Male impotence drugs may deserve a second look in women
AUGUSTA, Ga., 18 APRIL 2009 – New studies indicate the three drugs used to treat male impotence also appear to work in females, albeit a little differently, and should give the scientific community pause to take a second look at their potential in the 40 percent of women who report sexual dysfunction, researchers say.
In one of the first studies of the effect of phosphodiesterase Type 5 inhibitors - Viagra®, Levitra® and Cialis® - on the pudendal arteries that supply the penis, vagina and clitoris the blood needed to produce a satisfying sexual experience, Medical College of Georgia researchers showed the drugs relax the artery in male and female rats.
"It shows the drugs need to be investigated more for women and small alterations could make these compounds more effective for women living with these disorders," says Dr. Kyan J. Allahdadi, postdoctoral fellow in physiology at MCG. He's presenting the findings during the 122nd Annual Meeting of the American Physiological Society held in New Orleans April 18-22 as part of the Experimental Biology 2009 scientific conference.
Although there was talk years ago of a pink pill for women to parallel the blue Viagra for men, early clinical trials found essentially no response in women.
MCG researchers decided to look again, first giving a drug to constrict the internal pudendal arteries in male and female rats – as they would be in a non-erect state – then giving doses of each impotency drug to see the impact. The arteries from male rats displayed a relatively standard concentration-dependent relaxation – the more drug they got, the more they relaxed - while in females arteries, there was an initial relaxation then an odd oscillation between relaxation and contraction with subsequent dosing.
While they don't fully understand the swing, the unique female response likely provides more evidence that sexual function is more complex in females, says Dr. R. Clinton Webb, chair of the MCG Department of Physiology and a study author. Scientists define female sexual dysfunction as a multifaceted disorder that includes anatomical, psychological, physiological and social-interpersonal aspects.
MCG researchers have shown part of that complexity may be the smooth muscle cells in the internal pudendal arteries of females communicate, agreeing to contract and relax, while male smooth muscle cells make independent decisions to just relax.
They found one other distinction: females were more sensitive to Viagra®, or sildenafil, while males were most sensitive to Levitra®, or vardenafil.
Previous studies on the effectiveness of these drugs focused on the cavernosal tissue, or penis. The internal pudendal artery actually feeds the penile artery which is buried deep in the penis where numerous caverns enable it to be flaccid when not engorged with blood. Physical stimulation of the area causes the tissue, endothelial cells and nerves to release nitric oxide, a powerful dilator of blood vessels. The system works pretty much the same way in the vagina and clitoris.
"If you have too much constriction or not enough relaxation to allow blood to go through the internal pudendal artery, you are not going to get the net effect of an erection," Dr. Allahdadi says. "That is why we wanted to begin to characterize what was going on in this blood vessel."
Perhaps as importantly, the MCG scientists and others are beginning to believe sexual dysfunction provides an early, or at least visible, clue of vascular disease. Vascular problems, that can result from diabetes, hypertension, high cholesterol and the like, are a major cause of sexual dysfunction in men and women. "You don't feel atherosclerosis but you know darn well if you are not getting an erection," Dr. Webb says. In fact, the MCG scientists are beginning to look at animal models of disease states, such as diabetes, to see what it does to these internal pudendal arteries.
"What we have seen preliminarily is there is big difference in responsiveness in these arteries. The diabetic pudendal arteries are much more sensitive to contraction," Dr. Allahdadi says. They will look at how drugs like Viagra impact that contraction in the days ahead.
In fact MCG scientists suspect one reason that many of the women participants in previous studies of Viagra did not seem to respond is because they did not have vascular problems that could have been circumvented by a drug that relaxes arteries so blood can enter. In men with a healthy vasculature, the drugs likely would still produce a longer erection.
Dr. Rita C. Tostes, associate professor in the MCG Department of Physiology, is a co-author who contributed to the design and analysis of the study.
Showing posts with label Viagra. Show all posts
Showing posts with label Viagra. Show all posts
Saturday, April 18, 2009
Wednesday, November 26, 2008
New Suspect in Sports Doping Is, No Joke, Viagra
By JERÉ LONGMAN
SCRANTON, Pa., 26 nov 2008 — When George Downey volunteered along with other lacrosse players at Marywood University to take Viagra for a study, he received a snickering nickname from his high school coach. His parents jokingly told their friends. Inquiring minds sent messages to his Facebook page.
“They’re making fun of me,” Mr. Downey, 19, said good-naturedly. “Deep down, I think they’re looking for tips.”
Except that the Marywood study does not involve the bedroom, but the playing field. It is being financed by the World Anti-Doping Agency, which is investigating whether the diamond-shaped blue pills create an unfair competitive advantage in dilating an athlete’s blood vessels and unduly increasing oxygen-carrying capacity. If so, the agency will consider banning the drug.
Viagra, or sildenafil citrate, was devised to treat pulmonary hypertension, or high blood pressure in arteries of the lungs. The drug works by suppressing an enzyme that controls blood flow, allowing the vessels to relax and widen. The same mechanism facilitates blood flow into the penis of impotent men. In the case of athletes, increased cardiac output and more efficient transport of oxygenated fuel to the muscles can enhance endurance.
“Basically, it allows you to compete with a sea level, or near-sea level, aerobic capacity at altitude,” Kenneth W. Rundell, the director of the Human Performance Laboratory at Marywood, said of Viagra.
Some experts are more skeptical. Anthony Butch, the director of the Olympic drug-testing lab at U.C.L.A., said it would be “extremely difficult, if not impossible” to prove that Viagra provided a competitive edge, given that the differences in performance would be slight and that athletes would probably take it in combination with other drugs. Scientists have the same uncertainty about the performance-enhancing effects of human growth hormone, though it is banned. But some athletes do not need proof — only a belief — that a drug works before using it, Dr. Butch said.
“I think it’s going to be a problem,” he said.
Through the decades, athletes have tried everything from strychnine to bulls’ testicles to veterinary steroids in a desperate, and frequently illicit, effort to gain an advantage. Several years ago, word spread that Viagra was being given to dogs at racetracks, said Travis Tygart, the chief executive of the United States Anti-Doping Agency, based in Colorado Springs.
Interest in the drug among antidoping experts was further increased by a study conducted at Stanford University and published in 2006 in The Journal of Applied Physiology. The study indicated that some participants taking Viagra improved their performances by nearly 40 percent in 10-kilometer cycling time trials conducted at a simulated altitude of 12,700 feet — a height far above general elite athletic competition. Viagra did not significantly enhance performance at sea level, where blood vessels are fully dilated in healthy athletes.
A 2004 German study of climbers at 17,200 feet at a Mount Everest base camp, published in The Annals of Internal Medicine, found that Viagra relieved constriction of blood vessels in the lungs and increased maximum exercise capacity.
At this point, there is no evidence of widespread use of Viagra by elite athletes, Mr. Tygart said. Yet, because the drug is not prohibited and thus not screened for, there is no way to know precisely how popular it is.
There is some suspicion that Viagra may be used to circumvent doping controls in cycling, which has faced waves of scandal. Last May, the cyclist Andrea Moletta was removed from the Tour of Italy after a search of his father’s car turned up 82 Viagra pills, as well as syringes concealed in a tube of toothpaste, according to news accounts. An investigation ended without formal accusations of doping.
The former major league baseball player Rafael Palmeiro once served as a pitchman for Viagra and tested positive in 2005 for the steroid stanozolol, although the connection, if any, between the drugs in his case is not known. Some athletes are believed to take Viagra in an attempt to aid the delivery of steroids to the muscles and hasten recovery from workouts. Others take Viagra to counter the effects of impotence brought on by steroid use, said Dr. Gary I. Wadler, the chairman of the World Anti-Doping Agency’s committee on prohibited substances.
