Viagra/Sildenafil Effects & Side Effects: Complete Research

Viagra was the first and the most popular medication to reliably, safely and effectively treat erectile dysfunction symptoms.

Viagra is blue, film coated tablets and comes in 25mg, 50mg and 100 mg strengths. It’s active ingredient is “sildenafil citrate’.

In this article we study the actual effects and results of taking the medication and we do this by exploring clinical trial results and simplifying them with interactive graphs and simple explanations. We hope this should enable the patient to better understand the effects of the medication.

We have chosen studies that offer the clear insights on the important parameters that would be of interest to men suffering from sexual dysfunction.

How Viagra works?

The erection in the penis during arousal and sexual stimulation, is largely dependent on the release of nitric oxide, which activates guanylate cyclase enzyme that produces higher levels of cGMP into the corpus cavernosum (smooth muscle in the penis). This causes the smooth muscle to relax and allow inflow of blood, thereby causing erection.

Another enzyme, phosphodiesterase type 5 (PDE5), degrades cGMP and therefore decreases the erection. Viagra is an inhibitor of this enzyme that maintains the level of cGMP, , thereby enhancing the effects of existing NO (released during arousal) and maintaining the relaxed state of the smooth muscles in the penis. That’s how Viagra helps to produce and maintain erections.

How Long Does Viagra take to work? How long it lasts?

For most people Viagra starts working within 30 to 60 minutes and it’s peak effects usually occurs at the 1 hour mark. The effect lasts about 6 to 8 hours, although a negligible amount of the drug stays in the body for more than 24 hours.

The figure above is a graph submitted by Pfizer to the FDA, depicting the plasma concentrations of sildenafil over time.

How Viagra Helps Men with Differing Severity of ED

Multiple clinical trials were conducted before Viagra was approved by the FDA. We will focus our attention on the results of a more comprehensive set of 5 clinical trials that evaluated men with varying degree of erectile dysfunction (severe to mild) to see how they respond to Viagra.

The primary endpoint of these clinical trials was the International IIEF (International Index of Erectile Function), a survey with 15 questions answered by the participants.

One of the questions(and the most important) asked was if the patients were able to achieve erection and also were then able to maintain it after penetration.

The participants were evaluated before starting the treatment with Viagra or placebo. The baseline scores were categorized as follow

Then the patients were asked to take a pill of Viagra before intercourse for 4 weeks, and asked to answer the questions of the IIEF at the end (EndScore).

The results are depicted in the graph below.

This graph shows that the effect of Viagra depends on the BaseScore of the patient.

While on sildenafil, the men on those different BaseScore groups achieved different EndScore values as depicted by the bars. Hover over the bars to see the percentage of men who reached different scores while taking Sildenafil.

The men with severest ED and score 0 at baseline (before treatment), had improved scores of 5(30%), 4(9%), 3 (7%), 2(9%), 1 (19%), 0(26%) while on Sildenafil.  This means almost 40% of men with severest ED were able to achieve excellent erectile function(score 4 and 5) and 74% achieved meaningful improvement while on sildenafil. Only 26% could not achieve any improvement.

Men with moderate ED and a baseline score 3,  had improved scores of 5(56%), 4(24%), 3 (8%), 2(7%), 1 (3%), 0(2%) while on sildenafil. This means almost 80% of men with moderate ED were able to achieve excellent erectile function. Only 20% could not achieve any improvement.

Impact Of Viagra On Erection Quality of Men With Mild ED

Mild erectile dysfunction is a condition that is very prevalent among younger men.  It is also postulated that majority of men who use Viagra recreationally, experience mild ED or are borderline ED. So we chose this study that measures the Sildenafil’s effects on penile hardness in men who experience mild ED.

For the purpose of this study conducted by Pfizer, only men who experience mild ED were considered. Another inclusion criteria was sexual dissatisfaction.

Patients were divided into groups and it was a double blind study (patients did not know if the pill was placebo Viagra).

The graph above is self explanatory. Men who took sildenafil reported more number of “completely hard” erections.

The men in the above study had only mild ED and it is apparent that their main issue was not being able to get “fully hard” without medication.

With Viagra, many such men who at baseline were primarily in the “hard enough for penetration but not fully hard” category were able to get “completely hard”.

When the dose was optimized (people whose doses were bumped up or down based on response and side effects), the response was further improved. Most men with mild ED were able to achieve “completely hard” erections.

How Viagra Works Impacts Orgasmic Function & Sexual Desire in Men

For this purpose we reference Pfizer’s study where ‘patient reported orgasms’ and ‘sexual desire’ were measured along with other parameters. We narrow our focus to just orgasms and sexual desire. Results are depicted in the chart below.

