Erectile Dysfunction and Male Hypogonadism
Erectile dysfunction (ED), defined as the inability to maintain an erect penis with sufficient rigidity for sexual intercourse, is an increasingly common presenting complaint and is estimated to affect 10 million males in the United States. ED can include partial or brief erections to complete ED (impotence). With basic knowledge about the physiology and neuropharmacology of erection, we can approach the problems systematically and logically.
Male hypogonadism, defined as the decrease or absence of the hormone testosterone (T) secretion from the testes, is often associated with ED and general physiologic impairment. Low T levels are a common concern among the aging male population and variably referred to as andropause, androgen decline in the aging male (ADAM), late-onset hypogonadism, or testosterone deficiency syndrome (TDS). The most prominent generalized symptoms of TDS are tiredness, hypoactive sexual function, and dysphoria, although ED remains the most frequent reason for referral.
PHYSIOLOGY
Erectile Function
Briefly, the neurovascular mechanism of erection involves the following. In the flaccid state, cavernosal smooth muscle tone is high, causing an increased resistance to incoming blood. Erection occurs via stimulation by parasympathetic fibers of the pelvic plexus and cavernous nerves. Resulting arteriolar dilatation and sinusoidal smooth muscle relaxation within the corpora cavernosa allow increased arterial blood flow. As the cavernosal sinusoids distend with incoming blood, the subtunical venular plexuses become compressed, thus reducing venous outflow. With stretching of the tunica albuginea to its capacity, the emissary veins eventually close within the tunical layers, further decreasing venous outflow to a minimum. The direct inducer of sinusoidal smooth muscle relaxation has been identified as endothelium-derived
relaxing factor, now known to be nitric oxide (NO) by way of its action on cyclic guanosine monophosphate (cGMP). Tonic sinusoidal smooth muscle contraction of the normally flaccid penis may be mediated by the neurotransmitter endothelin-1. Thus, physiologic erections are the result of NO-induced cGMP. cGMP is broken down by the enzyme phosphodiesterase type 5 (PD-5).
relaxing factor, now known to be nitric oxide (NO) by way of its action on cyclic guanosine monophosphate (cGMP). Tonic sinusoidal smooth muscle contraction of the normally flaccid penis may be mediated by the neurotransmitter endothelin-1. Thus, physiologic erections are the result of NO-induced cGMP. cGMP is broken down by the enzyme phosphodiesterase type 5 (PD-5).
Sex Hormones
Ninety percent of T is synthesized by the Leydig cells of the testes under the control of hypothalamic-pituitary-gonadal axis. Luteinizing hormone (LH) modulates T biosynthesis via biofeedback inhibition at the level of the pituitary and gonadotropinreleasing hormone (GnRH) release from the hypothalamus. T circulates in the blood as free T (2%) or bound to albumin (38%) or sex hormone-binding globulin (SHBG) (60%). Bioavailable T (free or albumin-bound fractions −40%) is metabolically active. T bound to SHBG (60%) is inaccessible to tissues and not active. T can be aromatized to 17β-estradiol or reduced to 5α-dihydrotestosterone (DHT). The natural aging process results in decreased production of GnRH and LH and a decrease in the numbers of Leydig cells in the testes and more SHBG, thus resulting in less metabolically active T in circulation. T and DHT act through the cellular androgen receptor. Fat cells aromatize T into estradiol and increase circulating SHBG resulting in lower circulating bioavailable T and are thus perhaps the most common reason for TDS.
PHARMACOLOGY
Some drugs known to produce erections include papaverine, nitroglycerin, α-blockers such as phentolamine, prostaglandin E1 (PGE1), and PD-5 inhibitors. Some drugs known to cause detumescence include epinephrine, norepinephrine, phenylephrine, dopamine, and metaraminol.
ETIOLOGY
Psychogenic
Organic (50%-90%)
Vasculogenic. This is the most common single cause and is due to either poor inflow (e.g., arterial insufficiency, large vessel atherosclerosis, and small vessel diabetes) or enhanced outflow (e.g., venous leak).
Endocrine. Hypogonadotropic males with small atrophic testes and low serum T levels.
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