The Science Behind Erectile Dysfunction

Erectile dysfunction (ED) can be a tricky subject to discuss whether it be with your partner, doctor or pharmacist. There are several forms of male sexual dysfunction, including poor libido and problems with ejaculation. But ED refers specifically to problems achieving or maintaining an erection. Men with ED often have a healthy libido, yet the body fails to respond. In most cases, there is a physical basis for the problem. While erectile problems are widely thought to be an older man’s issue, ED can affect younger men as well. It can be both frustrating and embarrassing for a man to admit to having ED. Few young men, especially those under the age of 40, want to acknowledge that they may have it. Although ED is not as common in young men, it can affect about 25% of men under the age of 40. However, only about 5% of all men under 40 have complete ED. But this does not mean growing older is the end of your sex life. ED can be treated at any age as long as you are over 18 years old.  The treatment options are many and a discussion with our pharmacist or doctor will ensure you choose the right one for you.

 

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Erectile dysfunction (ED) is defined as the inability to achieve and maintain a penile erection adequate for satisfactory sexual intercourse. Up to 150 million men worldwide suffer from ED and this figure is likely to double by the year 2025.

A number of studies have attempted to characterise the true prevalence of ED. In a Danish study, Ventegodt reported that 5.4% of all patients had a decreased ability to achieve an erection. The prevalence was reported to be highest (18%) of those aged over 58 years. The Massachusetts Male Aging Study (MMAS) reported the results of a regional survey of 1709 men aged 40–69 years. In this study, 52% reported some degree of ED, with 10% having complete ED. Moreover, the results suggest that the probability of complete ED at age 70 was threefold compared to that at age 40; the probability of moderate ED was two-fold.

What are the symptoms of ED? You may have erectile dysfunction if you regularly have:

  • trouble getting an erection
  • difficulty maintaining an erection during sexual activities
  • reduced interest in sex

You’ve been getting erections since puberty, but have you ever stopped to think about the reason why? Understanding the physiological process of getting an erection can help you look at ED in a whole new light.

What Makes a Penis Erect? Your penis has two chambers inside it called the corpora cavernosa. These chambers extend from the head of your penis deep into the pelvis. The insides of these chambers are made of spongy tissue and have the ability to gain blood volume and grow in size.

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When you’re at work, hitting the gym, or running errands, the arteries supplying blood to your penis are only partially open. This provides the blood flow needed to keep your tissue healthy. The magic happens when you become aroused. In response to physical or mental stimulation, your brain sends signals to trigger a hormonal response that allows those same arteries to open completely. Open arteries allow more blood to enter the corpora cavernosa. The blood enters faster than it can leave through the veins. The veins get compressed, trapping blood in your penis. This chain reaction lets you achieve and maintain an erection. When your brain stops sending signals that indicate sexual arousal, the hormonal response ends. Your arteries go back to their normal state and your penis returns to a flaccid state.

What is the role of NO (nitric oxide) is getting an erection? Building on previous work indicating that the release of the neurotransmitter nitric oxide from nerve endings in the penis produces an erection, a team of Johns Hopkins University researchers led by Arthur Burnett focused on the role of the compound over time. Their research on rats and mice indicates that nitric oxide released at the onset of erection dilates the blood vessels, which enables blood to flow to the penis. That increased blood flow, the team discovered, slightly stresses the blood vessel wall, which prompts the release of more nitric oxide from the cells lining that wall, relaxing more tissue and allowing more blood to enter. The process repeats, sustaining an erection.

 

 

As with most other organ systems in the human body, changes and loss of function is a normal consequence of the aging process. This is also true of the endocrine system, specifically the levels of testosterone production from the Leydig cells of the testicle. Accompanying the decrease in testosterone is a decrease in erections which also has a component in a decrease in the blood supply to the penis making erection not as frequent and not as rigid compared with a young man’s erectile function. Although these changes are in itself not life-threatening, they can impact a man’s relationship with his partner.

