Effect of shock wave treatment for erectile dysfunction wanes

Low-intensity shock wave treatment is effective for short-term treatment of erectile dysfunction, but its efficacy declines after two years, particularly in those with initial severe dysfunction, according to a study published in the July issue of The Journal of Urology.

24 jun 2018--Noam D. Kitrey, M.D., from Sheba Medical Center in Ramat Gan, Israel, and colleagues studied the long-term efficacy of penile low intensity shock wave treatment two years after an initially successful outcome among 156 patients.
The researchers found that at one month, treatment was successful in 99 patients (63.5 percent), but during follow-up a gradual decrease in efficacy was observed. At two years, the beneficial effect was maintained in only 53.5 percent of patients in whom success was initially achieved. Over follow-up the treatment effect was lost in all patients with diabetes who initially had severe erectile dysfunction. However, for patients with milder forms of erectile dysfunction without diabetes there was a 76 percent chance that the beneficial effect of low-intensity shock wave treatment would be preserved after two years.
"Low-intensity shock wave treatment is effective in the short term but treatment efficacy was maintained after two years in only half of the patients," the authors write. "In patients with milder forms of erectile dysfunction the beneficial effect is more likely to be preserved."

More information: Abstract/Full Text

Depression Linked to Erectile Dysfunction May Raise CV Risk

Severe depressive symptoms in ED associated with higher incidence of major cardiovascular events

20 july 2010-- Depressive symptoms in men with erectile dysfunction (ED) constitute an independent risk factor for the incidence of a major cardiovascular event (MACE), according to a study published online July 13 in the Journal of Sexual Medicine.

Elisa Bandini, M.D., of the University of Florence in Italy, and colleagues interviewed 2,303 male patients at a clinic for sexual dysfunction using a Structured Interview on Erectile Dysfunction with three scales to explore the organic, relational, and intra-psychic factors of the condition. The researchers assessed depression in the cohort using the Middlesex Hospital Questionnaire for depressive symptoms (MHQ-D) and correlated it to the incidence of MACE, as recorded by the City of Florence Registry Office, in a subset of 1,687 subjects followed for a mean 4.3 years in a longitudinal study.

The researchers identified a positive relationship between MHQ-D score in the ED patients and increasing difficulty achieving an erection sufficient for penetration. Among the subjects in the longitudinal study, there were 139 MACE incidents (15 fatal), with the unadjusted incidence of MACE significantly associated with baseline depressive symptoms. Also, having severe depressive symptoms was independently associated with a higher MACE incidence in a regression model that also included arteriogenic ED, the partner's reduced sexual desire, age, chronic diseases, and an index of psychopathology.

"In particular, our study demonstrates that depressive symptomatology constitutes an independent risk factor for cardiac morbidity and mortality in men with ED. The need for a regular screening for cardiac morbidity in men with ED is even greater in those patients showing depressive symptoms associated with ED," the authors write.

Abstract
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Guidelines Urge Use of Erectile Dysfunction Drugs

26 oct 2009-- Doctors should prescribe oral phosphodiesterase type 5 (PDE-5) inhibitor drugs, such as Viagra, Cialis and Levitra, for men with erectile dysfunction, unless the patient is on nitrate therapy, according to a clinical practice guideline issued by the American College of Physicians.

The type of erectile dysfunction (ED) drug prescribed should be based on the individual preferences of patients, including cost of medication, ease of use and types of side effects, the authors noted.

"The evidence is insufficient to compare the effectiveness or adverse effects of different PDE-5 inhibitors for the treatment of ED because there were only a few head-to-head trials," guideline lead author Dr. Amir Qaseem, senior medical associate with the ACP, said in a news release.

Qaseem and colleagues analyzed the findings of 130 studies that evaluated PDE-5 inhibitors alone or combined. They found that treatment with the drugs led to statistically significant and clinically relevant improvements in sexual intercourse and erectile function in men with ED, regardless of the cause (e.g., diabetes, depression, prostate cancer) or ED severity at the start of the study.

Overall, PDE-5 inhibitors were relatively well-tolerated and associated with only mild or moderate side effects, such as headaches, flushing, upset stomach and runny nose, the authors found.

The guideline is published in the Oct. 20 issue of the journal Annals of Internal Medicine.