The agency, based in Montreal, is financing two studies related to Viagra and performance enhancement in sports. The University of Miami is studying whether Viagra benefits aerobic capacity at lower altitudes than the Stanford study — comparable to heights where elite competitions take place. This study is also examining whether there is a difference in the way Viagra affects male and female athletes.
The study at Marywood University is measuring the potential effects of Viagra as an antidote to air pollution, produced outdoors by the exhaust of factories and automobiles and indoors by ice-resurfacing machines. Studies involving animals, and children in Mexico City, have indicated that pollution causes pulmonary hypertension. If that could be alleviated for athletes by Viagra, “performance is going to be enhanced,” said Dr. Rundell, the lead researcher of the pollution study.
The Marywood study is expected to be completed by next month, and the Miami study is expected to conclude in February. The earliest that the World Anti-Doping Agency could place Viagra on its list of prohibited substances would be September 2009, five months before the 2010 Winter Olympics in Vancouver, British Columbia, a spokesman said.
“My guess is, it’s a pretty easy decision to make,” Dr. Rundell said. “It’s a compound that’s pretty easily measured. And it clearly provides an unfair advantage, at least at altitude. I couldn’t imagine it not going down on the list, but I’m not the one who makes those decisions.”
Because the air in Beijing is so polluted, some suspected that Viagra would be a popular drug at the 2008 Olympics. But there was no attempt to measure its presence because it was not prohibited, a spokeswoman for the International Olympic Committee said.
Even if Viagra increases athletic stamina by a small amount, it could have a significant effect on results in sports like distance running, or cycling and Nordic skiing, whose events can be held at altitudes of 6,000 feet or above, Dr. Rundell said. He noted that the time between first place and fourth place in the 15-kilometer cross-country ski race at the 2006 Turin Olympics amounted to a performance differential of less than 1 percent.
Even athletes in contact sports may benefit from Viagra, Dr. Rundell said. “If you are a football player going to Denver from Atlanta, I don’t see why it wouldn’t work,” he said.
Anne L. Friedlander, an author of the 2006 Stanford study, said that she expected Viagra would be banned for sports use. But, she noted, it does not benefit everyone. Only 4 of the 10 participants in her study responded to the drug. And Viagra merely elevated the performance of those four to the level of other participants less affected by altitude, rather than enhancing performance beyond normal, the way steroids do, Dr. Friedlander said.
“That’s something to think about,” she said.
Whether Viagra is allowed or prohibited, it remains illegal for athletes to use prescription medication not ordered for them, Mr. Tygart of Usada said. He and others cautioned that the use of Viagra could also result in side effects like severe headaches, changes in vision and priapism, which may require medical attention.
Meanwhile, at Marywood University, Mr. Downey and about a half-dozen other lacrosse players have joined a group of 30 participants in the study of Viagra’s effectiveness in countering air pollution. They will ride exercise bikes in clean air and in a room with the air polluted by the exhaust of leaf blowers and lawnmowers. And they will continue to endure teasing from their friends.
“It may take awhile to live this one down,” Mr. Downey said.
At least the participants are allowed to receive a stipend.
“You’ve got to pay for college somehow,” he said.
By JERÉ LONGMAN
SCRANTON, Pa., 26 nov 2008 — When George Downey volunteered along with other lacrosse players at Marywood University to take Viagra for a study, he received a snickering nickname from his high school coach. His parents jokingly told their friends. Inquiring minds sent messages to his Facebook page.
“They’re making fun of me,” Mr. Downey, 19, said good-naturedly. “Deep down, I think they’re looking for tips.”
Except that the Marywood study does not involve the bedroom, but the playing field. It is being financed by the World Anti-Doping Agency, which is investigating whether the diamond-shaped blue pills create an unfair competitive advantage in dilating an athlete’s blood vessels and unduly increasing oxygen-carrying capacity. If so, the agency will consider banning the drug.
Viagra, or sildenafil citrate, was devised to treat pulmonary hypertension, or high blood pressure in arteries of the lungs. The drug works by suppressing an enzyme that controls blood flow, allowing the vessels to relax and widen. The same mechanism facilitates blood flow into the penis of impotent men. In the case of athletes, increased cardiac output and more efficient transport of oxygenated fuel to the muscles can enhance endurance.
“Basically, it allows you to compete with a sea level, or near-sea level, aerobic capacity at altitude,” Kenneth W. Rundell, the director of the Human Performance Laboratory at Marywood, said of Viagra.
Some experts are more skeptical. Anthony Butch, the director of the Olympic drug-testing lab at U.C.L.A., said it would be “extremely difficult, if not impossible” to prove that Viagra provided a competitive edge, given that the differences in performance would be slight and that athletes would probably take it in combination with other drugs. Scientists have the same uncertainty about the performance-enhancing effects of human growth hormone, though it is banned. But some athletes do not need proof — only a belief — that a drug works before using it, Dr. Butch said.
“I think it’s going to be a problem,” he said.
Through the decades, athletes have tried everything from strychnine to bulls’ testicles to veterinary steroids in a desperate, and frequently illicit, effort to gain an advantage. Several years ago, word spread that Viagra was being given to dogs at racetracks, said Travis Tygart, the chief executive of the United States Anti-Doping Agency, based in Colorado Springs.
Interest in the drug among antidoping experts was further increased by a study conducted at Stanford University and published in 2006 in The Journal of Applied Physiology. The study indicated that some participants taking Viagra improved their performances by nearly 40 percent in 10-kilometer cycling time trials conducted at a simulated altitude of 12,700 feet — a height far above general elite athletic competition. Viagra did not significantly enhance performance at sea level, where blood vessels are fully dilated in healthy athletes.
A 2004 German study of climbers at 17,200 feet at a Mount Everest base camp, published in The Annals of Internal Medicine, found that Viagra relieved constriction of blood vessels in the lungs and increased maximum exercise capacity.
At this point, there is no evidence of widespread use of Viagra by elite athletes, Mr. Tygart said. Yet, because the drug is not prohibited and thus not screened for, there is no way to know precisely how popular it is.
There is some suspicion that Viagra may be used to circumvent doping controls in cycling, which has faced waves of scandal. Last May, the cyclist Andrea Moletta was removed from the Tour of Italy after a search of his father’s car turned up 82 Viagra pills, as well as syringes concealed in a tube of toothpaste, according to news accounts. An investigation ended without formal accusations of doping.
The former major league baseball player Rafael Palmeiro once served as a pitchman for Viagra and tested positive in 2005 for the steroid stanozolol, although the connection, if any, between the drugs in his case is not known. Some athletes are believed to take Viagra in an attempt to aid the delivery of steroids to the muscles and hasten recovery from workouts. Others take Viagra to counter the effects of impotence brought on by steroid use, said Dr. Gary I. Wadler, the chairman of the World Anti-Doping Agency’s committee on prohibited substances.
The agency, based in Montreal, is financing two studies related to Viagra and performance enhancement in sports. The University of Miami is studying whether Viagra benefits aerobic capacity at lower altitudes than the Stanford study — comparable to heights where elite competitions take place. This study is also examining whether there is a difference in the way Viagra affects male and female athletes.
The study at Marywood University is measuring the potential effects of Viagra as an antidote to air pollution, produced outdoors by the exhaust of factories and automobiles and indoors by ice-resurfacing machines. Studies involving animals, and children in Mexico City, have indicated that pollution causes pulmonary hypertension. If that could be alleviated for athletes by Viagra, “performance is going to be enhanced,” said Dr. Rundell, the lead researcher of the pollution study.
