed against the tunica albuginea, penile pressure approaches arterial pressure, causing rigidity. Once this state is achieved, arterial inflow is reduced to a level that matches venous outflow.
Sexual functioning involves a complex interaction among biologic, sociocultural, and psychological factors, and the complexity of this interaction makes it difficult to ascertain the clinical etiology of sexual dysfunction. Before any diagnosis of sexual dysfunction is made, problems that are explained by a nonsexual mental disorder or other stressors must first be addressed. Thus, in addition to the criteria for erectile disorder, the following must be considered:
Psychotherapy and/or behavioral therapy may be useful for some patients with erectile dysfunction without obvious organic cause, and for their partners. These may also be used as an adjunct to other therapies directed at the treatment of organic erectile dysfunction. Outcome data from such therapy, however, have not been well-documented or quantified, and additional studies along these lines are indicated.
The first step in treating the patient with ED is to take a thorough sexual, medical, and psychosocial history. Questionnaires are available to assist clinicians in obtaining important patient data. (See Presentation.) Successful treatment of sexual dysfunction has been demonstrated to improve sexual intimacy and satisfaction, improve sexual aspects of quality of life, improve overall quality of life, and relieve symptoms of depression. (See Treatment.)

In a prospective, multicenter, single-armed study of ED patients who exhibited a suboptimal response to PDE5 inhibitors, the investigators found that percutaneous implantation of zotarolimus-eluting stents in focal atherosclerotic lesions was both safe and feasible and was associated with clinically meaningful improvement on subjective and objective measures of erectile function. [3]
In a randomized double-blind, parallel, placebo-controlled trial, sildenafil plus testosterone was not superior to sildenafil plus placebo in improving erectile function in men with ED and low testosterone levels. [19] The objective of the study was to determine whether the addition of testosterone to sildenafil therapy improves erectile response in men with ED and low testosterone levels.
Other hormone levels: Measurement of other hormones beside testosterone (luteinizing hormone [LH], prolactin level, and cortisol level) may provide clues to other underlying causes of testosterone deficiency and erectile problems, such as pituitary disease or adrenal gland abnormalities. Doctors may check thyroid levels in some individuals as both hypothyroidism (low thyroid function) and hyperthyroidism (overactive thyroid function) can contribute to erectile dysfunction.

First realize that this is normal, and just because it happened once does not mean it will happen again (but freaking out about it could make it happen again). Then Skyler tells people to completely ditch the idea that sex is a goal-oriented act with orgasm being the big finish. Instead, take a pleasure-oriented mentality where various sex acts are done because they feel good — not because it's part of series of steps to get you to climax. This helps take away some of the anxiety, because when you're not so focused on the performance, it's not that big of a deal if there's a little bit of stage fright, she says. There's plenty of other things you can do while hanging out with a non-erect penis!
Although erectile dysfunction increases progressively with age, it is not an inevitable consequence of aging. Knowledge of the risk factors can guide prevention strategies. Specific antihypertensive, antidepressant, and antipsychotic drugs can be chosen to lessen the risk of erectile failure. Published lists of prescription drugs that may impair erectile functioning often are based on reports implicating a drug without systematic study. Such studies are needed to confirm the validity of these suggested associations. In the individual patient, the physician can modify the regimen in an effort to resolve the erectile problem.

So here’s something that’s really fascinating. Healthy eating is a way to reduce anxiety and stress. Now how, you may be asking, right? Well, think about it. We live in a world where there are so many variables and where we don’t have control over our lives. But now, with healthy eating, we have control over what goes into our body. And now having that control empowers us to be even healthier, to be more directive in what we do. And certainly, that begins then to reduce the anxiety and the stress. So all in one, you have a healthier body, but certainly a healthier mind.
Male/Female Perceptions and Influences. The diagnosis of erectile dysfunction may be understood as the presence of a condition limiting choices for sexual interaction and possibly limiting opportunity for sexual satisfaction. The impact of this condition depends very much on the dynamics of the relationship of the individual and his sexual partner and their expectation of performance. When changes in sexual function are perceived by the individual and his partner as a natural consequence of the aging process, they may modify their sexual behavior to accommodate the condition and maintain sexual satisfaction. Increasingly, men do not perceive erectile dysfunction as a normal part of aging and seek to identify means by which they may return to their previous level and range of sexual activities. Such levels and expectations and desires for future sexual interactions are important aspects of the evaluation of patients presenting with a chief complaint of erectile dysfunction.
Your erection problems may be putting a strain on your relationship. You may have stopped touching and cuddling your partner, scared that it could lead to sex - and then to disappointment because you cannot get hard. You may have found it has led to regular arguments. At its worst, erection problems can lead to the breakdown of relationships. So it is vitally important to talk things over with your partner.
For younger men, erection problems usually go hand-in-hand with anxiety. It goes something like this. He fancies you and wants to turn you on. But he’s also worried he might not get, or keep, his erection (particularly if he really likes you and/or if this has been a problem in past relationships). These worries mean that when you try and have sex he doesn’t get hard at all, or loses his erection when he tries to penetrate you.
But the main challenge to finding the best ED drug for you may turn out to be health insurance rules—not biochemistry. It's a common practice among insurers to limit the number of pills you can obtain per month. After you hit your limit, the out-of-pocket cost for a single pill can be as high as $20. "The main obstacle in my practice is the cost," Dr. Liou says. You'll need to work with your doctor to get the pill you need at a price you can afford.
NO is produced by the enzyme NO synthase (NOS). [13] NOS plays many roles, ranging from homeostasis to immune system regulation. To date, 3 subtypes have been identified: nNOS, iNOS, and eNOS, which are produced by the genes NOS1, NOS2, and NOS3, respectively. This nomenclature is derived from the sources of the original isolates: neuronal tissue (nNOS), immunoactivated macrophage cell lines (iNOS), and vascular endothelium (eNOS). The subtypes are not, however, limited to the tissues from which they were first isolated.
The role of the endothelium in erectile function became clearer with the observation that the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil, enhanced erectile function. Erection occurs with the release of nitric oxide (NO) from the vascular endothelial cells.17 The reduction in endothelial cell production of NO results in the negative impact on the smooth muscles in the corporal bodies and results in less relaxation of the smooth muscle cells with decrease in blood supply and resulting ED. A similar phenomenon is well known to impact the coronary arterial system resulting in CVD.

