Erectile dysfunction (ED) affects 50% of men older than 40 years,  exerting substantial effects on quality of life.  This common problem is complex and involves multiple pathways. Penile erections are produced by an integration of physiologic processes involving the central nervous, peripheral nervous, hormonal, and vascular systems. Any abnormality in these systems, whether from medication or disease, has a significant impact on the ability to develop and sustain an erection, ejaculate, and experience orgasm.
Some men should not take PDE5 inhibitors. They can cause hypotension (abnormally low blood pressure that can lead to fainting and even shock) when given to patients who are taking nitrates (medications taken for heart disease). Therefore, patients taking nitrates daily should not take any of the PDE5 inhibitors. Nitrates relieve angina (chest pain due to insufficient blood supply to the heart muscle because of narrowing of the coronary arteries); these include nitroglycerine tablets, patches, ointments, sprays, and pastes, as well as isosorbide dinitrate and isosorbide mononitrate. Other nitrates such as amyl nitrate and butyl nitrate also are in some recreational drugs called "poppers."
Adverse effects related to PDE5i use with mild-moderate and transient (58). Furthermore, side effects usually attenuate if use is not discontinued. Autonomic dysreflexia, a life-threatening phenomenon characterized by bradycardia, hypertension, facial flushing and headaches associated with SCI lesions above T6, has not been reported with use. However, hypotension leading to dizziness in individuals treated with sildenafil has been noted with high thoracic and cervical levels of injury (72). No adverse events were noted within the study; however, the dizziness was reported by use of sildenafil 50 mg in the cervical LOI and 100 mg in the thoracic LOI patients. Headache is the most reported side effect of all PDE5i, followed by dyspepsia and flushing. Priapism, and death have not been reported after use of PDE5i by SCI patients.
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.
Factors that mediate contraction in the penis include noradrenaline, endothelin-1, neuropeptide Y, prostanoids, angiotensin II, and others not yet identified. Factors that mediate relaxation include acetylcholine, nitric oxide (NO), vasoactive intestinal polypeptide, pituitary adenylyl cyclase–activating peptide, calcitonin gene–related peptide, adrenomedullin, adenosine triphosphate, and adenosine prostanoids.
Additionally, the physiologic processes involving erections begin at the genetic level. Certain genes become activated at critical times to produce proteins vital to sustaining this pathway. Some researchers have focused on identifying particular genes that place men at risk for ED. At present, these studies are limited to animal models, and little success has been reported to date.  Nevertheless, this research has given rise to many new treatment targets and a better understanding of the entire process.
Herbal supplements such as ginkgo biloba, saw palmetto, and yohimbe have been touted as sexual enhancers, and some men have been tempted to try them to treat erectile dysfunction. Bennett warns, however, that none has been approved by the FDA or even shown by any reliable studies to prevent, treat, or improve erectile dysfunction. Moreover, supplements are unregulated and can have many side effects or interfere with prescribed medications you’re already taking. Don’t jeopardize your health by taking a supplement to treat erectile dysfunction without first talking with your doctor.
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.
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
PDE5i use in PD has not been well studied; however its benefits have been shown. Raffaele performed an open label, prospective study evaluating the efficacy of sildenafil 50 mg on demand and depressive symptoms experienced by the PD patient (73). Erections were improved in approximately 85% of men and 75% noted improvements in their depressive symptoms as well. Sildenafil was well tolerated without significant side effects. Zesiewicz et al., performed a shorter study showing improvements in erectile function but no change in depression and parkinsonisms after ED treatment (74).
Six herbs for treating erectile dysfunction Erectile dysfunction can be an embarrassing condition that can leave men unable to achieve an erection or a full orgasm. This MNT Knowledge Center article talks about six different herbal supplements that could help people with erectile dysfunction, including ginkgo biloba, horny goat weed, and red ginseng. Read now
When a man becomes sexually excited, muscles in their penis relax. This relaxation allows for increased blood flow through the penile arteries. This blood fills two chambers inside the penis called the corpora cavernosa. As the chambers fill with blood, the penis grows rigid. Erection ends when the muscles contract and the accumulated blood can flow out through the penile veins.
Treatment. prostatitis or another acute infection affecting the genitalia can cause temporary impotence that clears up in response to antibiotics. The smooth muscle relaxant sildenafil (viagra) was introduced in 1998 as a treatment for organic impotence. Administration of testosterone may be indicated if low levels of this hormone are found in a blood sample. If impotence is organic and does not respond to other therapies, a penile prosthesis can be implanted; this is usually done surgically by a urologist. Other therapies include the use of vacuum tumescence devices and penile injection of pharmacologic agents that cause dilation.
The severity of ED has been correlated with the extent of CVD. Banks et al reported that the risk of future CV events increased progressively according to ED severity.28 This was shown in both men with and without known CVD at baseline and after controlling for confounders. Solomon and colleagues found an inverse correlation between international index of erectile function (IIEF) scores and plaque burden seen on coronary angiography.29 In addition, Yaman et al demonstrated a significant correlation between ED severity on IIEF questionnaires and coronary artery calcification.30
Recently, the US Food and Drug Administration (FDA) has issued a safety announcement regarding TRT. In part it reads ‘The benefit and safety of these medications have not been established. We are also requiring these manufacturers to add information to the labeling about a possible increased risk of heart attacks and strokes in patients taking testosterone.’37
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.
Total testosterone levels: Health care professionals should obtain a patient's blood samples for total testosterone levels in the early morning (before 8 a.m.) because the testosterone levels go up and down throughout the day. If you have a low testosterone level, a health care professional should check it again to confirm that it is truly low. In some men, a specialized test measuring the active form of testosterone (free or bioavailable testosterone) may be recommended.
On the horizon is gene therapy that would deliver genes that produce products or proteins that may not be functioning properly in the penile tissue of men with ED. Replacement of these proteins may result in improvement in erectile function. Experimental animal models have demonstrated improvement in erectile function with gene therapy. Human studies may also demonstrate success with this therapy. Gene therapy may take a long time for regulatory approval and public acceptance.
Besides PDE5 inhibitors and among second-line therapies are VCDs which are clear plastic chambers placed over the penis, tightened against the lower abdomen with a mechanism to create a vacuum inside the chamber. This directs blood into the penis. If an adequate erection occurs inside the chamber, the patient slips a small constriction band off the end of the VCD and onto the base of the penis. An erection beyond 30 min is not recommended. These devices can be a bit cumbersome, but are very safe.40
Stress is your body responding to your environment. And it’s a good thing—in limited doses. When you get stressed out your body makes chemicals like adrenaline that make you stronger, faster, fitter, and even able to think more clearly. Most people call this reaction the “fight-or-flight” response, and it’s a life-saver in dangerous situations. In a very real sense, adrenaline makes you a part-time superhero. The problems happen when your body deals with constant stress.
Alprostadil injections, which produce an erection in five to 20 minutes that lasts for about an hour. Patients use a fine needle to inject alprostadil (commonly known by the brand names Caverject Impulse and Edex) into the base or side of the penis. Side effects can include bleeding or fibrous tissue formation at the injection site as well as prolonged erection, according to the Mayo Clinic.
Knowing about your history of ED will help your health provider learn if your problems are because of your desire for sex, erection function, ejaculation, or orgasm (climax). Some of these questions may seem private or even embarrassing. However, be assured that your doctor is a professional and your honest answers will help find the cause and best treatment for you.