1. The physiology of ejaculation involves complex interactions between the central nervous system and peripheral pathways. It has two phases - emission and expulsion. 2. Premature ejaculation is defined as ejaculation that occurs within about one minute of penetration, the inability to delay ejaculation, and negative personal consequences. 3. The pathophysiology of premature ejaculation is multifactorial and not fully understood but likely involves genetic factors, psychological states like anxiety, and alterations in hormones like serotonin and testosterone.

1. PREMATURE
EJACULATION
Gaurav Nahar
DNB Urology(Std.)
MMHRC, Madurai

2. PHYSIOLOGY OF EJACULATION
 Accompanied by orgasm, ejaculation
constitutes the final phase of the sexual
response cycle in the male & represents a reflex
comprising sensory stimuli, cerebral and spinal
control centers, and efferent pathways.
 Ejaculation is a reflex, which requires a complex
interplay among somatic, sympathetic, and
parasympathetic pathways involving
predominantly central dopaminergic and
serotonergic neurons.

3.  Two basic phases of Antegrade Ejaculation:
Emission & Expulsion.
Emission:
 The first phase of ejaculation.
 a sympathetic spinal cord reflex.
 Defined as the deposition of seminal fluid into
the posterior urethra.
Expulsion:
 due to the combined action of sympathetic and
somatic pathways.

4. Antegrade ejaculation:
 Requires a synchronized interplay between
periurethral muscle contractions and bladder
neck closure, with relaxation of external urinary
sphincter.
Orgasm:
 Associated with ejaculation.
 A pleasurable sensation resulting from cerebral
processing of the increased pressure in the
posterior urethra and contraction of bulbar
urethra bulb and accessory sexual organs.

5. Coordination of Ejaculation
 Ejaculate: 1st
portion is provided by
bulbourethral glands followed by some fluid
from prostate. Afterwards, main fraction
including bulk of spermatozoa is contributed
by epididymis & vas deferens, along with
prostate & seminal vesicle contributions.
 Peripheral and central centers, as well as
sympathetic, parasympathetic, and somatic
pathways, participate in the physiologic control
of the ejaculatory reflex.

6. Mechanism of ejaculation

7.  Adequate sensory stimulation of the dorsal
penile nerve and posterior urethral distention
trigger an ejaculatory response.
EMISSION PHASE:
 Emission of seminal fluid is controlled by
sympathetic nervous system activating
propulsive contraction of smooth muscle of the
prostate, vas deferens and seminal vesicles, as
well as prostatic glandular secretion.

8. 1. Emission Phase
 Deposition of seminal
fluid from ampullary
deferens, seminal
vesicles & prostate
into the posterior
urethra.

9. PELVIC FLOOR MUSCLES

10. applied aspect…
 Interruption of innervation of bladder neck, vas
deferens, and prostate might lead to a
retrograde ejaculation or failure of emission.
 Protection of sympathetic efferents during
surgical procedures in retroperitoneum or
pelvis preserves normal ejaculatory function.

11. EXPULSION PHASE:
 Somatic nervous system (represented by
pudendal nerve) is exclusively responsible for
expulsion phase of ejaculate.
 Synchronous activation of ischiocavernosus,
bulbospongiosus and levator ani muscles as the
perineal striated muscles and the anal and
external urethral sphincters innervated by
pudendal nerve causes expulsion of seminal
fluid from the urethra.

12. 2. Expulsion Phase:
 It involves closure of
bladder neck,
followed by rhythmic
contraction of urethra
by pelvic-perineal &
bulbospongiosus
muscles &
intermittent
relaxation of external
urethral sphincter.

14. applied aspect…
 Patients with post traumatic sacral spinal cord
injuries (pudendal nerve: S2-4) or patients with
neuropathies (e.g., diabetes) typically show a
dribbling ejaculation due to missing motor
innervation of propulsive pelvic musculature.

15.  Areas of the brain most activated during
ejaculation include mesodiencephalic
transition zone including the ventral
tegmental area(VTA), medial & lateral
thalamus, and SPFp.
 There is intense activation of parietal cortex
during ejaculation.
 This site receives sensory signals from pudendal
sensory nerve fibers.

