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
PDE5i for ED in patients with MS can be considered as reasonably effective and safe. Fowler et al. performed a randomized, multicenter, double-blind, flexible dose trial with open label extensions comparing sildenafil to placebo (75). A nearly 4-fold increase in effective erections was noted in the treatment arm, 96% vs. 24%. Sexual satisfaction and overall satisfaction were also improved in the treatment group based on IIEF scores, and quality of life assessments. Lombardi et al. evaluated tadalafil use in men with MS (71). Seventy eight percent of the men responded with improved erections, better quality of life with regards to sexual function, partner relationship and family life. Just less than half the men who responded to the tadalafil did so at the lower dosage of 10 mg. Subjects in either studies did not have any significant adverse side effects beyond flushing, and headache with PDE5i use.
The success of treatment for sexual dysfunction depends on the underlying cause of the problem. The outlook is good for dysfunction that is related to a condition that can be treated or reversed. Mild dysfunction that is related to stress, fear, or anxiety often can be successfully treated with counseling, education, and improved communication between partners.
Now, there are lots of ways that you can reduce stress and anxiety in your life. One of those things you can do is exercising daily. Now, it doesn’t mean getting into a gym all the time, but it can just be doing sit-ups at home, long walks at the grocery store, bicycling, and if you can afford the gym, getting there maybe two to three days a week. But don’t forget, a healthy body equals a healthy mind. Meditation, yoga, breathing exercises– now, here’s where you can take a few moments to be centered and communicate with your inner self, peace. Healthy eating– now, taking control of the intake of what goes into your body makes you to start feeling better and looking better. That wellness is the opposite of anxiety. And treating issues and tackling things that are weighing you down, taking that very first step is liberating.
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

Oral medicines: The best known ED medications are the Big Three: Viagra (sildenafil citrate, made by Pfizer, Inc.), Levitra (vardenafil HCl, made by Bayer and GlaxoSmithKline), and Cialis (tadalafil, made by Eli Lilly). The three are chemically very similar, and all have proven very effective. Because they are effective, convenient, and relatively inexpensive (about nine dollars per pill), these medicines have become the treatment of choice for most men experiencing ED.
The sympathetic pathway originates from the 11th thoracic to the 2nd lumbar spinal segments and goes via the white rami to enter the sympathetic chain ganglia. Subsequently nerves travel through the lumbar splanchnic to inferior mesenteric and superior hypogastric nerves to the pelvic plexus. The T10 through T12 segments are most often the origin of sympathetic fibers, and the sympathetic chain ganglia that innervate the penis are located in the sacral and caudal ganglia (3).

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.
Patients at high cardiovascular risk should not be treated for ED until their cardiac condition is stabilize. These conditions include unstable or refractory angina, myocardial infarction or cerebrovascular accident within the past 2 weeks, uncontrolled hypertension, New York Heart Association (NYHA) Functional Classification III-IV congestive heart failure, high-risk arrhythmias, hypertrophic obstructive cardiomyopathies, and moderate-to-severe valvular disease.25 This class of drugs is also contraindicated in patients who use nitroglycerin or nitrate-containing compounds.26, 27
Several treatments were promoted in the pre-PGE1, pre-prostaglandin era, including yohimbine, trazodone, testosterone, and various herbal remedies. None of these is currently recommended under the updated American Urological Association Guidelines for the Treatment of Erectile Dysfunction.15 Testosterone supplementation is only recommended for men with low testosterone levels.

Psychotherapy, marital counseling, or sex therapy may be helpful in treating cases of impotence that have psychological or emotional causes. A range of other treatments exists for cases of impotence that arise from purely physiological causes. These treatments include vacuum devices, penile injections, and penile implants. These mechanical or physically invasive approaches have largely been superseded, however, by the drug sildenafil citrate (trade name Viagra), which is taken in pill form. This drug works by enhancing the effects of nitric oxide, a chemical that, upon sexual stimulation, is normally released to widen the blood vessels supplying the penis. The increased flow of blood through those vessels into certain tissues in the penis causes an erection. See also sexual dysfunction.


