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PDE5 inhibitors typically include sildenafil, tadalafil, vardenafil, and
avanafil. They differ in how long before they take effect, in cost, and in their common side effects.

Phosphodiesterase type 5 (PDE5) inhibitors are a group of medications most commonly used to treat erectile dysfunction (ED). Their ability to improve symptoms of ED was discovered accidentally while researchers were examining their potential use for high blood pressure and angina.

ED is often considered the most common form of sexual dysfunction in men, and it becomes more common with age. It’s estimated that anywhere between 30 million to 50 million men in the United States deal with ED.

PDE5 inhibitors are often the first treatment option for people with ED caused by poor blood flow to the penis.

In this article, we break down the most common types of PDE5 inhibitors on the market. We also take a look at how they work, what they’re used for, and how much they cost.

ED can be caused by psychological or physiological factors. PDE5 inhibitors are only effective at treating ED caused by physiological factors.

Psychotherapy or counseling are treatment options for psychological cause of ED, such as stress or anxiety.

The four major types of PDE5 inhibitors available include:

Let’s take a look at each.

Sildenafil was the first extensively researched PDE5 inhibitor, and it was FDA-approved in 1998 under the name Viagra to treat ED in men. Sildenafil usually takes action within an hour. Like with other PDE5 inhibitors, you’ll only achieve an erection once sexually aroused.

How long it lasts

Viagra’s effects usually last about 4 hours but can last as long as 12 hours. It’s typically taken in doses between 25 to 100 milligrams (mg) per day.

Common side effects

Common side effects include:

Cost

The exact price of sildenafil varies based on where you buy it. Brand-name Viagra often sells for more than $50. However, sildenafil has been sold under its generic name since 2017. Generic brands are often a fraction of the price.

Tadalafil has been on the market since 2003 to treat ED. It usually takes effect within 20 minutes and should be taken at least half an hour before intercourse.

Tadalafil is also FDA-approved to treat benign prostate hyperplasia (BPH).

How long it lasts

Tadalafil has the longest action of any available PDE5 inhibitor at 24 to 36 hours. A typical daily dose varies from about 2.5 to 20 mg.

Common side effects

Common side effects include:

Cost

The cost of Cialis varies between pharmacies and depends on the strength of the medication. Larger 20-mg tablets cost upwards of $70. Like sildenafil, Cialis is also sold under its generic name (tadalafil) for a fraction of the price.

Vardenafil has been approved since 2003 for treating ED. It has the shortest onset of any PDE5 inhibitor and takes effect within 10 minutes.

How long it lasts

Vardenafil usually lasts for 5 to 7 hours but may last up to 12 hours. A typical dose of vardenafil is 5 to 20 mg per day.

Common side effects

Side effects include:

  • headaches
  • flushing
  • indigestion
  • nasal congestion
  • cold-like symptoms
  • vision problems

Cost

Staxyn tends to be cheaper than Levitra, and you can expect to pay upward of $40 per tablet. Generic brands are also available.

Avanafil is the newest PDE5 inhibitor on the market and has been available since 2012. It generally takes effect within 30 to 45 minutes.

How long it lasts

Avanafil has a longer duration of effect than vardenafil and sildenafil but shorter than tadalafil with a half-life of around 5 hours. Avanafil is typically taken in a dose of 50 to 200 mg per day.

Common side effects

Common side effects include:

  • headache
  • flushing
  • indigestion
  • nasal congestion
  • cold-like symptoms

Cost

Stendra generally sells for more than $70 per 100-mg tablet, but prices fluctuate between pharmacies. There are currently no generic brands of avanafil available in the United States.

PDE5 inhibitors have a vasodilating effect on the penis, meaning they help the blood vessels relax and increase blood flow.

The science behind an erection

The process of achieving an erection is complex. When you become sexually aroused, your parasympathetic nervous system becomes activated. This neural activity leads to a release of a molecule called nitric oxide (NO) that increases the production of another molecule called cyclic GMP.

Cyclic GMP relaxes the smooth muscles inside the blood vessels of your penis and increases blood flow by 20 to 40 times.

An enzyme called PDE5 breaks down cyclic GMP molecules and reverses the erection process. However, PDE5 inhibitors are similar in structure to cyclic GMP and bind to PDE5 to block this breakdown. This action enhances the action of NO and helps promote blood flow.

PDE5 inhibitors naturally occur in some herbs. These herbs are often sold in supplement form and marketed to treat ED or enhance male vitality.

The FDA warns against dietary supplements for treating ED because many of these products contain undisclosed ingredients that may be harmful. The safety and effectiveness of these supplements also hasn’t been adequately studied.

Epimedium (horny goat weed)

Epimedium, commonly referred to as horny goat weed, is a flowering plant native to Eastern Asia.

The name horny goat weed comes from a legend of a Chinese goat herder who observed increased sexual activity in his herd after they ate the leaves of this plant.

Horny goat weed’s active ingredient is called icariin. It’s been suggested that icariin may inhibit PDE5, increase NO production in the penis, and have a number of possible benefits for ED. However, there are no long-term toxicity studies and there are no clinical trials in humans.

Kaempferia parviflora (black ginger)

Kaempferia parviflora, also known as black ginger or Thai ginger, is a plant native to Thailand. Lab and animal studies have found that it may have moderate PDE5-inhibiting effects.

One small study with 13 participants found that it may improve some parameters of ED in men age 50 to 70, but more research is needed to fully understand its potential benefits.

Tribulus terrestris

Tribulus terrestris is a leafy plant that grows in Europe, Asia, and Africa. Research has found that natural alkaloids in the plant may have PDE5-inhibiting effects.

A 2017 clinical trial found that Tribulus terrestris was able to significantly improve erectile function in men age 18 to 65 with moderate erectile dysfunction, and that it was generally well-tolerated.

Malculra pomifera (osage orange)

Isoflavones from the Malculra pomifera plant may have PDE5-inhibiting effects. Research has found that derivatives of these isoflavones may be a potential lead for future PDE5-inhibitor development.

PDE5 inhibitors are a group of medications usually used to treat ED. These medications are effective for ED caused by physiological factors, such as poor circulation. However, they aren’t effective for treating ED caused by psychological factors, such as stress or anxiety.

Some herbs like horny goat weed also contain PDE5 inhibitors, but research hasn’t yet evaluated the effectiveness or safety of herbal supplements for treating ED.