16. Neuropharmacology of Ejaculation
 Dopamine(D) and serotonin(5-hydroxytryptamine, 5-HT)
have a fundamental role in the regulation of ejaculation.
 14 different 5-HT receptor subtypes.
 5-HT1A, 5-HT1B, and 5-HT2C receptors involved in the
regulation of ejaculatory control.
 Stimulation of 5-HT1A receptors shortens ejaculatory
latency time and stimulation of presynaptic 5-HT1B
autoreceptors & postsynaptic 5-HT2C prolongs
ejaculatory latency time.

18. DEFINITION
 ISSM(2007) defined PE as having three
components:
(1) ejaculation that always or nearly always occurs
before or within about 1 minute of vaginal
penetration,
(2) inability to delay ejaculation on all or nearly
all vaginal penetrations, and
(3) negative personal consequences such as
distress, bother, frustration, and/or the
avoidance of sexual intimacy.

20.  No single factor defines PE.
 Definition should involve multiple dimensions such as
time, perceived control over ejaculation, personal and
partner distress, reduced sexual satisfaction, &
relationship difficulty.
 Time is measured by intravaginal ejaculatory latency
time (IELT, also known as IVELT), the duration in
seconds or minutes that pass from the first moment of
vaginal penetration to ejaculation/orgasm.

21. WALDINGER CLASSIFICATION
 (1) Lifelong
• PE at all or nearly all intercourse attempts
• With all or nearly all women
• In majority of cases within 1 minute
• Consistent during life
• Inability to control ejaculation may be lacking (not obligatory)
 (2) Acquired
• Rapid ejaculation occurring at some point in life
• Normal ejaculation before onset of premature ejaculation
• Often source of problem identifiable (organic, psychologic)
• Inability to control ejaculation may be lacking (not obligatory)

22.  (3) Natural variable
• Rapid ejaculation inconsistent and irregular
• Inability to control ejaculation may be lacking (not obligatory)
 (4) Premature-like ejaculatory dysfunction
• Subjective perception of rapid ejaculation
• Intravaginal ejaculatory latency time in normal range
• Preoccupation with imagined rapid ejaculation
• Preoccupation with poor control of ejaculation
• Preoccupation not accounted for by another mental disorder
• Inability to control ejaculation may be lacking (not obligatory)

27. EPIDEMIOLOGY
Prevalence:
 Most common male sexual dysfunction.(DSM-
IV)
 PE is common, affecting up to 30% of men of all
ages.
 PE is more common in younger men when
adjusted for acquired premature ejaculation in
older men resulting from erectile dysfunction.
 Self-reported time taken for an average man to
ejaculate varied greatly from 7 to 14 minutes.

28. Impact (Premature Ejaculation Profile(PEP) and Self-
Esteem And Relationship(SEAR) questionnaire):
 Men have a sense of shame and embarrassment at not
being able to satisfy their partner.
 Low self-esteem and feelings of inferiority.
 Erosion of sexual self-confidence, & general confidence.
 Anxiety & depression.
 Significant negative impact on the psychologic status &
interpersonal relationship of the sufferer and his partner.

29. PATHOPHYSIOLOGY OF PE
 A complete understanding of the
pathophysiologic mechanisms involved in PE
not yet achieved.
 The final common pathway in the genesis of PE
appears to be either a
hyposensitivity of 5-HT2C receptors or a
hypersensitivity of the 5-HT1A receptors.

30.  Ejaculatory threshold for men with low 5-HT levels
and/or 5-HT2C receptor hyposensitivity may be
genetically set at a lower point, resulting in more rapid
ejaculation.
 A number of potential explanations have been
postulated for genesis of PE including
(1) Genetic etiologies,
(2) Psychologic causes,
(3) Hormonal aberrations,
(4) Penile sensory changes, and
(5) Chronic prostatitis

31. GENETIC FACTORS:
 Genetic factors play a significant role in the
pathophysiology of PE.(Shapiro 1940s;
Waldinger 2004; Finnish study Jern 2007-2009).
 Target of genetic reseach: Serotonin transporter
(5-HTT) promoter region polymorphisms.
 5-HTT is a specific protein transporter that
permits serotonin reuptake from the synapse

32.  Short IELT values in men with PE d/t→
diminished synaptic 5-HT neurotransmission→
d/t an increase in the function of 5-HTT →
related to genetic polymorphisms of the
protein.

