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Acetylcholine released by the parasympathetic nerves is thought to act primarily on endothelial cells to release a second nonadrenergic-noncholinergic carrier of the signal that relaxes the trabecular smooth muscle. Nitric oxide released by the endothelial cells, and possibly also of neural origin, is currently thought to be the leading of several candidates as this nonadrenergic-noncholinergic transmitter; but this has not yet been conclusively demonstrated to the exclusion of other potentially important substances (e.g., vasoactive intestinal polypeptide). The relaxing effect of nitric oxide on the trabecular smooth muscle may be mediated through its stimulation of guanylate cyclase and the production of cyclic guanosine monophosphate (cGMP), which would then function as a second messenger in this system.
In most healthy men, some of the drug will remain in the body for more than two days after a single dose of tadalafil. Metabolism (clearing of the drug from the body) of tadalafil can be slowed by liver disease, kidney disease, and concurrent use of certain medications (such as erythromycin, ketoconazole, and protease inhibitors). Slowed breakdown allows tadalafil to stay in the body longer and potentially increase the risk for side effects. Therefore, doctors have to lower the dose and frequency of tadalafil in the following examples:
My boyfriend has a hard time getting and staying hard. It's obviously a difficult situation to talk about, but he says he feels pressure when he's with me (versus previous random hookups he wasn't invested in), so he psyches himself out. When we do have sex, I'm almost always really satisfied and I care a lot about him, both things I express in and outside of the bedroom. But the situation seems to be only getting worse. We've stopped having sex during the week because our busy lives mean we don't have an hour or more to devote to sex (which is sometimes what it takes), or we can't have sex at all because of what he's experiencing. I'm afraid this is going to continue to get worse, not only sexually but emotionally in our relationship. How can I help him fix this, and reassure him in the meantime that I care about him and want to support him?
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 U.S. FDA (Food and Drug Administration) has a list of 29 OTC products that claim to treat erectile dysfunction. Patients should avoid these because many contain harmful ingredients. Other natural or herbal remedies such as DHEA, L-arginine, ginseng, and yohimbe are supplements that have been used but have not been proven safe and effective according to some researchers. Before using such compounds, individuals should consult their doctor. According to some experts, acupuncture does not effectively treat erectile dysfunction. Other home remedies for reducing ED symptoms include diet changes such as eating blueberries and citrus fruits and drinking red wine.
#4 You’re just plain turned off. It happens. Whether it’s the weight your partner has put on, the realization that you’re having period sex, or you’re just not getting what you need in the bedroom, at some point in your life, you’re going to be turned off enough to lose *or be unable to attain* your hard-on. [Read: Not attracted to your girlfriend anymore? The why and the fixes]
There have been rare reports of priapism (prolonged and painful erections lasting more than six hours) with the use of PDE5 inhibitors such as sildenafil, vardenafil, and tadalafil. Patients with blood cell diseases such as sickle cell anemia, leukemia, and multiple myeloma have higher than normal risks of developing priapism. Untreated priapism can cause injury to the penis and lead to permanent impotence. Therefore, if your erection lasts four hours, you should seek emergency medical care.
The general medical history is important in identifying specific risk factors that may account for or contribute to the patient's erectile dysfunction. These include vascular risk factors such as hypertension, diabetes, smoking, coronary artery disease, peripheral vascular disorders, pelvic trauma or surgery, and blood lipid abnormalities. Decreased sexual desire or history suggesting a hypogonadal state could indicate a primary endocrine disorder. Neurologic causes may include a history of diabetes mellitus or alcoholism with associated peripheral neuropathy. Neurologic disorders such as multiple sclerosis, spinal injury, or cerebrovascular accidents are often obvious or well defined prior to presentation. It is essential to obtain a detailed medication and illicit drug history since an estimated 25 percent of cases of erectile dysfunction may be attributable to medications for other conditions. Past medical history can reveal important causes of erectile dysfunction, including radical pelvic surgery, radiation therapy, Peyronie's disease, penile or pelvic trauma, prostatitis, priapism, or voiding dysfunction. Information regarding prior evaluation or treatment for "impotence" should be obtained. A detailed sexual history, including current sexual techniques, is important in the general history obtained. It is also important to determine if there have been previous psychiatric illnesses such as depression or neuroses.
