Dr. Aaron Spitz's 2006 presentation on disorders of ejaculation. Presented as part of his work as an Assistant Clinical Professor at UC Irvine's Department of Urology.
2. Ejaculatory dysfunction
Any condition, whether it be medical, surgical, or
psychological, that disrupts the normal ejaculation pathway,
from the cortical influence to the sympathetic nervous
system to the somatic afferents from the penis or the
somatic efferents to the pelvic floor, can lead to ejaculatory
dysfunction
Delayed ejaculation
Premature ejaculation,
Retrograde ejaculation,
Anejaculation
3. Dopamine: excitatory
Seratonin: inhibitory
Oxytocin: excitatory
Glutamate,other NT:
excitatory
Sympathetic nerves release
acetylcholine to non-myelinated
neurons which release
norepinephrine to sv, vas,
epididymis, bladder neck
Pudendal efferents
arise from Onuf’s
nucleus in sacral spine
4. Sympathetic nerves release acetylcholine
to non-myelinated neurons which release
norepinephrine to sv, vas,
epididymis,bladder neck
Pudendal efferents
arise from Onuf’s
nucleus in sacral
spine
5. Delayed Ejaculation
The World Health Organization 2nd Consultation Sexual
Dysfunction:
The persistent or recurrent difficulty, delay in, or absence
of attaining orgasm after sufficient sexual stimulation,
which causes personal distress.
7. Determination of IELT
Stopwatch studies by Waldinger et al.
500 couples, five countries
IELT exists as a distribution
33 seconds to 44 minutes median: 5.4 minutes
21–23 minutes = +2 SD
Men who cannot climax after 25 minutes or experience
distress meet criteria for Delayed Ejaculation
Waldinger M,. J Sex Med 2005;2:498–507
McMahon C, J Sex Med 2013;10:204–29
8. Neurotransmitters/hormones
Dopamine: facilitates ejaculation
Dopamine levels increase steadily through copulation to
ejaculation in rats
Prolactin suppresses ejaculation when in excess
through testosterone inhibition and as a
neurotransmitter
Additional players:
Acetylcholine, norepinephrine, nitric oxide, GABA
9. Neurotransmitters/hormones
Spinal ejaculatory center is under central control
Serotonin: two receptors implicated
5-HT2C, 5-HT1A
5-HT2C delays ejaculatory latency time
5-HT1A shortens ejaculatory latency time
These receptors are found on oxytocin secreting nerves and
stimulate oxytocin release.
Oxytocin shortens IELT.
SSRIs cause desensitization of these receptors oxytocin
10. Designations
Primary (lifelong)
all partnered sexual activity from first opportunity onwards
Secondary (acquired)
Surgery
Medical disease
Psychosexual change
11. Primary: Psychological/behavioral
Conflicted masturbation
Auto sexual orientation
Increased masturbation
Idiosyncratic masturbation
Sensation therefore NOT easily reproduced with partner
Decreased sensitivity
Due to overuse vs causes overuse
Physical/Subjective mismatch
Arousal/Desire mismatch
13. Secondary (acquired)
Endocrine imbalance
Hypothyroid
Low testosterone
Elevated Prolactin
Inhibitory effect on GnRH
decreases LH then T
Direct action as a neurotransmitter
Interplay with dopamine
Dopamine may stimulate ejaculation
and it inhibits prolactin
Seratonin inhibits ejaculation and it
stimulates prolactin
Prolactin
14. Medications
SSRI: increased seratonin decreases receptor sensitivity
which decreases oxytocin release
Antipsychotics:
Antagonize dopamine (dopamine is pro ejaculatory)
Elevate prolactin (prolactin is counter ejaculatory)
Inhibit alpha adrenergic tone of bladder neck
Antiandrogens
15. Neurogenic
Interference with communication between the spinal
ejaculatory center and the sympathetic and
parasympathetic nervous system
Spinal cord injury
MS
DM
16. Age
Decreased penile sensitivity
Natural decline in fast-conducting peripheral nerves
starting in 3rd decade
Concurrent atrophy of dermis and underlying stroma
Accumulation of chronic medical conditions
19. Evaluation
History
Query regarding strong religious/ethical beliefs regarding
sex
Age of first ejaculation
Pattern of ejaculation
Difficulty with sex versus masturbation?