33. PSYCHOLOGIC FACTORS:
 Sympathetic nervous system, activated by anxiety, may
result in an earlier emission phase of ejaculation and
subsequently reduced ejaculatory threshold.
 It is suggested that men with PE have a hyperexcitable
ejaculatory reflex, resulting in faster emission and/or
expulsion.
 In addition, it is proposed that men with PE may have a
faster bulbocavernosus reflex, impairing their ability to
learn to control ejaculation.
 Yet no definitive evidence to prove such a link.

34. HORMONAL ALTERATIONS:
1. LEPTIN
 Role of Leptin in PE: only small number of studies.
 Serum leptin levels in patients with PE were significant
higher than healthy controls and levels were negatively
correlated with IELT values.
 Recent evidence suggests that one of its goals may be
signaling to the hypothalamus about sexual behavior.

35. 2. TESTOSTERONE & PROLACTIN:
 Men with delayed ejaculation had significantly
lower testosterone levels compared with men
without delayed ejaculation and men with PE.
 An association between hyperprolactinemia
and the presence of ED or PE in those patients
in the lowest quartile of serum prolactin levels.

36. 3. THYROID HORMONES:
 Hyperthyroid individuals are more lilely to
have PE, & with reversion to a euthyroid state,
the rate of PE dropped
 At present, role of hormones in the genesis of
PE is not completely understood.

37. PENILE SENSITIVITY & CIRCUMCISION
STATUS:
 Two schools of thought:
1. -Theoretically, circumcision leads to
keratinization of the glans penis, which might
potentially lower penile sensitivity & increase
IELT.
-Circumcision was an effective method to treat
the PE.

38. 2. Circumcision denudes the penis, exposing
corona of the glans penis to direct stimulation,
thereby causing circumcised men to have a
greater incidence of PE.

39. CHRONIC PROSTATITIS:
 Chronic prostatitis is more prevalent among
men with a diagnosis of PE.
 After 1 month of antibiotic treatment, most of
treated patients show a significant increase in
their IELT.
 Mechanism behind link between chronic
prostatitis and PE and the mean by which
antibiotic treatment improved IELT are unclear.

40. DIAGNOSIS & EVALUATION
 Diagnosis of PE: based on patient’s medical &
sexual history.
 History should classify PE as lifelong or acquired
& determine whether PE is situational (under
specific circumstances or with a specific partner)
or consistent.
 Special attention to duration time of ejaculation,
degree of sexual stimulus, impact on sexual
activity and QoL, and drug use or abuse.
 Also important to distinguish PE from ED.

41.  American Urological Association (AUA) guidelines on PE
management- fundamental basis of assessment: time to
ejaculation (IELT) is the most important feature.
In addition, AUA recommends following to be considered:
(1)duration and frequency of PE,
(2)rate of occurrence of PE with some or all sexual
encounters and partners,
(3)degree to which sexual stimuli cause PE, and
(4)the nature and frequency of sexual activity including
foreplay, masturbation, and intercourse.

42. A simple PE history algorithm that can be
undertaken is as follows:
(1) asking how long he has experienced PE;
whether lifelong or recently acquired.
(2) defining the IELT from a patient is useful,
appreciating that some men overestimate this. If
a partner is present, seeking corroboration of the
estimated IELT is helpful.

43. (3) asking the patient to define whether his
control over ejaculation is good, fair, or poor.
(4) assessing the bother related to PE and the
impact PE has on his relationship.
In everyday clinical practice, self-estimated IELT
is sufficient.
Stopwatch-measured IELT is necessary in
clinical trials.