The Marywood study is expected to be completed by next month, and the Miami study is expected to conclude in February. The earliest that the World Anti-Doping Agency could place Viagra on its list of prohibited substances would be September 2009, five months before the 2010 Winter Olympics in Vancouver, British Columbia, a spokesman said.
“My guess is, it’s a pretty easy decision to make,” Dr. Rundell said. “It’s a compound that’s pretty easily measured. And it clearly provides an unfair advantage, at least at altitude. I couldn’t imagine it not going down on the list, but I’m not the one who makes those decisions.”
Because the air in Beijing is so polluted, some suspected that Viagra would be a popular drug at the 2008 Olympics. But there was no attempt to measure its presence because it was not prohibited, a spokeswoman for the International Olympic Committee said.
Even if Viagra increases athletic stamina by a small amount, it could have a significant effect on results in sports like distance running, or cycling and Nordic skiing, whose events can be held at altitudes of 6,000 feet or above, Dr. Rundell said. He noted that the time between first place and fourth place in the 15-kilometer cross-country ski race at the 2006 Turin Olympics amounted to a performance differential of less than 1 percent.
Even athletes in contact sports may benefit from Viagra, Dr. Rundell said. “If you are a football player going to Denver from Atlanta, I don’t see why it wouldn’t work,” he said.
Anne L. Friedlander, an author of the 2006 Stanford study, said that she expected Viagra would be banned for sports use. But, she noted, it does not benefit everyone. Only 4 of the 10 participants in her study responded to the drug. And Viagra merely elevated the performance of those four to the level of other participants less affected by altitude, rather than enhancing performance beyond normal, the way steroids do, Dr. Friedlander said.
“That’s something to think about,” she said.
Whether Viagra is allowed or prohibited, it remains illegal for athletes to use prescription medication not ordered for them, Mr. Tygart of Usada said. He and others cautioned that the use of Viagra could also result in side effects like severe headaches, changes in vision and priapism, which may require medical attention.
Meanwhile, at Marywood University, Mr. Downey and about a half-dozen other lacrosse players have joined a group of 30 participants in the study of Viagra’s effectiveness in countering air pollution. They will ride exercise bikes in clean air and in a room with the air polluted by the exhaust of leaf blowers and lawnmowers. And they will continue to endure teasing from their friends.
“It may take awhile to live this one down,” Mr. Downey said.
At least the participants are allowed to receive a stipend.
“You’ve got to pay for college somehow,” he said.
Tuesday, July 22, 2008
CHICAGO , 22 july 2008-- The erectile dysfunction drug Viagra has proven effective at combating sexual dysfunction in depressed women, according to a study published Tuesday.
Sexual dysfunction is a common side effect of antidepressants and a major reason why people stop taking medication for their depression.
This is particularly problematic given that twice as many women as men are prescribed antidepressants but the most effective drugs used to combat sexual dysfunction in men are not approved for use in women, the authors wrote.
Researchers tested Viagra on 98 women whose depression was in remission but were still experiencing sexual dysfunction such as lack of arousal or pain during sex.
The women were told to take a pill one to two hours before sex for eight weeks. Half were given placebos pills which had no pharmacological effects.
Some 73 percent of the women given placebos reported no improvement with treatment while only 28 percent of the women taking Viagra said they did not notice an improvement, the study published in the Journal of the American Medical Association found.
Some of the women experienced headaches, flushing and indigestion but none of them withdrew from the trial because of side effects.
"By treating this bothersome treatment-associated adverse effect in patients who have been effectively treated for depression, but need to continue on their medication to avoid relapse or recurrence, patients can remain antidepressant-adherent, reduce the current high rates of premature medication discontinuation, and improve depression disease management outcomes," wrote lead author George Nurnberg of the University of New Mexico School of Medicine.
Thursday, May 01, 2008
Chilean town giving free Viagra to senior citizens
01 may 2008--A working class suburb of Chile's capital began handing out free Viagra to senior citizens on Wednesday. Lo Prado Mayor Gonzalo Navarrete said he launched the program because "an active sexuality improves the overall quality of life."
About 1,500 residents of the working-class area are eligible to receive as many as four pills of the erectile dysfunction drug each month, the mayor said. They have to be at least 60 and be registered with the municipality's health service.
"A doctor will have to certify that they suffer from erectile dysfunction and that their condition would not put them in danger of suffering cardio-respiratory side effects," Navarrete told The Associated Press by telephone.
He said he has assured about US$10,000 (euro6,400) in financing for the program through the end of the year.
Some government insurance plans in the United States and elsewhere provide Viagra, but Lo Prado hands the 50mg pills out free, with no membership in any public or private insurance plan required.
Navarrete said some other mayors in the Santiago area, which includes 34 municipalities, have told him they plan similar programs.
Navarrete said he did not know how many pills had been distributed so far.
01 may 2008--A working class suburb of Chile's capital began handing out free Viagra to senior citizens on Wednesday. Lo Prado Mayor Gonzalo Navarrete said he launched the program because "an active sexuality improves the overall quality of life."
About 1,500 residents of the working-class area are eligible to receive as many as four pills of the erectile dysfunction drug each month, the mayor said. They have to be at least 60 and be registered with the municipality's health service.
"A doctor will have to certify that they suffer from erectile dysfunction and that their condition would not put them in danger of suffering cardio-respiratory side effects," Navarrete told The Associated Press by telephone.
He said he has assured about US$10,000 (euro6,400) in financing for the program through the end of the year.
Some government insurance plans in the United States and elsewhere provide Viagra, but Lo Prado hands the 50mg pills out free, with no membership in any public or private insurance plan required.
Navarrete said some other mayors in the Santiago area, which includes 34 municipalities, have told him they plan similar programs.
Navarrete said he did not know how many pills had been distributed so far.
Monday, March 31, 2008
Recalling the Madness
By CHRIS CONWAY
Viagra is just another pill in the medicine cabinet these days, one of three on the market to treat the once all-but-unmentionable problem of erectile dysfunction. But 10 years ago last week, when government regulators approved it for sale, Viagra became the first pill available to treat the problem. The reaction was, well... Here’s what reporters for The New York Times found in the drug’s first months.
Beginning another day on the front lines of what he refers to as “Viagra madness,” Dr. Stanley Bloom, urologist and impotence specialist, flexed his hand to steel it against writing cramps. Men’s redemption from sexual malfunction was exacting its physical toll on his already ragged penmanship. So many craved a prescription for the little blue Pfizer pill that was sweeping the country, but how much could a 60-year-old right hand take?
Some urologists had acquired stamps to apply their signature on Viagra prescriptions. Dr. Bloom had his nurse prepare a tidy stack of prescriptions in advance. Then he authenticated them the old-fashioned way as the men tumbled in.
“I’m burning out,” he lamented as the chronically jammed waiting room of his Physicians in Urology offices on East Northfield Road emptied into the hive of examination rooms, though he was sincerely gratified to see a breakthrough against an affliction that consumes his practice.
In trooped the patients, something like 25 a day in the last three weeks for the diamond-shaped miracle pill, extending Dr. Bloom’s daily office hours three hours beyond the norm. Reflecting the very height of exuberance and expectation, John Dowling, 69, a retired packaging foreman for Budweiser, only half-jokingly asked for a prescription for 1,000 pills.
“They’re $10 apiece,” Dr. Bloom replied.
“Five hundred, then?”
“That’s $5,000. You’ve got to be kidding.”
He settled for 20.
It was already his second prescription. He had been in two weeks ago and had tested the pill five times, with gratifying results.
Bob Dole, the 1996 Republican presidential candidate, disclosed on “Larry King Live” that he had participated in clinical trials for Viagra. “It’s a great drug,” he told Mr. King. A few days later, his wife visited New York City. Dan Barry was there.
