Erection and Erectile Dysfunction
Penile erection is essentially a neurovascular event. Upon sexual stimulation, nerve impulses release neurotransmitters from the cavernous nerve terminals and relaxing factors from penile endothelial cells result in an erection. Nitric oxide released from parasympathetic nerve terminals is the principal neurotransmitter for penile erection. Within penile smooth muscle, nitric oxide activates a guanylyl cyclase that raises intracellular concentrations of cyclic guanosine monophosphate (GMP). Cyclic GMP in turn activates cGMP dependent protein kinase, which results in the opening of the potassium channels, hyperpolarization, and sequestration of intracellular calcium. As a result of a drop in cytosolic calcium, smooth muscle relaxation occurs, leading to erection.
Subsequent to the activation of this signal pathway, three events are required for a normal erection: (1) relaxation of smooth muscle in the arteries and arterioles supplying erectile tissue. This results in a several-fold increase in blood ﬂow. Concomitantly, there is (2) relaxation of the cavernous sinusoidal smooth muscle within the paired corporeal bodies, facilitating rapid ﬁlling and expansion of the sinusoids. As a result, (3) venous plexuses located between the cavernous sinusoidal spaces and the tunica albuginea covering the corporal bodies are compressed, resulting in almost total occlusion of venous outﬂow. These events effectively trap blood within the corpora cavernosa and raise the penis from a ﬂaccid to an erect position (tumescence phase). Both masturbation and sexual intercourse trigger the bulbocavernosus reﬂex (see Plate 2-11) that causes the ischiocavernosus muscles to forcefully compress the blood-ﬁlled corpora cavernosa. During ejaculation, penile intracavernous pressures reach several hundred millimeters of mercury (rigid phase). During this phase, vascular inﬂow and outﬂow temporarily cease. Detumescence results when erectile neurotransmitter release stops, when phosphodiesterases break down second messengers, or as a result of sympathetic discharge during ejaculation. On return to the ﬂaccid state, cyclic GMP is hydrolyzed to guanosine monophosphate by phosphodiesterase type 5. Currently, three oral agents prescribed for erectile dysfunction work by blocking phosphodiesterase enzyme activity.
Erectile dysfunction is traditionally classiﬁed as psychogenic or organic in nature. Among organic forms, there are neurogenic, hormonal, arterial, venous, or cavernosal and drug-induced. It is now clear that cardiovascular risk factors suggestive of the “metabolic syndrome,” such as hypertension, dyslipidemia, ischemic heart disease, and diabetes mellitus are associated with generalized penile arterial insufﬁciency. In fact, signiﬁcant erectile dysfunction precedes heart attacks and stroke events by 5 to 7 years. Common causes of psychogenic erectile dysfunction include performance anxiety, strained relationship, lack of sexual arousability, and overt psychiatric disorders, such as depression and schizophrenia. Neurologic disorders such as Parkinson and Alzheimer diseases, stroke, and cerebral trauma can cause erectile dysfunction by decreasing libido or affecting the cerebral control of erection. In men with spinal cord injury, the degree of erectile function varies widely and depends on the lesion. Hormonally, androgen deﬁciency causes a decrease in nocturnal erections and decreases libido. Hyperpro-lactinemia of any cause results in sexual dysfunction because of the inhibitory action of prolactin on gonadotropin-releasing hormone secretion, resulting in hypogonadotropic hypogonadism. Sexual function also 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.
Erectile Dysfunction Evaluation
Erectile dysfunction can be the presenting symptom of various diseases. Therefore, a thorough history (medical, sexual, and psychosocial), physical examination, and appropriate laboratory tests aimed at detecting these diseases should be performed. The physical examination should evaluate the breast, hair distribution, penis and testis, femoral and pedal pulses, and testing of genital and perineal sensation. Recommended laboratory tests include urinalysis, complete blood count, fasting blood glucose, lipid proﬁles, and testosterone. The physician should then assess the ﬁndings, inquire about the goals and preferences of the man (and partner), and discuss therapeutic options. Cardiovascular risk factors should be determined and an appropriate referral made if these risks exist. In most cases, erectile dys unction can be treated with systemic or local therapy.