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. [24] 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.

In order to establish whether normal erections are occurring overnight (nocturnal erections), the doctor may organise nocturnal penile tumescence (NPT) testing. This involves wearing a monitor overnight in your own home. The data from this monitor is then assessed to analyse how often erections occurred, how long they lasted, and how rigid and large the penis was during the erections. If NPT testing is normal, the cause of erectile dysfunction is usually psychological. If not, further testing of the blood flow in the genital area may be required to see if there is blockage or leakage. The doctor may also organise a blood test of levels of hormones such as testosterone, prolactin and thyroid stimulating hormone to see if these are contributing to the erectile dysfunction.
The most common inflatable prosthesis is the three-piece penile prosthesis. It is composed of a pair of cylinders that are surgically placed into the corpora cavernosa, a reservoir containing sterile fluid that is placed in the abdomen and a pump that is placed in the scrotum. Tubing connects the cylinders, reservoir, and the cylinders. By pressing the pump several times, fluid is transferred from the reservoir into the cylinders. As the cylinders fill with fluid, they increase in width and this causes the erection. When one is finished with sexual activity, pressing the release valve on the pump allows the fluid to drain out of the cylinders back into the reservoir. Given the mechanical nature of the three-piece prosthesis, it has a greater risk of mechanical malfunction; however, modifications have been made such as lock out valves to prevent the prosthesis from automatically inflating as well as improving the tubing to prevent tubing leaks.
Soler et al. compared sildenafil to vardenafil and tadalafil (69). Sildenafil was effective in 85% of SCI patients, 74% of the patients on vardenafil and 72% of the patients on tadalafil. Sildenafil was associated with more rigid and longer lasting erections. Additionally, 50 mg of sildenafil was effective in 55% of patients compared to more than 70% of the patients on vardenafil and tadalafil requiring 20 mg for a similar response. Men who used tadalafil were able to achieve erections 24 hours after administration, improving overall satisfaction related to the possible spontaneity of sexual encounters. Del Popolo also evaluated the time/duration effectiveness of PDE5i sildenafil 50 mg versus tadalafil 10 mg (64). Tadalafil 10 mg significantly increased the percentage of successful intercourse attempts at 12–24 hours compared with sildenafil. One can suspect that vardenafil, which has a longer half-life than sildenafil, could offer a similar benefit but a study investigating this occurrence has yet to be performed.
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.
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]
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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.
Alprostadil is an FDA-approved erectile dysfunction drug that can be injected directly into the penis to trigger an automatic erection. "Penile injection is the most effective type of ED treatment for men who can't take oral treatment," says Nelson Bennett, MD, a urologist at the Lahey Clinic in Burlington, Mass. In fact, it has an 85 percent success rate. Possible side effects include a burning sensation and priapism, an erection that lasts more than four hours and requires medical treatment.
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.
This penile tumescence monitor is placed at the base and near the corona of the penis. It is connected to a monitor that records a continuous graph depicting the force and duration of erections that occur during sleep. The monitor is strapped to the leg. The nocturnal penile tumescence test is conducted on several nights to obtain an accurate indication of erections that normally occur during the alpha phase of sleep.
When sexually stimulated/aroused, the nerves supplying the penis release a chemical, nitric oxide (NO). Nitric oxide is important because it stimulates the production of a chemical called cyclic guanosine monophosphate (cGMP). cGMP causes the muscle in arteries of the penis to relax and increase blood flow into the penis. NO is broken down in the body by phosphodiesterase enzymes. PDE5 inhibitors thus prevent the breakdown of NO and thus promote increased blood flow into the penis.
Erectile dysfunction is only one cause of sexual dysfunction. Other causes of sexual dysfunction include troubles with ejaculation, decreased libido, and troubles achieving an orgasm (climax). Some men may have premature ejaculation, which is a condition in which the entire process of arousal, erection, ejaculation, and climax occur very rapidly, often in just a few minutes or even seconds, leaving the partner unsatisfied. Premature ejaculation may accompany an erection problem such as ED but is generally treated differently. Troubles with erectile function may lead to decreased libido or interest in sex, however, many men with decreased libido have normal erectile dysfunction. Libido may be affected by psychologic factors, such as stress, anxiety, or depression but often is the result of a low testosterone (the male hormone) level.
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.
The mechanisms by which testosterone plays a role in erectile function are not completely understood. A study evaluating the effect of testosterone on erections in surgically castrated rabbits and control animals, in which the rabbits’ intracavernosal pressures were compared after cavernosal nerve stimulation, determined that castrated rabbits had much lower pressures after stimulation than control rabbits did. [21] Notably, the pressures increased when castrated rabbits received exogenous testosterone replacement.
If PDE5 drugs don't work or cannot be used because of potential side effects, your doctor can recommend other therapies. The drug alprostadil (Caverject, Edex, Muse) allows blood to flow more freely in the penis, leading to an erection. The drug can be injected with a tiny needle into your penis. Or, a small pellet (suppository) can be inserted into the opening of the penis. Suppositories and injections are effective in the majority of men.
In some cases, nocturnal penile tumescence testing is performed to find out whether the man has erections while asleep. Healthy men usually have about four or five erections throughout the night. The man applies a device to the penis called a Rigiscan before going to bed at night, and the device can determine whether he has had erections. (If a man is able to have normal erections at night, this suggests a psychological cause for his impotence.)
ICI Alprostadil may be used as a mixture with two other drugs to treat ED. This combination therapy called "bimix or trimix" is stronger than alprostadil alone and has become standard treatment for ED. Only the Alprostadil ingredient is FDA approved for ED. The amount of each drug used can be changed based on the severity of your ED, by an experienced health professional. You will be trained by your health professional on how to inject, how much to inject and how to safely raise the drug's dosage if necessary.
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