Everything to Know About Cialis: Use, Effectiveness, and Safety

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Questions and Answers for Cialis (tadalafil)

Cialis is approved for the treatment of men who experience difficulty having and maintaining an erection (impotence).

Cialis works by enhancing the effects of one of the chemicals the body normally releases into the penis during sexual arousal. This allows an increase of blood flow into the penis. An erection is the result of an increase in blood flow into certain internal areas of the penis.

3. How is Cialis different from the currently approved products for erectile dysfunction (ED)?

Cialis is different from other currently approved products for ED in that it stays in the body longer. However, there were no studies that directly compared the clinical efficacy and safety of Cialis to other products.

Cialis is taken orally before sexual activity, not more than once daily. Cialis may be taken with or without food. In some patients, the dose strength and maximum frequency of use may be adjusted. For more detailed information consult with your health care provider.

5. Are there any side effects with Cialis?

As with any drug product, there may be side effects. The most commonly reported side effects in patients treated with Cialis during the testing of the product were:

Patients who get back pain and muscle aches usually get them 12 to 24 hours after taking Cialis and these usually go away by themselves within 48 hours. A small number of patients taking Cialis also reported abnormal vision.

6. What important information should you know about Cialis?

CIALIS can cause your blood pressure to drop suddenly to an unsafe level if it is taken with any nitrate medication. You could get dizzy, faint or have a heart attack or stroke.
Tell your healthcare provider that you take Cialis. If you need emergency medical care for a heart problem, it will be important for your health care provider to know when you last took Cialis.
After taking a single tablet, some of the active ingredient of Cialis remains in your body for more than 2 days. The active ingredient can remain longer if you have problems with your kidneys or liver, or you are taking certain other medications.
Physicians should discuss with patients the potential for CIALIS to augment the blood-pressure-lowering effect of alpha-blockers and antihypertensive medications.

7. What should I talk to my doctor about when considering if Cialis is right for me?

Because sexual activity can increase the work of the heart, your doctors should talk to you about your heart’s general condition and if Cialis is right for you. Patients who have a condition called “left ventricular outlet obstruction” from valvular problems or heart muscle enlargement may get side effects such as fainting or light-headedness. Because patients with recent heart attacks or stroke, heart pains (angina), heart failure, uncontrolled blood pressure or uncontrolled irregular heart beats, severe liver disease, and retinal eye problems were not studied with Cialis, Cialis is not recommended for these patients. There may be rare occurrences of priapism or painful, prolonged erections. This is a serious condition that requires immediate medical attention. Patients should seek prompt medical attention if their erection lasts longer than four hours.

8. Who should not take Cialis?

Cialis should not be used by patients taking nitrates (such as nitroglycerin tablets or patches) because the combination of these with Cialis could significantly lower blood pressure and lead to fainting or even death in some men.

9. Can Cialis be used with other treatments for impotence?

The safety and effectiveness of Cialis when used with other treatments for impotence has not been studied. Combined use could lead to additional lowering of blood pressure, possibly to unsafe levels. Therefore the use of such treatments in combination with Cialis is not recommended.

10. What if I am taking other drugs?

Always discuss with your health care practitioner ALL of the medications you are taking (prescription and over-the-counter) that way, you can receive the best advice for your own situation. Cialis is not recommended for people taking any form of nitroglycerin because the combination may lower blood pressure to an unsafe level.

11. How will Cialis be supplied?

12. Will Cialis be prescription or OTC (over-the-counter)?

13. When will Cialis be available to pharmacies?

FDA has no control over when products are available in pharmacies after FDA approval for marketing. The decision of availability is completely up to the company marketing the product. For further information contact your pharmacist or Eli Lilly and Company directly.

14. How can I report a serious side effect with Cialis to FDA?

FDA encourages anyone aware of a serious side effect, including consumers or patients, to make a MedWatch report.

You can report an adverse event either online, by regular mail or by fax, using the contact information at the bottom of this page.

Related Information

Everything to Know About Cialis: Use, Effectiveness, and Safety

Cialis is a medication approved by the Food and Drug Administration (FDA) often used to treat erectile dysfunction (ED) and benign prostatic hyperplasia (BPH) in men. It is taken as an oral tablet either as a low-dose daily medication or as a higher-dose “on-demand” medication.

Cialis is the brand name for tadalafil, a medication that is also used to treat ED. Tadalafil is in a class of drugs called phosphodiesterase-5 (PDE5) inhibitors and is available in a generic form often called generic Cialis. Tadalafil has been on the market since 2018 and has the same primary ingredient as Cialis and is generally just as effective — the only difference is the price.

Pros

lasts up to 36 hours for some people, which is longer than Viagra
can be taken as needed or on a daily, regular basis
daily use allows for a more spontaneous sex life
can be taken with or without food
helps maintain erections longer
some users say their orgasms are more intense

Cons

can cause headaches and muscle aches
must be swallowed whole
can cause indigestion
can make you appear flushed
not available over-the-counter (OTC)

Cialis works by increasing blood flow to the penis to help a person get and maintain an erection. It also blocks the PDE5 enzyme, which enhances the effects of nitric oxide (NO). NO activates a series of chemical reactions that increase blood flow to the penis by relaxing blood vessels.

Cialis also relaxes the smooth muscle in the prostate and the bladder. It doesn’t protect against sexually transmitted infections (STIs).

PDE5 inhibitors work by binding to an enzyme called PDE5, which normally breaks down cyclic guanosine monophosphate (GMP) molecules.

Cyclic GMP helps relax the smooth muscles within the blood vessels of your penis. This process significantly increases blood flow to these blood vessels, leading to an erection.