Because there is no conclusive evidence about the effectiveness of hormonal blood tests or treatment in patients with low testosterone levels, the ACP doesn't recommend for or against routine use of the tests in ED patients. The college says doctors should make decisions to measure hormone levels based on an individual patient's clinical symptoms (decreased libido, premature ejaculation, fatigue, etc.) and physical signs (such as testicular or muscle atrophy) that suggest hormone problems.

Mayo Clinic study finds younger men with erectile dysfunction at double risk of heart disease

ROCHESTER, Minn., 03 feb 2009 -- Men who experience erectile dysfunction between the ages of 40 and 49 are twice as likely to develop heart disease than men without dysfunction, according to a new Mayo Clinic study.

Researchers also found that men with erectile dysfunction have an 80 percent higher risk of heart disease.

"The highest risk for coronary heart disease was in younger men," says researcher Jennifer St. Sauver, Ph.D. The study was published in the February 2009 issue of Mayo Clinic Proceedings. The results suggest that younger men and their doctors may need to consider erectile dysfunction a harbinger of future risk of coronary heart disease -- and take appropriate steps to prevent it, says Dr. St. Sauver.

"The importance of the study cannot be overstated," writes Martin Miner, M.D., in an editorial in the same issue of Mayo Clinic Proceedings. The results "raise the possibility of a 'window of curability,' in which progression of cardiac disease might be slowed or halted by medical intervention," writes Dr. Miner, who practices at the Men's Health Center, Miriam Hospital, Providence, R.I.

Erectile dysfunction is common, and prevalence increases with age. It affects 5 to 10 percent of men at age 40. By age 70, from 40 to 60 percent of men have the condition.

Dr. St. Sauver says researchers wanted to learn more about the connections between age, cardiovascular disease and erectile dysfunction. Two previous studies, both published in 2005, laid groundwork for the Mayo Clinic study. One found that erectile dysfunction predicted an increased risk of heart disease, but the erectile dysfunction of the study participants was not assessed with an externally validated questionnaire and cardiac events were not subjected to standardized review for diagnostic accuracy [Thompson et al, JAMA, 2005]. The second predicted that future cardiovascular disease would be higher in younger men with erectile dysfunction, but wasn't able to follow the men to determine if heart disease developed [Ponholzer et al, Eur Urol, 2005].

For the Mayo Clinic study, the investigators identified 1,402 men who lived in Olmsted County, Minn., in 1996 and did not have heart disease. Every two years for 10 years, these men were assessed for urological and sexual health.

Answers to questions from the Brief Male Sexual Function Inventory, a statistically validated questionnaire, were used to determine erectile dysfunction. The baseline prevalence of erectile dysfunction in study participants was: 2.4 percent in men aged 40-49; 5.6 percent in men aged 50-59; 17 percent in men aged 60-69 and 38.8 percent in men 70 years and older. Those initial data and the increasing incidence of erectile dysfunction over time were linked to data from a long-term study of heart disease in Olmsted County residents, led by Veronique Roger, M.D., Mayo Clinic cardiologist.

Over 10 years of follow-up, researchers found that men with erectile dysfunction were 80 percent more likely to develop coronary heart disease compared to men without erectile dysfunction. The highest risk of new heart disease was seen in the youngest study participants who had erectile dysfunction. In men 40 to 49 years old when the study began, the number of new cases in men with erectile dysfunction was more than 50-fold higher than in men without erectile dysfunction. Statistically, that's a cumulative incidence of 48.52 per 1,000 person years in those with erectile dysfunction compared to 0.94 per 1,000 person years in those without erectile dysfunction).

In men in their 50s, 60s and 70s, the total incidence of new cases of heart disease also was higher in those with erectile dysfunction. However, the differences were not as striking as those seen among the 40- to 49-year- olds.

"In older men, erectile dysfunction may be of less prognostic importance for development of future heart disease," says Dr. St. Sauver.

This study did not determine reasons for the increased risk of heart disease among men with erectile dysfunction. Some have theorized that erectile dysfunction and coronary artery disease may be different manifestations of the same underlying disease process. A buildup of plaque that can block arteries around the heart may plug the smaller penile arteries first, causing erectile dysfunction. Alternatively, arteries may lose elasticity over time, contributing to heart disease. This arterial stiffening may affect the smaller penile arteries first.

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Other Mayo Clinic researchers were: Brant Inman, M.D.; Debra Jacobson; Michaela Mc Gree; Ajay Nehra, M.D.; Michael Lieber, M.D.; Dr. Roger; and Steven Jacobsen, M.D., Ph.D.