Althought Pfizer does not claim that Viagra/Sildenafil can enhance orgasms in men with good erectile function, it certainly looks like it can enhance orgasms and even sexual desire in men who have some form of ED. The men in this study reported about 20% better orgasm function and sexual desire on Viagra in the study conducted by Pfizer.

How Viagra Works For ED in Men with Diabetes

An important clinical study published by The American Diabetes Association showed that Sildenafil significantly improved the number of intercourse attempts in diabetic patients suffering from varying severities of ED.

In Mild/Moderate ED patients the efficacy though is much more impressive with most patients able to successfully penetrate their partners.

How Sildenafil Helps Erectile Function in Men After Radical Prostatectomy

Radical prostatectomy (RP) is a common surgical treatment of localized prostate cancer. Unfortunately, the surgery carries a 60% to 70% risk of postoperative ED. A nerve-sparing radical prostatectomy (NSRP) may offer a greater likelihood of postoperative recovery of erectile function, but many men actually wait more than 2 years before a satisfactorily recovery of erectile function, and some don’t ever recover much sexual potency.

A study conducted by the Department of Urology, University Hospital Schleswig-Holstein, Campus Kiel, Germany; evaluated a daily low dose Viagra 25 mg after NSRP. Out of 45 men who had NSRP, 41 had some form of erectile function on the night after catheter removal and were included in the study: 23 of these patients were given low dose sildenafil 25 mg and the rest were not on Sildenafil or on any PDE5 inhibitors.

Before RP the base IIEF erection scores were a good 20.8 and 21.2 in the 2 groups. After RP it fell to around 3 in both groups. In the subsequent 52 weeks, the IIEF erections scores were evaluated and the group that was on daily low dose Sildenafil 25 mg showed much better progress compared to the control group.

The Sildenafil group reached a IIEF mean erection score of 14.1 compared to the control group which managed a mean erections core of only 9.1. Daily dose of Sildenafil certainly makes a marked positive difference in returning the erectile function of men who undergo nerve sparring radical prostatectomy.

How Sildenafil Helps Erectile Function in Men With Multiple Sclerosis

Erectile dysfunction begins to usually occur in multiple sclerosis patients at a time when the patient starting to experience more severe symptoms like impaired mobility that interfere with many aspects occupational and social life.

In a randomized double blind-study 218 multiple sclerosis patients were given placebo or sildenafil.

The patients started on 50 mg dose of sildenafil or matching placebo which was then optimized to 100 or 25 mg based on treatment response and tolerability.

The sildenafil group ended up with 64% receiving 100 mg dose, 32% receiving 50 mg dose, and 4% the 25 mg dose. Results are depicted in the graph below.

0: No Activity, 1: Almost Never/Never, 2: Few Times, 3: Sometimes, 4: Most Times, 5: Almost Always/Always

The results are very encouraging indeed. The average response score to questions about “achieving erections” and “maintaining erections” were about 4.0(Most Times) on Sildenafil compared to baseline mean score of 1.9 and 1.5.

Additionally, the overall improvement in erections were reported by 90% of men and in the patients who reported “Improved Erections”, 92% reported improvement in the ability to have satisfactory sexual activity. It appears multiple sclerosis patients respond very well to Viagra/Sildenafil.

How Sildenafil Helps Erectile Function Among Chronic Hemodialysis Patients

Erectile dysfunction is pretty common among end-stage renal disease (ESRD) patients who undergo hemodialysis (HD). In an Iranian Study, atotal of 27 patients who underwent chronic HD were given placebo or sildenafil and asked erectile function questions as per IIEF questionaire depicted in the table below.

The possible answers are given below
0: No Activity, 1: Almost Never/Never, 2: Few Times, 3: Sometimes, 4: Most Times, 5: Almost Always/Always

Results are depicted in the graph above. The placebo scores are a little improved and may have effect on important psychological factors such as depression in HD patients. However, sildenafil had a much better positive effect than placebo in improving the IIEF score among hemodialysis patients.

Viagra Side Effects

Viagra Interactions FAQ

Can You take Viagra With Food

Sildenafil can be taken with or without food, but it is best taken on an empty stomach before food. Of note, pharmacokinetic studies have shown that a high fat meal is associated with a 29% decrease of the max Viagra plasma concentration, and a delay of 1 hour to reach the max concentration, as compared to men who were fasting.

The relative bioavailability of sildenafil in men who were fed a high-fat meal was 89% (90% CI: 84–94) of that of men who were fasting.

Does grapefruit juice enhance the effects of Viagra

Grapefruit juice is known to enhance Viagra bioavailability (fraction of absorbed drug that reaches the systemic circulation) but can also delay absorption. The resulting boost in blood levels may enhance the effect on erection but could also trigger an increase in the risk of adverse effects, such as flushing, headaches, low blood pressure.

Seville orange also causes a similar effect.