Cialis and other PDE5 inhibitors don’t cure ED or increase libido. Physical and psychological arousal is still necessary for the medications to help achieve and sustain an erection.

When sexually aroused, the parasympathetic nervous system activates, triggering the release of NO. The increased presence of NO is what increases the production of cyclic GMP.

ED

Cialis is primarily used to treat ED. Guidelines unanimously agree in considering PDE5 inhibitors as first line treatments for ED as long as it doesn’t interfere with your other medications or cause you to have any severe side effects.

BPH

Cialis and generic tadalafil are also prescribed to treat the symptoms of BPH, also known as an enlarged prostate.

Pulmonary arterial hypertension

Tadalafil is also FDA approved to treat pulmonary arterial hypertension (PAH), which is high blood pressure affecting the arteries in the lungs. The typical dose for PAH is two 20 milligram tablets (40 mg) taken daily.

Adcirca is the brand name for tadalafil and is used to treat PAH.

Obtaining Cialis

Cialis and generic tadalafil are available with a prescription only. There is no OTC version, though there have been efforts in recent years to develop a nonprescription version of tadalafil.

Cialis is available as an oral tablet in several dosages, allowing individuals to take a low-dose tablet daily or a stronger dose on-demand before sexual activity.

The daily doses are available in 2.5- and 5-mg tablets. Doctors usually start their patients on the 2.5-mg dose, though 5 mg may be appropriate if needed for greater efficacy.

A daily dose of 5 mg may be too much for some people and lead to undesirable side effects.

On-demand doses are available in 10- and 20-mg doses. Doctors usually recommend starting with a 10-mg dose and moving up to 20 mg if a stronger dose is needed to achieve the desired results.

A 2016 study found that while low-dose daily use may have produced a slightly weaker effect than the higher-dose, on-demand use in some study participants, there did not appear to be a major benefit with one approach over the other.

With an on-demand dose, take Cialis at least 30 minutes prior to sexual activity, though understand that it could take up to 2 hours to take effect.
Take daily doses at about the same time every day.
Focus on managing stress.
Maintain healthy communication with your partner.

Some of the most common side effects associated with Cialis are:

Cialis is more likely to cause myalgia (muscle pain) when compared with other PDE5 inhibitors, according to a 2016 study on ED treatment published in the journal Nature Reviews Disease Primers .

Many Cialis or generic tadalafil users do not experience side effects, and those who do often have minor complaints that tend to go away once the drug is out of their system.

Muscle aches may last up to 2 days or so after taking your last dose.

More potential and serious symptoms include priapism, an abnormal, sometimes painful erection that lasts more than 4 hours.

Other concerning symptoms that should prompt a visit with a healthcare professional include sudden changes in vision and hearing, which occasionally occur with tinnitus and dizziness.

Unlike some other PED5 inhibitors, Cialis may be taken with or without food. It’s unlikely to have any impact on its effectiveness or side effects.

Avoid taking with high fat foods and meals

You should avoid high-fat meals when using Cialis. Too much fat may affect how well the medication works and how quickly it takes effect.

Avoid grapefruit juice

Grapefruit and grapefruit juice can enhance levels of Cialis in the bloodstream, potentially increasing negative side effects.

Avoid heavy alcohol drinking

Moderate alcohol consumption should have little effect on how Cialis works. But heavy alcohol consumption can make it difficult to achieve an erection even with an ED medication.

Know your other medications

Cialis may interact with certain medications. In particular, you should not take Cialis if you’re also taking nitrates, which are medications that widen arteries to allow greater blood flow.

Nitrates are typically prescribed to treat angina (chest pain brought on by narrowed coronary arteries) or heart failure.

When taken with nitrates or antihypertensive medications called alpha-blockers, Cialis could cause a dangerous drop in blood pressure.

Cialis may lead to similar problems when used in combination with other antihypertensive drugs.

Other classes of drugs that may interfere with Cialis include:

You should also avoid taking two PDE5 inhibitors in 1 day, as this can lead to a dangerous drop in blood pressure and other serious side effects.

Cialis and generic tadalafil are equally effective. The FDA works to ensure that the generic versions of all brand-name medications provide the same clinical benefits.

The main difference between Cialis and generic tadalafil is the cost.

Though prices vary considerably depending on the manufacturer and pharmacy where you’re buying the medication from, Cialis typically costs around $365 for 30 tablets. The generic versions cost about $100 for 30 tablets.

Cialis has been a widely available medication since gaining FDA approval in 2003. The medication is marketed and distributed by the company Eli Lilly and is sold in 2.5-, 5-, 10-, and 20-mg tablets. Eli Lilly is a large pharmaceutical company and manufacturer that also sells many other popular medications like Trulicity and Taltz.

Cialis has a generally positive reputation with customers because of its effectiveness and how long-acting it can be when taken daily. Since Cialis is available through pharmacies and several online ED medication services, overall customer satisfaction ratings can vary, especially since many of these online services put their most positive reviews out front.

If you are curious about user satisfaction with Cialis, make an appointment with your doctor or specialist to see if they think you could benefit from using Cialis.

While Cialis is widely prescribed around the world, the most well-known PDE5 inhibitor is Viagra (sildenafil), which is the first medication in this class of drugs to hit the market.

In addition to Cialis and Viagra, the other PDE5 inhibitors include:

These medications work best when used in combination with doing other things to support your overall health, especially those that directly impact your cardiovascular health.