Medical conditions, such as hypertension, diabetes mellitus, and cardiovascular disease (CVD), and psychological conditions, such as depression and anxiety, also contribute to sexual dysfunction in middle-aged or elderly men. CVD and hypertension cause a narrowing and hardening of the arteries, leading to reduced blood flow to the corporal bodies, which is essential for achieving an erection. Diabetes is a common etiology of sexual dysfunction because it can affect both the blood vessels and the nerves that supply the penis. Men with diabetes are four times more likely to experience ED, and on average, experience ED 15 years earlier than men without diabetes. Obesity is also correlated with the development of several types of dysfunction, including a decrease in sex drive and an increase in episodes of ED.

Historically ED has been treated in many ways, some methods were really quite unsavory! Impotence treatments were discussed in the oldest Chinese text, The Yellow Emperor’s Classic of Internal Medicine, which describes traditional Chinese medicine during the time of the Yellow Emperor’s rule which ended around 2600 BC. One of the treatments for impotence discussed is a potion with 22 ingredients.

Nearly 1000 years later, the Egyptian Papyrus Ebers, a medical Egyptian document dated 1600 BC, describes a cure for impotence in which baby crocodile hearts were mixed with wood oil and applied topically to the penis.

In 1973, Dr. Brantley Scott from Baylor College of Medicine reported on the implantable inflatable prosthesis that urologists still use today.

The major breakthrough occurred in 1998 when sildenafil became the first oral drug to be approved to treat ED. This was followed by the use of tadalafil and vardenafil as similar phosphodiesterase-5 inhibitor oral medications for treating ED in 2003.

The causes behind ED can be either psychological or physical or a combination of both. But how would you know the reason behind your ED? Is it possible to be diagnosed with this condition?

The first step in the management of ED is a thorough history that includes the following:

  • Sexual history
  • Medical history
  • Psychosocial history

A physical examination is necessary for every patient, emphasizing the genitourinary, vascular, and neurologic systems. A focused examination entails an evaluation of the following:

  • Blood pressure
  • Peripheral pulses
  • Sensation
  • Status of the genitalia and prostate
  • Size and texture of the testes
  • Presence of the epididymis and vas deferens
  • Abnormalities of the penis (eg, hypospadias, Peyronie plaques)

What options do I have for treating ED? In current practice, PDE5 inhibitors are the most commonly used treatment for ED. This drug class consists of sildenafil, vardenafil, tadalafil, and avanafil. They are all available to buy at Assured Pharmacy subject to filling in an online health questionnaire. Sildenafil was the first in this series of PDE inhibitors; avanafil is the newest, having been licensed for sale in the U.K in 2013. In a study of 390 men with diabetes and erectile dysfunction, avanafil was found to be a safe and effective treatment as early as 15 minutes and more than 6 hours after dosing.

How do PDE5 inhibitors work?  After sexual stimulation, postsynaptic neurons and endothelial cells in the penis release various erectogenic substances, the most important of which is nitric oxide (NO). Despite its very short half-life, this gaseous molecule can diffuse quickly across the smooth muscle cell membrane to activate a signaling cascade that ultimately results in arteriolar smooth muscle relaxation, vascular engorgement, and erection. NO activates soluble guanylyl cyclase (sGC) which produces cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). Cyclic GMP is the second messenger that sets in motion vascular smooth muscle relaxation. The enzyme PDE5 enzymatically inactivates cGMP to GMP, resulting in decreased downstream erectogenic signalling. Thus, PDE5 inhibitors promote erections by increasing the stability of cGMP and potentiating the NO/cGMP-dependent signalling cascade (Fig. 1). However, without sexual stimulation and the production of NO, there is no signal to potentiate, which explains why PDE5i do not cause erections in the absence of sexual stimulation.

 

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Figure 1. PDE5i promote penile smooth muscle cell relaxation and erection by preventing the degradation of cGMP.

 

Pharmacologically, the PDE5i are very similar, but slight differences in their chemical selectivity and bioavailability and/or metabolism can explain the slightly different side-effect profiles and the timing of the clinical response after dosing.

