Testosterone replacement therapy may improve energy, mood, and bone density, increase muscle mass and weight, and heighten sexual interest in older men who may have deficient levels of testosterone. Testosterone supplementation is not recommended for men who have normal testosterone levels for their age group due to the risk of prostate enlargement and other side effects. Testosterone replacement therapy is available as a cream or gel, topical solution, skin patch, injectable form and pellet form placed under the skin.
Prior to the introduction of PDE5i in 1998, intracavernosal vasoactive medications and penile implant surgery were the mainstays of treatment. Penile implant surgery involves placement of inflatable or malleable rods within the corpora cavernosa to provide rigidity for intercourse. Choice of which implant to place usually depends upon manual dexterity and function of the patient, patient anatomy, physician preference and surgical approach.
ED can also occur as a side effect of some medications, for example some high blood pressure medications such as certain diuretics and beta blockers. If you think that a medication you are taking has a negative effect on your sex life, you should discuss this with your prescribing doctor. Your doctor may be able to recommend an alternative treatment.
Inside the cell, NOS catalyzes the oxidation of L-arginine to NO and L-citrulline. Endogenous blockers of this pathway have been identified. The gaseous NO that is produced acts as a neurotransmitter or paracrine messenger. Its biologic half-life is only 5 seconds. NO may act within the cell or diffuse and interact with nearby target cells. In the corpora cavernosa, NO activates guanylate cyclase, which in turn increases cyclic guanosine monophosphate (cGMP). Relaxation of vascular smooth muscles by cGMP leads to vasodilation and increased blood flow.
ED is often the result of atherosclerosis, and as a result, men with ED frequently have cardiovascular disease. Sexual activity is associated with increased physical exertion, which in some men may increase the risk of having a heart attack (myocardial infarction or MI). The major risk factors associated with cardiovascular disease are age, hypertension, diabetes mellitus, obesity, smoking, abnormal lipid/cholesterol levels in the blood, and lack of exercise. Individuals with three or more of these risk factors are at increased risk for a heart attack during sexual activity. The Princeton Consensus Panel developed guidelines for treating ED in men with cardiovascular disease. Thus, if you have ED and cardiovascular disease (for example, angina or prior heart attack), you should discuss whether or not treatment of ED and sexual activity are appropriate for you.
As blood flows into the penis, the corpora cavernosa swell, and this swelling compresses the veins (blood vessels that drain the blood out of the penis) against the tunica albuginea. Compression of the veins prevents blood from leaving the penis. This creates a hard erection. When the amount of cGMP decreases by the action of a chemical called phosphodiesterase type 5 (PDE5), the muscles in the penis tighten, and the blood flow into the penis decreases. With less blood coming into the penis, the veins are not compressed, allowing blood to drain out of the penis, and the erection goes down.
Commercials for drugs to improve “low T,” or testosterone, the male hormone, are now vying for airtime, but they address desire, not performance. "Male hormone is not an approved treatment for erectile dysfunction," notes Bennett. "It may be used to increase desire in men who have low testosterone, but it doesn’t improve blood flow to an erection." A doctor can do a blood test to check you for low testosterone, but it is a rare cause of ED. Hormone therapy with injections, patches, or gels applied to the skin may improve mood and sex drive, but it likely won’t fix any mechanical issues. Also, testosterone drugs should not be used by men with prostate cancer. Side effects include acne, breast enlargement, prostate enlargement, and fluid retention.
Is your erectile dysfunction due to psychological (stress, relationship problems, etc.) or physical factors? Your doctor may ask if you note erections at night or in the early morning. Men have involuntary erections in the early morning and during REM sleep (a stage in the sleep cycle with rapid eye movements). Men with psychogenic erectile dysfunction (erectile dysfunction due to psychological factors such as stress and anxiety rather than physical factors) usually maintain these involuntary erections. Men with physical causes of erectile dysfunction (for example, atherosclerosis, smoking, and diabetes) usually do not have these involuntary erections. Men with psychogenic erectile dysfunction may relate the onset of problems to a "stressor," such as failed relationship. Your doctor may suggest a test to determine if you have erections during sleep, which may suggest that there may be a psychological cause of the erectile dysfunction.
