Cigarette smoking significantly increases the risk of erectile dysfunction, according to a study reported today at the American Heart Association's 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention.

Men who smoked more than 20 cigarettes daily had 60 percent higher risk of erectile dysfunction, compared to men who never smoked. The data showed a dose-related impact of smoking: the risk of erectile dysfunction was lower in men who smoked fewer cigarettes, but still increased compared to non-smokers.

The effect of smoking remained significant after considering other factors known to affect erectile function such as age, blood pressure, cholesterol levels, diabetes and body mass index (BMI).

"This is not the first study to document an association between cigarette smoking and erectile dysfunction," says Jiang He, M.D., Ph.D., Steward Associate Professor of Epidemiology and Medicine at Tulane University School of Public Health and Tropical Medicine in New Orleans. "However, our study is very unique because it is able to adjust for important confounders, such as blood pressure, serum cholesterol, and diabetes."

Erectile dysfunction is often associated with atherosclerosis, the build-up of wax-like plaque that obstructs blood flow through vessels. Smoking is a well-recognized risk factor for cardiovascular disease and studies have shown there are strong parallels and shared risks among smoking, coronary artery disease, atherosclerosis, and erectile dysfunction, says He.

Researchers examined data on 4,764 Chinese men (average age 47) involved in the InterASIA study, a national cross-sectional health survey conducted during 2000-2001. The survey included questions about respondents' current smoking status and history and quality of sexual relations. All men reported having sexual relations within the past six months.

Survey respondents were defined as current smokers if they were smoking at the time of the survey and had smoked at least 100 cigarettes in their lifetime. Former smokers were defined as having smoked more than 100 cigarettes in their lifetime but were not smoking at the time of the survey.

The average blood pressure and cholesterol values for the men were within normal ranges, and the average body mass index (BMI, an indicator of weight and body size) indicated the men were not overweight as a group. Of the survey respondents, 62.1 percent were current smokers, and 9.5 percent were former smokers.

Overall, 14.6 percent of the men experienced erectile dysfunction. Current and former smokers had identical rates of 15.1 percent, and the rate among men who had never smoked was 11.5 percent. After statistically accounting for other erectile function influences, researchers found that current smokers had a 31 percent higher risk for dysfunction compared to men who had never smoked. A similar difference was seen in former smokers, who had a 35 percent higher risk.

"We did not see a difference between current and former smokers," He says. "However, the number of former smokers is small in this study."

Focusing on current smokers, researchers evaluated the impact of increasingly heavy cigarette smoking on erectile dysfunction. Men who reported smoking fewer than 10 cigarettes a day had a 16 percent higher risk of erectile dysfunction, compared to men who had never smoked. The risk increased to 36 percent in men who reported smoking 11-20 cigarettes daily and was 60 percent higher in men who smoked more than 20 cigarettes (one pack) daily.

The findings build on and strengthen data from other studies suggesting that cigarette smoking is a risk factor for erectile dysfunction.

"These findings provide additional information that smoking has important adverse health effects," says Robert O. Bonow, M.D., president of the American Heart Association. "This gives male smokers another reason to kick the habit, and provides another area of emphasis and education for smoking cessation programs."

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"Our data support the potential benefits of a combination therapy with testosterone gel for men with erectile dysfunction and low testosterone who find sildenafil by itself ineffective," said Dr. Shabsigh of Columbia University. "When assessing erectile dysfunction, doctors and patients should consider using a simple blood test to determine if low testosterone is a contributing factor. If the root cause is low testosterone, sildenafil alone won't fix the problem."

It is estimated that four to five million American men have low testosterone (hypogonadism). Low testosterone may lead to decreased libido, erectile dysfunction, osteoporosis, reduced lean body mass and fatigue.

Sildenafil enhances the effects of nitric oxide, a chemical in the body that allows increased blood flow to the penis during sexual stimulation. "Research suggests nitric oxide may be dependent on testosterone to function properly," said Dr. Shabsigh. "While further studies are needed, this concept may explain why testosterone replacement therapy could help hypogonadal men who do not respond to sildenafil."