In addition to PDE5 inhibitors, there are alternatives to medications some people consider, along with healthy habits. Among them are supplements and pill-free options, like:

L-arginine, an amino acid that helps manufacture nitric oxide
red ginseng, also known as Panax ginseng, an herb sometimes taken to lower inflammation
acupuncture, though research has shown conflicting results

Other habits that help sexual function

Making certain lifestyle changes can help fight ED, too. This includes things like:

getting regular exercise when possible
quitting smoking (if you smoke)
getting 7 to 8 hours of sleep each night
consuming nutrient-dense foods when possible
finding ways to manage stress

Cialis and Viagra each have their pros and cons, though the medications work similarly in the body.

Cialis has the advantage of lasting longer, with effects often lingering as long as 36 hours after taking the tablet.

Viagra usually lasts about 4 hours. Viagra is also an on-demand medication only, so the spontaneity that daily Cialis use allows is not an option with Viagra.

But Cialis is associated with muscle aches in the limbs in some users, a side effect not associated with Viagra. However, some research suggests that Viagra use may be associated with vision problems.

You can also find generic versions of both Cialis and Viagra.

Your lifestyle and personal experience with a particular medication may help you determine if Cialis, Viagra, or another PDE5 inhibitor is the right choice.

Cialis isn’t available over the counter. Your doctor has to prescribe Cialis for ED or other conditions the medication treats.

You may also be able to obtain this medication with the help of telemedicine services.

Companies like Hims and Roman offer online consultations with physicians who can prescribe ED medications that are then mailed to your home.

The cost of these online services can sometimes exceed conventional healthcare, though the convenience and discretion of this type of telemedicine service are appealing to many individuals.

Online ED treatment services

How long does Cialis last?

Taking Cialis daily will make it easier for you to get and keep an erection for as long as you regularly take the medication. If you are only taking a higher dose of Cialis as needed, the ability to get an erection could last up to 36 hours, for some people.

What are the downsides of Cialis?

Cialis can cause some side effects, including headaches, muscle aches, congestion, and indigestion.

Does Cialis last longer than Viagra?

Yes, Cialis in higher dosages can last up to 36 hours, while Viagra commonly lasts up to 4 hours. Talk with your doctor to see which medication best fits your sexual lifestyle.

Cialis, the brand version of the PDE5 inhibitor tadalafil, is one of the world’s most widely prescribed ED medications.

Generic tadalafil has been available since 2018 and has proven to be just as effective and safe as the brand name.

The drug is available in low daily doses that keep the medication in your system and allow for greater spontaneity. It’s also available in stronger, on-demand doses.

While Cialis and other ED drugs don’t “cure” the condition, they can treat the primary symptom by helping achieve and maintain erections.

If ED is affecting your life and relationship, you may want to consider trying tadalafil in some form.

It’s available by prescription only, so consult with a doctor about this and other possible ED treatments.

Last medically reviewed on October 30, 2022

How we reviewed this article:

Healthline has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions, and medical associations. We avoid using tertiary references. You can learn more about how we ensure our content is accurate and current by reading our editorial policy.

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ncbi.nlm.nih.gov/pmc/articles/PMC5411983/
Coward RM, et al. (2008). Tadalafil in the treatment of erectile dysfunction.
ncbi.nlm.nih.gov/pmc/articles/PMC2643112/
Cui X, et al. (2016). Acupuncture for erectile dysfunction: A systematic review.
hindawi.com/journals/bmri/2016/2171923/
Eli Lilly and Company Staff. (2017). Lilly reaches settlement agreement in U.S. Cialis patent litigation [Press release].
investor.lilly.com/news-releases/news-release-details/lilly-reaches-settlement-agreement-us-cialis-patent-litigation
Henrie AM, et al. (2015). Clinical utility of tadalafil in the treatment of pulmonary arterial hypertension: An evidence-based review.
ncbi.nlm.nih.gov/pmc/articles/PMC4636095/
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Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available.

Daily Cialis®: Costs and Benefits of the Daily Cialis Dose

Thanks to its long-lasting effects, Cialis®, which contains the active ingredient tadalafil, is one of the most popular medications on the market for treating erectile dysfunction (ED).

Unlike other ED medications, such as Viagra® (sildenafil) and Levitra® (vardenafil), which work for four to five hours per dose, Cialis is a long-lasting medication that can provide relief from ED for up to 36 hours per dose.

Cialis’s long duration of action has earned it the nickname as the “weekend” pill for dealing with erectile dysfunction.

Cialis is available in a range of dosages. Although most people are familiar with the original 10 and 20mg Cialis tablets, far fewer are aware that Cialis is also sold as a lower dosage tablet for use every day.

Below, we’ve explained how daily use of Cialis works. We’ve also looked at the advantages and disadvantages of using Cialis every day, from its effects on your sexual performance to its range of side effects, its convenience and more.

What is Cialis (Tadalafil)?

Before we get into the finer details of daily-use Cialis, it’s worth going over the basics to explain how Cialis differs from other erectile dysfunction medications.

Like other ED medications, Cialis is a PDE5 inhibitor. It works by blocking the effects of PDE5, or cGMP-specific phosphodiesterase type 5 — an enzyme that’s responsible for controlling the flow of blood to certain parts of your body, including your penis.

By inhibiting the effects of PDE5, Cialis helps to dilate the blood vessels that supply your penis, allowing for improved blood flow.

When you’re aroused, blood naturally flows to your penis. This increase in blood supply causes the bodies of erectile tissue inside your penis, referred to as the corpora cavernosa, to gradually expand and become firmer, creating an erection.

As you reach orgasm and ejaculate, the same process occurs in reverse, with blood flowing out from your penis and the erectile tissue decreasing in size.

