Medical symptoms

Erectile dysfunction is characterised by the inability to maintain erection. Normal erections during sleep and in the early morning suggest a psychogenic cause, while loss of these erections may signify underlying disease, often cardiovascular in origin. Other things leading to erectile dysfunction are diabetes mellitus (causing neuropathy) or hypogonadism (decreased testosterone levels due to disease affecting the testicles or the pituitary gland).

Medical diagnosis

There are no formal tests to diagnose erectile dysfunction. Some blood tests are generally done to exclude underlying disease. Studies have shown that male circumcision may result in an increased risk of impotence (Palmer). [1] (http://www.cirp.org/library/complications/palmer/) This has also been verified in China. [2] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14979200&dopt=Abstract)

Pathophysiology

Penile erection is managed by two different mechanisms. The first one is the reflex erection, which is achieved by directly touching the penile shaft. The second is the psychogenic erection, which is achieved by erotic stimuli. The former uses the peripheral nerves and the lower parts of the spinal cord, whereas the latter uses the limbic system of the brain. In both conditions an intact neural system is required for a successful and complete erection. Stimulation of penile shaft by the nervous system leads to the secretion of nitric oxide (NO), which causes the relaxation of smooth muscles of corpora cavernosa (the main erectile tissue of penis), and subsequently penile erection. Additionally, adequate levels of testosterone (produced by the testes) and an intact pituitary gland are required for the development of a healthy male erectile system. As can be understood from the mechanisms of a normal erection, impotence may develop due to hormonal deficiency, disorders of the neural system, lack of adequate penile blood supply or psychological problems.

A few causes of impotence may be iatrogenic (medically caused). Various medications intended to control blood pressure or to modify central nervous system response, may inhibit erection by denying blood supply or by altering nerve activity. Surgical intervention for a number of different conditions may remove anatomical structures necessary to erection, damage nerves, or impair blood supply.

Treatment

Treatment depends on the cause. Testosterone supplements may be used for cases with hormonal deficiency. However, usually the cause is lack of adequate penile blood supply as a result of age-dependent damage of inner walls of blood vessels. Previously, medical substances (e.g. apomorphine) were directly injected into the erectile tissue of penile shaft to treat impotence. In some cases refractory to the medical treatment, a penile implant (penile prosthesis) could be advised. After the discovery of orally active agents that increase the efficacy of NO, which dilates the blood vessels of corpora cavernosa, more conservative methods started to be used.

Sildenafil (Viagra)

Sildenafil citrate, sold under the name Viagra, is a drug used to treat male erectile dysfunction (impotence), developed by the pharmaceutical company Pfizer. The pills are blue with the words "Pfizer" on one side and "VGR xx" (with xx being either 25, 50 or 100 as the dose of that pill in milligrams) on the other.

Viagra was initially developed to treat heart disease (angina). In trial studies, the penile erection enhancing effects were noticed. The drug was patented in 1996, approved by the FDA on March 27, 1998 (becoming the first pill approved to treat erectile dysfunction in the United States) and offered for sale in the United States later that year. It soon became a smashing success. Even though Viagra is only available by prescription from a doctor, it was advertised directly to consumers on TV (famously being endorsed by Bob Dole). Numerous sites on the Internet offer Viagra for sale after an "online consultation," a mere web questionnaire. It is likely that many men (and some women) experiment with the drug to increase sexual prowess or pleasure. Annual sales of Viagra in the period 1999-2001 exceeded $1 billion.

It has been suggested that Viagra would lead to a marked drop in the demand for certain traditional remedies, such as tiger penises and rhinoceros horns and that the drug may therefore help to preserve these endangered species. However, this is unlikely in that these parts of endangered species are not only used to treat impotence. Rhinoceros horns, for example, are used as a treatment for high fever. Further, since Viagra has not been shown to possess aphrodisiac properties, it is unclear that the natural remedies would compete with this new clinical drug.

The "Viagra" name has become so well known that many fake aphrodisiacs now call themselves "herbal Viagra" or are presented as blue tablets imitating the shape and colour of Pfizer's product. Pfizer's worldwide patents on sildenafil citrate will expire in 2011 - 2013. The UK patent held by Pfizer on the use of PDE5 inhibitors (see below) as treatment of impotence has been invalidated in 2000 because of obviousness; this decision was upheld on appeal in 2002.