Erectile dysfunction related to sleep apnea may persist, but is treatable

15 sept 2008--For sufferers of sleep apnea, erectile dysfunction (ED) is often part of the package. New research indicates that ED in cases of obstructive sleep apnea syndrome (OSAS) may be linked to the chronic intermittent hypoxia—oxygen deprivation— (CIH) that patients with OSAS experience during episodes of obstructed breathing.
In the first model to address this possibility experimentally, researchers from the University of Louisville found that after one week of being exposed to CIH similar to that which a human with PSAS would experience, mice showed a 55 percent decline in their daily spontaneous erections. After five weeks of CIFH exposure, the "latency to mount" period— the average interval between mounting a mate— increased 60-fold.
"Even relatively short periods of CIH...are associated with significant effects on sexual activity and erectile function," wrote David Gozal, M.D., professor of pediatrics at the University of Louisville.
The results appeared in the second issue for September of the American Journal of Respiratory and Critical Care Medicine, a publication of the American Thoracic Society.
The study examined the behavioral and physiological effects in mice exposed to CIH for anywhere from five to 24 weeks. Control mice were kept under identical conditions, but were not subjected to nocturnal CIH. The mice were evaluated on a series of complex sexual behaviors, including erection frequency and mating behavior and measured associated biomarkers of sexual function that may be affected by CIH, such as testosterone and estradiol levels, and also the expression of endothelial and neuronal nitric oxide synthase (eNOS and nNOS respectively). eNOS, which is increased by drugs such as sildenafil (Viagra), plays a major role in male sexual drive and activity.
After just five weeks exposure to CIH, not only did latency-to-mount time increase by 60-fold, latency to intromission increased by 40-fold. Latency to ejaculation was also severely affected. In five out of seven mice tested, ejaculation did not occur at all, but in one mouse, latency to ejaculation was 660 minutes—eleven hours—whereas in control mice the median time to ejaculation was "only a few minutes, said Dr. Gozal. Interestingly, one mouse appeared to be unaffected in this respect.
"The disparity in responses among mice is very similar to the heterogeneity of the magnitude of end-organ morbidity in sleep apnea among patients, and shows that not everyone will be affected to the same extent," said Dr. Gozal.
While there were no differences in testosterone and estradiol levels, there was also a significant reduction in eNOS expression with mice exposed to CIH for eight weeks.
Even after six weeks' recovery time with standard oxygen levels, mice exposed to CIH for as little as one week only recovered 74 percent of their original erectile function. "[T]his could suggest either chronic residual deficits after CIH or that full recovery would require longer periods," wrote Dr. Gozal.
Despite the lingering negative effects of CIH on sexual behavior in mice, the researchers did find that it was largely reversible. In the second phase of the experiment, Dr. Gozal administered tadalafil, which increases the availability of nitric oxide through PDE5. Treatment with tadalafil improved erectile and sexual functioning in CIH-exposed mice to near-normal levels in almost all cases.
"In the present study, tadalafil restored CIH-induced impairments of latencies to mounts, intromissions and ejaculations, significantly improving performance during spontaneous erections and during mating and noncontact activity," wrote Dr. Gozal. "The effects of tadalafil were not limited to the erectile tissue but extended to behavioral components, suggesting a possible role for PDE5 in central nervous system mechanisms that control sexual behavior."
"Further studies are needed to explore the effects of sleep disruption and episodic hypoxia during sleep on the central nervous system that mediates sexual drive," said Dr. Gozal. "Exploration of alternative interventions aiming at preventing and treating this infrequently spoken of, yet extremely frequent complication of OSA, will certainly require improved understanding of the complex mechanisms affecting sexual activity and how it is affected by diseases such as sleep apnea."
"These findings add sexual dysfunction to a long list of disorders associated with – and probably caused by – OSA," stated John Heffner, past president of the ATS. "Although this study was performed in research animals, chronic intermittent hypoxia has profound effects on multiple organ systems and a strong biologic plausibility exists that similar findings will be observed in humans. Early identification and effective therapy of OSA is critically important especially considering the high prevalence of this disorder."