44. PE ASSESSMENT QUESTIONNAIRES:
 Only two questionnaires can discriminate between
patients who have PE and those who do not.
(1) Premature Ejaculation Diagnostic Tool (PEDT)
(2) Arabic Index of Premature Ejaculation (AIPE)
 Other questionnaires used to characterise PE and
determine treatment effects: PEP, Index of Premature
Ejaculation (IPE), and Male Sexual Health Questionnaire
Ejaculatory Dysfunction (MSHQ-EjD)

45. Physical examination rarely helps to define the
etiology of patient’s PE or change the
management plan.
Assessment of signs and symptoms of conditions
associated with PE such as thyroid dysfunction
and chronic prostatitis.
A routine urologic genital examination should
be conducted, and some recommend assessment
of the sacral reflexes and lower limb
neuromuscular evaluation.

46. PE & ED
 It is critical to differentiate PE from ED.
 Both are common conditions & may coexist in
the same patient.
 Many ED patients develop secondary PE;
specifically with loss of sustaining capability
condition themselves to ejaculate rapidly in
order to achieve orgasm before loss of erectile
rigidity. ED should be treated first.

47.  Patients with lifelong PE may develop ED as
they age.
 Treatment is erectogenic pharmacotherapy,
followed by treatment for PE as well if the
patient’s bother is high.

48. TREATMENT
I. BEHAVIORAL/PSYCHOSEXUAL THERAPY
1. Stop-start technique(James Semans): partner
stimulates the penis until the patient feels the
urge to ejaculate. At this point, he instructs
his partner to stop, waits for the sensation to
pass and then stimulation is resumed.
2. Squeeze technique(Masters & Johnson):
similar but partner applies manual pressure to
the glans or penile frenulum just before
ejaculation until the patient loses his urge.

49.  Both applied in a cycle of three pauses before
proceeding to orgasm.
 Based on the theory that PE occurs as patient
fails to pay sufficient attention to preorgasmic
levels of sexual tension.
 Main goal of traditional psychosexual treatment
for PE: to help men identify the premonitory
sense of ejaculation/orgasm and to improve
self-control.

50.  Secondary benefits: improved sexual self-
confidence, less anxiety, resolution of any
interpersonal difficulties, and increased couple
communication.
 Success rates between 45% and 65%, but Short-
lived.

51. II. ORAL CENTRALLY ACTING MEDICATIONS:
 Pharmacotherapy is the basis of treatment in
lifelong PE.
 All medical treatments are off-label indications,
since no drugs are currently approved.

52. 1. Clomipramine:
 Clomipramine is a TCA that inhibits uptake of
noradrenaline & 5-HT by adrenergic & 5-HT
neurons.
 Daily use of clomipramine significantly
increased stopwatch-measured IELT compared
with a placebo.
06/21/15

53. 2. SSRI(Selective Serotonin Reuptake Inhibitors):
 2009 (ICSM) suggest the off-label use of SSRI for
managing PE.
 As in depression, SSRIs must be given for 1 to 2
weeks to be effective in PE.
 Chronic SSRI administration causes prolonged
increases in synaptic cleft serotonin, which
desensitise the 5-HT1A and 5-HT1B receptors.
 Commonly used SSRIs include citalopram,
fluoxetine, fluvoxamine, paroxetine and
Sertraline.

54. SSRI drug e.g. blocks the reuptake of serotonin thus causing the
concentration in the synaptic cleft to be increased . Consequently more
serotonin makes it to the receptor sites & the next nerve cell & the
functioning returns to normal

55. SSRIs: The most common short-term adverse
effects are yawning, mild nausea, excessive
sweating, fatigue, and changes in bowel function.
Loss of bone mineral density is the most
concerning adverse effect of longterm treatment.
Sexual side effects such as reduced libido and
erectile rigidity.

56.  A sudden reduction or cessation of long-term
treatment of SSRIs can lead to the “SSRI
discontinuation syndrome,” a group of symptoms
including nausea, vomiting, dizziness, headache,
ataxia, drowsiness, anxiety, and insomnia.
 Begin 1 to 3 days after drug cessation and may
continue for more than a week in some patients.
 Usually reversible by SSRI reintroduction.
 Thus it is recommended that SSRI agents should be
gradually withdrawn over a 2- to 4-week period.

