Fuelling the black market for ED drugs

It’s estimated that one in five South African men suffer from erectile dysfunction and only a fraction seek medical help.

The globalisation of drug manufacturing and the anonymity and ubiquity of the internet are fuelling the traffic in male enhancement pills, and generating a market for the more questionable manufacturers.

A study, published in JAMA Internal Medicine, by Pieter Cohen, Assistant Professor of Medicine at Harvard Medical School and a colleague collected some of the lesser known facts about an industry that produces millions of pills — and likely generates tens of millions, if not billions in profits.

Here’s what they found

Here’s what they found:

*  A product sold as ‘Rock Hard for Men’ in 2012 turned out to contain not only counterfeit Cialis (tadalafil) — but also a diabetes drug that can be deadly if used incorrectly. A similar combination killed more than a dozen men in Asia in 2009.

*  One Utah company alone produced more than a million pharmaceutically-tainted pills monthly, earning $2 million (R25 964 766,33) between 2007 and 2010, according to an indictment issued in one of the few cases brought against such manufacturers.

*  More than three-quarters of male enhancement supplements tested in one study in Singapore contained pharmaceuticals that were not disclosed — and half of them were present in higher doses than recommended.

*  Over 45 different versions of drugs in the same class of Viagra have now been found in male sexual supplements. A Dutch study found that 75% of the products sold in the Netherlands contained at least one analogue, or chemical variant that has the same effect as Viagra.

* A product called ‘Mojo Nights’ recently analysed by the Food and Drug Administration (FDA) included not just counterfeit Viagra, but also three different analogue drugs.

* The FDA identified three tainted supplements: ‘Vicerex’ and ‘Bullet Proof,’ which contain counterfeit Cialis and ‘Lightning ROD,’ which includes an analogue of Viagra.

Male sexual enhancement pills are considered to be one of the most counterfeited drugs in the world, and South Africans are among the biggest consumers of black market ED drugs.

Fatal drug interactions

When used in conjunction with nitrate containing medications, PDE5 inhibitors can cause excessive vasodilation and hypotension, which can result in death. The use of nitrate containing medication is a definite contraindication to prescribing PDE5 inhibitors. Nitrate-containing drugs are commonly used to treat diabetes, heart conditions, hypertension and hypercholesterolaemia.

The conditions these medications are used to treat are often widespread in men who have ED, suggesting that a significant proportion of men using counterfeit male sexual enhancement drugs, are putting their lives at risk.

A real drug masquerading as an herbal remedy can be dangerous, even life-threatening. It is imperative that clinicians warn patients about the dangers of purchasing of black market ED drugs online.

Background epidemiology of ED
ED is defined as the inability to have or sustain an erection adequate for satisfactory sexual activity. It is one of the most common chronic medical disorders in men over the age of 40.

A global study of sexual attitudes and behaviours, targeting an adult population aged 40 – 80 years across 29 countries, identified early ejaculation and difficulty in achieving and maintaining an erection as the problems most commonly reported by men, affecting 24% and 17%, respectively.

The prevalence and severity of the disorder increases with age; men in their 50s are three times more likely to experience ED than men in their twenties. It is estimated that moderate to complete ED affects 45% of men in their mid-60s, with a further increasing prevalence in older age groups.

Pathophysiology

Two-thirds of cases of ED are organic in origin and comorbid conditions should therefore be actively evaluated. Heart and vascular diseases (especially those associated with hyperlipidemia, diabetes, and hypertension) are associated with ED.

The combination of these conditions and aging increases ED risk in older men. Other hormonal and metabolic problems including primary and secondary hypogonadism, hypothyroidism, chronic renal failure, and hepatic failure, also negatively impact on erectile function.

Testosterone levels do decline slightly with age, but are only related to ED in the small minority of men (~3-5%) who are truly hypogonadal and have low hormone levels. Substance abuse, such as excessive intake of alcohol or other recreational drugs is a major contributor to ED.

Smoking, a known cause of arterio-occlusive disease, is clearly a co-factor and probably an independent etiologic factor itself. Penile anatomical defects and Peyronie’s disease may contribute to erectile problems. Spinal cord injuries, pelvic and prostate surgery and pelvic trauma are less common causes of dysfunction. Psychogenic disorders, including depression, dysphoria, and anxiety states are associated with an increased incidence of multiple sexual dysfunctions including erectile difficulties.

Iatrogenic ED can result from nerve disrupting pelvic or prostate surgery; inadequate glycemic, blood pressure, or lipid control; and many of the medications commonly used in primary care. Antihypertensive medications, notably diuretics and central acting agents, can cause ED, as can digoxin, psychopharmacologic agents, including some of the newer antidepressants, and antitestosterone hormonal agents.

Investigation medical history

The medical history should include review for risk factors and screening for psychological problems. A medication review, including over-the-counter drugs may reveal the source of the problem since medications have been implicated in up to 25% of cases of ED.

When evaluating for the presence of psychological problems, brief screening for depression may elicit responses. Other psychiatric conditions, such as anxiety, may also be responsible for ED. It is critical that the social history include assessing for stress regarding a relationship or substance abuse including alcohol and cigarettes. Specific questions regarding the presence of claudication during activity (e.g., walking up stairs) or decreased thigh muscle strength or size increases suspicion for pelvic inflow vascular occlusive disease.