A medication used to treat ED should have predictable efficacy and time of onset should be well tolerated and easy to administer, and should be associated with minimal side effects. For patients taking an ED medication, they should have the option to choose a medication that works immediately and then wears off, or take a medication that may be slightly delayed in its effects but remains effective for hours. In recent years, the definition has changed to include medications that could be taken every day instead of only when needed. 

Sildenafil (Viagra) was the original PDE5I to be released and has been extensively researched. It is the one that most people have heard about. It has a quick onset of action of 30 minutes after the initial dose, although patients are instructed to wait at least 1 hour prior to attempting intercourse to receive the most benefit from the medication. It has been shown to have a duration of action of 4–6 hours and a maximum duration of 12 hours.

Tadalafil (Cialis) was released in 2003 making it the third PDE5I on the market for the treatment of ED. It has an onset of 20 minutes and should be taken 30 minutes prior to intercourse. Tadalafil has the longest duration of action in the class (24–36 hours) and a reported maximum duration of 72 hours.

Tadalafil is approved for once daily use for the treatment of ED in its lower dose form. This means you can have sex at any time, rather than needing to take a pill from time to time as needed like other ED brands. The starting dose for daily-use Cialis is 2.5 milligrams (mg). If that doesn’t work, you can increase your daily dose up to 5 mg. But is this the right approach for you—or are you better off with traditional ED drugs like Viagra, Levitra, or even the non-daily version of Cialis? If you are contemplating Cialis for daily use, consider these questions and then discuss it with our pharmacist:

  • How often do you have sex? If it’s two or more times a week, a daily pill might be a reasonable choice, since the drug continually circulates in your bloodstream.
  • How important is spontaneity? A daily pill clears the path for sex at any time.

Vardenafil (Levitra) was approved in 2003 for the treatment of ED. It has the shortest reported onset of action (10 minutes), but it is recommended to be used within 30–60 minutes of planned intercourse. The duration of action is between 5 and 7 hours and has a maximum duration of 12 hours.

Avanafil (Spedra) is the newest of the PDE5Is on the market. It was licensed for the treatment of erectile dysfunction is 2013 and became the fourth PDE5I on the market. The onset of action is 15-30 minutes and duration of action is up to 6 hours.

When taking a medication for erectile dysfunction (ED), you’ll want to do everything you can to make sure it’s doing its job. Take a few minutes to learn how to get the most out of your medication. It will pay off later in the bedroom.

  Avanafil Sildenafil Vardenafil Tadalafil
Onset of action 15-30 minutes 30-60 minutes 30-60 minutes 60-120 minutes
Plasma half-life 3 hours 4 hours 4 hours 17.5 hours
Duration of action Up to 6 hours Up to 12 hours Up to 10 hours Up to 36 hours
Effect of food intake Not affected High-fat meals decrease efficacy High-fat meals decrease efficacy Not affected

 

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When Spedra (avanafil) was introduced to the field of erectile dysfunction (ED) drugs in 2012, it was the first ED medication to hit the market in more than a decade. It also brought the number of ED drug options up to five, a fact that has triggered more and more men to wonder, which ED drug is best?

The answer is, it depends. According to Dr. Laurence Levine, a professor in the department of urology at Rush University Medical Center in Chicago, “There is no drug that is the best.” Each man’s individual body chemistry “may make one drug better than another. There are certain advantages and disadvantages to all of these drugs.”

There will be several factors to consider when choosing a suitable ED medication, including your own personal circumstances.

  • How quickly you can expect the drug to take effect. Use of PDE5 inhibitors usually requires planning on the patient’s part. Avanafil has a particularly rapid onset of action: many patients are able to successfully engage in sexual intercourse after 15 minutes, making it attractive for quicker on-demand use.
  • How long the drug’s effect is expected to last. Tadalafil has a particularly long duration of action, up to 36 hours, and can be dosed once daily. This allows for a longer window of opportunity for the patient to successfully engage in intercourse.
  • The effect of food intake before dosing. High-fat food intake before dosing can decrease the efficacy of sildenafil and vardenafil. It is recommended that these drugs be taken on an empty stomach.