The lab testing obtained for the evaluation of erectile dysfunction may vary with the information obtained on the health history, physical examination, and recent lab testing. A testosterone level is not necessary in all men; however, a physician will order labs to determine a patient's testosterone level if other signs and symptoms of hypogonadism (low testosterone) such as decreased libido, loss of body hair, muscle loss, breast enlargement, osteoporosis, infertility, and decreased penile/testicular size are present.
It appears that testosterone has NOS-independent pathways as well. In one study, castrated rats were implanted with testosterone pellets and then divided into a group that received an NOS inhibitor (L-nitro-L-arginine methyl ester [L-NAME]) and a control group that received no enzyme.  The castrated rats that were given testosterone pellets and L-NAME still had partial erections, a result suggesting the presence of a pathway independent of NOS activity.
The first stem cell study for the treatment of ED was published in 2004. This study used embryonic stem cells to treat ED. At this time, there is a total of 36 published basic studies assessing stem cell therapy for ED, with two clinical trials. The mechanism of action of stem cells is to generate angiogenesis with subsequent increase in cavernosal smooth muscle cells within the corporal bodies.46
Injection therapy involves injecting a substance into the penis to enhance blood flow and cause an erection. The Food and Drug Administration (FDA) approved a drug called alprostadil (Caverject) for this purpose in July of 1995. Alprostadil relaxes smooth muscle tissue to enhance blood flow into the penis. It must be injected shortly before intercourse. Another, similar drug that is sometimes used is papaverine—not yet been approved by the FDA for this use. Either drug may sometimes cause painful erections or priapism (uncomfortable, prolonged erections) that must be treated with a shot of epinephrine.
The Massachusetts Male Aging Study (MMAS) documented an inverse correlation between ED risk and high-density lipoprotein (HDL) cholesterol levels but did not identify any effect from elevated total cholesterol levels.  Another study involving male subjects aged 45-54 years found a correlation with abnormal HDL cholesterol levels but also found a correlation with elevated total cholesterol levels. The MMAS included a preponderance of older men.
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.
All studies demonstrate a strong association with age, even when data are adjusted for the confounding effects of other risk factors. The independent association with aging suggests that vascular changes in the arteries and sinusoids of the corpora cavernosa, similar to those found elsewhere in the body, are contributing factors. Other risk factors associated with aging include depression, sleep apnea, and low HDL levels.
Usually there will not be a specific treatment that will lead to the improvement of erectile dysfunction. However, there are treatments that will allow erections to happen and can be used to allow sexual activity to take place. There are three main types of treatments: non-invasive treatments such as tablet medicines and external devices (e.g. vacuum device); penile injections; or for men who have not had success with other treatments, surgery may be an option.
In a prospective study from the Prostate Cancer Prevention Trial database, Thompson et al reported that men presenting with ED had a significantly higher chance of developing a cardiovascular event over a 7-year follow-up period.  The hazard ratio was 1.45, which is in the range of risk associated with current smoking or a family history of MI.
Some men report being helped by an oral medication called yohimbine, which comes from the bark of a tree that grows in India and Africa. This drug, which needs to be taken every day, has been reported to help about 20 to 25 percent of the men taking it. A relatively new but widely used oral medication called Viagra requires a careful medical evaluation by your doctor.
It is estimated that up to 20 million American men frequently suffer from impotence and that it strikes up to half of all men between the ages of 40 and 70. Doctors used to think that most cases of impotence were psychological in origin, but they now recognize that, at least in older men, physical causes may play a primary role in 60% or more of all cases. In men over the age of 60, the leading cause is atherosclerosis, or narrowing of the arteries, which can restrict the flow of blood to the penis. Injury or disease of the connective tissue, such as Peyronie's disease, may prevent the corpora cavernosa from completely expanding. Damage to the nerves of the penis, from certain types of surgery or neurological conditions, such as Parkinson's disease or multiple sclerosis, may also cause impotence. Men with diabetes are especially at risk for impotence because of their high risk of both atherosclerosis and a nerve disease called diabetic neuropathy.
I think that a very powerful argument to young men who want to perform at the highest level is to point out the destructive nature of what they’re doing. If they’re having 18 drinks per week, if they’re having three, four, five drinks at any one time, they’re going to guarantee that their erections are not going to be at the highest level. I can’t tell you the number of men who come in saying, they went out, they had a date, they had a big dinner– which, by the way, is also not a great thing for erections, because all the blood is now going to your gut instead of to the genital area. And how important lifestyle changes are to improving your performance, as well, if not better, than the medications. So make certain that you exercise modestly, not excessively. Make certain that you have a smaller meal on an evening or a day that you want to have a sexual encounter, because you want the blood to go, once again, to the penile area and not to your gut. And really, the whole idea of stress– if you’re stressed out, if you’re worried about a lot of things, if you’re distracted, you can’t initiate that psychic stimulus to your spinal cord and then ultimately to your penis. So stress management is incredibly important.