Lifelong versus gradual versus abrupt onset
Temporal association with other medical conditions
Relationship stress/female sexual dysfunction
20. Physical Exam
Signs of low T: genitals/breasts/pelvis/hair
Signs of hypothyroidism
Abnormal prostate (mullerian duct cysts)
21. Labs
Rule out chronic medical conditions/endocrine
imbalance
CBC, CHEM 20, lipid panel, TSH, Testosterone, Prolactin
22. Treatment
Psychosexual counseling
Basic education in mechanics of sexual intercourse and
orgasm
Establish an anxiety-free environment
Engagement of partner in therapy
23. Treatment
Sensate focus:
Couple based “homework”
First: Achieve ejaculation without coitus
Then: bring the male to the brink and then insert penis
into vagina to provide final stimulation
Breaks mental barrier to ejaculating within the vagina
Masturbation retraining to acclimatize the male to
stimulation similar to partnered intercourse
Reducing the frequency of masturbation
24. Surgical treatment
Sperm harvesting for purpose of fertility
Electroejacultion under anesthesia: for use with
insemination
Percutanous or open epididymal or testicular sperm
extraction: for use with in vitro fertility
25. Neuro/endocrine treatment
Hypogonadism: androgens
Hypothyroidism: levothyroid
Hyperprolactinemia: cabergoline
SSRI related: switch meds if possible
Most to least inhibition
Paroxetine (Paxil) – fluoxetine (Prozac) –sertraline (Zoloft)
Fluvoxamine (Luvox) does not cause ejaculatory delay
Bupropion: not associated with sexual dysfunction
Antipsychotics: newer agents affect dopamine less and
cause less hyperprolactinemia
26. Pharmaceutical treatment
Alpha -1-adrenergic receptor agonists: imipramine,
ephedrine, pseudoephedrine, midodrine
Increase sympathetic tone for emission and ejaculation
Midodrine: very effective for organic anejaculation (58%
improved, 30% cured)
MS responded best, sympathectomy worst
27. Pharmaceutical continued
Yohimbine: central apha-2-adrenergic receptor agonist
70% “much improved” in SRI associated sexual
dysfunction
Increases HR and BP
Cyproheptadine: antihistamine/antiseratonergic (blocks
5-HT1A, 5-HT2A r)
Effective for delayed ejaculation due to SSRI, MOA,
Imipramine
High rates of sedation, possible relapse of depression
28. Pharmaceutical
Amantadine: indirect stimulation of dopaminergic
nerves: 40% improvement in SRI induced delayed
ejaculation
Cabergoline: dopamine receptor agonist. Used to treat
hyperprolactinemia. Prolactin surges AFTER orgasm.
69% of 72 men improved
50% normalization
Works within one month
0.5mg twice a week
30. Dosages
Buproprione 75mg daily dopamine agonist (welbutrin)
Ropinirole 0.25mg daily dopamine agonist
Adderal 10mg at least 30 min. before intercourse prn
but not after 2pm. increases activity related to domaine
and norepinehrine in the brain.
Oxytocin 250u lozenge 1 hour before sex
31. Conclusions
Difficult, but common
Psycho-sexual causes make this condition complex to
treat
Pharmacologic treatments are evolving
32. Premature Ejaculation
Definition: Premature ejaculation is ejaculation that
occurs sooner than desired, either before or shortly
after penetration, causing distress to either one or both
partners.