It is not often that City Hall reporters dare to ask visiting dignitaries about their sex lives. But these are the days of Viagra, when frank discussions of impotence can seem as natural as talking about fiscal conservatism.
So when Elizabeth Dole, president of the American Red Cross, graced a City Hall news conference with her meticulous presence yesterday, everyone in the room knew for certain that one question would be asked — a rather indelicate question that had nothing to do with her organization ....
Mrs. Dole accepted a proclamation from Mayor Rudolph W. Giuliani. After talking passionately about how important the Red Cross’s efforts are in places like Rwanda and Bosnia, she invited questions. There was a brief inquiry about mudslides in Italy, and then The Question was posed.
“In a normal time, I would ask you what would be your view of the Presidential candidacy of Mayor Giuliani,” the reporter said. “But there are more pressing matters of national importance. And it seems your husband was one of the first people who used Viagra. What advice would you give to men and women in this nation about the use of that pill?”
Mr. Giuliani laughed nervously and shook his head in disgust. Mrs. Dole, however, had been prepped.
“I’ll make this statement,” she said, smiling without a hint of fluster. “He was in the protocol, and it’s a great drug, O.K.?”
Jon Nordheimer traveled to Miami to check the reaction there.
Retirement communities are buzzing with speculation on Viagra and its restorative promise.... But marriage and sex counselors are uneasy that men, whatever their age, are overhauling their sex lives without any guidelines to the possible earthquake they may introduce into their emotional lives....
“Many elderly couples are very active sexually, but there are those who have lost interest and haven’t been intimate for years,” said Dr. Elliot Klorfein, a Florida urologist, who has many retirees as patients. He said he has written “a zillion” prescriptions for Viagra in the last few weeks, and much of the demand is coming from retirees he’s never treated before.
“Typically, an older man is still interested in sex, and he jumps at an idea that here’s a pill he can take orally that will make him a new man,” Dr. Klorfein said. “The trouble is his wife is no longer interested .... So her husband is all dressed up with nowhere to go.”
•
A Wall Street titan was inspired to generosity, as Ian Fisher reported.
Alan C. Greenberg bettered his own life by becoming rich on Wall Street, and yesterday he gave away $1 million of that money to better the lives of other aging men in a very specific way: He will pay for Viagra prescriptions for people who cannot afford them.
“I guess you could say I’m kind of into basics,” said Mr. Greenberg, 70, the chairman of Bear, Stearns Companies, who received a $20 million bonus last year. “And I think it’s something that will give a lot of pleasure to a lot of people.”
•
Perhaps inevitably, women wondered what Viagra might do for them. Alex Kuczynski talked to a few of them, including a 42-year-old nurse in New Jersey who described the first time she took Viagra.
“I only see my boyfriend every two weeks because we live in different states,” she explained. “And if I’m not in the mood on one of those weekends, well, then there goes the month. I’ve been with him for about two and a half years, and it’s just not as exciting as it used to be.”
Last Saturday night, she swallowed a blue, diamond-shaped Viagra pill, which she sneaked from a cache in the office where she works. The dosage was 50 milligrams, the standard for male sexual dysfunction. She chose not to tell her partner. “We were watching television, just a regular movie,” she said, noting that after an hour she began to feel “a fullness. I can’t say it was a tingling, but it was some effect of the increased blood flow to the area.” The couple retreated to the bedroom, and the pill began to work its alleged magic.
“I have to say it was great,” the woman said. ”It was animalistic. I can definitely say it was not a placebo effect. I’m a nurse, and I’m trained to recognize those things.”
By CHRIS CONWAY
Viagra is just another pill in the medicine cabinet these days, one of three on the market to treat the once all-but-unmentionable problem of erectile dysfunction. But 10 years ago last week, when government regulators approved it for sale, Viagra became the first pill available to treat the problem. The reaction was, well... Here’s what reporters for The New York Times found in the drug’s first months.
Beginning another day on the front lines of what he refers to as “Viagra madness,” Dr. Stanley Bloom, urologist and impotence specialist, flexed his hand to steel it against writing cramps. Men’s redemption from sexual malfunction was exacting its physical toll on his already ragged penmanship. So many craved a prescription for the little blue Pfizer pill that was sweeping the country, but how much could a 60-year-old right hand take?
Some urologists had acquired stamps to apply their signature on Viagra prescriptions. Dr. Bloom had his nurse prepare a tidy stack of prescriptions in advance. Then he authenticated them the old-fashioned way as the men tumbled in.
“I’m burning out,” he lamented as the chronically jammed waiting room of his Physicians in Urology offices on East Northfield Road emptied into the hive of examination rooms, though he was sincerely gratified to see a breakthrough against an affliction that consumes his practice.
In trooped the patients, something like 25 a day in the last three weeks for the diamond-shaped miracle pill, extending Dr. Bloom’s daily office hours three hours beyond the norm. Reflecting the very height of exuberance and expectation, John Dowling, 69, a retired packaging foreman for Budweiser, only half-jokingly asked for a prescription for 1,000 pills.
“They’re $10 apiece,” Dr. Bloom replied.
“Five hundred, then?”
“That’s $5,000. You’ve got to be kidding.”
He settled for 20.
It was already his second prescription. He had been in two weeks ago and had tested the pill five times, with gratifying results.
Bob Dole, the 1996 Republican presidential candidate, disclosed on “Larry King Live” that he had participated in clinical trials for Viagra. “It’s a great drug,” he told Mr. King. A few days later, his wife visited New York City. Dan Barry was there.
It is not often that City Hall reporters dare to ask visiting dignitaries about their sex lives. But these are the days of Viagra, when frank discussions of impotence can seem as natural as talking about fiscal conservatism.
So when Elizabeth Dole, president of the American Red Cross, graced a City Hall news conference with her meticulous presence yesterday, everyone in the room knew for certain that one question would be asked — a rather indelicate question that had nothing to do with her organization ....
Mrs. Dole accepted a proclamation from Mayor Rudolph W. Giuliani. After talking passionately about how important the Red Cross’s efforts are in places like Rwanda and Bosnia, she invited questions. There was a brief inquiry about mudslides in Italy, and then The Question was posed.
“In a normal time, I would ask you what would be your view of the Presidential candidacy of Mayor Giuliani,” the reporter said. “But there are more pressing matters of national importance. And it seems your husband was one of the first people who used Viagra. What advice would you give to men and women in this nation about the use of that pill?”
Mr. Giuliani laughed nervously and shook his head in disgust. Mrs. Dole, however, had been prepped.
“I’ll make this statement,” she said, smiling without a hint of fluster. “He was in the protocol, and it’s a great drug, O.K.?”
Jon Nordheimer traveled to Miami to check the reaction there.
Retirement communities are buzzing with speculation on Viagra and its restorative promise.... But marriage and sex counselors are uneasy that men, whatever their age, are overhauling their sex lives without any guidelines to the possible earthquake they may introduce into their emotional lives....
“Many elderly couples are very active sexually, but there are those who have lost interest and haven’t been intimate for years,” said Dr. Elliot Klorfein, a Florida urologist, who has many retirees as patients. He said he has written “a zillion” prescriptions for Viagra in the last few weeks, and much of the demand is coming from retirees he’s never treated before.
“Typically, an older man is still interested in sex, and he jumps at an idea that here’s a pill he can take orally that will make him a new man,” Dr. Klorfein said. “The trouble is his wife is no longer interested .... So her husband is all dressed up with nowhere to go.”
•
A Wall Street titan was inspired to generosity, as Ian Fisher reported.
