Medical treatment of erectile dysfunction

The medical treatment of erectile dysfunction follows two lines: oral PDE5 inhibitors as first-line therapy, effective in over 70–80% of cases, and local alprostadil (Prostaglandin E1) as second-line therapy when the first line proves insufficient. Only certain forms of ED have a cause-specific cure; most men are treated with options that are not cause-specific, which requires a structured approach involving the partner and weighing efficacy, safety, invasiveness and cost.

Cause-specific treatment: when the cause can be cured

Only two forms of ED can be treated at the root:

• Psychogenic ED: several psychotherapeutic approaches can be offered — behavioural, cognitive, analytic — depending on the factors involved, either alone or alongside another therapeutic approach
• Hormonal ED: testosterone replacement therapy is effective when an androgen deficiency is documented, but it should be used only once other endocrine causes of ED have been excluded, such as hyperprolactinaemia, hyperthyroidism or hypothyroidism

In all other cases — ED with neurovascular components related to metabolic disease such as diabetes, hypercholesterolaemia or hypertriglyceridaemia — treatment does not act on the cause but on the mechanism of erection.

First line: oral drugs (PDE5 inhibitors)

Phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) are the first-line therapy set out in international guidelines. They act by producing vasodilation at penile level and, when correctly used, prove effective in over 70–80% of cases, depending on the factors underlying the disorder.

They can be taken in two ways:

• Acute (on-demand) administration: at the time of intercourse
• Chronic administration: as part of a programme to rehabilitate penile circulation

These are not aphrodisiacs or supplements. They are prescription-only medicines, each with its own indications and contraindications, used to treat a pathological condition. They must therefore be assessed and prescribed under close specialist medical supervision.

Second line: local alprostadil (PGE1) therapy

When first-line therapy is not effective, treatment moves to local therapy with alprostadil (Prostaglandin E1, PGE1), a vasoactive drug delivered directly to the penis. There are three routes of administration.

1. Intracavernous microinjection

The drug is injected into the penis with a very fine needle. As with oral drugs, it can be used on demand at the time of intercourse or in chronic administration as rehabilitation of penile circulation. It can be used alone or together with a vacuum device, which creates a vacuum around the penis and draws blood into it.

The first injections are performed by the specialist to establish the correct dose for the individual patient (outpatient training). The patient may then, if he wishes, self-administer the therapy by learning a very simple manual technique — not only to obtain an erection, but to continue rehabilitating penile circulation.

Important: prolonged or painful erections, or penile curvature occurring during the use of intracavernous injections, must always be reported to the specialist. An erection lasting more than four hours (priapism) is a medical emergency.

2. Transurethral administration

A transurethral device consisting of an applicator and a medicated pellet containing alprostadil, released into the urethra by inserting the stick and pressing the top of the applicator. It acts rapidly, within 10 minutes, and produces an erection lasting 30–60 minutes. The drug is rapidly metabolised, both locally and in the pulmonary capillaries; metabolites are excreted in the urine (90% within 24 hours) and in the faeces.

3. Topical urethral cream

Alprostadil cream is applied to the tip of the penis, inside the external urethral meatus, using a single-dose container. It is available in two strengths, 200 and 300 micrograms of alprostadil in 100 mg of cream. The erectile effect appears 5–30 minutes after administration and lasts approximately 1–2 hours. Alprostadil is rapidly absorbed into the corpus spongiosum of the urethra and into the corpora cavernosa, metabolised locally by enzymatic oxidation, and eliminated via the kidneys, liver and faeces.

Why transurethral and topical routes rather than injection

Compared with alprostadil given by intracavernous injection, the transurethral and topical forms are less invasive, have fewer side effects and significantly improve patient compliance: less pain, less burning, greater satisfaction.

When medical therapy is not enough

For cases that do not respond to medical treatment, the remaining options are surgical treatment and the penile prosthesis. The choice is always shared with the patient and, where possible, with his partner.

Frequently asked questions about medical treatment of erectile dysfunction

Do oral drugs for erectile dysfunction always work?