57.  Daily administration of an SSRI is associated
with superior fold increases in IELT compared
to on-demand administration(4-6hrs before).
 Due to greatly enhanced 5-HT
neurotransmission resulting from several
adaptive processes which may include
presynaptic 5-HT1a and 5HT1b/1d receptor
desensitisation.
 Paroxetine- strongest activity.

58. 3. Dapoxetine:
 Dapoxetine is a potent short acting SSRI.
 Designed as an on-demand oral treatment for
PE(1-2 hours prior to intercourse).
 Time to maximum serum concentration (Tmax)
of 1.3 hours and a short half-life (T1/2 ) of 1.5
hours.
 Treatment-related side effects uncommon,
dose-dependent, included nausea, diarrhoea,
headache, dizziness. 06/21/15

59. 4. Tramadol:
 A centrally acting synthetic opioid analgesic.
 An unclear mode of action: binding of the
parent compound and M1 metabolite to μ-
opioid receptors and weak inhibition of
reuptake of norepinephrine and serotonin.
 On demand tramadol 50mg taken 2 hours
before intercourse.
06/21/15

60. 5. Phosphodiesterase V Inhibitors:
 Multiple mechanisms of action: 1) a central effect
involving increased NO and reduced sympathetic
tone, 2) smooth muscle dilatation of vas deferens
and seminal vesicles and 3) reduced performance
anxiety.
 PDE5i monotherapy for PE treatment has no
solid foundation.
 However, in difficult-to-treat cases, addition of a
PDE5i to an SSRI may offer select patients some
benefit. 06/21/15

61. 6. Alpha adrenoceptor antagonist:
 Terazosin & Alfuzosin.
 Adrenergic blockade for PE aims to decrease
the sympathetic tone of seminal tract and
therefore delay ejaculation.
06/21/15

62. III. TOPICAL AGENTS:
1. Severance Secret Cream(SS Cream):
 made with the extracts of nine natural products.
 available only in Korea and is not approved for
use elsewhere.
 applied to the glans penis 1hr before and washed
off immediately prior to coitus.
 Sensory thresholds & stopwatch-IELT increase.
 The main disadvantage of SS-cream is an
unpleasant odor, which makes it unpalatable to
many patients.
06/21/15

63. 2. Lidocaine:
3. Lidocaine-Prilocaine(EMLA):
 Lidocaine-prilocaine cream (5%) is applied 20-30
min prior to intercourse.
 Prolonged application of topical anaesthetic (30-
45 min) may result in loss of erection due to
numbness of the penis.
 A condom is required to avoid diffusion of topical
anaesthetic agent into the vaginal wall causing
numbness in the partner
06/21/15

64.  The topical eutectic mixture for PE (TEMPE, also
known as PST-502) is a recently developed
metered-dose aerosol spray delivery system of
lidocaine and prilocaine, specifically designed for
use in PE.
 The system delivers 7.5 mg lidocaine plus 2.5 mg
prilocaine per spray.
 Can penetrate the glans within 5–10 min, but
penetrates intact keratinised skin less easily,
reducing penile numbness and ED.

65. IV. INTRACAVERNOSAL INJECTION(ICI):
 In cases refractory to first-line and combination
therapy, ICI(Alprostadil, Papaverine,
Phentolamine) used to increase sexual
satisfaction in recalcitrant PE.
 Despite early ejaculation, erection maintained-
permitted penetrative intercourse.
06/21/15

66. V. SURGICAL TREATMENT:
 Selective resection(neurectomy) of branches of
dorsal penile nerve should decrease penile
sensitivity & prolong ILET significantly.
 No definitive data; only in some asian countries.
06/21/15

67. MANAGEMENT ALGORITHM OF
PE
06/21/15

68. MANAGEMENT ALGORITHM OF
PE
06/21/15

69. THANK YOU
06/21/15