PDE 5 inhibitors are broken down primarily by enzyme, cytochrome P450enzyme CYP3A4. Medications that decrease or increase the activity of CYP3A4 may affect levels and effectiveness of PDE 5 inhibitors. Such drugs include medications for the treatment of HIV (protease inhibitors) and the antifungal medications ketoconazole and itraconazole. Thus caution is recommended.
Malleable implants usually consist of paired rods, inserted surgically into each of the corpora cavernosa. The rods are stiff, and to have an erection, one bends them up and then when finished with intercourse one bends them down. They do not change in length or width. The malleable implants are the least mechanical and thus have the lowest risk of malfunction. However, also have the least "normal appearance."
Conditions associated with reduced nerve and endothelium function (eg, aging, hypertension, smoking, hypercholesterolemia, and diabetes) alter the balance between contraction and relaxation factors (see Pathophysiology). These conditions cause circulatory and structural changes in penile tissues, resulting in arterial insufficiency and defective smooth muscle relaxation. In some patients, sexual dysfunction may be the presenting symptom of these disorders.
Unfortunately, some patients may have an overly simplified understanding of the role of PDE5 inhibitors in ED management. Such patients may not expect or be willing to undergo a long evaluation and testing process to obtain a better understanding of their sexual problem, and they may be less likely to involve their partner in discussing their sexual relationship with the physician. They may expect to obtain medications through a phone call to their doctor or even over the Internet, with minimal or no physician contact at all.
Men with a rare heart condition known as long QT syndrome should not take vardenafil since this may lead to abnormal heart rhythms. The QT interval is the time it takes for the heart's muscle to recover after it has contracted. An electrocardiogram (EKG) measures the QT interval. Some people have longer than normal QT intervals, and they may develop potentially life-threatening abnormal heart rhythms, especially when given certain medications. Men with a family history of long QT syndrome should not take vardenafil, as it is possible to inherit long QT syndrome. Furthermore, vardenafil is not recommended for men who are taking medications that can affect the QT interval such as quinidine (Quinaglute, Quinidex), procainamide (Pronestyl, Procan-SR, Procanbid), amiodarone (Cordarone), and sotalol (Betapace).
Psychological factors — Psychological issues such as depression, anxiety, guilt or fear can sometimes cause sexual problems. At one time, these factors were thought to be the major cause of impotence. Doctors now know that physical factors cause impotence in most men with the problem. However, embarrassment or "performance anxiety" can make a physical problem worse.
The causes of erectile dysfunction include aging, high blood pressure, diabetes mellitus, cigarette smoking, atherosclerosis (hardening of the arteries), depression, nerve or spinal cord damage, medication side effects, alcoholism or other substance (drug) abuse, pelvic surgery including radical prostatectomy, pelvic radiation, penile/perineal/pelvic trauma such as pelvic fracture, Peyronie's disease (a disorder that causes curvature of the penis and sometimes painful erections), and low testosterone levels.
It is common for a healthy older man to still want sex and be able to have sex within appropriate limitations. Understanding what is normal in older age is important to avoid frustration and concern. Older men and their partners often value being able to continue sexual activity and there is no age where the man is ‘too old’ to think about getting help with his erection or other sexual problems.
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.
A vacuum erection device helps draw blood into the penis by applying negative pressure. This type of device is sometimes referred to as penis pump and may be used just prior to sexual intercourse. Several types of FDA approved vacuum therapy devices are available under prescription. When pharmacological methods fail, a purpose-designed external vacuum pump can be used to attain erection, with a separate compression ring fitted to the base of the penis to maintain it. These pumps should be distinguished from other penis pumps (supplied without compression rings) which, rather than being used for temporary treatment of impotence, are claimed to increase penis length if used frequently, or vibrate as an aid to masturbation. More drastically, inflatable or rigid penile implants may be fitted surgically.
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.

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.

High cholesterol and triglyceride levels increase the risk of cardiovascular disease. Getting your cholesterol and triglyceride levels in an optimal range will help protect your heart and blood vessels. Cholesterol management may include lifestyle interventions (diet and exercise) as well as medications to get your total cholesterol, LDL, HDL, and triglycerides in an optimal range.
Watts and coworkers, in their review article, make several points about this ED/CAD nexus. Endothelial dysfunction is present in both CVD and ED, and is linked through the NO mechanism. The authors note that PDE5 inhibitors improve endothelial function and have a salutary effect on both CVD and ED. Both ED and cardiac disease respond to modifications in lifestyle as well as pharmacologic manipulation. These authors also report that the presence of ED gives the clinician an opportunity to assess CVD and prevention as well.20
Having your current medication checked – if you are taking medication already, it could be that your erection problems are a side effect. Have a doctor check whether this is the cause of your problems and if it is, you might be able to switch medications and then find that your erectile dysfunction goes away completely – or at least improves. Medications that can cause erection problems include:
The various PDE5 inhibitors for the treatment of ED share several common side effects, including headache, flushing, nasal congestion, nausea, dyspepsia (stomach discomfort), and diarrhea. Differences exist in side effects of the different PDE5 inhibitors, and thus it is important to be familiar with the prescribing information of the PDE5 inhibitor you are prescribed.
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.
One study examined the role of testosterone supplementation in hypogonadal men with ED. These men were considered nonresponders to sildenafil, and their erections were monitored by assessing nocturnal penile tumescence (NPT). After these men were given testosterone transdermally for 6 months, the number of NPTs increased, as did the maximum rigidity with sildenafil. [18] This study suggests that a certain level of testosterone may be necessary for PDE5 inhibitors to function properly.
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.
Penile prosthesis is the primary form of surgical therapy and is reserved for those men who fail, are intolerant of, or have contraindications to other forms of therapy. Currently, there are several different types of penile prostheses. The simplest is the malleable penile prosthesis, and the most complex is the three-piece inflatable penile prosthesis.
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.
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
Sexual dysfunction and ED become more common as men age. The percentage of complete ED increases from 5% to 15% as age increases from 40 to 70 years. But this does not mean growing older is the end of your sex life. ED can be treated at any age. Also, ED may be more common in Hispanic men and in those with a history of diabetes, obesity, smoking, and hypertension. Research shows that African-American men sought medical care for ED twice the rate of other racial groups.
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