Incidence 20 to 30%
For clinical trials, it’s usually under 2 minutes
33. Diagnosis
History
frequency and duration of PE,
relationship to specific partners,
occurrence with all or some attempts,
degree of stimulus resulting in PE,
nature and frequency of sexual activity (foreplay, masturbation,
intercourse, use of visual clues, etc.),
impact of PE on sexual activity,
types and quality of personal relationships and quality of life,
aggravating or alleviating factors, and
relationship to drug use or abuse
34. Medical Treatments
(AUA Guidelines)
Oral Therapies Trade Names†
Nonselective serotonin reuptake inhibitor
Clomipramine Anafranil® 25-50 mg/day or
25mg 4 to 24 h pre-intercourse
Selective serotonin reuptake inhibitors
Fluoxetine Prozac®, 5 to 20 mg/day
may go up to 40 to 60mg/day
Paroxetine Paxil® 10, 20, 40 mg/day or
20 mg 3 to 4 h pre-intercourse
Sertraline Zoloft® 25 to 200 mg/day or
50 mg 4 to 8 h pre-intercourse
Topical Therapies
Lidocaine/prilocaine cream EMLA® C Lidocaine2.5%/Prilocaine 2.5%
20 to 30 minutes pre-intercourse
36. Medical Treatment
(AUA Guidelines)
Alpha blockers: alfuzosin and terazosin have shown
mild benefit in clinical trials: counteraction of
sympathetic stimulation of ejaculation
37. Tramadol
Opioid analgesic: opioid receptor
Lelt increases 2 to 10 fold
Well-tolerated
Possible decrease in efficacy over time
10 to 20 percent nausea and somnolence
Head to head less effective than Paxil
50mg po 2 hours prior to Sex
38. Promescent
Promescent: thymol and ethanol in the eutectic formula
of lidocaine
Follows FDA monograph
2 to 6 sprays 10 minutes prior to intercourse
Available OTC/Promescent.com
39. Dapoxatine
On-demand SSRI treatment
Quick uptake and quick elimination
In European/Asian studies: good results
Common adverse event: nausea usually mild
Approved in 30 to 40 countries
Failed to be approved by FDA but will likely try again
40. Retrograde ejaculation
Bladder neck/internal sphincter fails to close during
ejaculation and the emitted semen flows along the path of
least resistance into the bladder, while the external sphincter
is closed and the bulbocavernosus muscle is contracting the
prostatic urethra
Diabetic neuropathy of the bladder
Multiple Sclerosis
Surgical injury to the bladder neck
TURP
Pediatric surgery
41. Anejaculation
Failure of emission into the prostatic urethra
Interference with somatic efferent contraction of the
ejaculatory structures including the epididymis, vas
deferens, ampulla of the vas deferens and seminal
vesicles.
42. Anejaculation
Diabetic sympathetic neuropathy
ejaculatory structures are not stimulated to contract
effectively
Diabetic microvascular disease
concomitant fibrosis of smooth musculature impairs the
contractility of the ejaculatory apparatus.
43. Spinal Cord Injury
Most common neurological cause of anejaculation
Complete injury above the spinal ejaculation center will
prevent cortical excitation
Injury below the spinal ejaculation center will diminish
afferent penile sensory excitation as well as efferent
control of emission and ejaculation
45. Latrogenic--Surgical
Surgical injury to the sympathetic chain or pelvic
nerves
RPLND may disrupt the sympathetic outflow to the
ejaculatory structures
Pelvic surgery: lower sympathetic pelvic nerve
Colorectal surgery
Aorto-iliac reconstruction
Lumbar spine exploration
46. Alpha Blockers
The more alpha-1A specific inhibit seminal emission
FDA label for silodosin reports 28% retrograde ejaculation
while
FDA label for tamsulosin reports an “abnormal ejaculation”
rate of only 8.4%
FDA approval label for alfusosin reports no adverse effects
on abnormal ejaculation
A Japanese study of 15 healthy urologist volunteers
reported a 100% rate of anejaculation with Silodosin vs a
35% rate for tamsulosin 4mg vs a 0% rate for alfuzosin
10mg
47. Differentiation:
Retrograde vs. Anejaculation
Normal orgasm
No or low volume ejaculate (<1.5ml)
Post-orgasm void should be checked for sperm
The bladder should be emptied before ejaculation, and
immediately after
Greater than 10 sperm per high powered field in a centrifuged