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The researchers, from the Brady Urological Institute at Johns Hopkins, suspected O-GlcNAc, a blood sugar present in hyperglycemic circumstances, to be the culprit. "We were interested to determine whether high glucose in diabetes mellitus modifies the endothelial nitric oxide synthase (eNOS) enzyme, which is responsible for the achievement and maintenance of erection," says Biljana Musicki, lead investigator of the study.

Erection begins when a sexual stimulus activates an enzyme that causes the short-term release of nitric oxide (NO) at the nerve endings in the penis, Musicki explained. This causes rapid and short-term increases in penile blood flow and short-term relaxation of the penile smooth muscle, initiating an erection. The resulting expansion of penile blood vessels and smooth-muscle relaxation allows more blood to flow into the penis. O-GlcNAc hinders this normal chain of events and prevents the smooth muscle in the penis from relaxing. Without this relaxation, the production of NO is hindered and a normal, sustained erection cannot occur.

The researchers emphasized the important role blood vessel function played. "The mechanism we describe here stresses the critical importance of vascular function in the erectile response. It may suggest new ways of treating erectile dysfunction by targeting specifically this mechanism in penile erection," said Musicki.

Arthur Burnett, head of the research team, said the study related to more than just sexual issues. "This paper gets back to the physiological relevance of hyperglycemia and how it affects erection. We show here - using erection as a model - the vascular damage caused by diabetes and provide insights into vascular disease beyond this dysfunction."

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The study appears in the The Journal of Sexual Medicine and was carried out by researchers from Pfizer and the Case School of Medicine. The study authors say it is the first study to look at erectile dysfunction in the context of sexual function, sexual self-confidence, self-esteem and overall relationship satisfaction.

It involved men with erectile dysfunction in stable relationships, using sildenafil citrate (Viagra) on an as-needed basis for 10 weeks. These men were compared with a control group of male volunteers with no history of erectile dysfunction and also in a stable relationship. All the men involved a completed a self-esteem and relationship questionnaire before and after the trial.

The study found that while there were substantive differences in the questionnaire scores between the two groups at the start of the trial, those differences largely disappeared at the conclusion of the trial.

"This research indicates that men with erectile dysfunction before treatment with sildenafil have sexual relationship satisfaction, confidence, self-esteem, and overall relationship satisfaction that are much less than men with normal erectile function. This investigation is the first to report that men with erectile dysfunction who are later given treatment with sildenafil are equivalent to men with normal erectile function in terms of sexual relationship satisfaction, confidence, self-esteem, and overall relationship satisfaction. Hence, the data suggest that sildenafil is associated with normalization of relationship satisfaction, confidence, and self-esteem," said Dr. Joseph C. Cappelleri, a director in Global Research and Development at Pfizer.

The notion that erectile dysfunction medications can deliver a significant psychological improvement in men's lives was echoed by one of the study's co-authors. "The restoration of sexual self-confidence is arguably the most important psychological variable in the successful treatment of erectile dysfunction," said Dr. Stan Althof, a psychologist at the Case School of Medicine.

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Led by HSPH's Constance Bacon, the researchers surveyed more than 22,000 men between the ages of 40 and 75 who reported good or very good erectile function prior to 1986. Among those participants, 18 percent reported the onset of erectile dysfunction between 1986 and 2000. The results showed that both smoking and obesity were associated with a higher risk of the development of erectile dysfunction among previously healthy men.

But the researchers added that regular physical activity was shown to significantly lower erectile dysfunction risk. "We found a 2.5-fold difference in risk of erectile dysfunction when we compared obese men who did little exercise with men who were not overweight and averaged 30 minutes of vigorous exercise a day. For men younger than 55, there was a 4-fold difference in risk for the same comparison," said co-researcher Eric Rimm. Interestingly, the researchers also noted that alcohol consumption did not increase the risk of erectile dysfunction.

Based on these results, the researchers suggest that erectile dysfunction and coronary heart disease may share many of the same risk factors. Rimm said the results should encourage men to follow a more healthy lifestyle. "Many men may choose not to change to a healthier lifestyle, which includes exercise and a prudent diet, because they perceive heart disease as something that may only develop decades in the future. Hopefully, these results will help to motivate men to adopt a more active lifestyle to avoid a problem which may be more immediate."