They are effective in over 70–80% of cases when correctly used, but not in every case. The success rate depends on the underlying cause: long-standing diabetes, radical pelvic surgery and advanced vascular damage all reduce the response. Where there is no response, second-line therapy is available.

Are erectile dysfunction drugs aphrodisiacs?

No. They are prescription-only vasodilator drugs with precise indications and contraindications, used to treat a medical condition. They do not increase sexual desire and still require sexual stimulation in order to work.

Are penile injections painful?

They are given with a very fine needle. The initial training is carried out by the specialist in an outpatient setting to establish the correct dose; the patient can then self-administer using a simple manual technique. Burning or pain should be reported to the specialist, as should prolonged erections or penile curvature.

Are there alternatives to injection?

Yes. Alprostadil can be given transurethrally or as a cream applied inside the urethral meatus. These are less invasive options, with fewer side effects and better compliance than injection.

Does medical therapy cure erectile dysfunction or just mask it?

It depends on how it is used. Taken on demand, the drug enables intercourse; taken chronically, it forms part of a programme to rehabilitate penile circulation, with a therapeutic rather than purely symptomatic aim. The strategy is defined with the specialist after diagnosis.

Would you like to find out which treatment is right for you? Ask Prof. Natali for a consultation or book an appointment at his practices in Florence and Empoli, Italy.

The information on this page is provided for general educational purposes and does not replace a medical examination, which remains the only diagnostic tool for correct and effective treatment. All medicines mentioned are prescription-only.

SECOND LINE THERAPY

Patients not responding to ED-oral drugs may be offered the so called intracavernous therapy with high success rates of 85%. Intracavernous administration of vasoactive drugs was the first medical treatment for ED more than 20 years ago. Alprostadil (Caverject®) is the first and only drug approved for intracavernous ED treatment. It is necessary to perform a microinjection into the penis with this drug and then the erection appears after 5-15 minutes and lasts according to the dose injected. These drugs as well as those given orally, have the goal to treat and improve the circulation as well as the function of the penis. These penile microinjections can be used alone or together with Vacuum constriction Devices (devices which provide passive engorgement of the penis in conjunction with a constrictor ring placed at the base of the penis to retain blood within the penis). An office-training programme (one or two visits) is required for the patients to learn the correct injection process. After at home the patient can use intracavernous therapy not only to achieve a temporary erection to have sex, but also to continue the rehabilitation of the penile circulation (cavernosal gym).

Today it is possible to use  Topical Prostaglandin E1 (Alprostadil) also by MUSE® (Medical Urethral System for Erection )  and VITAROS®.

MUSE ® (Medical Urethral System for Erection )i s a single-use, medicated transurethral system  to deliver the drug  to the male urethra. Alprostadil is suspended in polyethylene glycol 1450 (as excipient) and is formed into a medicated pellet (micro-suppository measuring 1.4 mm in diameter by 3 mm or 6 mm in length) that resides in the tip of a translucent hollow applicator. MUSE is administered by inserting the applicator stem into the urethra after urination. The pellet containing alprostadil is delivered by depressing the applicator button  The components of the delivery system are constructed of medical grade polypropylene. Each MUSE system is packaged in an individual foil pouch. MUSE is available in 4 dosage strengths: 125 mcg, 250 mcg, 500 mcg, and 1000 mcg. 

VITAROS® is a new topical, non-invasive treatment for ED that offers the combination of an active drug (alprostadil, a synthetic PGE1) with a skin enhancer that improves its local absorption directly at the site of action. VITAROS has a favorable pharmacodynamic profile and is poorly absorbed in systemic circulation. This makes it suitable in any circumstances and results in a reduced risk of adverse events (AEs), being systemic AEs reported in only 3% of the treated population. Its clinical efficacy has been demonstrated in both phase II and III trials, showing a global efficacy up to 83% with the 300 μg dose in patients with severe ED significantly better than placebo. Its fast onset of action together with its favorable toxicity profile and lack of interactions with other drugs makes VITAROS a second-line therapeutic option for patients with ED, particularly for individuals who are reluctant to take systemic treatments or with AEs. It may also have an important role in patients not responding to PDE5 inhibitors. VITAROS is available in 2 dosage strenghts:200 mcg and 300mcg