This document discusses the anatomy, physiology, and pathophysiology of erectile dysfunction. It begins with the anatomy of the penis and details the structures involved in erection, including arteries, veins, nerves, and erectile tissue. It then discusses the physiology of the erectile process and factors involved in both attaining and maintaining an erection. It outlines various etiologies of erectile dysfunction including neurogenic, vasculogenic, hormonal abnormalities, medications, lifestyle factors, and aging.

1. Dr. Syaad Sarwar
Moderator: Dr. Mazahir

2.  ANATOMY
 PHYSIOLOGY
 EPIDEMIOLOGY
 HISTORY AND CLINICAL EXAMINATION
 AETIOLOGY
 INVESTIGATIONS

3.  Erectile dysfunction is defined as ‘inability to attain and /or maintain an erection
sufficient for satisfactory sexual intercourse’
 Previously called ‘IMPOTENCE’

4.  Penis is composed of 3 cylindric structures.
 Dorsally there are paired corpora cavernosa that extend from the pubic rami to tip
of penis.
 Ventrally corpus spongiosum encircles the urethra.
 Interconnected sinusoids are separated by smooth muscle trabeculae surrounded
by elastic fibers, collagen, and loose areolar tissue.

5.  The tunica is composed of elastic fibers that form an irregular, latticed network
on which the collagen fibers(Type I & Type III) rest.
 Outer layer of tunica collagen bundles are oriented longitudinally, extending from
the glans penis to the proximal crura; they insert into the inferior pubic rami but
are absent between the 5 and the 7 o’clock positions.
 In contrast, the corpus spongiosum lacks an outer layer or intracorporeal struts,
ensuring a low-pressure structure during erection.

6.  The outer tunical layer appears to play an additional role in compression of the
emissary veins during erection.
 External penile support consists of two ligamentous structures: the fundiform
(arises from Colle’s fascia) and suspensory ligaments (Buck fascia)..
 Its main function is to attach the tunica albuginea of the corpora cavernosa to the
pubis, and it provides support for the mobile portion of the penis.

7.  Arteries:
 Internal Iliac artery > Internal Pudendal artery > Penile Artery
 3 branches of penile artery:
1. Dorsal penile Artery: Responsible for engorgement of the glans during erection.
2. Bulbourethral Artery: supplies the bulb and corpus spongiosum.
3. Cavernous Artery: Effects tumescence of the corpus cavernosum and enters it at
the hilum of the penis, where the two crura merge:
It gives off many helicine arteries along its course, which supply the trabecular
erectile tissue and the sinusoids.
 Helicine arteries > contracted and tortuous > flaccid state.
 Helicine arteries >dilated and straight > erection.

9.  VEINS:
 Venous drainage (3-corpora) originates in tiny venules < peripheral sinusoids
immediately beneath the tunica albuginea.
 These venules travel in the trabeculae between the tunica and the peripheral
sinusoids to form the subtunical venous plexus before exiting as the emissary
veins.
 In Skin and Subcutaneous tissue multiple superficial veins run subcutaneously
and unite near the root of the penis to form a single (or paired) superficial dorsal
vein, which drains into the saphenous veins.
 Beginning at the coronal sulcus, multiple venous channels coalesce to form the
deep dorsal vein, which is the main venous drainage of the glans penis and distal
two thirds of the corpora cavernosa.

11.  NERVES:
 AUTONOMIC PATHWAYS:
Lumber splanchnic nerves > inferior mesenteric and superior hypogastric plexus >
hypogastric nerves to pelvic plexus.
 Sympathetic:
Innervation to penis from T12 to L2 segments. (Detumescence, Control Ejaculation)
 Parasympathetic:
 Innervation S2-S4. (Tumescence)
 Somatic nerves(sensory and motor): are primarily responsible for sensation
of penile skin, glans, urethra and within the corpus cavernosum.
• Free nerve endings, A and C fibers (thinly myelinated) > dorsal nerve of penis >
pudendal nerve > S2-S4.
• Onuf’s nucleus centre of somatomotor penile innervation localized to S2-S4.