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The researchers conducted the study to gauge the prevalence of erectile dysfunction amongst U.S. males and to determine possible associations of cardiovascular risk factors, including lack of physical activity. Worryingly, they found that around 18 percent of men 20 years and older experienced erectile dysfunction (defined as "sometimes able" or "never able" to get and keep an erection).

While oral medications to treat erectile dysfunction can help, the researchers suggest that lifestyle changes like increase of physical activity and stricter dietary control for the prevention of cardiovascular disease and diabetes may be a better option.

"The association between erectile dysfunction and lack of physical activity suggests that lifestyle changes, especially increasing exercise levels, may be effective [non-drug] treatments. The associations between erectile dysfunction and diabetes and other known cardiovascular risk factors should serve as powerful motivators for male patients for whom diet and lifestyle changes are needed," said Hopkins' researcher Elizabeth Selvin.

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With the luxury of 21st century hindsight we can of course scoff at this, but before we get all flush with the self-satisfaction that arises from being so superior to those ignorant saps who lived in the past, it should be considered that within the living memory of just about every guy reading this, it was widely accepted that the root cause of our erectile dysfunction was unresolved jealousy stemming from the fact that our mothers had sex with our fathers instead of us. Frankly, when one appreciates the knowledge available at the time, magic makes a lot more sense. In the ancient world, and frankly up until the Newtonian revolution, it was thought that the world was controlled by supernatural forces and few things were as obviously under their mysterious control as the erection. After all, it seemed to come and goes as it pleased. It tented the toga at the most inconvenient moments yet would fail to arise when it was actually needed.

Even for those keen on rationalism the erection was largely a mystery. The ancient Greeks attributed the erection to "inflation by wind" or "spirit." And who else controlled this "wind" but Gods. The Gods were known to be capricious and temperamental but not generally speaking malicious. If the problem persisted, as erectile dysfunction often does when it takes hold in the latter stages of a man's life, then it stood to reason that malicious intent must lie behind it. And of course then, as now, the tendency was to blame some chick.

It wasn't a ridiculous assumption either. Curse tablets, providing incantations on how to induce impotence, date back almost as far as the remedies to thwart such curses. One of the more eloquent sought to "dry it up like wood and make it like a rag on the manure pile," There were no doubt many women who would have willed such a fate to befall husbands or lovers who strayed, just as there were many men who feared such a curse. One of life's ironies is that men achieve power, and the concomitant ability to attract new mates just as their ability to fully capitalize on it diminishes.

It's a scenario that plays out to this day. Man leaves wife for bimbo - finds he can't perform - blames former wife. Ditto for the men who suspected their wives didn't want to have sex with them in the first place. A not unreasonable suspicion, given the manner in which wives were treated, certainly in ancient Greece. According to the Greek historian, Herodotus, the Egyptian Pharaoh Amasis was convinced that his political marriage to Ladice of Cyrene was unconsummated because his new bride had bewitched him. She denied this but was unable to appease his anger and eventually had to swing a deal with Aphrodite to give him back his manhood. Aphrodite agreed and eventually it all worked out for the crazy kids. As you might imagine though, not all such stories had "happy endings."

To counter the curse of impotence - either imagined or admitted by their gleeful wives - men resorted to whatever they believed was necessary, including, as we've learned, ingesting the vilest of concoctions. Those with weaker stomachs tried to make do with wearing magical amulets while others opted for old standards of appeasement, incantation and sacrifice to whichever Gods it was thought were responsible.

After Christianity became the dominant religion in Europe, the pagan Gods were abandoned but impotence remained. Who was to blame now? For St. Augustine, the eminent 4th century Christian theologian, impotence (which he described poetically as the "desire that cools off in the body while it is at boiling heat in the mind"), was divine punishment for what went down in the Garden of Eden. The traditional cures of counter-potions and amulets were seen as the work of the devil and fell out of favor (at least with the church). Prayer, recitations and pious self-denial were the only accepted recourse. In other words: appeasement, incantation and sacrifice. Plus ca change.