Hormone deficiency or hypogonadism, whether primary or secondary, has been thought to impact erectile function. Approximately a third of men in the European Male Aging Study demonstrated low testosterone, suggesting that hypogonadism is overrepresented among men with ED.11 Hormone deficiency, however, is less frequently the cause of ED than diabetes or vascular disease. Many entities with a strong relationship to ED also diminish bioavailable testosterone, including obesity, diabetes, and opioid use. Other hormones involved in testosterone metabolism or availability, like thyroid stimulating hormone and gonadotropins, also may impact erectile quality, presumably through regulating bioavailable testosterone. Understanding the relationship between testosterone and ED has been impaired by a lack of standardized measurement of this hormone and the cyclic nature of its release and consumption.
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Several pathways have been described to explain how information travels from the hypothalamus to the sacral autonomic centers. One pathway travels from the dorsomedial hypothalamus through the dorsal and central gray matter, descends to the locus ceruleus, and projects ventrally in the mesencephalic reticular formation. Input from the brain is conveyed through the dorsal spinal columns to the thoracolumbar and sacral autonomic nuclei.
Obesity and metabolic syndrome can cause changes in blood pressure, body composition, and cholesterol which may lead to ED. Other conditions that may contribute to erectile dysfunction include Parkinson’s, multiple sclerosis, Peyronie’s disease, sleep disorders, alcoholism, and drug abuse. Taking certain medications can also increase your risk for ED.
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If a trial of oral therapy and withdrawal of offending medications do not restore erectile function or if a patient has medical or financial contraindications to pharmacologic therapy, most primary care practitioners should consider referring the patient to a specialist for additional evaluation and discussion of alternative treatment options. However, some primary care practitioners may recommend vacuum constriction devices.
It is normal for a man to have five to six erections during sleep, especially during rapid eye movement (REM). Their absence may indicate a problem with nerve function or blood supply in the penis. There are two methods for measuring changes in penile rigidity and circumference during nocturnal erection: snap gauge and strain gauge. A significant proportion of men who have no sexual dysfunction nonetheless do not have regular nocturnal erections.
Once a complete sexual and medical history has been completed, appropriate laboratory studies should be conducted. In the initial evaluation of ED, sophisticated laboratory testing is rarely necessary. For example, serum testosterone (and sometimes prolactin) is typically only useful when the patient demonstrates hypogonadal features or testicular atrophy, or when clinical history is suggestive. Additional hormonal evaluation may include thyroid stimulating hormone in those with a clinical suspicion of hypothyroidism or appropriate diabetes screening in those presenting with a concern for impaired glucose metabolism. If the patient has not been evaluated with a lipid panel and hyperlipidemia is suspected, measurement and appropriate referral to internal medicine or cardiology is recommended. In most cases, a tentative diagnosis can be established with a complete sexual and medical history, physical examination, and limited or no laboratory testing.
Erectile dysfunction in younger men, unless they're diabetic or have suffered some unusually cruel injury, is generally caused by stress, rather than any physical condition. High levels of cortisol or adrenaline (both byproducts of stress) in the body stymie the supply of oxygen to the organs, thereby decreasing blood flow to the penis. And the penis without blood has as much chance of getting up as a balloon without air. Which is why I found it easier to have sex with people I wasn't emotionally invested in: Once the fear of rejection is removed, sex is no big deal.
Melanocortin receptor agonists were found to induce erections serendipitously. A study investigating the dermatologic use of Melanotan-II (MT-II) was found to generate erections unexpectedly leading to the development of MTII derivatives for ED treatment (120). MT-II was initially used to induce pigment changes in the skin for artificial tanning but has been suspected to induce melanoma, however (121).
Experiencing ED can also be a reason to try not penetrative sex.  Try planning a sex session with your partner hat isn't focused on your erection at all.  Things like kissing, licking, sucking, foreplay and teasing all are super stimulating and don't focus on penetration.  Feel free to bring each other to orgasm using these ideas and see if you are able to relax and enjoy the experience.  Many men feel like failures when their erections become unreliable.  Having a few successful sexual sessions that lead to orgasm without penetration can put the fun back into having sex.  Many couples find success using this technique and begin to reengage sexually instead of avoiding being sexual for fear of failure.
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
Research has even found possible links to frequent ejaculation and a lower risk of prostate cancer. In one study of 32,000 men published in 2016 in the journal European Urology, for example, men who ejaculated at least 21 times per month while in their 20s were less likely to be diagnosed with prostate cancer than those who ejaculated four to seven times per month. And men who ejaculated more often in their 40s were 22 percent less likely to get a prostate cancer diagnosis.
Examples of common neurologic conditions that can lead to ED include cerebral vascular accident, multiple sclerosis, Parkinson’s disease, and spinal cord injury. Microvascular disease associated with diabetes is thought to compound the endothelial and neural injuries associated with this disease. Pelvic surgery may disrupt both neural and vascular pathways, resulting in ED.
Can apple cider vinegar treat erectile dysfunction? Apple cider vinegar is thought to have many health benefits, but can it help treat erectile dysfunction (ED)? ED can result from cardiovascular problems, diabetes, and other factors. Apple cider vinegar may help improve symptoms of conditions related to ED. Find out how it may help, and how to use it safely. Read now
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.
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Research has even found possible links to frequent ejaculation and a lower risk of prostate cancer. In one study of 32,000 men published in 2016 in the journal European Urology, for example, men who ejaculated at least 21 times per month while in their 20s were less likely to be diagnosed with prostate cancer than those who ejaculated four to seven times per month. And men who ejaculated more often in their 40s were 22 percent less likely to get a prostate cancer diagnosis.
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.