Statins Might Reverse ED in Some Men

By Alan Mozes
16 aug 2008 -- Statins might quickly help reverse erectile dysfunction among men who have metabolic syndrome, new animal research suggests.
A threat to cardiovascular health, metabolic syndrome is also known to raise the risk for erectile dysfunction (ED). The current finding indicates that statins may reduce levels of a specific protein that contributes to ED.
"Each condition of metabolic syndrome phenomenon -- high blood pressure, type 2 diabetes and obesity -- independently raises the risk for erectile dysfunction just on their own," explained study author Christopher J. Wingard, an associate professor of physiology with the Brody School of Medicine at East Carolina University in Greenville, N.C. "And so, when all are present in combination as part of this syndrome, you have a situation where you don't even need to be as diabetic or hypertensive as you might otherwise have to be to experience erectile dysfunction. And that fact has been raising concern among clinicians."
"So, we followed up on case reports and anecdotal evidence that statins being used to lower cholesterol over a six- to eight-week period among patients with metabolic syndrome seemed to also quickly improve erections -- even before cholesterol levels go down," Wingard added. "And in an animal model, we found this to be the case."
Wingard and his colleagues presented their findings recently at the American Urological Association Research Conference, in Linthicum, Md.
The effort to evaluate the possibility of using statins to treat ED focused on 16- to 20-week-old lean and obese rats, all of whom were given one of three statins on a daily basis for between three to five days.
The researchers then assessed erectile function in the rats. At the same time, they also measured any changes in levels of certain key proteins that they believed could be involved in triggering the onset of ED.
The authors found that the statins were able to quickly relieve some of the vascular constriction associated with metabolic syndrome that can bring about ED.
They further noted that the way in which the statins appeared to have their effect was by inhibiting the expression -- and lowering the levels -- of a particular protein known as Rho-kinase. This protein had previously been cited as a possible culprit in vascular constriction of penile smooth muscle.
Wingard suggested that more research is sure to follow, to explore whether the findings would apply to patients following a long-term regimen of statin treatment.
However, Dr. Arnold Melman, chairman of the department of urology at Albert Einstein College of Medicine in New York City, described the findings as "very preliminary."
"Statins are used by everyone under the sun, and, as far as I know, there's been no hard evidence that it can be used to treat erectile dysfunction," he said. "On the other hand, it may be that it could prevent or modify some of the other risk factors for erectile dysfunction."
"This is because we do know that an increase in Rho-kinase leads to heightened tone of the corpus smooth muscle, which is one of the causes of erectile dysfunction," Melman noted. "So, while I wouldn't go too far with this, and I would probably not see statins becoming a primary treatment for erectile dysfunction, if these findings turn out to be true, then there could perhaps be an additional good use for statins."

Erectile dysfunction may be "normal" with age

By Will Boggs
05 aug2008--Erectile dysfunction may be a feature of normal aging in men, while urinary or bowel function doesn't necessarily decline with age, according to a Dutch study.
"I had expected that the association between urological function and age would be stronger," Dr. Ida J. Korfage from Erasmus University Medical Center Rotterdam told Reuters Health.
Using data from more than 3,800 participants in the European Randomized Study on Screening for Prostate Cancer, Korfage and her colleagues assessed whether urinary, bowel, and sexual dysfunction "and the associated bother" were part of the "normal" aging process.
As described in the medical journal Urology, the men -- all of whom were cancer-free -- were divided into five groups by age: 58-61, 62-64, 65-67, 68-70, and 71 years and older.
According to the investigators, the proportion of men with erectile dysfunction was significantly higher among older men, with more of them reporting either that they were sexually active but having problems with erections, or sexually inactive because of erectile problems.
Korfage added, "I like to stress that sexual inactivity is not necessarily the same as erectile dysfunction. Reasons for not being sexually active can also be not being interested (anymore) or not having a partner. Not everybody who is sexually inactive is in need of medication."
Although urinary function was poorer and more bothersome in older age groups, the differences between age groups were not very great.
Bowel problems were uncommon, with no significant differences among age groups, the report indicates.
So, when these problems are seen in older men who have been treated for prostate cancer, they are more likely due to the treatment rather than to age alone, the team points out.
SOURCE: Urology, July 2008.