Finally, a review of daily activities and of cardiovascular status are important to determine the potential risk for enhancing ED in patients who may have a sedentary lifestyle and who may be at risk for an adverse cardiac event when sexual activity potential is increased.

Sexual history

A sexual history is the most important component of diagnosis. Some physicians may find it useful to use a sexual health questionnaire, and to involve the partner as this will not only confirm the problem, but also may reveal other causes of sexual dysfunction.

Focused physical examination

The physical examination should be comprehensive, with emphasis on several areas. Evaluation of blood pressure, cardiac size and heart sounds, and a complete peripheral vascular examination looking specifically for abdominal or femoral bruits, diminished femoral pulses, orthigh muscle wasting (signs of decreased pelvic inflow), may contribute to the diagnosis of vascular disease as an associated cause.

A neurologic examination that includes the evaluation of pelvic sensory function and anal sphincter tone is needed to confirm both sympathetic and parasympathetic function.

A digital rectal examination of the prostate should be conducted, and a visual and manual exam of the penis to discover any anatomical defects and help to identify Peyronie’s disease. Immature secondary sex characteristics, including lack of male hair distribution, poor penile and testicular development, gynecomastia, and fine wrinkling at the corners of the eyes and mouth, indicate the possibility of hypogonadism.

Laboratory evaluation

Laboratory testing to evaluate ED will confirm risk factors/entities previously identified. A urine analysis to rule out renal disease or infection; a complete blood count to note any potential hematologic disorder; a chemistry profile to check for fasting glucose, renal, and hepatic function; a lipid profile to rule out hyperlipidemia; and TSH to evaluate thyroid function.

Prostate specific antigen (PSA) should be considered in men over age 45 years with risk factors for prostate cancer especially if testosterone treatment is a possibility. A morning serum total testosterone and prolactin level should be measured on all patients, although the threshold level of testosterone for maintaining an erection is unknown.

Borderline or unequivocally low levels require confirmation of diagnosis by measuring calculated free or bioavailable testosterone and sex hormone binding globulin (SHBG) levels. SHBG binds 60% of testosterone and often is low or low normal in obesity and many normal men and therefore results in artifactually low serum total testosterone measurements.

Unequivocally low testosterone measurements additionally require measuring luteinising hormone (LH) and prolactin for differential diagnosis. However, the majority of causes of ED are not due to low testosterone.

If the patient is well known to the physician and the problem is clearly not related to libido or ejaculatory disorders, and there are other contributing factors that can account for the ED, these tests can be ordered on an individual basis. If there is any evidence of hypogonadism or the dysfunction is particularly consistent at a young age, then further hormone evaluation is obligatory.

Management counselling

Because ED often has a psychological component, patient or couple counseling may help reduce anxiety and overcome the condition. This therapy is sometimes used in combination with other treatments as directed by the practitioner.

Lifestyle modification

Making healthy lifestyle changes may reduce the symptoms of ED and improve general physical health. Patients should understand that lifestyle habits that negatively affect the heart and the peripheral vascular system or the nervous system will also negatively affect the penis.

Recommended lifestyle changes:

  • Stop smoking
  • Reduce fat and cholesterol in diet
  •  Increase exercise
  • Lose weight if overweight
  • Comply with prescribed diabetes and cardiovascular medication regimens
  • Reduce stress

Oral medications

The most effective and useful drugs available are inhibitors of phosphodiesterase type V, an enzyme present predominantly in the penile smooth muscles and responsible for vasoconstriction.

Currently, sildenafil, tadalafil and vardenafil are marketed. Randomised trials demonstrate that sildenafil is effective in most etiologies of ED with efficacies of up to 80%.

In some groups, i.e., post radical prostatectomy or diabetes, sildenafil may have lower efficacy ranging from 40 to 57%. Lower doses (25mg) of sildenafil may be given to patients who are elderly; have renal or hepatic insufficiency; have spinal cord injury (where there is an increased sensitivity to sildenafil); have moderate to severe coronary vascular insufficiency and not using nitrates; or are taking another drug that is a cytochrome P450 inhibitor.

Note: When used in conjunction with nitrate containing medications, PDE5 inhibitors can cause excessive vasodilation and hypotension, which can result in death. The use of nitrate containing medication is a definite contraindication to prescribing PDE5 inhibitors.

Recent data suggest severe coronary disease may not be a contraindication to PDE5 inhibitors. However, data is limited and caution is strongly advised in these situations.

Intracavernosal injection therapy

Intracavernosal injection therapy can be considered when oral medications appear to be ineffective. This injection is given directly into the corpus cavernosum through the side of the penis. The success rate is high, but problems may include pain, prolonged erections or priapism, and penile fibrosis and plaques.

It is recommended to start with the minimal effective dose and titrate upwards. Spinal cord injury patients often have an exaggerated response and require lower doses. The recommended maximal frequency of usage is three times weekly with 48 hours between dosages. Urologic consultation is recommended for patients in whom this treatment is being considered. Note: Caution should be exercised for patients on anticoagulation medications.

Penile implant surgery is a successful therapy, although it should be reserved for patients who have considered or tried several other treatments. The surgery is irreversible and the normal function of the corpus cavernosa is obliterated. The surgery carries low morbidity and mortality and the satisfaction rate is high. It is a well-established urological procedure.

References:

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