Vascular damage may result from radiation therapy to the pelvis and prostate in the treatment of prostate cancer.  Both the blood vessels and the nerves to the penis may be affected. Radiation damage to the crura of the penis, which are highly susceptible to radiation damage, can induce ED. Data indicate that 50% of men undergoing radiation therapy lose erectile function within 5 years after completing therapy; fortunately, some respond to one of the PDE5 inhibitors.
The medications are extremely effective, which is very good. And the medications are, for the most part, extremely well-tolerated. But there are, like with any medications, a potential downside. The one absolute downside to the use of any of these erection what we call PDE5 medications is if a patient is using a nitroglycerin medication. And nitroglycerins are used for heart disease and for angina, for the most part, although there are some recreational uses of nitrites. And that’s important because your blood vessels will dilate and your blood pressure will drop. And that is an absolute contraindication.
Erectile dysfunction or ED (It used to be called impotence) is the inability to achieve or sustain an erection suitable for sexual intercourse. Problems with erections may stem from medications, chronic illnesses, poor blood flow to the penis, drinking too much alcohol, or being too tired. Erectile dysfunction can occur at any age, but it is more common in men older than 75.
It is important to understand that ED is frequently, if not usually, directly related to endothelial dysfunction, and that the release of NO by the vasculature of the penile arteries is directly related to the function of intact, healthy endothelium. In the face of endothelial dysfunction, the process of erection fails to occur in a normal fashion.16
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).
The neurovascular events that ultimately occur result in the inhibition of adrenergic tone and the release of the nonadrenergic, noncholinergic neurotransmitter, nitric oxide. Nitric oxide is believed to be released from nonadrenergic, noncholinergic nerves and endothelial cells. It subsequently stimulates the guanylate cyclase enzyme system in penile smooth muscle. This results in increased levels of cyclic guanosine monophosphate (cGMP) and ultimately in smooth muscle relaxation, enhancement of arterial inflow, and veno-occlusion, producing adequate firmness for sexual activity.
Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.
Erectile dysfunction is defined as the persistent inability to achieve or maintain penile erection sufficient for satisfactory sexual performance. The Massachusetts Male Aging Study surveyed 1,709 men aged 40–70 years between 1987 and 1989 and found there was a total prevalence of erectile dysfunction of 52 percent. It was estimated that, in 1995, over 152 million men worldwide experienced ED. For 2025, the prevalence of ED is predicted to be approximately 322 million worldwide.
The recommended starting dose of vardenafil is 10 mg taken orally approximately one hour before sexual activity. A doctor may adjust the dose higher or lower depending on efficacy and side effects. The maximum recommended dose is 20 mg, and the maximum recommended dosing frequency is no more than once per day. Patients can take vardenafil with or without food. As with sildenafil, for vardenafil to be effective, sexual stimulation must occur.
Poor sleep patterns can be a contributing factor for erectile dysfunction, Mucher says. One review published in the journal Brain Research emphasized the intricate relationship between the level of sex hormones like testosterone, sexual function, and sleep, noting that testosterone levels increase with improved sleep, and lower levels are associated with sexual dysfunction. Hormone secretion is controlled by the body’s internal clock, and sleep patterns likely help the body determine when to release certain hormones.
Alprostadil self-injection. With this method, you use a fine needle to inject alprostadil (Caverject Impulse, Edex) into the base or side of your penis. In some cases, medications generally used for other conditions are used for penile injections on their own or in combination. Examples include papaverine, alprostadil and phentolamine. Often these combination medications are known as bimix (if two medications are included) or trimix (if three are included).
The main surgical treatment of ED involves insertion of a penile implant (also called penile prostheses). Because penile vascular surgery is not recommended for aging males who have failed oral PDE5 inhibitors, ICI or IU therapies, implants are the next step for these patients. Although placement of a penile implant is a surgery which carries risks, they have the highest rates of success and satisfaction among ED treatment options.