ED an Indicator of Men's Health

16 june 2008 -- Erectile dysfunction could be an indicator of testosterone deficiency and the metabolic syndrome, a set of factors that may indicate an increased risk of heart and vascular disease and type 2 diabetes, a new international study shows.
"Erectile dysfunction is a portal into men's health," the study's senior author, Dr. Aksam Yassin, of the Clinic for Urology and Andrology of the Segeberger Clinics in Norderstedt, Germany, wrote in a prepared statement.
"It is becoming clear that obesity, diabetes, high blood pressure, cholesterol problems and erectile difficulties are intertwined, and a common denominator is testosterone deficiency."
The research, conducted by scientists from The Netherlands, Germany and the United Arab Emirates, was expected to be presented over the weekend at the Endocrine Society's annual meeting in San Francisco.
Yassin recommended that men with erectile dysfunction be evaluated for testosterone deficiency and any underlying signs of the metabolic syndrome.
Metabolic syndrome has any three of the following characteristics:Increased abdominal fat. Low HDL ("good") cholesterol. High triglycerides (fats in the blood). High blood pressure. High blood sugar.
The findings are based on screenings for testosterone deficiency, also known as hypogonadism, and metabolic syndrome done on 771 patients seeking treatment for erectile dysfunction.
Among the results: 18.3 percent of those studied had previously undetected testosterone deficiency, slighter higher than the 12 percent average for men older than 45. 35 percent had type 1 or type 2 diabetes. 31 percent had high blood pressure. 21 percent had dyslipidemia -- abnormal cholesterol or triglycerides. 14 percent had varying degrees of coronary heart disease.
In each group, a small handful of those diagnosed did not know they had the condition before the screening, Yassin said.

Erectile Dysfunction a Strong Harbinger of Heart Trouble

By Ed Edelson
MONDAY, 20 may 2008-- Findings from two studies of men with diabetes add to the evidence that erectile dysfunction can be a powerful early warning sign for serious heart disease.
A Hong Kong study of 2,306 men with diabetes but no signs of heart disease found that those with erectile dysfunction at the start were 58 percent more likely to have a heart attack or other major cardiac problem over the next four years than those with adequate sexual function.
And Italian physicians who followed 291 men who had diabetes and early coronary heart disease for four years reported similar numbers -- those with erectile dysfunction were twice as likely as men without the problem to have major adverse events, including strokes.
There's a physical connection between male sexual failure and heart disease, involving the effect of diabetes on the nervous system and the blood vessels, said Dr. E. Scott Monrad, a professor of clinical medicine at Albert Einstein College of Medicine in New York City.
"Neuropathy would interfere with the neurogenic responses feeding into proper erection," Monrad said. "And obstruction of blood flow into the arteries reduces the pressure needed to achieve erection."
It has been known that erectile dysfunction shares many risk factors with coronary heart disease, such as high blood pressure, smoking and diabetes, according to Dr. Robert A. Kloner, a professor of medicine at the University of Southern California, who wrote an accompanying editorial on the reports, which were expected to be published in the May 27 issue of the Journal of the American College of Cardiology.
"What is new here is that erectile dysfunction remained a significant risk factor for developing heart disease after controlling for other cardiovascular risk factors," Kloner said in a statement.
"These reports add two things to what we already know," said Dr. R. Parker Ward, an associate professor of medicine at the University of Chicago, who led an earlier study linking erectile dysfunction with heart disease. "One is that they indicate the importance of erectile dysfunction in diabetic patients in terms of predicting future cardiovascular events. These studies suggest that the additional presence of erectile dysfunction places them at incrementally higher risk. Secondly, they show that even when considered in combination with traditional risk factors, erectile dysfunction offers incremental information about the risk of future cardiovascular events."
Cholesterol-reducing statins lowered the incidence of cardiac events by a third, the Italian researchers reported, and Viagra and other drugs for erectile dysfunction also appeared to lower the risk, although the reduction was not statistically significant, meaning that it could be due to chance.
"I strongly caution that we do not have enough evidence at this point that the drugs used for the treatment of erectile dysfunction have any beneficial effects on the development of heart disease," Ward said.
Physicians should be more forward in talking about sexual performance with men, Monrad said, since "this may prove to be a very sensitive marker for all the other things we measure for cardiovascular risk, an early and more sensitive measure if we could get over all our puritanic inhibitions."
Acknowledgment of erectile dysfunction "should prompt us to be even more aggressive about lifestyle change, in diet and exercise," Page said. "It potentially may suggest more aggressive treatment of risk factors such as high blood pressure and cholesterol."