Chemical name: 1-[4-ethoxy- 3-(6,7-dihydro- 1-methyl- 7-oxo- 3-propyl- 1H-pyrazolo [4,3-d]pyrimidin-5-yl) phenylsulfonyl]- 4-methylpiperazine citrate Chemical formula: C₂₂H₃₀N₆O₄S·C₆H₈O₇ Molecular weight: 666.7 g/mol Molecular structure (as the base, not the citrate salt):

Part of the physiological process of erection involves the release of nitric oxide (NO) in the corpus cavernosum. This then activates the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation in the corpus cavernosum, resulting in increased inflow of blood and an erection.

Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum. This means that, with Viagra on board, normal sexual stimulation leads to increased levels of cGMP in the corpus cavernosum which leads to better erections. Without sexual stimulation and no activation of the NO/cGMP system, Viagra should not cause an erection.

Viagra is metabolised by hepatic enzymes and excreted by both the liver and kidneys. If taken with a high fat meal, there may be a delay in absorption of Viagra and the net effect might be muted slightly as the plasma concentration will be lowered. Some reports have claimed that Viagra causes enhanced sexual pleasure for women by increasing blood flow to the sexual organs.

Contraindications and side effects include:

• When taking other nitric oxide donors, organic nitrites and nitrates (which includes glyceryl trinitrate, sodium nitroprusside, amyl nitrite)
• In men for whom sexual intercourse is inadvisable due to cardiovascular risk factors
• Severe hepatic impairment
• Severe impairment in renal function
• Hypotension
• Recent stroke or heart attack (myocardial infarct)
• Hereditary degenerative retinal disorders (including genetic disorders of retinal phosphodiesterases)

Amongst Viagra's serious adverse effects are: priapism, severe hypotension, myocardial infarction, ventricular arrhythmias, sudden death, stroke and increased intraocular pressure. Common side effects include sneezing, headache, flushing, dyspepsia, prolonged erections, palpitations and photophobia. Visual changes including blurring of vision and a curious bluish tinge have also been reported.

As with all prescription drugs, proper dosage is at the discretion of a licensed medical doctor. The dose of Viagra is 25mg to 100mg taken once per day between 0.5 to 4 hours before sexual intercourse. It is usually recommended to start with a dosage of 50 mg and then lower or raise the dosage as appropriate. The drug is sold in three dosages (25, 50, and 100 mg), all three costing about USD$10 per pill. Viagra is not scored, meaning there is no guarantee that the drug is evenly distributed throughout the tablet, therefore it is not advisable to cut it to change dosage.

Vardenafil (Levitra)

Vardenafil (Levitra) is a prescription drug used in the treatment of erectile dysfunction. It can assist men with this disorder in achieving and maintaining an erection during sexual activity. It should not be used with types of medicines called nitrates and alpha-blockers because of potentially dangerous interactions with these drugs. Television commercials for the drug also warn that in the event an erection lasts for more than four hours, a condition known as priapism, medical advice should be sought immediately.

Vardenafil was co-marketed by Bayer Pharmaceuticals and GlaxoSmithKline under the trade name Levitra. According to a press release issued by the Bayer group on January 10, 2005, the co-promotion rights of GlaxoSmithKline on Levitra have been "transferred back" to Bayer for major markets in Asia, Europe, Africa, and other areas outside of the United States. Both companies continue to co-promote Levitra in the United States. In Italy, Bayer markets the product as Levitra and GSK markets the product as Vivanza.

As a PDE5 inhibitor, vardenafil is closely related in both function and marketing to sildenafil and tadalafil; it has a relatively short effective time, comparable to sildenafil. It is available in 2.5 mg, 5 mg, 10 mg, and 20 mg doses in round orange tablets. The normal starting dose is 10 mg, roughly equivalent to 50 mg of sildenafil, and like sildenafil the maximum recommended frequency of use is once daily.