Other erectile dysfunction medications work in the same way as Cialis — by inhibiting PDE5 and increasing blood flow.

However, Cialis differs in that it’s much longer lasting than other ED medications. While Viagra typically works for three to five hours and Levitra for four to six, a single dose of Cialis can stay active in your body for up to 36 hours.

This long duration of action makes Cialis a great option if you’d like a long-lasting, easy to use medication for the treatment of erectile dysfunction.

Contrary to popular belief, Cialis and other ED medications can not cause you to get erections at random. Instead, they only work when you’re already aroused due to sexual stimulation.

Cialis comes in tablet form. When used as-needed, it’s designed for consumption about one to two hours prior to sex. Like other ED treatments, Cialis is available as a brand name drug and as a generic medication in the form of tadalafil.

How Daily Cialis Works

Most ED medications, such as Viagra, Levitra and Stendra® (avanafil) are designed for use on an as-needed basis, meaning they’re taken before sex.

Cialis is also prescribed for use as needed. However, it’s also available at a reduced dosage as a daily-use medication.

For as-needed use, which means you take the medication as you need it, Cialis typically comes in two different dosages: 10mg and a maximum dose of 20mg. It’s also occasionally prescribed at a dosage of 5mg, usually to treat mild or moderate ED.

Using Cialis or generic tadalafil as needed is a good option if you typically have sex a few times per week — for example, every other day. Since it lasts for a long time, you can take Cialis close to the time you plan to have sex for stronger erections and a helpful confidence boost.

For daily use, Cialis comes in two dosages: 2.5mg and 5mg. The idea behind daily use of Cialis is that you’ll be prepared for sex whenever you feel like it, as the medication will remain active in your body all day.

This means that you can have more fulfilling, pleasurable sex with your partner without needing to worry about taking your medication at a specific time of day.

Advantages of Daily Cialis

Cialis offers several advantages, including a long duration of action and the convenience of not having to take medication right before sex. When used daily, it’s especially convenient thanks to its ability to make having sex at any time of day easier.

When it comes to efficacy, Cialis compares well to other erectile dysfunction medications, such as Viagra, Levitra and Stendra.

For example, clinical trials have found that 57 percent of men with ED who use Cialis on a daily basis at a dosage of 5mg are able to maintain an erection, compared to just 31 percent of men treated with a non-therapeutic placebo.

Other advantages of using Cialis on a daily basis include:

A simple, once-per-day dosage. When you use Cialis daily, adding it to your routine can be much easier. Instead of needing to remember to use Cialis before sex, you can take it every morning or at a consistent time throughout the day.
This also means that there’s no need to carry your medication with you if you’re going out on a date and want to take Cialis in time to have sex the same night.
Easier spontaneous sex. Because Cialis has a long half-life, it can remain active for the full day if it’s taken on a daily basis. This means that you’ll always be prepared for sex, even if it’s been many hours since you took your medication.
This long-lasting duration of action makes daily-use Cialis a good option if you want to enjoy spontaneous, unplanned sex with your partner without worrying about ED.
Increased sexual confidence. Because Cialis works all the time, it can give a helpful confidence boost that reduces anxiety before sexual intercourse — something that may increase your level of sexual desire.
A reduced risk of side effects. Because daily-use Cialis is taken at a lower dosage than as-needed CIalis, you may have a reduced risk of experiencing side effects from your medication.
Many side effects are less common when Cialis is used daily. For example, headache, which is one of the most common Cialis side effects, affects 11 to 15 percent of people who use Cialis as needed, compared to just three to six percent of daily users.

Disadvantages of Daily Cialis

Using Cialis on a daily basis is mostly positive, but it does have a few potential disadvantages, including the risk of mild side effects lasting for longer and the medication potentially needing a little extra time to start working to its fullest:

When used daily, Cialis is always “on.” Although this is mostly an advantage, the fact that daily-use Cialis is always working to treat erectile dysfunction could be inconvenient in some situations.
For example, if you only have sex once or twice each week and know when you’ll spend time with your partner, using Cialis every day may not be totally necessary.
Cialis can take three to five days to reach its peak concentration. Because Cialis is prescribed at a reduced dosage for daily use, it can take several days before it reaches its peak concentration in your bloodstream.
This means that you may need to wait for several days before you notice the full effects of Cialis after starting treatment.
Some side effects of Cialis may be more persistent. Because Cialis is always active within your body when it’s taken on a daily basis, side effects such as headaches, nasal congestion, dyspepsia (heartburn) and muscle pain, may be more persistent.
However, because Cialis is prescribed at a lower dose for daily use, certain side effects may be less severe and intense.

Is Daily Cialis Right for You?

There are several ED medications currently available, making choosing the “right” one for you a difficult process.

If you can’t decide between daily-use Cialis and another option, try asking yourself the following questions:

How often do you have sex during the week? If you have sex more than two to three times a week, using Cialis daily will generally be more convenient for you, as there’s no need to take medication an hour ahead of time.
Do you often have spontaneous sex? If you often have sex without planning ahead of time, or just don’t want to wait for Cialis to start working, using Cialis daily can give you a greater degree of control over your sexual schedule.
Do you use other prescription medications? Cialis and other medications for ED may interact with other drugs, including medications for high blood pressure, congestive heart failure and antifungal medications used to treat skin and/or nail infections.
If you use other prescription medications, make sure to talk with your healthcare provider before using Cialis.
Do you have an existing health condition? Some medical conditions may make Cialis unsafe or unsuitable for you. Make sure to fully inform your healthcare provider about all of your pre-existing conditions before using Cialis or similar medication for ED.
Do you drink alcohol often? Although it’s okay to consume a small amount of alcohol while using Cialis, drinking large amounts of alcohol can cause orthostatic hypotension, a form of low blood pressure that may cause dizziness, headache and other issues.
If you’re a frequent and/or heavy drinker, using Cialis or other ED medication on a daily basis may not be suitable for you.
Do you get side effects from Cialis? Although the lower dose of Cialis used daily may make some side effects less severe, daily use of Cialis may cause some unwanted side effects to occur for a longer period of time.
How effective is Cialis for you? If you still occasionally deal with ED after using Cialis at a 10mg or 20mg dosage, switching to a lower dosage for daily use might make Cialis work less effectively for you.