post-orgasm urine is indicative of retrograde ejaculation
In the case of lack of emission: no sperm in urine
Exception: diabetic patient may suffer neuropathic changes
resulting in both bladder neck dysfunction and lack of emission
48. Treatment
Alpha agonists
Sympathomimetic stimulation to augment the sympathetic
tone in the vas deferens, seminal vesicles, and bladder neck
May be enough to overcome the disrupted sympathetic
plexus as long as there is not a complete injury
The patients who would most benefit from this actually feel,
at baseline, a climax and rhythmic pelvic contractions with
little or no flow of fluid per urethra
49. Treatment
MEDICATION DOSING FOR ASPERMIA (retro or an-)
Ephedrine 25-50 mg po qid for 2 to 3 doses
Pseudoephedrine 60 mg po qid or 120 mg po bid for 2
to 3 doses
Imipramine 50 to 75mg po a day for 1 to 2 weeks
Midodrine 2.5 mg po tid titrated up to 10mg po tid,
titrate by 2.5mg/week
51. Treatment
Spinal cord injury below T10
Intact spinal cord (vibratory stim. won’t work)
ELECTROEJACULATION
For patients with very high lesions at or above C4, general anesthesia is
recommended for safer patient control.
Brackett et al showed a sperm retrieval rate of 92% in SCI patients
undergoing EEJ after failed PVS. (J Urol 2010)
(2)
52. Differential Dx
Ejaculatory duct obstruction
Low volume
Low PH
Negative post ejaculatory urine analysis
Dx by TRUS/Aspiration/contrast study
57. Post Operative TURED
Dramatic Improvement immediately
OR Retrograde Ejaculation
OR No Change----
Secondary epididymal “blow out”
Possible epididymo-vasostomy
Retrieve sperm for IVF-ICSI
OR COMPLICATIONS
25% incidence of chronic epipdidymitis/seminal vesiculitis
58. Sperm retrieval/ICSI
Due to the high complication rate of TURED sperm
retrieval and ICSI is now more commonly
recommended
Sperm retrieval has lower morbidity and can be
performed with local anesthesia
ICSI has a high success rate (up to 75%)
Stimulation from a few sources leads ultimately to emission and ejaculation. Erotic visual stimulation as well as psychological stimulation is processed in the cerebral cortex, which in turn modulate signals from various brain centers including the medial preoptic area, which is excitatory to ejaculation via dopamine (2), as well as the paraventricular nucleus of the hypothalamus which is excitatory via oxytocin (3). Inhibitory signals arise from the nucleus paragigantocellularis, which is seratonergic (4). These excitatory and inhibitory signals descend to a specialized area of the spine known as the “spinal ejaculation generator” which spans T12 to L2. (5)
Figure 1
Tactile penile stimulation from afferent dorsal penile nerves passes through the pudendal nerves to the S2-S4 spinal cord level and continues cephalad to the spinal ejaculation generator. (6)
The spinal ejaculation generator is comprised of lumbar spinothalamic cells under the influence of glutamate and other neurotransmitters. These cells process the cortical and sensory input and generate coordinated efferent signals via sympathetic, parasympathetic and somatic nerve pathways. (7) Sympathetic fibers, arising from level T10-L2 in the gray matter lateral columns, exit via the ventral roots to pass through the paravertebral sympathetic ganglia down to the hypogastric plexus and on to the end organ targets, where they synapse with and release acetylcholine to non-myelinated neurons which innervate the tissues and release norepinephrine to trigger contraction of the seminal vesicles, epididymis and vas deferens resulting in seminal fluid deposition in the posterior urethra while simultaneously triggering the bladder neck to contract. (8-10)
The spinal ejaculaton generator activates Onuf nucleus in the sacral spine which gives rise to pudendal efferent nerves that cause contraction of the pelvic floor, the bulbocavernosus and ischiocavernosus muscles and the periurethral muscles. (11-12) The tonic contractions reach a certain pressure in the external urethral sphincter before the ejaculatory reflex is elicited. (13)