Men who smoke risk erectile dysfunction: study

Wed Sep 26, 2:22 PM ET
Otherwise healthy men who smoke risk developing erectile dysfunction -- and the more cigarettes they smoke, the greater the risk of erectile dysfunction, according to a new study.
Erectile dysfunction is the consistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance. In a study of 4,763 Chinese men aged 35 to 74 years who were free of blood vessel disease and who reported that they had been sexually active within the last 6 months, the researchers found a significant statistical link between the number of cigarettes smoked and the likelihood of erectile dysfunction.
"The association between cigarette smoking and erectile dysfunction was found in earlier studies," said first author Dr. Jiang He of Tulane University School of Public Health, New Orleans. "However, most of those studies were conducted in patients with hypertension (high blood pressure), diabetes and cardiovascular disease. What distinguishes this study is that it is the first to find this association among healthy men."
Overall, men who smoked had a 41-percent greater risk of erectile dysfunction than men who did not, the team reports in the American Journal of Epidemiology.
And there was a clear "dose-response" relationship, meaning that the more the men smoked, the higher was their risk of erectile dysfunction. Compared with non-smokers, men who smoked up to 10 cigarettes per day had a 27-percent greater likelihood of erectile dysfunction ; those who smoked 11 to 20 butts a day had a 45-percent greater likelihood of erectile dysfunction; and those who smoked more than 20 cigarettes daily had a-65 percent greater chance of suffering erectile dysfunction.
The investigators estimate that 22.7 percent of erectile all dysfunction cases among healthy Chinese men - or 11.8 million cases -- might be caused by cigarette smoking.
And even when cigarette smokers quit, their risk of developing erectile dysfunction did not decrease. The risk of erectile dysfunction was statistically about the same for former cigarette smokers as for current cigarette smokers, the authors found.
"This study really has a strong message for young men," He said. "It may get their attention if they know that smoking is associated with erectile dysfunction -- even in the healthy population."
"So the message is: Don't start."
SOURCE: American Journal of Epidemiology, October 1, 2007.

Erectile Drugs May Promote Pleasure as Well as Performance

MADISON, Wis., Aug. 24 -- Erectile dysfunction drugs may enhance sexual pleasure over and above mere performance. In addition to making intercourse possible for many men with erectile dysfunction, sildenafil (Viagra) and its analogues seem to stimulate release of oxytocin from the pituitary, at least in rats, Meyer Jackson, P.D., of the University of Wisconsin here, and colleagues, reported online in the Journal of Physiology.
Sildenafil, vardenafil (Levitra) and tadalafil (Cialis) are classified as sexual stimulants, not aphrodisiacs, in that they improve sexual function but are not known to affect arousal. They work indirectly to cause smooth muscle relaxation and enhanced blood flow to the penis by inhibiting phosphodiesterase 5 (PDE5), an enzyme that would otherwise break down the smooth muscle relaxant cyclic guanosine monophosphate.
But PDE5 also plays a key role in regulating release of oxytocin from the pituitary, the investigators noted in an early online release from.
"The same stimulation will produce more [oxytocin] release," said Dr. Jackson. "I think this is a missing link in terms of trying to sort out the issues around whether there are additional effects of phosphodiesterase type-5 inhibitors."
Oxytocin is released by the neurohypophysis, or posterior pituitary, during orgasm, and is also involved in milk ejection (letdown) and stimulus of uterine contractions during labor. It has also been shown in animal and human studies to foster maternal attachments to offspring.
"Oxytocin also serves as a signal in central neuronal pathways associated with the erectile response," the investigators wrote. "If PDE5 inhibitors influence central oxytocin nerve terminals in the same way as peripheral nerve terminals of the posterior pituitary, then the activity of these central oxytocin pathways would be enhanced."
The recent findings of two research groups that PDE5 inhibitors enhance sexual function in women as well as in men suggest that the drugs may have other, non-vascular effects, such as hormonal influences, the Wisconsin investigators noted.
They measured oxytocin release from rat pituitaries during neural stimulation. They found that stimulation of the glands in the presence of sildenafil resulted in a three-fold release of oxytocin compared with no sildenafil. In addition, there was little or no effect of sildenafil on oxytocin release in the absence of stimulation, the authors noted.
"Erectile dysfunction drugs do not induce erections spontaneously, they enhance the response to sexual stimulation," Dr. Jackson said. "The same thing is happening in the posterior pituitary: Viagra will not induce the release of oxytocin on its own, but it will enhance the amount of release you get in response to electrical stimulation."
The findings point to new avenues of research into other possible physiologic effects of PDE5 inhibitors.
"A big question raised by our study is, will sildenafil do the same thing to the nerve terminals that release oxytocin?" Dr. Jackson said.
The study was supported by a National Institutes of Health grant. Author conflicts of interest were not reported.Primary source: Journal of PhysiologySource reference: Zhang Z et al. "Blockade of Phosphodiesterase Type 5 Enhances Rat Neurohypophysial Excitability and Electrically-Evoked Oxytocin Release." J Physiol Aug. 9 (E-pub ahead of print).