Still need help? Try talking to your healthcare provider about the advantages and downsides of using Cialis on a daily basis.

genuine Viagra® makes it possible

Side Effects of Daily Cialis

Like other ED medications, Cialis and generic tadalafil can cause side effects. Most side effects of daily-use Cialis are identical to those that can occur when Cialis is used as needed, although the lower dosage that’s prescribed for daily use makes some side effects less common.

The most frequently reported side effects of Cialis include headaches, dyspepsia (indigestion or heartburn), back pain, muscle aches, facial flushing, nasal congestion, dizziness and a range of cold-like symptoms.

These side effects only occur in a small percentage of men who use Cialis. According to clinical trials, headaches — the most common side effect of Cialis — affected three to six percent of men with ED who were prescribed Cialis at a dosage of 2.5 to 5mg per day.

In comparison, five percent of men who received a placebo also reported headaches during the trial period.

Other side effects, such as dyspepsia, nasopharyngitis (cold-like symptoms) and various forms of muscle and joint pain, were reported by less than five percent of men with ED who received Cialis on a daily basis.

Put simply, side effects from daily-use Cialis tend to be mild and only affect a small percentage of men who use this medication.

Our guide to Cialis side effects goes into more detail about the potential side effects associated with Cialis, as well as the steps that you can take to deal with them if you’re affected.

As with other medications for erectile dysfunction, Cialis can interact with certain drugs used to treat hypertension (high blood pressure), cardiovascular disease, chest pain and other medical conditions that affect the heart and vascular system.

For example, Cialis and other PDE5 inhibitors can cause severe interactions when used at the same time as blood pressure medications such as nitrates and alpha-blockers.

When used together, these medications can cause a sudden drop in blood pressure that could lead to dizziness, fainting or cardiovascular events such as heart attack or stroke.

To reduce your risk of experiencing interactions while using Cialis, whether as needed or on a daily basis, it’s important to inform your healthcare provider about all medications you currently use or have recently used.

It’s also important to avoid using illicit drugs, including “poppers” that contain nitrates, while you use Cialis.

Effect of tadalafil 5mg daily treatment on the ejaculatory times, lower urinary tract symptoms and erectile function in patients with erectile dysfunction

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Objective

To investigate the effect of a 5mg daily tadalafil treatment on the ejaculation time, erectile function and lower urinary tract symptoms (LUTS) in patients with erectile dysfunction.

Materials and Methods

A total of 60 patients diagnosed with erectile dysfunction were retrospectively evaluated using the international index of erectile function questionnaire-5 (IIEF-5), intravaginal ejaculatory latency time (IELT) and international prostate symptoms scores (IPSS). After the patients were treated with 5mg tadalafil once a day for three months, their erection, ejaculation and LUTS were assessed again. The fasting levels of blood glucose, total testosterone, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were measured. The independent-samples t-test was used to compare the pre- and post-treatment scores of the patients.

Results

The mean age of the 60 participants was 50.4±7.9 and the mean baseline serum total testosterone, total cholesterol, and fasting blood sugar were 444.6±178.6ng dL -1 , 188.7±29.6mg/dL -1 ,104 (80-360) mg dL -1 , respectively. The mean baseline scores were 2.2±1.4 min for IELT, 9.5±3.7 for IIEF-5 and 14.1±4.5 for IPSS. Following the three-month daily 5mg tadalafil treatment, the scores were found to be 3.4±1.9 min, 16.1±4.7, and 10.4±3.8 for IELT, IIEF and IPSS, respectively. When the baseline and post-treatment scores were compared, a statistically significant increase was observed in the IELTs and IIEF-5 values whereas there was a significant decrease in IPSS (p<0.01).

Conclusion

A daily dose of 5mg tadalafil can be safely used in the treatment of erectile dysfunction and LUTS, that prolongs the ejaculatory latency time.

INTRODUCTION

Premature ejaculation (PE) is considered one of the most common sexual function disorders in men with a prevalence of 9-30% (1-5). PE is defined as ejaculation with minimal sexual stimulation before or shortly after penetration, resulting in anxiety and distress. Patients have minimal or no voluntary control over PE (5). There are two types of PE: lifelong or primary, and acquired or secondary (5). Based on modern evidence, the causes of PE have been found to be psychogenic and performance anxiety (1, 5). Organic factors have been suggested as significant predictors of PE (2, 6). Genetic factors have also been listed among the factors affecting lifelong PE (7). Other common organic factors that have an impact on acquired PE include hormonal abnormalities (2), prostatitis (6), and erectile dysfunction (ED) (8). It has been reported that in many cases of lifelong PE, the men do not suffer from ED (9); however, approximately one third of the patients with ED have PE (10). Similarly, in a recent large-scale survey in the Asian-Pacific region administered to 4997 heterosexual men aged 18 to 65 years in a stable sexual relationship, ED was found to accompany PE in more than 30% of the respondents (11).

