Other causes may affect one or more of the factors controlling the erectile mechanism. Because of the lack of scientific studies, however, their precise pathogenetic relationship remains speculative.

A. Drugs
Many drugs have been reported to cause ED, although the mechanism of action is largely unknown and there are few controlled studies on the sexual effects of a particular drug. In general, drugs that interfere with central neuroendocrine or local neurovascular control of penile smooth muscle have the potential to cause ED. Central neurotransmitter pathways, including serotonergic, noradrenergic, and dopaminergic pathways involved in sexual function, may be disturbed by antipsychotics, antidepressants, and centrally acting antihypertensive drugs.

Alpha-adrenergic blocking drugs, such as prazosin, terazosin, and doxazosin, may cause retrograde ejaculation owing to relaxation of the bladder neck. Beta-adrenergic blocking drugs may cause ED by potentiating α-1 adrenergic activity in the penis. Thiazide diuretics have been reported to cause ED, but the cause is unknown. Spironolactone can cause erectile failure as well as decrease in libido and gynecomastia.

Cigarette smoking may induce vasoconstriction and penile venous leakage because of its contractile effect on the cavernous smooth muscle. Alcohol in small amounts improves erection and increases libido because of its vasodilatory effect and the suppression of anxiety; however, large amounts can cause central sedation, decreased libido, and transient ED. Chronic alcoholism may cause hypogonadism and polyneuropathy, which may affect penile nerve function. Cimetidine, a histamine-H2 receptor antagonist, has been reported to decrease libido and cause erectile failure; it acts as an antiandrogen and can cause hyperprolactinemia. Other drugs known to cause ED are estrogens and drugs with antiandrogenic action, such as ketoconazole and cyproterone acetate.

B. Systemic Disease, Aging, and Other Disorders
About 50% of men with chronic diabetes mellitus reportedly have ED. In addition to the disease’s effect on small vessels, it may also affect the cavernous nerve terminals, cavernous smooth muscle, and endothelial cells. The harmful effect of long-term diabetes on both neural and vascular components makes diabetic ED one of the least responsive to oral sildenafil therapy.

Sexual function progressively declines in “healthy” aging men. For example, the latent period between sexual stimulation and erection increases, erections are less turgid, ejaculation is less forceful, ejaculatory volume decreases, and the refractory period between erections lengthens. There is also a decrease in penile sensitivity to tactile stimulation.

Men with severe pulmonary disease may have ED because of fear of aggravating dyspnea during sexual intercourse. Men with angina, myocardial infarction, or heart failure may have ED from anxiety, depression, or concomitant penile arterial insufficiency, which is quite common in these patients. Chronic renal failure has frequently been associated with diminished erectile function, impaired libido, and infertility. In men with chronic renal failure and ED, many were found to have cavernous artery occlusive disease and veno-occlusive dysfunction. The mechanism is probably multifactorial: low serum testosterone concentrations, diabetes mellitus, vascular insufficiency, multiple medications, autonomic and somatic neuropathy, and psychological stress. Other systemic disorders such as cirrhosis, chronic debilitation, and cachexia can cause ED due to loss of libido or neurovascular dysfunction.