13. Corpora Cavernosa:
In flaccid state blood slowly diffuses from central to peripheral sinusoids and the
blood gas levels are similar to those found in venous blood.
Penile erectile tissue (cavernous smooth musculature and the smooth muscles of the
arteriolar walls) plays a key role in the erectile process.
In the flaccid state, these smooth muscles are tonically contracted, allowing only a
small amount of arterial flow into the corpora.

14.  Corpus Spongiosum and Glans Penis:
• During erection, the arterial flow increases in a similar manner; however, the
pressure in the corpus spongiosum and glans is only one third to one half that in
the corpora cavernosa because the tunical covering, which is thin over the corpus
spongiosum and virtually absent over the glans, ensures minimal venous
occlusion.
• During the full-erection phase, partial compression of the deep dorsal and
circumflex veins between bucks fascia and the engorged corpora cavernosa
contributes to glanular tumescence.

19.  ED is usually a mixed condition that may be predominantly functional or physical.
 Two possible mechanisms have been proposed to explain the inhibition of erection
in psychogenic dysfunction:
i. Direct inhibition of the spinal erection center by the brain as an exaggeration of
the normal suprasacral inhibition.
ii. Excessive sympathetic outflow or elevated peripheral catecholamine levels,
which may increase penile smooth muscle tone to prevent its necessary
relaxation.

21.  10% to 19% of ED is neurogenic. Common in thalamic CVA.
 Parkinson disease, stroke, encephalitis, tumors, dementias, Alzheimer disease,
Shy-Drager syndrome, and trauma.
 Spinal level (e.g., spina bifida, disc herniation, syringomyelia, tumor, transverse
myelitis, and multiple sclerosis)
 Iatrogenic impotence from pelvic surgical procedures is reportedly high radical
prostatectomy, 43% to 100% due to closed relation.
 In men with posterior urethral injury, early realignment has been associated with
better potency preservation rate relative to delayed anastomosis (ED rate 34% vs.
42%).

22.  Any dysfunction of the hypothalamic-pituitary axis can result in hypogonadism.
 Hyper and hypogonadotropic hypogonadism may result from a tumor, injury,
surgery, or mumps orchitis
 Testosterone:
(1) Enhances sexual interest.
(2) Increases the frequency of sexual acts.
(3) Increases the frequency of nocturnal erection, but has little or no effect on
fantasy-induced or visually stimulated erections.
 HYPERPROLACTINEMIA.
 HYPERTHYRODISM.
 HYPOTHYROIDISM.

23.  Atherosclerotic or traumatic arterial occlusive disease of the hypogastric-
cavernous-helicine arterial tree > dec: perfusion pressure and arterial flow to the
sinusoidal spaces > increasing the time to maximal erection & dec: the rigidity of
the erect penis.
 Atherosclerosis/Cardiovascular Diseases:
High prevalence of ED has been reported in men with coronary, cerebral, and
peripheral vascular diseases.
 Hyperlipidemia:
Corpus cavernosum arterial atherosclerotic process in the sinusoids.
 Hypertension:
Independent risk factor for ED.
Its consequent are CVS complications such as ischemic heart disease and renal
failure.

24. Mechanism of Vascular Erectile Dysfunction:
In arteriogenic ED, oxygen tension in corpus cavernosum blood is less than that in
psychogenic ED.
I. Structural Changes:
 A decrease in oxygen tension may diminish cavernous trabecular smooth muscle
content and lead to diffuse venous leakage.
II. Enhanced Smooth Muscle Contraction and Vasoconstriction:
 Enhanced basal and myogenic tone has been observed in arteries from
hypertensive.
III. Impaired Endothelium-Dependent Smooth Muscle Relaxation.