If it is determined that ED is a problem, the patient evaluation should include a detailed sexual and medical history and a physical exam. In particular, it is important to evaluate the ED within the context of ejaculatory problems. There is a strong interplay between premature ejaculation (PE) and ED, with about a third of ED patients reporting PE. The relationship between the PE and ED is bidirectional and successful treatment of one often requires treatment of the other.14


If a trial of oral ED therapy and withdrawal of offending medications prove to be ineffective in restoring erectile function, it is appropriate for most primary care practitioners to consider referral to a specialist for additional evaluation and discussion of alternative treatment options. These include intracavernous injection therapy, vacuum constriction devices, intraurethral therapy, and possible surgery.
There are hundreds of medications that have the side effect of ED and/or decreased libido. Examples of drugs implicated as a cause of ED include hydrochlorothiazides and beta-blocking agents. Medications used to treat depression, particularly the SSRIs such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Prozac Weekly, Sarafem), fluvoxamine (Luvox, Luvox CR), paroxetine (Paxil, Paxil CR, Pexeva) and sertraline (Zoloft), may also contribute to ED.9 Bupropion (Wellbutrin) which has a predominant effect on blocking the reuptake of dopamine is an antidepressant with lower incidence of ED.10 The side effects of 5ARIs occurring in fewer than 5% of patients can include gynaecomastia, ED, loss of libido and ejaculatory dysfunction.11
Can’t or don’t want to take ED drugs? The vacuum pump method is the next most common choice among men with erectile dysfunction who pass on pills, says Dr. Bennett. To create an erection, you place a plastic cylinder over the penis and pump the air out of the cylinder to force blood to flow into the penis. An elastic ring that you slide onto the base of your penis holds the erection. This ED treatment device is effective for about 75 percent of men. Side effects include numbness, bruising, and weak ejaculation — and the ring must be removed after 30 minutes.
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.

Size matters, so get slim and stay slim. A trim waistline is one good defense — a man with a 42-inch waist is 50% more likely to have ED than one with a 32-inch waist. Losing weight can help fight erectile dysfunction, so getting to a healthy weight and staying there is another good strategy for avoiding or fixing ED. Obesity raises risks for vascular disease and diabetes, two major causes of ED. And excess fat interferes with several hormones that may be part of the problem as well.


According to a review of all randomized controlled trials evaluating sildenafil by the American Urological Association (AUA) Consensus Panel on Erectile Dysfunction, 36% to 76% of patients receiving the drug were "able to achieve intercourse" during treatment. For tadalafil, four randomized controlled trials revealed that 11% to 47% of patients were "able to achieve intercourse." Similar efficacy has been observed with vardenafil, although studies are fewer.19 A meta-analysis published in 2013 clearly demonstrated increased efficacy over placebo for all PDE5 inhibitors.24 Head-to-head comparison suggested that tadalafil outperforms sildenafil on validated measures of erectile dysfunction, including the international index of erectile function and sexual encounter profile-2 and -3.


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MSA is a neurodegenerative disease of undetermined etiology, where ED is an early prominent sign occurring in 40% of men at the time of diagnosis (46,47). ED occurs in the majority of patients and the exact cause of it is unknown (48). Like PD, MSA likely affects the dopaminergic pathways within the brain essential for arousal (49). Orthostatic hypotension (OH) as a causal factor has been refuted by evidence that sildenafil can overcome reduced filling pressures, and the ED usually precedes the development of OH (46,49,50). Similar to other neurologic disorders that lead to ED, other disease related factors such as psychosocial stress, the burden of chronic illness, changed appearance, fatigue, decreased fine motor movement of fingers, immobility and diminished self-esteem due to loss of independence may contribute as well (51).
Experiencing ED can also be a reason to try not penetrative sex.  Try planning a sex session with your partner hat isn't focused on your erection at all.  Things like kissing, licking, sucking, foreplay and teasing all are super stimulating and don't focus on penetration.  Feel free to bring each other to orgasm using these ideas and see if you are able to relax and enjoy the experience.  Many men feel like failures when their erections become unreliable.  Having a few successful sexual sessions that lead to orgasm without penetration can put the fun back into having sex.  Many couples find success using this technique and begin to reengage sexually instead of avoiding being sexual for fear of failure.
Meditation is known to lower the heart rate and regulate blood flow around the body, which bodes well for ED sufferers, as what's an erection if not a big gathering of blood? Meditation has also been shown to reduce anxiety and change negative thought associations. Sara Lazar, a neuroscientist at Harvard, was one of the first people to scan meditators' brains and discovered that the amygdala, the part of the brain where anxiety calls home, was smaller for meditators than the control group.
Martha K Terris, MD, FACS is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Institute of Ultrasound in Medicine, American Society of Clinical Oncology, American Urological Association, Association of Women Surgeons, New York Academy of Sciences, Society of Government Service Urologists, Society of University Urologists, Society of Urology Chairpersons and Program Directors, and Society of Women in Urology

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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