AUA: ED Drug May Boost Psyche and Functional Performance

ANAHEIM, Calif., May 24 -- An investigational centrally active melanocortin agonist gives men with erectile dysfunction a psychological boost as well as a physical one, researchers reported here.
Men who used bremelanotide in an intranasal formulation reported improvement in sexual relationships, sexual satisfaction, confidence, and self-esteem. The synthetic peptide also led to significant improvement in erectile function during 12 weeks of on-demand therapy.
"These results indicate that bremelanotide improves sexual confidence and has the potential to be an important treatment option for patients with erectile dysfunction," said psychologist Stanley Althof, Ph.D., of Case Western Reserve in Cleveland, at the American Urological Association meeting.
Bremelanotide is the first of a new class of erectile dysfunction drugs known as melanocortin receptor agonists. Unlike PDE-5 inhibitors, which have a vascular mechanism of action, bremelanotide exerts its effects through the central nervous system. According to the manufacturer, Palatin Technologies of Cranbury, N.J., the agent binds primarily to melanocortin receptor 4 in the hypothalamus, triggering descending neural signals to the penis.
In a multicenter, randomized, placebo-controlled trial, 726 nondiabetic men with erectile dysfunction were randomized to placebo or to one of five intranasal bremelanotide doses ranging between 5 mg and 15 mg, said Dr. Althof. Patients self-administered therapy as needed, 45 minutes before sexual activity.
The study participants had a mean age of 55 years and a six-year history of erectile dysfunction. The population comprised similar numbers of men with mild, moderate, and severe erectile dysfunction, and most of the men had experience with PDE5 inhibitors.
Sexual function was assessed by means of the International Index of Erectile Function (IIEF) at baseline and at the end of the study. Patients assigned to placebo averaged a one-point improvement in IIEF score over the course of the trial. In contrast, patients assigned to bremelanotide doses of 7.5 mg to 15 mg had four- to five-point improvements in IIEF score (P≤0.05 compared with placebo).
As part of the study protocol, participants completed the Self Esteem and Relationship (SEAR) Questionnaire, a 14-item survey instrument that assesses change in two major domains: sexual relationship and confidence, said Dr. Althof. The confidence domain has two sub-domains of self-esteem and overall relationship.
Patients randomized to all but the lowest (5 mg) bremelanotide doses improved by about 15 to 17 points on the sexual relationship domain of SEAR, compared to about a five-point improvement in the placebo group (p≤0.01) In general, the bremelanotide groups had greater improvement in the remaining major and minor domains compared to placebo, but the differences were not statistically significant.
Dr. Althof said that SEAR scores improved across all categories of erectile dysfunction severity, although patients with mild or severe ED tended to derive the greatest overall benefit. In addition, IIEF and SEAR domains exhibited statistically significant correlations.
Another bremelanotide study reported here involved 294 men with diabetes and erectile dysfunction. The patients were randomized to placebo or one of three doses of bremelanotide (10, 12.5, or 15 mg) and self-administered treatment as needed for 12 weeks.
Patients assigned to the two highest bremelanotide doses had significantly greater improvement in the erectile function domain of the IIEF compared to placebo (P<0.05), said urologist Christopher Steidle, M.D., of Indiana University in Indianapolis.
In both studies, bremelanotide-treated patients had higher rates of adverse effects compared to placebo, but the effects tended to be mild or moderate in severity. More common adverse events reported by bremelanotide patients included nausea, emesis, flushing, transient increases in blood pressure, headache, spontaneous erection, skin darkening, and nasal symptoms.
Bremelanotide is not a new drug, commented Ira Sharlip, M.D., of the University of California San Francisco, and a spokesperson for the AUA. The agent originally was developed as a skin-tanning product. Thus far, clinical results with the intranasal formulation developed for management of erectile dysfunction have been promising, he said.
"It has a different mechanism of action, so that creates the potential for combination therapy with a PDE5 inhibitor," said Dr. Sharlip. "Right now the manufacturer is evaluating it as monotherapy, but I wouldn't be surprised to see bremelanotide and a PDE5 inhibitor used in combination."