Are there any lifestyle changes I can make to help with ED? Well, the same healthy lifestyle tips your doctor has been recommending for years can also help treat your ED:

  • Quitting smoking
  • Reducing alcohol consumption
  • Losing weight
  • Exercising regularly
  • Reducing stress

 

These steps aren’t an instant fix, but they’ll improve your blood flow and nerve functioning. This should give you more energy and may reduce the severity of your ED in the process.

If you’re having trouble sticking to these goals, ask your spouse or partner to join you. Getting healthy together and trying new things as a couple can be a great bonding experience that will strengthen your relationship.

 

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References

  1. https://www.webmd.com/erectile-dysfunction/ss/slideshow-erectile-dysfunction
  2. What’s to know about erectile dysfunction, Jenna Fletcher, https://www.medicalnewstoday.com/articles/316215.php
  3. Erectile dysfunction – an update of current practice and future strategies, Jas KalsiAsif Muneer
  4. www.healthline.com/health/erectile-dysfunction
  5. https://www.coloplastmenshealth.com/learn-more/erectile-dysfunction/how-does-an-erection-occur/
  6. https://www.scientificamerican.com/article/study-lays-bare-the-physi/
  7. Roumeguère T, Wespes E, Carpentier Y, et al  Erectile Dysfunction is associated with a high prevalence of hyperlipidemia and Coronary Heart Disease Risk European Urology.44:355–9.
  8. Recent advances in the treatment of erectile dysfunction, David Mobley, Mohit Khera, Neil Baum.  www.pmj.bmj.com/content/93/1105/679#xref-ref-7-1
  9. Klein R, Klein BE, Lee KE, et al. Prevalence of self-reported erectile dysfunction in people with long-term IDDM. Diabetes Care 1996;19:135–41.
  10. Larsen SH, Wagner G, Heitmann BL. Sexual function and obesity. Int J Obes 2007;31:1189–98.
  11. Shah J. Erectile dysfunction through the ages. BJU Int 2002;90:433–41.
  12.  Mobley D. Early history of inflatable penile prosthesis surgery. Asian J Androl 2015;17:225–9.
  13. Erectile dysfunction,  Edward David Kim, MD, FACS
  14.    https://emedicine.medscape.com/article/444220-overview
  15. Pharmacological management of erectile dysfunction. BJU Int.  2003; 91(5):446-54 (ISSN: 1464-4096) Montorsi F; Salonia A; Deho’ F; Cestari A; Guazzoni G; Rigatti P; Stief C
  16. Avanafil for the treatment of erectile dysfunction: a multicenter, randomized, double-blind study in men with diabetes mellitus. Mayo Clin Proc.  2012; 87(9):843-52 (ISSN: 1942-5546) Goldstein I; Jones LA; Belkoff LH; Karlin GS; Bowden CH; Peterson CA; Trask BA; Day W
  17. H.A. Ghofrani, I.H. Osterloh, F. Grimminger et al Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond
  18. Nat Rev Drug Discov, 5 (2006), pp. 689-702
  19. Phosphodiesterase type 5 inhibitors as a treatment for erectile dysfunction: Current information and new horizons, James E.Ferguson, Culley C.Carson
  20. www.health.harvard.edu/mens-health/should-you-take-a-daily-erectile-dysfunction-pill
  21. A comparison of the available phosphodiesterase-5 inhibitors in the treatment of erectile dysfunction: a focus on avanafil, Jeffery D Evans, and Stephen R Hill
  22. https://www.webmd.com/erectile-dysfunction/how-make-ed-drugs-work-better#1
  23. How Does Avanafil Compare for Erectile Dysfunction? Wayne J.G. Hellstrom, MD; Laura M. Douglass, BS; Mary K. Powers, MD https://www.medscape.com/viewarticle/768904
  24. https://prostate.net/articles/which-ed-drug-is-best/
  25. www.coloplastmenshealth.com/treatments/erectile-dysfunction-treatment

 

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