Erectile dysfunction (ED)

Part 1 – Chemistry, Biochemistry and Molecular Biology

Erectile dysfunction (ED) or impotence (consistent inability to sustain an erection), is a type of sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual activity in humans.

Penile rigidity depends on maximizing inflow while minimizing outflow. Penile erection is a hemodynamic event in the smooth muscle of corpus cavernous. PDE5(1) is the main cGMP(2) hydrolysing enzyme found in penile corpus cavernous. PDE5 inhibitors(3) such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) are clinically indicated for the treatment of erectile dysfunction. Sildenafil and tadalafil are also indicated for the treatment of pulmonary hypertension.

[In recent years there has been an alarming increase in the reporting of sudden loss of vision due to non-arteritic anterior ischaemic optic neuropathy (NAION) occurring in men taking PDEIs (Phosphodiesterase Inhibitors). Disturbances in colour vision and excessive brightness have been reported as adverse events of PDEIs. Such medications are contraindicated in patients with hereditary degenerative retinal disorders such as retinitis pigmentosa].

Aging and poor lifestyle choices are associated with metabolic impediments to Nitric oxide (NO) production. NO is the principal factor increasing blood flow into the penis. NO is produced from the amino acid l‑arginine by the members of the NO synthase (NOS) family of proteins, and is involved in several cellular functions, including neurotransmission, regulation of blood-vessel tone and the immune response. Different members of the NOS family are known to regulate different functions.

In the Central Nervous System (CNS), NO production is associated with cognitive function, its role spanning from the induction and maintenance of synaptic plasticity to the control of sleep, appetite, and body temperature. In the Peripheral Nervous System (PNS), NO regulates the non-adrenergic, non-cholinergic relaxation of smooth muscle cells. This has consequences for a number of tissues: smooth muscle relaxation in the corpora cavernosa, promoting penile erection and it regulates the muscle tone of intestinal sphincters.

Penile engorgement (swelling up) and the pelvic floor muscles, maintain an adequate erection by impeding outflow of blood by exerting pressure on the penile veins from within and from outside of the penile tunica. Extrinsic pressure by the pelvic floor muscles further raises intracavernosal pressure above maximum inflow pressure to achieve full penile rigidity. Aging is also associated with fewer smooth muscle cells and increased fibrosis within the corpora cavernosa, preventing adequate penile engorgement and pressure on the penile veins. Pelvic floor muscles(4) may also decrease in tone and bulk with age, and pelvic floor muscle exercises (Kegel exercises) have been shown to improve erectile function to a similar degree compared with a PDE5 inhibitor in men with erectile dysfunction (ED).
The desire and motivation to pursue sex is basically kicked off by dopamine. Dopamine is a neurotransmitter and heads up the reward circuitry part of the brain. Dopamine causes a person to want, desire, seek out and search, and it’s where a person experiences cravings and anticipation of pleasures.

Dopamine deficiency can have many causes, but some of the most common ones are: stress, alcohol/substance abuse, obesity, poor diet, lack of sleep, exposure to heavy metals, and excessive exposure to porn and sex.

Studies on dopamine are not conclusive but results are encouraging. The use of the D1/D2 dopamine receptor agonist apomorphine(5) for the treatment of erectile dysfunction provides strong support in the control of sexual function. Dopamine is the central player in sexual desire, erections, sexual fetishes and sexual addictions. When a porn user asks why they have sexual dysfunctions – the answer is dopamine. One of the most common complaints is erectile dysfunction, which is due to overstimulation of the reward circuitry. Overstimulation leads to a reduction of dopamine receptors (D2), which are necessary for erections.

While Testosterone increases sexual desire by stimulating dopamine in the brain, sexual satiety leads to fewer testosterone receptors, thus less dopamine. Sexual function doesn’t correlate with blood levels of testosterone. There is also a very interesting interaction between testosterone, nitric oxide and dopamine. Testosterone is not only a necessary ingredient for dopamine to be created, but also a necessary ingredient for nitric oxide production to take place. Increased nitric oxide production in turn causes further dopamine release. And more dopamine will normally mean a stronger response to sexual stimulation.

Article by A B M Procaccini © – Counselling Psychologist, Naturopathist


  1. The essential biological function of phosphodiesterase (PDE) type enzymes is to regulate the cytoplasmic levels of intracellular second messengers, 3′,5′-cyclic guanosine monophosphate (cGMP) and/or 3′,5′-cyclic adenosine monophosphate (cAMP). PDE targets have 11 isoenzymes. Of these enzymes, PDE5 has attracted a special attention over the years after its recognition as being the target enzyme in treating erectile dysfunction.
  2. Guanosine monophosphate synthetase, also known as GMPS is an enzyme that converts xanthosine monophosphate to guanosine monophosphate.
  3. PDE5 inhibitors are contraindicated in those taking nitrate medications, such as isosorbide-mononitrate or isosorbide-dinitrate (Nitrostat, Nitroquick, Nitrolingual, Imdur, Ismo, Monoket). Concurrent use of these medications can lead to life-threatening low blood pressure or heart attack.
  4. Pelvic floor muscles are the layer of muscles that support the pelvic organs and span the bottom of the pelvis. The pelvic organs are the bladder and bowel in men. Having strong pelvic floor muscles gives us control over the bladder and bowel. Weakened pelvic floor muscles mean the internal organs are not fully supported and you may have difficulty controlling the release of urine, faeces or flatus.
  5. Apomorphine SL (Ixense, Uprima) is a new oral medication shown to be effective in the treatment of erectile dysfunction.