25. Veno-occlusive dysfunction may result from a variety of pathophysiologic
processes:
 Degenerative tunical changes:
Peyronie disease,old age, diabetes or traumatic injury to the tunica albuginea
(penile fracture) can impair the compression of the subtunical and emissary veins.
 In Peyronie disease, the inelastic tunica albuginea may prevent the emissary
veins from closing.
 Fibroelastic structural alterations:
Loss of compliance of the penile sinusoids associated with increased deposition of
collagen and decreased elastic fiber.
 Smooth Muscle:
Alteration of an α adrenoceptor or a decrease in NO release may heighten smooth
muscle tone and impair relaxation in response to endogenous muscle relaxant.

26.  Gap Junctions:
These intercellular communication channels are responsible for synchronization
and coordination of the erectile response.
Acquired venous shunts—the result of operative correction of priapism—may cause
persistent glans/ cavernosum or cavernosum/spongiosum shunting.
 Endothelium:
Activation of cholinergic receptors on endothelial cells by acetylcholine or the cells’
expansion as a result of increased blood flow may elicit underlying smooth muscle
relaxation through the release of NO.

27.  Maintenance of Structural Integrity:
Sonic hedgehog homolog (SHH)has been shown to regulate cavernous smooth
muscle apoptosis in response to signals from cavernous nerve.
 Markers of Erectile Function:
Variable coding sequence protein has been proposed as a marker of erectile
function. At least three homologues gene (hSMR3A, hSMR3B, and PROL1).
Downregulation of hSMR3A has been reported in men with ED.

28.  ANTI HYPERTENSIVE:
1. DIURETICS: Thiazides
2. BETA-BLOCKER(NON SELECTIVE):
 ANTI PSYCHOTICS: Haloperidol,
phenothiazines and Flupenthixol.
 ANTI DEPRESSANTS:
1. TCA: Citalopram, Paroxetine.
2. MAOIs: Isocarboxazide
3. SSRIs: Paroxetin
 ANXIOLYTICS:
Lithium and Benzodiazepines.
 ANTICONVULSANTS:
1. CARBEMAZEPINE > Orgasmic
dysfunction.
2. VALPROATE > Loss of sexual desire.
 ANTIANDROGEN:
1. Flutamide (Non steroidal) or cyproterone
(steroidal) > Loss of sexual desire.
2. Bicalutamide > Loss of erectile function.
 MISCELLANEOUS DRUGS:
1) DIGOXIN
2) STATINS: Atorvastatine, simvastatine
3) H2 RECEPTOR BLOCKKER;
Cimetidine and Ranitidine.
4) OPIATES: Morphine.
5) CYTOTOXIC AGENTS:
Cyclophosphamid, Methtrexate.
6) ANTIRETROVIRAL: Ritonavir
7) TOBAACO: Oxidative stress and
apoptosis.
8) ALCOHOL: Sedation, dec: libido.

30. AGING: Progressive decline in sexual function in “healthy” aging men.
 Greater latency to erection, less turgidity, loss of forceful ejaculation and
decreased volume, and a longer refractory period.
 Decreased frequency and duration of nocturnal erection.
 Decrease in penile tactile sensitivity with age.
 Heightened cavernous muscle tone may also contribute to the decreased erectile
response.
 Progressive decline of smooth muscle content and increase in the caliber of
vascular spaces in the corpus cavernosum with increasing age.
 Significant dec: in gap junction protein connexin43.
 Change of nitric oxide expression or activity.

31. METABOLIC SYNDROME:
 Includes glucose intolerance, insulin resistance, obesity, dyslipidemia and
hypertension.
 Higher prevalence of ED (26.7%) in men with MetS relative to controls (13%) has
been reported.
 The prevalence of MetS increases with age and is associated with lower androgen
levels.
 They also found that lower total T levels, along with lower sex hormone binding
globulin (SHBG) levels, predicts a higher incidence of MetS.