Many studies have suggested that assessing the effect of PE treatment is to measure the time taken to achieve ejaculation using the intra-vaginal ejaculation latency time (IELT). IELT is based on self-report and measured by a chronometer. It has 80% specificity and sensitivity for PE (12). Behavioral and pharmacological therapies are the common treatment options for PE. Behavioral therapy includes several techniques such as squeezing and start-stop methods but many couples have reported these to be inadequate. The first choice in pharmacological therapy is the use of serotonin reuptake inhibitors (SSRIs) (e.g., citalopram, sertraline, fluoxetine, dapoxetine or paroxetine); however, other options include phosphodiesterase type 5 (PDE 5) inhibitor therapy (tadalafil or sildenafil), topical desensitizing agents (prilocaine or lidocaine) and other agents (tramadol or pindolol) (13). PDE5 inhibitors are frequently used in the treatment of ED and clinical studies have reported their positive effect on patients with PE (14-16). In a recent study, a daily dose of 5mg tadalafil has been shown to significantly increase IELT in patients diagnosed with lifelong PE (17). However, to our knowledge, there is no study in the literature that determined the effect of tadalafil 5mg daily on ejaculatory time in patients with ED.

The current study investigated the effect of 5mg daily tadalafil treatment on the time taken to achieve ejaculation, erectile function and lower urinary tract symptoms in patients diagnosed with ED.

MATERIALS AND METHODS

A total of 60 patients who were referred to the urology policlinic of the hospital with the complaint of erectile dysfunction between January 2015 and January 2016 were included in the study. The study was approved by the local ethics committee of Erzincan University and all patients gave informed consent for the treatment. All patients reported to be heterosexual and in a stable sexual relationship for more than six months. The exclusion criteria were neurological disorders such as depression, Parkinson’s disease, diabetic neuropathy, and cerebrovascular damage, an active urinary system infection, history of chronic prostate; alcohol, drug or substance abuse, organic diseases limiting the use of PDE5 inhibitors, pelvic trauma, anemia, thyroid disease, hypogonadism (total testosterone) end-stage renal failure; and having used medication affecting the sex hormone and/or vitamin metabolism or for the treatment of PE and ED within the last three months. The information related to patient’s age, duration of sexual dysfunction, smoking status, and sexual and medical history was obtained and a complete physical examination was performed on all patients. PE was assessed by IELT, which is defined as the time from vaginal intromission to intravaginal ejaculation (18). IELT was measured using a self-report method. It was measured by the female sexual partner using a stopwatch and expressed in minutes. If ejaculation occurred before or during penis vaginal intromission, it was defined as 0 minute. The same company calibrated all the stopwatches (12). The erectile functions of the patients were evaluated using the five-item international index of erectile function questionnaire (IIEF-5). According to their IIEF-5 scores, the ED patients were divided into three groups as severe ED (score: 1-7), moderate ED (8-11) and mild ED (11-21). The patient’s intra-vaginal ejaculation times were recorded. The lower urinary system symptoms (LUTS) of the patients were assessed using the international prostate symptom score (IPSS). Following fasting for 12 h, at 8 a.m., blood samples for the laboratory tests were obtained to measure the levels of fasting blood glucose (FBG), total testosterone (TT), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). The accepted normal values were: TT: 271-965ng dL -1 , FBG: 70-110mg dL -1 , TG: 40mg dL -1 .

For the treatment of ED, the patients were prescribed 5mg tadalafil daily for three months. At the end of this period, the patients were re-evaluated using IIEF-5, IELT and IPSS. In addition, the side effects of the treatment were recorded and the patient’s baseline and post-treatment scores were compared.

Statistical analysis

A power analysis was conducted, in which the Biostatistics power of 80.193% was evaluated and the sample width was determined as a minimum of 19 individuals in each group. The statistical software SPSS (Statistical Package for Social Sciences, Version 20, Chicago IL, USA) was used for calculations. All values were presented as mean±standard deviation, means (maximum-minimum), percentages and frequencies. The results of the homogeneity (Levene’s Test) and normality tests (Shapiro Wilk) were used to decide which statistical methods had to be applied in the comparison of the study groups. Groups that were normally distributed and those with homogeneous variances were compared using the Student’s t test, and three or more groups were compared by the Analysis of Variance. According to the results of these tests, parametric test assumptions were not available for some of the variables and therefore the comparisons of two independent groups were performed by Mann-Whitney U test, and the comparisons of three independent groups were performed using Kruskal-Wallis test. For the multiple comparison tests, the adjusted Bonferroni method was used. The repeated measures of analysis of variance were analyzed by Mauchy’s sphericity test and Box’s Test of Equality of Covariance Matrices. For comparisons of the means of repeated measures, the Repeated Measures Analysis of Variance was used. When the parametric tests (factorial design for repeated measures analysis) did not meet the preconditions, methods by Greenhouse-Geisser (1959) or Huynh-Feldt (1976) were used for corrections to the Degrees of Freedom or Friedman Test. The Corrected Bonferroni test was used in multiple comparisons. The categorical data was analyzed with Fischer’s Exact Test and chi-square test. p values of

RESULTS

The mean age of the 60 participants was 50.4±7.9 (range 36–67). The mean serum total testosterone, fasting blood sugar, total cholesterol, LDL-C, HDL-C were found to be 444.6±178.6ng/dL -1 (310–900), 104 (80-260) mg/dL -1 ,188.7±29.6mg/dL -1 , 111.9± 32.4mg/dL -1 , and 43.2±9mg/dL -1 , respectively ( Table-1 ). The mean baseline scores were 2.2±1.4 for IELTs, 9.5±3.7 for IIEF-5, and 14.1±4.5 for IPSS. At the end of the three-month tadalafil treatment, the patient’s scores were found to be 3.4±1.9, 16.1±4.7 and 10.4±3.8 for IELTs, IIEF-5 and IPSS, respectively ( Table-2 ). The results indicated a statistical improvement in all parameters (p= <0.001). The pre- and post-treatment scores of the patients were compared according to the severe, moderate and mild ED groups. In all three groups, a statistically significant difference was found between the pre- and post-treatment values of IPSS variables (p<0.01) and a statistically significant difference was found between the pre- and post-treatment values of IELT variables (p<0.01) (Table-3 ). However, there was no significant difference between the ED groups in terms of the baseline and post-treatment values of IPSS (p=0.10; p=0.23) or IELT (p=0.83; p=0.48).

