Nerve or spinal cord damage: Damage to the spinal cord and nerves in the pelvis can cause erectile dysfunction. Nerve damage can be due to disease, trauma, or surgical procedures. Examples include injury to the spinal cord from automobile accidents, injury to the pelvic nerves from prostate surgery for cancer (prostatectomy), and some surgeries for colorectal cancer, radiation to the prostate, surgery for benign prostatic enlargement, multiple sclerosis (a neurological disease with the potential to cause widespread damage to nerves), and long-term diabetes mellitus.
If you have symptoms of ED, it’s important to check with your doctor before trying any treatments on your own. This is because ED can be a sign of other health problems. For instance, heart disease or high cholesterol could cause ED symptoms. With a diagnosis, your doctor could recommend a number of steps that would likely improve both your heart health and your ED. These steps include lowering your cholesterol, reducing your weight, or taking medications to unclog your blood vessels.
VIP is a neurotransmitter with regulatory actions on blood flow, secretion and muscle tone with intracorporal adenylate cyclase activation and smooth muscle relaxation. VIP has been shown to elevate cAMP intracellular concentrations without affecting cGMP levels. However, when VIP is given alone it may not induce erection and requires combination with phentolamine or papaverine for it to be effective (88). Common associated adverse effects were facial flushing and headache. VIP in combination with phentolamine is currently being used in the UK and Europe and is seeking regulatory approval for use in the United States.
Both ED and low testosterone (hypogonadism) increase with age. The incidence of the latter is 40% in men aged 45 years and older.  Testosterone is known to be important in mood, cognition, vitality, bone health, and muscle and fat composition. It also plays a key role in sexual dysfunction (eg, low libido, poor erection quality, ejaculatory or orgasmic dysfunction, reduced spontaneous erections, or reduced sexual activity). 
Several pathways have been described to explain how information travels from the hypothalamus to the sacral autonomic centers. One pathway travels from the dorsomedial hypothalamus through the dorsal and central gray matter, descends to the locus ceruleus, and projects ventrally in the mesencephalic reticular formation. Input from the brain is conveyed through the dorsal spinal columns to the thoracolumbar and sacral autonomic nuclei.
PDE 5 inhibitors are broken down primarily by enzyme, cytochrome P450enzyme CYP3A4. Medications that decrease or increase the activity of CYP3A4 may affect levels and effectiveness of PDE 5 inhibitors. Such drugs include medications for the treatment of HIV (protease inhibitors) and the antifungal medications ketoconazole and itraconazole. Thus caution is recommended.