Tadalafil (Cialis)

Tadalafil (Cialis®) is a drug used to treat male erectile dysfunction (impotence), developed by the biotech ICOS, and marketed worldwide by Eli Lilly. The generic name for this compound is tadalafil. The tablet are yellow and oval-shaped.

Cialis's main selling points: It works for up to 36 hours after being swallowed and can be taken with or without food (Viagra works for some 4 hours). It has the same mode of action as sildenafil (Viagra), and vardenafil (Levitra).

Men taking nitrates or or alpha blockers should not take Cialis because it could cause blood pressure problems. Some of the side effects of the drug include back ache, stomach ache, muscle aches, or headaches. The company advises that in the rare event that an erection lasts for more than four hours (a condition called priapism), the man should seek emergency medical attention. Cialis has a multiyear promotional deal with professional golf. Cialis has FDA approval and appeared in U.S. stores in December, 2003.

PT-141

The new drug PT-141 does not act on the vascular system like the former compounds but increases sexual desire and drive in male as well as female. It is apllied as a nasal spray PT-141 and works by activation of melanocortin receptors in the brain.

Ginseng

A double-blind study appears to show evidence that ginseng is better than placebo: see the ginseng article for links and more details.

Enzyte

Enzyte is a product that has been advertised by saturation coverage on television channels such as Court-TV. However, the Center for Science in the Public Interest (CSPI) has filed a complaint with the Federal Trade Commission (FTC) about Enzyte for deceptive advertising. It is manufactured by Berkeley Nutritionals, which is alleged to be the subject of an investigation by the Attorney General of Ohio and the defendant in class-action lawsuits.

Enzyte is a supplement that claims to increase the frequency of erections of the male penis or libido. Commercials for Enzyte are shown regularly on television. These commercials feature a man named Bob who never stops smiling, apparently because he had taken Enzyte and improved the size of his sex organs. The commercials are riddled with symbolic phallic imagery, e.g. golf clubs, remarkably tall glasses of iced tea, and a hose spraying barely a trickle of water (carried by someone who doesn't use Enzyte).

The effectiveness of Enzyte is in dispute. Some medical professionals in fact advise against taking Enzyte, saying that it can lead to damage. The Center for Science in the Public Interest have urged the Federal Trade Commission to disallow further television advertising for Enzyte due to a lack of proper studies supporting claims. Enzyte maker Berkeley Premium Nutraceuticals, Inc., is currently under a class action lawsuit for false advertising.

Enzyte is said to contain: Tribulus terrestris; Yohimbe Extract; Niacin; Epimedium; Avena sativa; Zinc Oxide; Maca; Muira Pauma; Ginkgo biloba; L-Arginine; Saw Palmetto. Other ingredients: gelatin, rice bran, oat fiber, magnesium stearate, silicon dioxide.

References

• Dr. John R. Brinkley began a fad for finding cures for male impotence during the 1930s. He used the medium of radio to achieve the same kind of advertising boom to treat the same kind of symptoms. Today the medium of television is being used for that same purpose. Time will tell how history will rate the current advertising campaigns by Viagra, Cialis, Levitra and Enzyte.

External sources

• Home Page for Viagra (http://www.viagra.com/)
• Pfizer Pharmaceutical (Company website) (http://www.pfizer.com/) - manufacturer of Viagra; prescribing information (http://www.pfizer.com/download/uspi_viagra.pdf) available in PDF format.
• FDA Web Site for Viagra Consumer Information (http://www.fda.gov/cder/consumerinfo/viagra/)
• Viagra Misunderstood (http://www.usrf.org/breakingnews/bn_111202_viagra/bn_111202_viagra.html) Article describing what Viagra feels like
• Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, Zusman RM. ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association. J Am Coll Cardiol. 1999 Jan;33(1):273-82. (Medline abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9935041)) (Full text (http://www.acc.org/clinical/consensus/viagra.htm))
• Official Levitra website (http://www.levitra.com/)
• FDA's Consumer Information (http://www.fda.gov/cder/consumerinfo/druginfo/levitra.htm)
• Enzyte investigation reported on CBS-TV news site (http://www.cbsnews.com/stories/2004/09/23/health/webmd/main645232.shtml)
• Enzyte Company website (http://www.mgsglaw.com/enzyte.html)