Can we take pomegranate juice and Viagra together

Pomegranate juice is know to majorly enhance the effects of Viagra, to a point where it is advisable not to consume both together. It can also make the absorption and elimination of the drug unpredictable.

Studies have revealed that the antioxidant properties of Pomegranate juice enhances the bioavailability of endothelial nitric oxide levels. In addition, a distinct synergistic effect has been noticed between sildenafil and pomegranate juice, which could cause priapism (persistant erection that doesn’t subside) in some men.

Viagra and Alcohol Interaction

Alcohol can inhibit and interfere with the positive effects of Viagra on penile erection. Not only that, it can also accentuate the common side effects associated with Viagra.

Drinking alcohol can lead to reduced testosterone secretion. It is also widely thought to affect the nerves in the penis. Many men with normal erectile function report reduced penile hardness when on alcohol.

A glass or two may be okay for most people. but it is probablybest to avoid alcohol if you plan to take sildenafil or any PDE5 inhibitors.

On the flip side, certain animal studies have revealed a possible positive effect associated with sildenafil and alcohol.  PDE5 inhibitors like sildenafil could help prevent some of the unwanted gastric side effects of alcohol and infact may reduce mucosal injury induced by chronic alcoholism.

Can you take Viagra if you have asthma?

Viagra has no negative interaction with Asthma. Infact some case studies have shown moderate improvement in lung function parameters in asthma patients taking 50mg of sildenafil; which is thought to be attributed to the enhanced dilatory effect induced by higher levels of cGMP on the smooth muscle of blood vessels supplying the airway.

Can you take Viagra with statins like Atorvastatin?

Statins like atorvastatin could actually help erections in men who don’t otherwise respond to sildenafil.

A Clinical study published in the International Journal of Impotence Research has revealed that men with hypercholesterolemia(LDL) cholesterol >120 mg per 100 m) who don’t respond favorably to sildenafil, are able to achieve better erections when their LDL cholesterol is reduced while on atorvastatin. However, they were unable to reach normal erectile function.

Can you take viagra with antidepressants?

Yes. The Journal of the American Medical Association has found in a study that atleast 50% of the men who took sildenafil in addition to their prescribed antidepressants had a marked improvement in erectile function.

This is of significance as it is estimated that 30-70% of men who take SSRI antidepressants experience some form of sexual dysfunction.

Can you take viagra if you have high blood pressure?

Viagra causes a mild drop(around 5%) in blood pressure. If you are on a blood pressure medication, it is usually safe to take it with viagra. It may not be a bad idea to take a slightly milder dose on the day you take Viagra, but talk to your doctor.

Viagra and body temperature

Oral sildenafil was found to significantly increase skin temperature from a mean baseline of 28°C  to 29.3°C 50 min after taking sildenafil. When the dose was bumped to 100 mg, sildenafil caused a higher increase in skin temperature from a mean of 28.9°C to 30.7°C.

Viagra and blue vision

In the various clinical trials conducted by Pfizer, a particular side effect is abnormal vision which is found to be experienced by 11% of men taking 100mg dose and 2% of men taking 50mg dose. Blurred vision, changes to colour perception(especially blue-coloured vision), sensitivity to light and reduced eyesight are the complaints.

The vision changes are almost always temporary and goes away in few hours, but in very rare cases it might persist for upto 3 weeks.

Men who have retinitis pigmentosa gene mutation are considered to be at increased risk of eye problems. For such men it maybe best to tread with caution , consult a doctor and cautiously adopt the lower dose.

Does caffeine drinks like Red Bull affect Viagra?

There is a noticeable pharmaco kinetic interaction between sildenafil and caffeine drink RED BULL^® when administered concomitantly in rats.  Mean plasma concentrations were much reduced making sildenafil less effective.

Does Viagra dehydrate you?

Yes Viagra can cause some dehydration. Sildenafil being a mild diuretic, can cause your body to expel water while it is present in significant concentrations in the body (upto 8 hours).

Can you take Viagra and Metformin together?

Yes. Infact a popular study revealed that insulin resistant men who were poor responders to sildenafil showed better response to Viagra when on metformin. When the men in the study were given daily metformin (1700 mg in two doses), erection score (IIEF) increased by 19% by 2nd month and by 38% by 4th month.

Role of Viagra in Alzheimer’s and Dementia patients

Single dose of 50 mg sildenafil enhances the cerebral hemodynamic function and improves cerebral oxygen metabolism in patients suffering from Alzheimer’s Disease.[Research Study]

Clinical trials are underway to further strengthen the preliminary findings that sildenafil could help prevent onset of dementia by enhancing blood flow to the brain.

Viagra and Exercise

A Stanford University clinical study that was published back in 2006 in the Journal of Applied Physiology postulated that in certain high altitude oxygen deficient conditions , sildenafil actually lowered times by mean times by 15% in 10 trained male cyclists who performed 3.7-mile time trials.