Defined as experiencing difficulty having an erection at least 50 percent of the time, about 30 million men in the U.S. suffer from erectile dysfunction (ED), according to the National Institutes of Health. So, if odds are pretty good you’ll experience a failure to launch at some point in your life, take solace in this finding from the University of Adelaide: You can reverse ED by focusing on lifestyle factors, not just popping a blue pill.

Impotence, also called erectile dysfunction, in general, the inability of a man to achieve or maintain penile erection and hence the inability to participate fully in sexual intercourse. In its broadest sense the term impotence refers to the inability to become sexually aroused; in this sense it can apply to women as well as to men. In common practice, however, the term has traditionally been used to describe only male sexual dysfunctions. Professional sex therapists, while they identify two distinct dysfunctions as forms of impotence, prefer not to use the term impotence per se. Thus, because of its pejorative connotation in lay usage and because of confusion about its definition, the word impotence has been eliminated from the technical vocabulary in favour of the term “erectile dysfunction.”
The most important organic causes of impotence are cardiovascular disease and diabetes, neurological problems (for example, trauma from prostatectomy surgery), hormonal insufficiencies (hypogonadism) and drug side effects. Psychological impotence is where erection or penetration fails due to thoughts or feelings (psychological reasons) rather than physical impossibility; this is somewhat less frequent but can often be helped. In psychological impotence, there is a strong response to placebo treatment.
Vascular: Anything that affects the flow of blood to the penis can result in erectile dysfunction. The main culprit tends to be atherosclerosis, the condition that narrows arteries and which can result in poor blood circulation, high blood pressure, heart disease and stroke. Atherosclerosis causes about half the cases of erectile dysfunction in men over 50. Also, the veins through which the blood leaves the penis may not be working properly, allowing the blood to leave too soon.
Jump up ^ Reepmeyer JC, Woodruff JT (2007). "Use of liquid chromatography-mass spectrometry and a chemical cleavage reaction for the structure elucidation of a new sildenafil analogue detected as an adulterant in an herbal dietary supplement". Journal of Pharmaceutical and Biomedical Analysis. 44 (4): 887–93. doi:10.1016/j.jpba.2007.04.011. PMID 17532168.

Most bouts of ED can be explained away by stress, anxiety, or nervousness. If erectile dysfunction becomes frequent, don’t panic, but cover your bases by seeing a doctor to rule out scarier causes like diabetes or prostate cancer. Medications like antidepressants can also cause boner loss. Unless you can’t get it up after a date because you spent the day snorting coke and fucking your ex (in which case figure some shit out before you see other people) this line places the blame on the stress of work and away from your partner. While a woman will usually be understanding, she may fear you can’t get hard because you’re not attracted to her. Ease these anxieties with this line. Even if work was great and you’re having trouble getting it up because of other stress, like a text from an ex or family shit you’re not ready to disclose, I’ll allow a little white lie in this instance.


Alteration of NO levels is the focus of several approaches to the treatment of ED. Inhibitors of phosphodiesterase, which primarily hydrolyze cGMP type 5, provided the basis for the development of the PDE5 inhibitors. Chen et al administered oral L-arginine and reported subjective improvement in 50 men with ED. [14] These supplements are readily available commercially. Reported adverse effects include nausea, diarrhea, headache, flushing, numbness, and hypotension.
Other medical therapies under evaluation include ROCK inhibitors and soluble guanyl cyclase activators. Melanocortin receptor agonists are a new set of medications being developed in the field of erectile dysfunction. Their action is on the nervous system rather than the vascular system. PT-141 is a nasal preparation that appears to be effective alone or in combination with PDE5 inhibitors. The main side effects include flushing and nausea. These drugs are currently not approved for commercial use.

The inflatable type of device consists of cylinders that are implanted in the corpora cavernosa, a fluid reservoir implanted in the abdomen, and a pump placed in the scrotum. The man squeezes the pump to move fluid into the cylinders and cause them to become rigid. (He reverses the process by squeezing the pump again.) While these devices allow for intermittent erections, they have a slightly higher malfunction rate than the silicon rods.


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).

Not to give your already stressed-out dude one more thing to worry about, but stress is the cause of 20 percent of all erectile problems, from one-off boner blunders to a lingering inability to get and maintain an erection. Of course, sex difficulties are just the tip of the stress-induced health problem iceberg — sustained stress can also lead to insomnia, stomach troubles, chest pains, anxiety, and more severe health issues in the long term.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is sage, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

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