Alan C. Greenberg bettered his own life by becoming rich on Wall Street, and yesterday he gave away $1 million of that money to better the lives of other aging men in a very specific way: He will pay for Viagra prescriptions for people who cannot afford them.
“I guess you could say I’m kind of into basics,” said Mr. Greenberg, 70, the chairman of Bear, Stearns Companies, who received a $20 million bonus last year. “And I think it’s something that will give a lot of pleasure to a lot of people.”
•
Perhaps inevitably, women wondered what Viagra might do for them. Alex Kuczynski talked to a few of them, including a 42-year-old nurse in New Jersey who described the first time she took Viagra.
“I only see my boyfriend every two weeks because we live in different states,” she explained. “And if I’m not in the mood on one of those weekends, well, then there goes the month. I’ve been with him for about two and a half years, and it’s just not as exciting as it used to be.”
Last Saturday night, she swallowed a blue, diamond-shaped Viagra pill, which she sneaked from a cache in the office where she works. The dosage was 50 milligrams, the standard for male sexual dysfunction. She chose not to tell her partner. “We were watching television, just a regular movie,” she said, noting that after an hour she began to feel “a fullness. I can’t say it was a tingling, but it was some effect of the increased blood flow to the area.” The couple retreated to the bedroom, and the pill began to work its alleged magic.
“I have to say it was great,” the woman said. ”It was animalistic. I can definitely say it was not a placebo effect. I’m a nurse, and I’m trained to recognize those things.”
Monday, March 24, 2008
Viagra: still going strong 10 years on
by Karin Zeitvogel
Ten years ago this month the lives of millions of men and women were changed almost overnight by the advent of a little blue pill -- the first oral treatment for impotence.
Viagra, developed by accident by scientists at Pfizer Laboratories, was first approved for use by the US Food and Drug Administration on March 27, 1998.
"Originally, we were testing sildenafil, the active drug in Viagra, as a cardiovascular drug and for its ability to lower blood pressure," said Dr Brian Klee, senior medical director at Pfizer.
"But one thing that was found during those trials is that people didn't want to give the medication back because of the side effect of having erections that were harder, firmer and lasted longer."
Since Viagra went on the market it has been used by 35 million men around the globe, and it took impotence off the taboo list, making it infinitely easier to treat.
Urologists' waiting rooms became busier as news got round that the condition, which was rechristened with a new, scientific name -- erectile dysfunction, or ED -- could be treated with a triangular blue pill.
Previous treatments had involved surgically inserting a prosthesis into the penis, injecting a substance into the male sex organ or using urethral suppositories.
"Viagra brought a lot more people into the office because of the ease of treatment," Dr Irwin Shuman, a urologist of 40 years' experience in Washington, told AFP.
"In the old days, when we didn't have much in the way of treatment, we would do a lot more evaluation, looking for answers as to why somebody had the problem," he said.
In one test, men would be observed while sleeping to see if erections occurred.
Men who failed to get the usual five to six erections per night were deemed to have a physical problem, and those who did get nocturnal erections were said to have a psychological problem and were sent to see a sex counsellor.
So Viagra helped move impotence out of the psychological realm and into the world of physical illnesses. "What we have come to understand in the past 10 years is that ED is a vascular disease," said Klee.
"What happens is veins and arteries that deliver and remove blood from the penis are not working the way they should, and Viagra allows those vessels to dilate and increase blood flow to the penis," he said.
Dr Abraham Morgentaler, director of Men's Health Boston, and associate clinical professor of urology at Harvard Medical School, hailed Viagra as a "benefit to medicine."
But, he added, the drug has not delighted all those who took it.
"There are two truths to Viagra: for those who refill (get a new prescription), it's wonderful and they're happy," Morgentaler told AFP.
"But a lot of people look to Viagra for personal happiness, thinking a hard penis can resolve relationship issues," and they end up disappointed, added the doctor and author of the book "The Viagra Myth."
Some patients say taking Viagra "does not correspond to the way they want to have sex," Morgentaler said.
Viagra works best on an empty stomach or after eating a low-fat meal, the medication's official website says. It kicks in about 30 minutes after being taken, works for four hours, and only with sexual arousal, the website says.
But it's not the answer for everyone. Morgentaler said he had a 78-year-old patient in his office who "didn't like the idea of programming sex. Guys, and often women, too, don't necessarily want to compromise the ideal of sex as something magical, spontaneous, romantic."
Morgentaler also spoke of the darker side of Viagra, which has evolved since it and two other ED treatments became easily available over the Internet.
"It's the use of Viagra by healthy young men who don't need it," he said.
"These young men take a pill whenever they go out ... Maybe because they are inexperienced or shy and Viagra makes them more confident, or maybe because they have inflated ideas about what sex is supposed to be like from seeing Internet porn, which they also have easy access to, and they want to heighten their feelings of masculinity," he said.
"I am concerned -- not that these young men will get addicted physically, but that they will become psychologically dependent on Viagra," said Morgentaler.
"Sex is an entree into a relationship, and most often what we want from a relationship is to be loved for what we are.
"But some of these young men feel they have to take a pill to be acceptable, and I fear they are potentially missing the opportunity to have true emotional connections with a partner, based on reality, not mythology."
by Karin Zeitvogel
Ten years ago this month the lives of millions of men and women were changed almost overnight by the advent of a little blue pill -- the first oral treatment for impotence.
Viagra, developed by accident by scientists at Pfizer Laboratories, was first approved for use by the US Food and Drug Administration on March 27, 1998.
"Originally, we were testing sildenafil, the active drug in Viagra, as a cardiovascular drug and for its ability to lower blood pressure," said Dr Brian Klee, senior medical director at Pfizer.
"But one thing that was found during those trials is that people didn't want to give the medication back because of the side effect of having erections that were harder, firmer and lasted longer."
Since Viagra went on the market it has been used by 35 million men around the globe, and it took impotence off the taboo list, making it infinitely easier to treat.
Urologists' waiting rooms became busier as news got round that the condition, which was rechristened with a new, scientific name -- erectile dysfunction, or ED -- could be treated with a triangular blue pill.
Previous treatments had involved surgically inserting a prosthesis into the penis, injecting a substance into the male sex organ or using urethral suppositories.
"Viagra brought a lot more people into the office because of the ease of treatment," Dr Irwin Shuman, a urologist of 40 years' experience in Washington, told AFP.
"In the old days, when we didn't have much in the way of treatment, we would do a lot more evaluation, looking for answers as to why somebody had the problem," he said.
In one test, men would be observed while sleeping to see if erections occurred.
Men who failed to get the usual five to six erections per night were deemed to have a physical problem, and those who did get nocturnal erections were said to have a psychological problem and were sent to see a sex counsellor.
So Viagra helped move impotence out of the psychological realm and into the world of physical illnesses. "What we have come to understand in the past 10 years is that ED is a vascular disease," said Klee.
"What happens is veins and arteries that deliver and remove blood from the penis are not working the way they should, and Viagra allows those vessels to dilate and increase blood flow to the penis," he said.
Dr Abraham Morgentaler, director of Men's Health Boston, and associate clinical professor of urology at Harvard Medical School, hailed Viagra as a "benefit to medicine."
But, he added, the drug has not delighted all those who took it.
"There are two truths to Viagra: for those who refill (get a new prescription), it's wonderful and they're happy," Morgentaler told AFP.
"But a lot of people look to Viagra for personal happiness, thinking a hard penis can resolve relationship issues," and they end up disappointed, added the doctor and author of the book "The Viagra Myth."
Some patients say taking Viagra "does not correspond to the way they want to have sex," Morgentaler said.
Viagra works best on an empty stomach or after eating a low-fat meal, the medication's official website says. It kicks in about 30 minutes after being taken, works for four hours, and only with sexual arousal, the website says.