As the dark ages darkened however, the idea of impotence as the working of malevolent spirits reasserted itself big time. Now, instead of Gods doing the dirty work it was demons operating at the behest of... you guessed it... women. Impotentia Maleficium it was called - impotence as a result of malicious witchcraft. Maleficium covered all manner of nasty stuff (it's also, not surprisingly, the title of a heavy metal album by the Swedish group Morgana Lefay) including turning milk sour, striking people dead, causing diseases, preventing hens from laying... whatever. If something, anything went wrong, it was generally assumed that some dastardly woman was responsible. But impotence in particular seems to have been a hex favored by witches. It is discussed almost obsessively in the Malleus Maleficarum, the 15th century witch hunter's handbook, which for a couple of centuries was the best selling book after the bible.

While witchcraft was originally a pagan concept, it eventually became adopted by the Christian church, with deadly consequences. Between 1350 and 1650, thousands of innocent women were burned at the stake for any number of crimes, not least of which was making men impotent. Save for the violence visited on the denizens of the New World, the persecution of witches was perhaps the greatest tragedy of the High Middle Ages, and was made all the more poignant by the fact that every women so condemned was innocent. As much as women may have wished it, they had no more control over a man's erectile function than did the man himself.

But even while the witch hunt terror was sweeping Europe, the light of truth was finding its way. In 1477, a 25 year old Leonardo Da Vinci attended a public hanging and observed that some of the executed men developed erections after death. Struck by curiosity, Leonardo gained permission to dissect the corpses and made what was then a startling discovery. Rather than being inflated by wind, as the ancient Greeks had asserted (and which was, astonishingly, still the "standard model" of penis function), Leonardo learned that the penis was in fact inflated by blood (hydraulics as opposed to pneumatics). It would be another five centuries before we would learn what actually caused the blood to enter and stay, but the door of science had been opened, if only just a crack, and the history of erectile dysfunction would never be the same...

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Nevertheless it was seen at the time as a slam-dunk marketing ploy. After all, if Viagra was an impotence drug then it seemed reasonable to assume that the primary market would be limp dicked geezers like well... Bob Dole.

But while this early campaign was successful and helped launch the Viagra brand, a brand that is still dominant in spite of recent market incursions from johnny-come-latelys such as Cialis and Levitra, the early marketing efforts are understood by many hind-sighted experts as a marketing failure. Why? Because as the last decade has demonstrated, the natural market for Viagra wasn't old geezers or even men who suffered from erectile dysfunction (ED). Rather, the fastest growing market segment is younger men from 18 to 50.

Apparently, the natural market for Viagra is every sexually mature adult male on planet earth.

But you won't find industry statistics showing this. Most such data is pulled from pharmacies and few young men are going to tell their doctors "they need to drop a little Viagra with their ecstasy for a well rounded night out." But doctors no longer keep the keys to the medicine cabinet. Anyone can log on to an online pharmacy and get a trunk load of blue pills delivered in the mail. In fact, the price structure of online pharmacies strongly encourages volume purchases. Ten pills will cost you $6 each. Buy two hundred and that price drops to $1.35. As such, a large secondary market has emerged in campus dormitories. The same guy who sells you your ecstasy and your pot will happily throw in some Viagra at $3 a pop.

I know what you're thinking; guys that young don't need Viagra. They can get it up anytime they want. Well, yes, but erectile function is variable. Erection quality can be affected by anxiety, hormones, level of intoxication etc. And it's ironic that the drugs (alcohol, pot, ecstasy, cocaine) that enhance our sexual desire actually diminish our ability to perform. But with Viagra, sexual doubts (and irony) are vanquished.

Viagra works by keeping the walls of the arteries leading to the penis relaxed. Blood flows in and for the most part it stays in. If your erection has a tendency to flag when you're thinking about Mom or putting on a condom, Viagra will take care of that. If you're pissed to the gills or floating on ecstasy and your dick is a separate unknowable entity, not to worry, Viagra will see you through. And if you're prone to ejaculate just as she's working herself to a climax, relax, thanks to Viagra you'll be ready to go in just a few minutes and this time you'll be able to go for half an hour. It turns out that Viagra's killer app isn't erectile dysfunction so much as erectile imperfection. It's a competitive world out there. Women expect more. Why not use every advantage? Come to think of it, that should be Pfizer's slogan...

