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Erectile Dysfunction is an extremely common disorder among men worldwide. So much so that it is estimated that 322 million men will be afflicted by the year 2025. Men experience increased symptoms of ED as they age by 10% per decade of life and researchers are seeing onset of symptoms in younger men due to changes in lifestyle like higher rates of obesity and alcohol or substance abuse. Other factors that contribute to erectile dysfunction are conditions related to vascular disease that impede circulatory function, neurological conditions, physiological and hormonal issues, surgeries, injuries, and mental health conditions or side effects caused by the medication used to treat these conditions.

Since ED is so common, it is probably accepted as a part of life and men just roll with it, right? Nothing is further from the truth. ED impacts men physically, emotionally, psychologically and impacts relationships and quality of life. Sexual function is a key element in our lives, and it is easy to see why ED has such a strong impact on men. Looking up the definition of ED in the Miriam-Webster Dictionary offers all the explanation needed.

Erectile Dysfunction: Chronic inability to achieve or maintain an erection satisfactory for sexual intercourse… (see impotence)

Impotence: Lack of power, strength, or vigor: WEAKNESS

An ABNORMAL physical or psychological state of a male characterized by inability to engage in sexual intercourse due to FAILURE to achieve or maintain an erection.

The terms failure, weakness, and abnormal go a long way to understanding why finding solutions for men who suffer with ED is so critically important. This also emphasizes the need for individualized, comprehensive therapeutic approaches based on each patient’s condition delivered with empathy and respect.

The first step to helping patients is understanding what contributing factors lead to the development of ED and worsening of the condition. To further complicate the basic concept of erectile function, we need to acknowledge that other aspects of sexual function like premature ejaculation, delayed ejaculation, performance anxiety, and even Peyronie’s disease are all encompassed by the term ED. To simplify my approach in working with patients, I use my own definition for ED. “I am not able to perform the way I would like to.”

Age certainly is a big factor in disease progression but contributing conditions like heart disease, diabetes, hormone imbalance, hypertension, depression, seizure disorders, Parkinson’s, MS, and others accelerate and intensify ED. While diagnosis of ED is more of a formality for most men, there are clinical tests and exams (cardiac exam, ultrasounds, nocturnal tumescence tests) as well as questionnaires that take psychosocial history into account.

Urologists employ the SHIM (Sexual Health Inventory for Men) test as part of the diagnostic process to establish a standardized measure of erectile function. Other conditions under the banner of ED also have diagnostic tools used to determine the existence and extent of the disease.

Premature ejaculation is the most common male sexual dysfunction that affects 30% to 75% of men depending on what criteria is used for diagnosis. The most widely used diagnostic measure for PE is intravaginal ejaculatory latency time (IELT), which is the amount of time from initial penetration to climax. An average IELT is 5.5 minutes and PE is defined as IELT less than 2 minutes with levels of severity designated as mild PE (IELT < or = 2 mins), moderate PE (< or = 1 min), and severe PE (< or = 15 seconds). In real world terms, subjective or relational PE is defined as loss of ejaculatory control resulting in emotional distress for one or both partners. To put it simply, if it bothers you, it’s an issue.

Treatment options for ED start with basic diet and exercise, herbs, and supplements to boost circulatory function like nitric oxide, and hormones like testosterone to maintain energy and libido. Many of the first line pharmaceutical agents rely on systemic nitric oxide and testosterone for optimal sexual function. Testosterone is the key hormone that drives libido, which I call “The want to”, while PDE5 Inhibitors (Viagra, Cialis, Levitra, Stendra) promote erectile function, or as I call it “The can do”.

PDE5 inhibitors prolong the activity of cGMP which allows for healthy erections and cGMP relies on healthy levels of nitric oxide to function at levels required for satisfactory sexual function. Since there are frequently psychological components in each form of ED, any therapy that offers benefits for one aspect may very well improve subsequent issues. Because of this, there is significant overlap in therapies for different types of ED.

Medicines like Viagra (sildenafil), Cialis (tadalafil), Levitra (vardenafil), and Stendra (avanafil) have proven to be game changers for men suffering from various degrees of ED. They promote erectile function, can significantly benefit patients with premature ejaculation and performance anxiety and have proven to be safe and effective for millions of men.

The medications

Sildenafil (Viagra/Revatio) — Onset of action is 30-60 mins/duration is 4-8 hrs, full stomach (especially fatty foods) impair absorption so dose 1 hour before or 2 hours after eating. Least selective of the PDE5s so side effects are more prevalent. (Side effects include congestion, headache, flushing, palpitations, visual anomalies.)

Tadalafil (Cialis) — Onset of action is 30-60 mins BUT full effect may take 2-4 hrs, while duration is 36 hrs which makes it an excellent daily dose candidate. Stomach content is not an issue. More selective than sildenafil, so similar but slightly better side effect profile but higher incidence of heartburn, back pain, and leg cramps.

Vardenafil (Levitra/Staxyn ODT) — Onset of action is 30-60 mins (faster for ODT)/duration is 4-5 hours. Stomach content not a big issue, especially for ODT. Similar but milder side effects because vardenafil is more selective than either sildenafil or tadalafil.

Avanafil (Stendra) — Onset of action is 15-30 mins/duration is 4-6 hrs BUT needs to be taken on an empty stomach. Most selective PDE5 so much less severe side effect profile.