But it's not the answer for everyone. Morgentaler said he had a 78-year-old patient in his office who "didn't like the idea of programming sex. Guys, and often women, too, don't necessarily want to compromise the ideal of sex as something magical, spontaneous, romantic."
Morgentaler also spoke of the darker side of Viagra, which has evolved since it and two other ED treatments became easily available over the Internet.
"It's the use of Viagra by healthy young men who don't need it," he said.
"These young men take a pill whenever they go out ... Maybe because they are inexperienced or shy and Viagra makes them more confident, or maybe because they have inflated ideas about what sex is supposed to be like from seeing Internet porn, which they also have easy access to, and they want to heighten their feelings of masculinity," he said.
"I am concerned -- not that these young men will get addicted physically, but that they will become psychologically dependent on Viagra," said Morgentaler.
"Sex is an entree into a relationship, and most often what we want from a relationship is to be loved for what we are.
"But some of these young men feel they have to take a pill to be acceptable, and I fear they are potentially missing the opportunity to have true emotional connections with a partner, based on reality, not mythology."
Friday, October 19, 2007
FDA to warn Viagra users of hearing loss
Thu Oct 18, 6:20 PM ET
Viagra and other impotence drugs are about to bear new warnings that users may experience sudden hearing loss.
It's not clear that the drugs truly trigger hearing loss, but the Food and Drug Administration decided Thursday to add a warning about the possible risk after counting 29 reports of the problem since 1996 among users of this family of medicines.
The impotence drugs Viagra, Cialis and Levitra will bear the warnings. So will Revatio, a drug for pulmonary hypertension, which contains the same ingredient as Viagra.
Viagra's label already mentioned hearing loss as a possibility, because a few cases were reported during initial testing of that drug. But given that hearing loss is a risk of advancing age and certain conditions, such as diabetes and heart disease, that can lead to impotence, it wasn't clear if the link was real.
That still isn't clear, said FDA ear nose and throat specialist Dr. Robert Boucher.
But in poring over FDA's database of possible drug reactions, what struck him was these 29 reports said the hearing loss occurred without hours to two days of taking one of the drugs.
"We don't know enough to say that it's ironclad caused by the drugs, but we see enough to say we can't ignore it either," he said.
The reports involve hearing loss in one ear, which in a third of cases was temporary.
FDA urged patients who experience any hearing problems — loss or ringing in the ears — to promptly call their doctors and stop taking the impotence drugs.
Thu Oct 18, 6:20 PM ET
Viagra and other impotence drugs are about to bear new warnings that users may experience sudden hearing loss.
It's not clear that the drugs truly trigger hearing loss, but the Food and Drug Administration decided Thursday to add a warning about the possible risk after counting 29 reports of the problem since 1996 among users of this family of medicines.
The impotence drugs Viagra, Cialis and Levitra will bear the warnings. So will Revatio, a drug for pulmonary hypertension, which contains the same ingredient as Viagra.
Viagra's label already mentioned hearing loss as a possibility, because a few cases were reported during initial testing of that drug. But given that hearing loss is a risk of advancing age and certain conditions, such as diabetes and heart disease, that can lead to impotence, it wasn't clear if the link was real.
That still isn't clear, said FDA ear nose and throat specialist Dr. Robert Boucher.
But in poring over FDA's database of possible drug reactions, what struck him was these 29 reports said the hearing loss occurred without hours to two days of taking one of the drugs.
"We don't know enough to say that it's ironclad caused by the drugs, but we see enough to say we can't ignore it either," he said.
The reports involve hearing loss in one ear, which in a third of cases was temporary.
FDA urged patients who experience any hearing problems — loss or ringing in the ears — to promptly call their doctors and stop taking the impotence drugs.
Friday, August 24, 2007
Viagra boosts feel-good "love" hormone: study
By Maggie Fox, Health and Science EditorThu Aug 23, 6:36 PM ET
Impotence drugs such as Viagra may do more than help men physically have sex -- they may also boost levels of a hormone linked with feelings of love, U.S. researchers reported on Thursday.
Viagra, known generically as sildenafil, raised levels of the hormone oxytocin in rats, the team at the University of Wisconsin-Madison said in a report published in the Journal of Physiology.
This hormone is involved in nursing and childbirth but also in orgasm and feelings of sexual pleasure.
And it seems Viagra and related drugs act on the part of the brain that controls release of oxytocin, said Wisconsin physiology professor Meyer Jackson.
"This is one piece in a puzzle in which many pieces are still not available," Jackson said in a statement. "But it raises the possibility that erectile dysfunction drugs could be doing more than just affecting erectile dysfunction."
Viagra, made by Pfizer Inc., is an inhibitor of an enzyme called phosphodiesterase type 5. Related drugs such as Eli Lilly and Co.'s Cialis, known generically as tadalafil, and Levitra or vardenafil, sold by GlaxoSmithKline, Bayer AG and Schering-Plough, are also PDE-5 inhibitors.
They block this enzyme, which in turn breaks down other compounds. This increases blood flow in the muscles but it also affects a brain structure known as the posterior pituitary.
This, in turn, boosts oxytocin, at least in the rats. It probably does the same thing in people, Jackson said.
"It does the same thing it does in smooth muscle -- instead of (levels) coming down in a minute or two, they stay up a little longer," Jackson said in a telephone interview.
Oxytocin was known for years to be involved in labor and it is the hormone that causes the "let-down" of milk in breastfeeding babies. Only in recent decades has it been found to have a function in men -- in sexual arousal and function.
This could suggest other uses for Viagra and related drugs, Jackson said -- perhaps promoting social bonding.
"What I hope is that people read our paper who can test these ideas in animals and humans," Jackson said.
"I hope that this doesn't cause some wild orgy of inappropriate recreational use."
Some groups have complained that people use the impotence drugs for fun, instead of using them as prescribed for sexual dysfunction caused by low blood flow to the genitals.
The drugs can cause fatal side effects if used with certain other drugs, and some studies also suggest they may affect the eyes in some patients, so doctors stress they are not for casual use.
By Maggie Fox, Health and Science EditorThu Aug 23, 6:36 PM ET
Impotence drugs such as Viagra may do more than help men physically have sex -- they may also boost levels of a hormone linked with feelings of love, U.S. researchers reported on Thursday.
Viagra, known generically as sildenafil, raised levels of the hormone oxytocin in rats, the team at the University of Wisconsin-Madison said in a report published in the Journal of Physiology.
This hormone is involved in nursing and childbirth but also in orgasm and feelings of sexual pleasure.
And it seems Viagra and related drugs act on the part of the brain that controls release of oxytocin, said Wisconsin physiology professor Meyer Jackson.
"This is one piece in a puzzle in which many pieces are still not available," Jackson said in a statement. "But it raises the possibility that erectile dysfunction drugs could be doing more than just affecting erectile dysfunction."
Viagra, made by Pfizer Inc., is an inhibitor of an enzyme called phosphodiesterase type 5. Related drugs such as Eli Lilly and Co.'s Cialis, known generically as tadalafil, and Levitra or vardenafil, sold by GlaxoSmithKline, Bayer AG and Schering-Plough, are also PDE-5 inhibitors.
They block this enzyme, which in turn breaks down other compounds. This increases blood flow in the muscles but it also affects a brain structure known as the posterior pituitary.
This, in turn, boosts oxytocin, at least in the rats. It probably does the same thing in people, Jackson said.
"It does the same thing it does in smooth muscle -- instead of (levels) coming down in a minute or two, they stay up a little longer," Jackson said in a telephone interview.
Oxytocin was known for years to be involved in labor and it is the hormone that causes the "let-down" of milk in breastfeeding babies. Only in recent decades has it been found to have a function in men -- in sexual arousal and function.