How’s this for a win-win: The more sex you have, the less likely you are to suffer from erectile dysfunction, according to a 2008 study published in The American Journal of Medicine. Men aged 55-75 who reported having sex less than once per week had twice the incidence of erectile dysfunction (there were 79 cases of ED per 1,000) as men who have sex once a week (32 cases of ED per 1,000). But if you really want to up your odds, shoot for three times per week (only 16 cases of ED per 1,000). Can you really argue with science, or a perscription to have more sex?
For the patient whose history suggests organic impotence, further history, physical and laboratory data will help identify the cause. The classification listed in Table 187.2 is based on the pathophysiologic scheme presented above, and includes mechanical problems that can interfere with erection. Vascular disease is the most common cause of impotence. In advanced cases, Lehriche's syndrome of aortoiliac occlusion will be suggested by bilateral thigh or calf claudication, loss of muscle mass in the buttocks and legs, and impotence. However, the majority of patients with vascular impotence have less severe vascular disease and many will have occlusive disease of the hypogastric-cavernous bed only. Even among patients without claudication, vascular disease is still a likely cause of impotence, especially if risk factors for atherosclerosis are present. Nonatherosclerotic disease is a consideration in the patient with a history of trauma or radiation to the pelvis, both of which cause fibrosis of vessels.

It is essential to discuss erectile dysfunction with your doctor, so any serious underlying causes can be excluded and treatment options can be discussed. Many men are embarrassed discussing this issue with their doctor, or even their partner. Open communication with your doctor, and in your relationship, is important for effectively managing this common problem.
Tadalafil (Cialis) is the third oral medicine approved by the U.S. FDA for the treatment of erectile dysfunction. Like sildenafil (Viagra) and vardenafil (Levitra), tadalafil inhibits PDE5 (as described earlier). Unlike the other PDE 5 inhibitors, patients should take tadalafil once daily and is approved for the treatment of BPH (benign enlargement of the prostate).
Parasympathetic input allows erection by relaxation of trabecular smooth muscle and dilation of the helicine arteries of the penis. This leads to expansion of the lacunar spaces and entrapment of blood by compressing venules against the tunica albuginea, a process referred to as the corporal veno-occlusive mechanism. The tunica albuginea must have sufficient stiffness to compress the venules penetrating it so that venous outflow is blocked and sufficient tumescence and rigidity can occur.
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The symptoms of erectile dysfunction include difficulty achieving an erection, trouble maintaining an erection, and a reduced interest in sex. Because male sexual arousal is a fairly complex process, it can sometimes be difficult to identify a specific cause. Arousal starts in the brain but it also involves the nerves, muscles, and blood vessels and can be impacted by hormones and emotions. If a problem develops with any of these things, erectile dysfunction could be the consequence.
ED usually has a multifactorial etiology. Organic, physiologic, endocrine, and psychogenic factors are involved in the ability to obtain and maintain erections. In general, ED is divided into 2 broad categories, organic and psychogenic. Although most ED was once attributed to psychological factors, pure psychogenic ED is in fact uncommon; however, many men with organic etiologies may also have an associated psychogenic component.
Over the past century, Western culture has become more focused on working, working out, working on this and that, and eating right that so many Americans are stressed and … quite simply … overworked. Stress is a leading cause of erectile dysfunction as it takes away focus. When a man is intent on being intimate with his wife, thoughts of deadlines, paychecks, and bills may creep into his mind. This can lead to difficulties achieving or maintaining an erection, and unfortunately, this only leads to more stress, anxiety, and depression within a marriage.
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).
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.
In some cases, ED can be a warning sign of more serious disease. One study suggests ED is a strong predictor of heart attack, stroke, and death from cardiovascular disease. The researchers say all men diagnosed with ED should be evaluated for cardiovascular disease. This does not mean every man with ED will develop heart disease, or that every man with heart disease has ED, but patients should be aware of the link.
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