But the results were significant but not uniformly consistent.  Four of the ten cyclists who responded strongly to sildenafil and six cyclists showed very little improvement in performance. Among the four strong responders times improved by as much as 39% compared to sildenafil-free performance.

Viagra’s reputation as a blood flow increasing drug has also prompted some athletes to even consider it as a pre-workout drug, especially since nitric oxide is a key ingredient in many bopdy building supplements. It is however worth mentioning that these perceived benefits are unclear.

Additionally, clinical trials have proven that men with coronary artery disease who were able to exercise, sildenafil did not have a detrimental effect on the ability to exercise and there was no significant exercise-induced regional wall motion abnormalities or arrhythmias. In the patients who are not on nitrates and who have a history of stable coronary artery disease, sildenafil did not increase the risk of myocardial ischemia.

Can Viagra cause seizures

Very rarely, maybe. Sildenafil has caused seizures in men who have no history of epilepsy, according to a study in the British Medical Journal. Nevertheless, a clear correlation between the seizures and the effects of the medication was not found.

In a study on rats it was concluded that the NO–cGMP pathway could play a role in the increased susceptibility to seizures when the rats were fed very high doses of sildenafil (around 10-15 times the equivalent per kg dose in humans).

Does taking Viagra affect fertility

Less than 0.001% of the administered sildenafil dose appears in the patients’ semen. A study funded by Pfizer Central Research found that 100 mg dose of Sildenafil did not have a statistically significant effect on sperm count, sperm density, motility.  It did not increase the percentage of abnormal sperm forms or decrease the percentage of living sperm. Furthermore, it did not affect the viscosity or volume of the ejaculate. All sperm measures were within normal ranges when on sildenafil.

A much older study conducted in 2000 also indicated that sildenafil did not have any acute impact on sperm function.

In another interesting study which studied a very large group of 1317 men, postulated that Oral PDE5 inhibitors like sildenafil could actually modestly increase the sperm motility and also improve sperm morphology in infertile men.

On the other end of the spectrum is a test tube experiment conducted at Queen’s University in Belfast, wheerein sildenafil was manually added to sperm samples in the lab at levels that are normally found in blood plasma.

It was found that this triggered the acrosome reaction quicker and so could impair fertility levels. Acrosome reaction is the process that causes the head of the sperm to release certain digestive enzymes in order to break the exterior shell of the egg, so that it can enter and fertilise the egg.

However, John Dean, who is the secretary general of the European Society for Sexual Medicine has cautioned the findingsof the study stating that the lab results do not usually reflect what actually happens in the body.

In a small controlversial study on rats it was found that there was 33% lesser fertilization in the group treated with Sildenafil. This was however a very limited study to by any means ascertain the effects of sildenafil on fertility.

Most doctors do not restrict sildenafil prescriptions to men who are trying to father a child. Some consider the increased motility with sildenafil a postive factor for conception. A few though might limit the dose to 50mg.

Does Viagra boost testosterone?

When on sildenafil, men with erectile dysfunction and low baseline serum testosterone exhibited increased levels of serum testosterone which is thought to be due to its direct action on the testes.

Mean total and free testosterone increased significantly with oral sildenafil by 3.58 nmol/L (103 ng/dL; p < 0.001) and 110 pmol/L (31.7 pg/mL; p < 0.001;) respectively.

Does Viagra help BPH

Mechanical obstruction is the main cause BPH related lower urinary tract symptoms. This means that sildenafil should be able to help ease symptoms as it is known to enhance levels of cGMP in the prostate and bladder, thereby causing muscle cells to noticeably relax so that urine can pass through more easily.

In randomized clinical trials, sildenafil seems to ease lower urinary tract symptoms in men suffering from BPH.  In several studies involving more than 1000 men it is seen that lower urinary tract symptoms of varying severity improved and improvements were also seen in men with normal sexual function.

Can Viagra affect kidneys?

Sildenafil is in general safe with mild side effects. But in patients with an existing kidney disease higher doses could cause  complications.

The chances of kidney injury (Acute tubular necrosis) may be even greater if the drug is taken with nitrates. If you are taking sildenafil and have a history of kidney disease, it may be best to limit yourself to a milder dose and consume plenty of fluids so as to prevent or reduce the chances of a kidney injury.

If the renal impairment is severe, sildenafil clearance is reduced, resulting in approximately doubling of the sildenafil plasma concentrations in the blood.

Does Viagra/sildenafil cause liver damage?

Usually considered safe, however there are odd few cases that suggest that liver damage is a very rare adverse effect, but not a completely impossible event. It is also to be noted that new clinical study has postulated that blood flow is not positively or negatively affected by sildenafil in cirrhosis patients.