Table 1

Characteristic	Patients (n:60)
Age (year) *	50.4±7.9
Total Testosterone (ng dL -1 ) *	444.6±178.6
Total Cholesterol ( mg/dL -1 ) *	188.7±29.6
Fasting blood sugar (mg dL -1 ) *	104 (80-360)
HDL (mg dL -1 ) *	43.2± 9
LDL (mg dL -1 ) *	111.9± 32.4
Hypertension (%)	33.9
Smoking (%)	45.8
DM (%)	15.0

LDL cholesterol = Low-density lipoprotein cholesterol; HDL cholesterol = High-density lipoprotein cholesterol; DM = Diabetes mellitus.

Table 2

IIEF-5 = International Index of Erectile Function-5; IPSS = International prostate symptom score; IELT = intravaginal ejaculation latency time

*p values were derived from the statistical analysis using the independent t-test.

Table 3

Comparison of ED groups in terms of IPSS and IELT scores before and after tadalafil 5 mg daily treatment.

Group		IPSS_PRE	IPSS_POST	p	IELT_PRE (min)	IELT_POST (min)	p
severe ED	N	20	20	0.001**	20	20	0.001**
	Mean	15.70	11.20		2.30	3.10
	Std. Deviation	3.83	2.97		1.17	1.41
moderate ED	N	22	22	0.002**	22	22	0.001**
	Mean	13.95	10.64		2.09	3.50
	Std. Deviation	5.35	4.74		1.48	2.32
mild ED	N	18	18	0.001**	18	18	0.001**
	Mean	12.47	9.12		2.35	3.88
	Std. Deviation	3.79	3.04		1.62	2.00
Total	N	60	60	0.001**	60	60	0.001**
	Mean	14.12	10.39		2.24	3.47
	Std. Deviation	4.56	3.78		1.41	1.95
p		0,10	0.23	0.83	0.48

Table-2 presents the mean pre- and post-treatment IELT, IIEF-5, and IPSS of the patients. The common side effects were gastrointestinal problems or nausea in 6 patients (10%) and headache in 5 patients (8.3%). In addition, flushing was reported by 3 patients (5%) and muscle and lower back pain by 2 patients (3.3%). Most of the side effects disappeared over time.

DISCUSSION

In this study, the effect of tadalafil 5mg daily treatment on ejaculation time, erectile function and lower urinary tract symptoms was investigated in patients diagnosed with ED. Corona et al. (19) recently conducted a meta-analysis on the relationship between PE and ED, and reported that PE increases the risk of ED approximately fourfold. In addition, this risk was found to be significantly higher in patients with depression and anxiety symptoms, followed by those with diabetes, hypertension and dyslipidemia. The IIEF scores of PE patients and the IELT scores of ED patients were found lower. According to the hypothesis proposed by Jannini et al. (8), PE and ED are part of a vicious cycle in which trying to control ejaculation reduces the instinctive level of stimulation resulting in ED. Similarly, in the effort to have an erection, the patient may try to increase his stimulation, which may result in PE. In order to test this hypothesis, Jannini et al. (8) retrospectively analyzed 184 cases (age range: 18-83), who were referred to the clinic with sexual function problems. The authors found that 29 cases with isolated ED had developed PE before ED. In the same study, 21 cases with isolated PE were found to be accompanied by, or have a history of mild to moderate ED (diagnosed using IIEF). Resulting in low satisfaction with sexual intercourse, PE can create psychological issues, which may lead to the development of ED.

PE can also develop secondarily to the increased stimulation for the creation and maintenance of erection in ED patients or accompanying anxiety (8). In parallel to this hypothesis, it was suggested that there is a higher risk of developing PE-associated ED for cases in which there is a direct correlation between ED and symptoms of anxiety or depression, and for those who do not have a stable sexual partner and experience stressful sexual relationships (19). Waldinger (9) suggested that ED is more commonly seen in patients with acquired PE compared to those with lifelong PE. Lifelong PE reduces sexual stimulation in patients, thus resulting in sexual intercourse accompanied by ED. On the other hand, McMohan et al. (20) used validated diagnostic tests and reported that 33% of the PE patients had been diagnosed with false positive ED. Today, the available PE treatment options include behavior therapy, topical anesthetics, and more predominantly SSRIs. However, studies concerning PDE5 inhibitors have also reported the clinical efficiency of these drugs in the treatment of PE. Studies investigating the therapeutic effects of PDE5 inhibitors alone and in combination with SSRIs have reported the benefits of these inhibitors for PE treatment (14-17). In a well-designed, randomized and double blind study, sildenafil was compared to a placebo (21). The authors reported that sildenafil increased the perception of ejaculatory control and overall sexual satisfaction, and reduced the time between the first and second ejaculation; however, it did not significantly increase IELT. Other studies (22, 23) have demonstrated that the combination of PDE5 inhibitors and SSRIs are more efficient in increasing IELT and overall sexual satisfaction compared to the individual use of these medications. These studies used sildenafil 50mg as the main PDE5 inhibitor.