But you won't be seeing ad copy like that anytime soon. ED drug manufactures go to great lengths to distance themselves from this booming youth market. Spokespersons for both Pfizer and Eli Lilly (which makes Cialis) insist that their product is intended to treat medically confirmed erectile dysfunction and deny any role in promoting the drug for sexual enhancement. Indeed, most advertising is still directed at men in their fifties, guys that while not technically impotent, could use a leg up.

The drug companies are nervous because there is a backlash against what is being called Viagra Abuse. Some of this is being driven by doctors, who are understandably miffed at being sidelined by this emerging trend in self-medication via the Internet. It's also driven by the media, always on the lookout for juicy copy and by religious groups who are against sex and drugs in equal measure.

But is unsanctioned drug use necessarily abuse? Popping a Viagra as a back-up to ensure a successful conclusion to a third date is a rational choice. There is something to be gained and little if anything to be lost. Surely to be considered abuse, the negative effects of any drug must outweigh the positive.

So what is the potential downside of Viagra abuse? The first is the problem of self-medication. Viagra was approved by the FDA as a prescribed drug. An overdose can lead to priapism (a painful unrelenting erection). When mixed with other nitrate based medications (which lower blood pressure) Viagra can be fatal. Ditto when mixed with nitroglycerin (poppers) which also lower blood pressure. A good doctor will take the time to spell out the risks. Online pharmacies generally don't.

Then there's the problem of over-reliance. I personally doubt there are Viagra addicts but it stands to reason that any drug that is perceived to have a positive effect can be habit forming, especially if you're using it to allay performance concerns. Drug dependence of any kind is unhealthy; psychologically and physiologically. Part of the problem is that over time efficacy is reduced and more of the drug is needed to achieve the same effect. This might be OK if there were no side effects, but Viagra has several potentially deleterious effects.

One of these is sperm damage. According to a recent study conducted by David Glenn at Queen's University, Belfast, Viagra damaged sperm acrosomes (the enzymes that break down the zona pellucida surrounding the egg). Mice, force fed Viagra produced 40 percent fewer embryos. This may not be entirely a bad thing. Most guys out clubbing aren't looking to knock-up their mates. And frankly, there are too many people in the world anyway. But for couples anxious to conceive it's potentially a problem. So far it's unknown whether the effects are permanent or cumulative.

One of the main complaints about unsupervised Viagra use is from health officials concerned about renewed outbreaks of HIV/AIDS. It seems that many younger Viagra users are gay. According to a survey conducted by the San Francisco Department of Public Health, 31 percent of a group of sexually active homosexuals reported taking Viagra without medical supervision. Another study found that Viagra users are also twice as likely as non-users to be HIV positive. This is not to say that Viagra is making gay men have unsafe sex. Men who are inclined to have unsafe sex are using Viagra and it just allows them to have more unsafe sex.

When it comes to Viagra use/abuse, I tend to be a libertarian. Hell, I've used it myself (for research purposes, of course). It basically turns you into a teenager again. If guys are stupid enough to double-up their dosage then they deserve to spend their Saturday night in the emergency room with a tent pole in their pants. If Viagra allows them to drink and still have great sex, I say rock on.

My only real concern with Viagra abuse is what I would call the enhancement cycle problem. This is akin to the doping problem with athletes or genetic enhancement. It is a competitive world out there. If Viagra becomes used widely as an enhancement drug then those drug users will set a new standard of performance. Women will expect more and men will be under greater pressure to use Viagra. Pretty soon everybody will be using it.

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A new penis pill formulation for men claims to both boost testosterone and increase blood flow to the penis. SizePro pills are a herbal preparation marketed by Creative Science Labs via the Internet. Rather than making extravagant claims about enlarging the penis, Joshua Andrews of SizePro prefers to call his pills "a penis enhancement formulation".

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