This could suggest other uses for Viagra and related drugs, Jackson said -- perhaps promoting social bonding.
"What I hope is that people read our paper who can test these ideas in animals and humans," Jackson said.
"I hope that this doesn't cause some wild orgy of inappropriate recreational use."
Some groups have complained that people use the impotence drugs for fun, instead of using them as prescribed for sexual dysfunction caused by low blood flow to the genitals.
The drugs can cause fatal side effects if used with certain other drugs, and some studies also suggest they may affect the eyes in some patients, so doctors stress they are not for casual use.
Friday, July 13, 2007
Sildenafil Boosts the Heart's Performance, Too
EDMONTON, Alberta, July 12 -- Phosphodiesterase type 5 (PDE5) drugs, such as sildenafil (Viagra), may improve right ventricular contractility in hearts with right ventricular hypertrophy, an unexpected benefit that looks promising for treatment of right ventricular heart failure.
Although it was thought that PDE5 was not expressed in the heart, Evangelos D. Michelakis, M.D., of the University of Alberta, and colleagues discovered that levels of the protein were high in diseased right ventricles of human hearts.
Testing PDE5 inhibition in rats with right ventricular hypertrophy, they found it improved right ventricle contractility and decreased afterload without significantly affecting systemic hemodynamics, they reported online in the journal Circulation.
Because there are no treatments available for patients with a failing right ventricle, they said, "our findings might have direct implications for the growing patient population with right ventricle dysfunction, including patients with pulmonary arterial hypertension, chronic thromboembolic disease, or congenital heart disease, and those after lung transplantation."
The researchers examined cardiac expression of PDE5 in hypertrophied right ventricles using human heart samples from biopsy or surgical resection from nine patients.
Specimens were from seven patients with right ventricle hypertrophy, one patient with left ventricle hypertrophy but a normal right ventricle, and one patient with normal left and right ventricles.
In tissue from normal human left and right ventricles, as expected from previous studies, the investigators found PDE5 expressed only in the coronary artery media and not in the myocardium.
But in all the hypertrophied right ventricles, PDE5 was markedly upregulated on immunohistochemistry. The difference was confirmed in a normal and a hypertrophied sample with an immunoblot.
The same pattern was seen in tissue from the patient with a hypertrophied left ventricle but normal right ventricle. PDE5 expression was upregulated only in the left ventricle myocardium.
This "suggests that the PDE5 upregulation is restricted only to the pressure-overloaded chamber and is likely not induced by circulating factors," the researchers wrote.
Because right ventricle hypertrophy patients do not have PDE5 expressed in the left ventricle, "PDE5 inhibition should not affect the left ventricle myocardium," the researchers noted. "In that sense, PDE5 inhibitors are truly right ventricle hypertrophy chamber specific."
Likewise, the researchers found significantly higher levels of PDE5 messenger RNA in the damaged right ventricle myocardium than in normal tissue. Levels were similar between groups in the coronary arteries.
The researchers reproduced these results in a rat model of pulmonary arterial hypertension and right ventricular hypertrophy produced by intraperitoneal injection of monocrotaline.
To see if their findings would be physiologically significant, Dr. Michelakis and colleagues mimicked clinical conditions by feeding sildenafil to rats with normal hearts and those with right ventricle hypertrophy.
To exclude confounding factors, the researchers looked at right ventricle contractility while recording right ventricle pressure, occluding the pulmonary artery afterload, and keeping the preload constant in an isolated perfused heart preparation.
Contractile pressure did not change in hearts from normal sildenafil-treated rats compared with nontreated controls. But, hypertrophied right ventricles from sildenafil-treated rats with had a significant increase in baseline developed pressure and maximum rate of change in right ventricular pressure (dP/dt) compared with untreated controls with right ventricle hypertrophy in the isolated perfused heart model.
Myocardial cell shortening showed the same improvement in contractility with PDE5 inhibition.
Further experiments in human heart tissue showed that sildenafil increased cyclic guanosine monophosphate (cGMP) levels and cyclic adenosine monophosphate (cAMP) only in hypertrophied right ventricle tissue but not in normal tissue.
The researchers cautioned that most patients in the study did not have overt right ventricular failure nor did the rats, so the results cannot be extrapolated for patients with advanced disease or dilated or thin-walled right ventricles.
Also, they said, "more work is needed to study the long-term effect of PDE5 inhibitors in both compensated and decompensated right ventricular disease."
Nevertheless, they concluded, "our findings have immediate clinical applications. PDE5 inhibition might be a new means of enhancing right ventricular function, which has repeatedly been shown to be a critical predictor of functional status in many cardiovascular diseases."
Dr. Michelakis reported receiving consultant fees from Pfizer and grants from the Canadian Institutes of Health Research, Alberta Heart and Stroke Foundation, Alberta Heritage Foundation for Medical Research, Canadian Foundation for Innovation, and Canada Research Chairs program. Another researcher was funded by the Canadian Institutes of Health Research, Alberta Heritage Foundation for Medical Research, and University of Alberta.Primary source: CirculationSource reference: Nagendran J, et al "Phosphodiesterase Type 5 Is Highly Expressed in the Hypertrophied Human Right Ventricle, and Acute Inhibition of Phosphodiesterase Type 5 Improves Contractility" Circulation. 2007; 116: DOI:10.1161/CIRCULATIONAHA.106.655266.
EDMONTON, Alberta, July 12 -- Phosphodiesterase type 5 (PDE5) drugs, such as sildenafil (Viagra), may improve right ventricular contractility in hearts with right ventricular hypertrophy, an unexpected benefit that looks promising for treatment of right ventricular heart failure.
Although it was thought that PDE5 was not expressed in the heart, Evangelos D. Michelakis, M.D., of the University of Alberta, and colleagues discovered that levels of the protein were high in diseased right ventricles of human hearts.
Testing PDE5 inhibition in rats with right ventricular hypertrophy, they found it improved right ventricle contractility and decreased afterload without significantly affecting systemic hemodynamics, they reported online in the journal Circulation.
Because there are no treatments available for patients with a failing right ventricle, they said, "our findings might have direct implications for the growing patient population with right ventricle dysfunction, including patients with pulmonary arterial hypertension, chronic thromboembolic disease, or congenital heart disease, and those after lung transplantation."
The researchers examined cardiac expression of PDE5 in hypertrophied right ventricles using human heart samples from biopsy or surgical resection from nine patients.
Specimens were from seven patients with right ventricle hypertrophy, one patient with left ventricle hypertrophy but a normal right ventricle, and one patient with normal left and right ventricles.
In tissue from normal human left and right ventricles, as expected from previous studies, the investigators found PDE5 expressed only in the coronary artery media and not in the myocardium.
But in all the hypertrophied right ventricles, PDE5 was markedly upregulated on immunohistochemistry. The difference was confirmed in a normal and a hypertrophied sample with an immunoblot.
The same pattern was seen in tissue from the patient with a hypertrophied left ventricle but normal right ventricle. PDE5 expression was upregulated only in the left ventricle myocardium.
This "suggests that the PDE5 upregulation is restricted only to the pressure-overloaded chamber and is likely not induced by circulating factors," the researchers wrote.
Because right ventricle hypertrophy patients do not have PDE5 expressed in the left ventricle, "PDE5 inhibition should not affect the left ventricle myocardium," the researchers noted. "In that sense, PDE5 inhibitors are truly right ventricle hypertrophy chamber specific."
Likewise, the researchers found significantly higher levels of PDE5 messenger RNA in the damaged right ventricle myocardium than in normal tissue. Levels were similar between groups in the coronary arteries.