32. DIABETES MELLITUS:
The prevalence of ED is three times higher in diabetic men (28% vs. 9.6).
CHRONIC RENAL FAILURE:
Uremia contribute to the development of ED including disturbance of the
hypothalamic-pituitary-testis sex hormone axis, hyperprolactinemia, accelerated
atheromatous disease, and psychologic factors.
 Pulmonary Disease:
Feels fear aggravating dyspnea during sexual intercourse.

33. PRIMARY ED:
Life-long inability to initiate and/or maintain erections beginning with the first
sexual encounter.
 Usually related to anxiety about sexual performance, traumatic early sexual
experience, or misinformation.
MICROPENIS:
 Symmetric hypoplasia of the phallus, is often related to urethral maldevelopment
such as hypospadias and epispadias.
 The erectile tissue in such cases often functions normally; sexual dysfunction
usually relates to lack of penile length or the degree of chordee, rather than to ED.

34. Vascular Abnormalities:
 Structural abnormalities of the cavernous tissue such as absence or replacement
by fibrous tissue but externally normal phalus
 Others including hypoplasia of the cavernous arteries or veno-occlusive
dysfunction results cavernous venous drainage.
SECONDARY ED:
Patient develop ED after a period of normal function.

35. A. SEXUAL: ask about onset of ED.
I. Sudden or Gradual onset.
II. DURATION
III. Presence nocturnal penile tumescence
IV. Unable to maintain erection
V. Loss of libido
VI. Sexual function symptom questionnaires
(IIEF 5)
B. MEDICAL:
I. DM: Affects 50%
II. CVD (CAD & PVD)
III. HTN
IV. DYSLIPIDAEMIA
V. ENDOCRINE
VI. NEUROLOGICAL
C. SURGERY(PENILE & PELVIC),
RADIOTHERAPY TRAUMA AND
MALIGNANCY:
Around 1/3rd of men undergoing prostate cancer
treatment.
Following open or robotic assisted prostectomy
ED reported around 2%.
D. PSYCHOSOCIAL:
I. Stress
II. Anxiety
III. Depression
IV. Patients expectation
V. Relationship details
E. DRUGS:
F. SOCIAL:
I. Smoking
II. Alcohol consumption

36.  Full physical examination:
i. CVS:
ii. NEUROLOGICAL;
iii. ABDOMINAL:
iv. SECONDAR SEXUAL CHARACTERISTIC’S:
v. EXTERNAL GENITALIA EXAMINATION:
Phimosis, Penile deformity and Lesions (Peyronie’s plaques)
vi. DRE: To asses prostate size

38.  Complete blood count
 Serum chemistries
 Fasting glucose or HbA1c
 Lipid profile
 Total testosterone, measured from a morning-time blood draw.
 Prolactin measurement
 Thyroid function tests
 Prostate-specific antigen (PSA)
 Dipstick analysis of urine may show glucosuria, which suggests the diagnosis of
diabetes.

39.  Combined Intracavernous Injection and Stimulation:
 It involves intracavernous injection of a vasodilatory drug or as a direct
pharmacologic stimulus, combined with genital or audiovisual sexual stimulation,
and the erectile response is observed and rated by an independent assessor.
 A normal CIS test, based on the assessment of a sustainably rigid erection, is
understood to signify normal erectile hemodynamics.

40.  A normal CIS test = normal erectile hemodynamics.
 False-positive results may occur in 20% of patients with borderline arterial inflow
(as defined by the measurement of 25 to 35 cm/s peak cavernous artery systolic
flow on duplex ultrasonography).
 False-negative results occur most commonly because of inadequate dosage.

41.  Most reliable and least invasive.
 Color-coded duplex ultrasound indicates the direction of blood flow within vessels,
with red designating direction toward the probe and blue designating direction
away from the probe.