In a randomized study, Salonia et al. (24) compared the efficacy of sildenafil, various SSRIs and the pause-squeeze technique, and reported that sildenafil increased IELT and sexual satisfaction and reduced anxiety. In addition, sildenafil, clomipramine, paroxetine and the pause-squeeze technique were found to increase IELT by 1 to 15 min, 4 min, 3 min, 4 min and 3 min, respectively in comparison to the baseline values (24). Recently, Ozcan et al. (17) reported a significant increase in IELT of patients with lifelong PE following 5mg daily tadalafil treatment. Although the study had limitations in terms of the small sample size (30 patients) and the short duration of treatment (1 month), it is significant in terms of being the first report on 5mg daily tadalafil treatment. In this study it was reported that IELT increased approximately 2.5 min while in our study increased 1.2 min. Our results showed that tadalafil 5mg daily treatment led to statistically significant improvement in all the measured parameters. Our results are supported by Ozcan et al. (17) who demonstrated that tadalafil 5mg alone could significantly prolong IELT. At the same time, in our study, there was no statistically significant difference between the ED groups in terms of IELT and IPSS following tadalafil 5mg daily treatment. Mattos et al. (16) study involving effect of tadalafil (20mg) alone and in combination with fluoxetine (90mg) found that the increase in IELT was better in patients who received combined treatment compared with placebo, fluoxetine, or tadalafil alone.

In the treatment of PE, regarding the effect of PDE5 inhibitors, there are several mechanisms involved. All central and peripheral mechanisms are probably important but the particular role that each plays in delaying ejaculation is not known. However, the mechanism that is most speculated to be involved is the reduced sympathetic tone and smooth muscle dilatation. Aversa et al. (25) reported that PDE5 inhibitors display activities through central and peripheral mechanisms. The NO/cGMP signaling pathway is considered to control sexual behavior through a central effect. The possible mechanism of the PDE5 inhibitor action lessens the contracting response of vas deferens (VD), seminal vesicles (SV) and prostate and urethra. This creates a state of peripheral analgesia, which prolongs the duration of the erection and reduces the central sympathetic output (26). The results of these studies demonstrate that PDE5 inhibitors relax VD, SV and smooth muscle tissue in the prostate, and increase the duration of the erection and sexual confidence, resulting in increased overall sexual satisfaction.

Studies have suggested that LUTS cause erectile dysfunction (27) and ejaculatory problems (28). The pathophysiological links between LUTS and ED are not fully understood, and these conditions are suitable to therapy with phosphodiesterase type 5 inhibitors (PDE5-Is). Some studies have determined the role of phosphodiesterase type 5 inhibitors in the treatment of men with LUTS associated with benign prostatic enlargement. Yan et al. (29) conducted a meta-analysis on the use of PDE5 inhibitors in the treatment of LUTS and reported that these inhibitors reduced IPSS by 4.21 points. Similarly, in this study, we found a significant decrease of 4.3 points in IPSS and an increase in the IIEF-5 score after using tadalafil 5mg daily treatment. Oelke et al. study, a post-hoc analysis of four randomized studies in 1477 men, showed that patients treated with tadalafil 5mg once daily versus placebo presented a clinically-meaningful symptom improvement (decrease more than 3 points of total IPSS) (30). Wein et al. (28) study reported that LUTS caused ejaculatory problems. Alpha blockers drugs are very important for the treatment of LUTS. On the other hand, Akın et al. (31) showed that all this alpha-blocker drugs were statistically effective in preventing PE. The authors found that the IPSS score significantly decreased in all groups while there was a statistically significant increase in IELT and a decrease in premature ejaculation profile scores in all alpha-blocker drugs groups in the post-treatment period. In this study, it was observed that tadalafil 5mg daily treatment led to statistically significant improvement in IPSS and IELT. Similarly, Choi et al. (32) reported a significant change using in the LUTS+PE patients after tamsulosin administration according to the results of the premature ejaculation diagnostic tool (PEDT). The positive effect of tamsulosin on PE can be attributed to the decreased contractility of the seminal vesicle or the vas deferens by the drug itself. Furthermore, the improvement of PE could be secondarily affected by the improvement of LUTS. This effect was also demonstrated by Aversa et al. (25), who used PDE5 inhibitors to relax VD, SV and smooth muscle tissues in the prostate.

PE has been found to be related to comorbid disorders such as diabetes. El-Sakka et al. (33) showed that men with diabetes had a high prevalence of PE. Many patients with ED develop PE probably due to the need for intense stimulation or anxiety to initiate and maintain an erection (34). In our study, only 9 patients (15%) had DM and their fasting blood glucose was controlled.

The limitations of our study include a small sample size and the absence of a non-ED control or placebo group. Treatment with PDE5 inhibitors is significant not only in terms of the relationship between ED and PE but also due to improving the erection and reducing the ejaculation problems caused by LUTS. This study is a valuable contribution to the literature in terms of being the first study investigating the effect of tadalafil 5mg daily treatment on ejaculatory time in patients with ED.

Daily 5mg tadalafil treatment is considered to have beneficial effects on ED and PE patients. Therefore, we recommend the use of 5mg tadalafil once daily, specially in those men with PE with erectile dysfunction. Further studies must be conducted with a placebo-controlled larger series and a longer follow-up to contribute to the literature in terms of the effects of daily 5mg tadalafil treatment.

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