The researchers reproduced these results in a rat model of pulmonary arterial hypertension and right ventricular hypertrophy produced by intraperitoneal injection of monocrotaline.
To see if their findings would be physiologically significant, Dr. Michelakis and colleagues mimicked clinical conditions by feeding sildenafil to rats with normal hearts and those with right ventricle hypertrophy.
To exclude confounding factors, the researchers looked at right ventricle contractility while recording right ventricle pressure, occluding the pulmonary artery afterload, and keeping the preload constant in an isolated perfused heart preparation.
Contractile pressure did not change in hearts from normal sildenafil-treated rats compared with nontreated controls. But, hypertrophied right ventricles from sildenafil-treated rats with had a significant increase in baseline developed pressure and maximum rate of change in right ventricular pressure (dP/dt) compared with untreated controls with right ventricle hypertrophy in the isolated perfused heart model.
Myocardial cell shortening showed the same improvement in contractility with PDE5 inhibition.
Further experiments in human heart tissue showed that sildenafil increased cyclic guanosine monophosphate (cGMP) levels and cyclic adenosine monophosphate (cAMP) only in hypertrophied right ventricle tissue but not in normal tissue.
The researchers cautioned that most patients in the study did not have overt right ventricular failure nor did the rats, so the results cannot be extrapolated for patients with advanced disease or dilated or thin-walled right ventricles.
Also, they said, "more work is needed to study the long-term effect of PDE5 inhibitors in both compensated and decompensated right ventricular disease."
Nevertheless, they concluded, "our findings have immediate clinical applications. PDE5 inhibition might be a new means of enhancing right ventricular function, which has repeatedly been shown to be a critical predictor of functional status in many cardiovascular diseases."
Dr. Michelakis reported receiving consultant fees from Pfizer and grants from the Canadian Institutes of Health Research, Alberta Heart and Stroke Foundation, Alberta Heritage Foundation for Medical Research, Canadian Foundation for Innovation, and Canada Research Chairs program. Another researcher was funded by the Canadian Institutes of Health Research, Alberta Heritage Foundation for Medical Research, and University of Alberta.Primary source: CirculationSource reference: Nagendran J, et al "Phosphodiesterase Type 5 Is Highly Expressed in the Hypertrophied Human Right Ventricle, and Acute Inhibition of Phosphodiesterase Type 5 Improves Contractility" Circulation. 2007; 116: DOI:10.1161/CIRCULATIONAHA.106.655266.
Friday, June 01, 2007
Lab study hints Viagra may harm male fertility
Laboratory studies conducted at Queen's University Belfast, UK suggest that taking the erectile dysfunction drug Viagra may adversely affect sperm function and possibly male fertility.
Recreational users of Viagra need to be informed of the drug's potentially harmful effects on sperm function, the investigators say.
In their experiments, Dr. David R. J. Glenn and colleagues observed that exposure of cultured sperm to Viagra, compared to no exposure, led to a "sustained enhancement of motility," both in numbers of progressively motile sperm and their velocity.
However, exposure to Viagra -- at concentrations equivalent to the average maximum total blood concentration present 30 minutes after a single oral dose of 100 milligrams -- also caused a premature "acrosome reaction." Acrosomes are structures that cover the head of the sperm and contain a variety of enzymes that help the sperm penetrate the outer membrane of the egg.
That Viagra may induce early activation of the acrosome reaction has "important clinical implications because sperm that acrosome-react before contact with the oocyte are incapable of fertilization," the researchers note in the journal Fertility and Sterility.
"Given that the majority of sperm acrosome react on exposure to (Viagra), the drug may cause significant impairment to their fertilizing potential," they write.
This is a concern, Glenn and colleagues say, given that Viagra and other like-drugs are widely available on the Internet and are increasingly being used "recreationally" by young healthy men of reproductive age as sexual enhancers -- not just by older men who have erectile dysfunction.
SOURCE: Fertility and Sterility, May 2007.
Recreational users of Viagra need to be informed of the drug's potentially harmful effects on sperm function, the investigators say.
In their experiments, Dr. David R. J. Glenn and colleagues observed that exposure of cultured sperm to Viagra, compared to no exposure, led to a "sustained enhancement of motility," both in numbers of progressively motile sperm and their velocity.
However, exposure to Viagra -- at concentrations equivalent to the average maximum total blood concentration present 30 minutes after a single oral dose of 100 milligrams -- also caused a premature "acrosome reaction." Acrosomes are structures that cover the head of the sperm and contain a variety of enzymes that help the sperm penetrate the outer membrane of the egg.
That Viagra may induce early activation of the acrosome reaction has "important clinical implications because sperm that acrosome-react before contact with the oocyte are incapable of fertilization," the researchers note in the journal Fertility and Sterility.
"Given that the majority of sperm acrosome react on exposure to (Viagra), the drug may cause significant impairment to their fertilizing potential," they write.
This is a concern, Glenn and colleagues say, given that Viagra and other like-drugs are widely available on the Internet and are increasingly being used "recreationally" by young healthy men of reproductive age as sexual enhancers -- not just by older men who have erectile dysfunction.
SOURCE: Fertility and Sterility, May 2007.
Tuesday, May 22, 2007
Viagra helps jet-lagged hamsters, maybe humans, too: study
A shot of Viagra may one day help shift workers and flight crews recover their normal sleep cycles, according to a study on hamsters released Monday.
Viagra, otherwise known as sildenafil, could be "useful in other circadian disorders that involve poor synchronization with the environment, including delayed sleep-phase syndrome and adaptation to changing light schedules," said the study published in the Proceedings of the National Academy of Sciences.
Researchers at Argentina's National University at Quilmes in Buenos Aires injected male hamsters with small amounts of the drug and switched off the lights six hours earlier, which researchers compared with taking an eastbound flight, as would occur from the Americas to Europe.
Hamsters receiving a dose of the drug adapted 20-50 percent more quickly to the new schedule than hamsters receiving a placebo, the study said, as judged by how quickly they resumed running on their exercise wheels.
However, the trick worked only when moving the schedule ahead, as on the so-called eastbound change, without helping hamsters shifted six hours in the other direction.
Mammals, such as humans and hamsters, regulate their circadian rhythms by releasing chemicals in the brain, such as melatonin. However, repeated injections of melatonin are required to achieve a shift in sleep-wake cycles, compared with the single-dose effectiveness of sildenafil.
The drug interferes with an enzyme that reduces the levels of cyclic guanine monophosphate in the brain, which helps regulate circadian rhythm, the body's inner clock.
Viagra, otherwise known as sildenafil, could be "useful in other circadian disorders that involve poor synchronization with the environment, including delayed sleep-phase syndrome and adaptation to changing light schedules," said the study published in the Proceedings of the National Academy of Sciences.
Researchers at Argentina's National University at Quilmes in Buenos Aires injected male hamsters with small amounts of the drug and switched off the lights six hours earlier, which researchers compared with taking an eastbound flight, as would occur from the Americas to Europe.
Hamsters receiving a dose of the drug adapted 20-50 percent more quickly to the new schedule than hamsters receiving a placebo, the study said, as judged by how quickly they resumed running on their exercise wheels.
However, the trick worked only when moving the schedule ahead, as on the so-called eastbound change, without helping hamsters shifted six hours in the other direction.
Mammals, such as humans and hamsters, regulate their circadian rhythms by releasing chemicals in the brain, such as melatonin. However, repeated injections of melatonin are required to achieve a shift in sleep-wake cycles, compared with the single-dose effectiveness of sildenafil.
The drug interferes with an enzyme that reduces the levels of cyclic guanine monophosphate in the brain, which helps regulate circadian rhythm, the body's inner clock.
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