As impressive as these medicines are, they are not without caveats. Delayed onset of action and interference from stomach contents make preplanning and dose scheduling important. In addition, oral dosage forms are affected by first pass metabolism which can account for elimination of up to a third of the medication before it reaches the bloodstream.

Sublingual dosage forms of these medications (compounded troches/ODTs/RDTs) alleviate many issues that impede effective therapy. SL dosage forms bypass the GI system, improve onset of action by 50-65%, and deliver higher levels of active drug to the bloodstream because they avoid first pass metabolism. Compounded preparations also have the added benefit of being able to combine multiple active ingredients into a single dosage form to augment patient response.

Combining active ingredients, like multiple PDE5Is, allows us to maximize the potential benefits and navigate side effects. Incorporating other ingredients like apomorphine, a D2 dopamine agonist that boosts libido and is involved in the initiation of the erectile cascade, adds elements to the therapeutic approach the commercially available products cannot. Oxytocin is another favorable ingredient that boosts feelings of intimacy and promotes erectile and orgasmic function. Even testosterone can be added to a sublingual troche to boost libido, and energy and augment erectile response. Apomorphine, oxytocin, and testosterone may also benefit patients dealing with delayed ejaculation (DE), performance anxiety (PA), or anorgasmia. Thinking out of the box with these therapies allows us to address multiple issues a patient may be dealing with in a single dosage form.

Medication options

In patients who either cannot take these medications or do not respond to them, urethral inserts and penile injections may be appropriate options. In both instances, vasodilators are used to illicit erectile response, but the routes of administration are very different. Urethral inserts are available commercially as Muse suppositories and compounding pharmacies offer urethral gels or suppositories. (Muse is a prostaglandin (alprostadil) urethral insert that is available in 250mcg, 500mcg, and 1000mcg strengths.)

The urethra is not a good route of absorption which is why the doses are up to 100x higher than what we see in penile injections. Even though compounding pharmacies can increase potency by incorporating multiple vasodilators, urethral administration is still not optimal. In addition, urethral application can be uncomfortable, and patients need to be instructed to wear a condom to avoid discharging highly concentrated vasodilators into their partners.

Most patients who move on from PDE5Is will graduate to penile injections. Once the initial shock of “you want me to stick a needle where?” wears off, these medicines can be highly effective for treatment of ED, performance anxiety, and even premature ejaculation. Penile injections are composed of vasodilators (1, 2, 3 or more ingredients) that are injected into the corpus cavernosa (chambers within the penis) using insulin or TB syringes.

There are commercially available options (Edex/Caverject) composed of alprostadil (prostaglandin), but they are expensive. Many prescribers call on compounding pharmacies after being denied by insurance companies for prior authorizations on these medicines or told by patients the medicine is not affordable. Compounding pharmacies are able to use single ingredient formulas, like the commercial products, or combine multiple vasodilators to best address the particular needs of individual patients. Formula adjustments, dose titrations, and administration instructions allow for improved outcomes and quality erectile function at a fraction of the cost of the trade products.

For patients who cannot use these approaches, or choose against medication therapy, all is not lost. Vacuum erection devices — penis pumps — are a nonpharmaceutical option to maintain erections adequate for intercourse (even though they are somewhat mechanical in nature). VEDs have been around for decades and when used with retention rings (AKA “cock rings”) allow men to sustain firmness and return intimacy to their relationships.

As you can see, there is a vast array of options to aid the overwhelming number of patients who suffer from various forms of erectile dysfunction. Many of these therapeutic approaches are somewhat novel and may not be familiar to some prescribers. Resources are available to help both practitioners and patients find the solutions most appropriate for their condition. Becoming familiar with these therapies and resources is the first step to building a practice that is positioned to grow and expand into the sexual health arena.

References: Erectile Dysfunction

  1. Epidemiology Update of Erectile Dysfunction in Eight Countries with High Burden – Irwin Goldstein MD, Amir Goren PhD, Vicky W Li MPH, Wing Y Tong MPH, Torek A Hassan MD; Sexual Medicine Reviews, Vol 8, Issue 1, Jan 2020, pgs. 48-58
  2. Erectile Dysfunction (ED): Symptoms, Causes, Diagnosis, and Treatment – Roger Bielinski MD; The Healthline Editorial Team Nov 29, 2023
  3. Sexual Health Inventory for Men Questionnaire as a Screening Method for Erectile Dysfunction in a General Urology Clinic. Amjad Alwaal MD, Mohannad Awad MD, Nathan Boggs APRN, Jake Kuzbel BS, Brian Snoad BS; Sexual Medicine, Vol 8, Issue 4, December 2020, Pgs. 660-663
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  9. Effects of PDE5 Inhibitors on choroid and ocular vasculature: A literature review. Natasha Ferreira Santos Da Cruz, Murilo ubukata Polizelli, Lais Maia Cezar, E B Cardosa, Fernando Penha, Michael Eid Farah, Eduardo B Rodrigues, Eduardo A Novais; International Journal of Retina and Vitreous, 6. Article number: 38(2020)
  10. National Library of Medicine; PDE5 Inhibitors. Armaan Dhaliwal, Mohit Gupta, Statpearls August 10, 2023Review – Urol Int: 2001;67(4):257-63, doi:10.1159/000051001
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