43.  Indicated for patients who are suspected to have a site-specific vasculogenic leak
resulting from perineal or pelvic trauma or who have had life-long ED (primary
ED).
 Existence of veno-occlusive dysfunction is indicated by the failure to increase
intracavernous pressure to the level of the mean systolic blood pressure with
saline infusion or the demonstration of a rapid drop of intracavernous pressure
after cessation of saline infusion.

44.  Reserved for the patient with ED secondary to a traumatic arterial disruption or
the patient with a history of penile compression injury, who is being considered for
penile revascularization surgery.
 Injection of contrast in Internal Pudendal Artery.
 To evaluate anatomy and radiographic appearance of the iliac, internal pudendal,
and penile arteries.

45.  Penile brachial pressure index.
 Penile Plethysmography (Penile Pulse Volume Recording).
 Radioisotopic Penography.
 Penile Magnetic Resonance Imaging.
 Penile Near-Infrared Spectrophotometry.
 Cavernous smooth muscle content.

46.  Penile Tumescence and Rigidity Monitoring:
It measures the number of episodes, tumescence (circumference change by strain
gauges), maximal penile rigidity, and duration of nocturnal erections.
 Normal NPTR include 4-5 erectile episodes per night

47.  Erotic stimulation by explicit videotape material with monitoring has been used
as a reliable as well as a time- and cost effective alternative to NPTR for
differentiating between organic and psychogenic ED presentations.

48.  PET and functional MRI have been used in association with video sexual
stimulation or an erectogenic pharmacologic stimulus (e.g., oral apomorphine).
 Brain areas associated with sexual arousal that induce penile erection (i.e.,
anterior cingulate, insula, amygdala, hypothalamus, and secondary
somatosensory cortices).

49. Somatic Nervous System:
 Biothesiometry.
 Genito-cerebral Evoked Potential.
 Dorsal Nerve Conduction Velocity.
 Sacral Evoked Response: Bulbocavernosus Reflex Latency.

50. Autonomic Nervous System:
 Heart Rate Variability and Sympathetic Skin Response.
 Penile Thermal Sensory Testing.
 Corpus Cavernosum Electromyography and Single Potential Analysis of Cavernous
Electrical Activity

51. Several endocrine conditions are particularly relevant in this regard:
 Testosterone Deficiency,
 Hyperthyroidism
 Diabetes Mellitus (altered modulation of androgen function).

52.  Testosterone circulates in three fractions:
Free (0.5% to 3%),
Tightly bound to sex hormone–binding globulin (SHBG) (~30%),
and
Loosely bound to albumin and other serum proteins (~67%).
 Free testosterone and albumin-bound portions make up the
bioavailable testosterone fraction.
 The relative concentrations of the carrier proteins (SHBG and
albumin) modulate androgen function.

53.  Measurement of serum gonadotropins helps to localize the source of the
hypogonadism.
 Testosterone release involves the integrative activity of the hypothalamic-
pituitary-gonadal axis and its regulatory feedback mechanisms, and disruption at
any level of this axis may account for hypogonadism

54.  Primary hypogonadism:
Low testosterone > decreased negative feedback to the hypothalamus and pituitary >
increased secretion of LH and FSH.
 Secondary hypogonadism:
Normal or low serum LH and FSH with low serum testosterone levels-suggest a central
disorder.

55.  Hyperprolactinemia, whether from a pituitary adenoma or drugs, results in both reproductive and
sexual dysfunction.
 Hyperprolactinemia is associated with low circulating levels of testosterone due to suppression of
GNRH,
Also impairs LH secretion required for testosterone production.

56. Indications:
 Severe central hypogonadism
 Suspicion of pituitary disease
 To rule out mass lesion in brain.

57. Hyperthyroidism is associated with ED:
i. Hyperthyroidism:
 Diminished libido (Increases aromatization of testosterone into estrogen.
 Increasing adrenergic tone
ii. Hypothyroidism:
 Low testosterone secretion and elevated prolactin levels contribute to ED.