Editing Disorders of Ejaculation and Orgasm (section)

== Premature Ejaculation ==

=== Definition ===

*'''ISSM Committee for the Definition of Premature Ejaculation (2013) defined PE (lifelong and acquired PE) as a male sexual dysfunction characterized by the following (3):'''
*# '''<span style="color:#ff0000">Ejaculation that always or nearly always occurs before or within ≈1 minute of vaginal penetration (lifelong PE) or a clinically significant and bothersome reduction in latency time, often to ≈3 minutes or less (acquired PE) AND'''
*# '''<span style="color:#ff0000">The inability to delay ejaculation on all or nearly all vaginal penetrations AND'''
*# '''<span style="color:#ff0000">Negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy'''

=== Classification (4): ===
# '''<span style="color:#ff0000">Lifelong: characterized by a cluster of core symptoms, including early ejaculation at nearly every intercourse within 30-60 seconds in the majority of cases (80%) or between 1-2 minutes (20%), with every or nearly every sexual partner and from the first sexual encounters onward'''
# '''<span style="color:#ff0000">Acquired: men develop early ejaculation at some point in their life, which is often situational, having previously had normal ejaculation experiences'''
# '''<span style="color:#ff0000">Variable: occasionally experience an early ejaculation; should not be regarded as a disorder''', but as a natural variation of the ejaculation time in men
# '''<span style="color:#ff0000">Subjective: patients report premature ejaculation but actually have normal or even extended ejaculation time'''

=== Epidemiology ===
* '''<span style="color:#ff0000">Most common sexual dysfunction in males aged 18-59 years'''
*Prevalence difficult to characterize given varying definitions
** One study reported overall PE prevalence as 19.8% comprising '''(most common to least common):'''
*** '''Variable PE (8.5%)'''
*** '''Subjective PE''' (5.1%)
*** '''Acquired PE''' (3.9%)
*** '''Lifelong PE''' (2.3%)
* '''≈2.5% in general population of intravaginal ejaculation latency time (IELT) ≤1 minute, a substantially higher percentage of men with normal IELT report premature ejaculation'''
** Distribution of the IELT is positively skewed, with a '''median of 5.4 minutes''' (range 0.55-44.1 minutes), decreases with age, varies across countries
*** 21-23 minutes represents about 2 standard deviations above the mean
** IELT is lower in men with lifelong PE compared with acquired PE and highest in men with subjective PE.

=== Causes ===
* '''Lifelong: in some men, neurobiologic and genetic variations could contribute to the pathophysiology of lifelong PE'''
* '''Acquired:'''
*# '''Sexual performance anxiety:''' anxiety activates the sympathetic nervous system and reduces the ejaculatory threshold
*# '''Psychological or relationship problems'''
*# '''Erectile dysfunction: as many as half of subjects with ED also experience PE'''
*# '''Prostatitis/CPPS: PE can be the main sexual disorder symptom in men with chronic prostatitis or CPPS'''
*# '''Hyperthyroidism'''
*# '''Withdrawal/detoxification from prescribed or recreational drugs'''

=== Diagnosis and Evaluation ===
* Inclusion of the partner in the evaluation and management process is important but not mandatory
*'''PE is associated with negative psychological consequences, including distress, bother, and frustration that may affect quality of life, partner relationships, self-esteem, and self-confidence and can act as an obstacle to single men forming new partner relationships'''

==== History and Physical Exam ====
* '''History (medical and sexual)'''
** '''Recommended questions (related to definition above):'''
*** '''What is the time between penetration and ejaculation?'''
**** Self-estimation by the patient and partner of IELT should be used; studies have indicated that patient or partner self-report of ejaculatory latency correlate relatively well with objective stopwatch latency and might be useful as a proxy measure of IELT
*** '''Can you delay ejaculation?'''
*** '''Do you feel bothered, annoyed, and/or frustrated by your PE?'''
** '''Optional questions:'''
*** '''Differentiate Lifelong and Acquired PE'''
**** When did you first experience PE? Have you experienced PE since your first sexual experience on every/almost every attempt and with every partner?
*** '''Assess Erectile Function'''
**** Is your erection hard enough to penetrate? Do you have difficulty in maintaining your erection until you ejaculate during intercourse? Do you ever rush intercourse to prevent loss of your erection?
*** '''Assess Relationship Impact'''
**** How upset is your partner with your PE? Does your partner avoid sexual intercourse? Is your PE affecting your overall relationship?
*** '''Previous Treatment of PE'''
*** '''Impact on Quality of Life'''
**** Do you avoid sexual intercourse because of embarrassment? Do you feel anxious, depressed, or embarrassed because of your PE?
* '''Physical exam'''
** Screen for cardiovascular and gender-specific diseases
** In men with acquired PE, a physical examination is mandatory in an effort to identify the cause of the PE and to alleviate its possible cause
** '''Digital rectal examination''', routine in an andrologic setting for all men age ≥ 40 years, '''is useful in identifying possible evidence of prostatic inflammation or infection.'''

==== Other ====

===== Questionnaires =====
* Standardized assessment measures such as validated questionnaires (Premature Ejaculation Profile (PEP) and the Index of Premature Ejaculation (IPE)) and PRO measures can be used as an adjunct to a full medical and sexual history and self-estimation of ejaculatory latency in the evaluation of males presenting with self-reported PE. These measures are all relatively new and were developed primarily for use as research tools.

===== Assessment of erectile function =====
* Possible comorbid ED should be evaluated using a validated instrument such as the International Index of Erectile Function (IIEF) or the IIEF-5 (SHIM).
** Normal erectile function should be defined as an IIEF Erectile Function Domain of ≥26 or IIEF-5 > 21

=== Management ===
* '''<span style="color:#ff0000">Patients with ED and premature ejaculation should have their ED addressed first.'''
*'''Based on subtype'''
** '''Lifelong PE: pharmacotherapy alone or in combination with graded levels of patient and couple psychosexual therapy'''
** '''Acquired PE: cause-specific treatment''' (e.g., psychosexual counseling or ED pharmacotherapy, alone or in combination with PE pharmacotherapy).
** '''Variable PE or PE-like ejaculatory dysfunction: psychosexual education and graded patient and couple psychotherapy'''

==== First-line: Psychosexual therapy ====
* '''<span style="color:#ff0000">All men seeking treatment for PE should receive basic psychosexual education or coaching'''
* '''Most frequently used treatments (2):'''
*#'''Squeeze technique'''
*#'''Stop-start technique'''
* Efficacy
**At laast moderately successful in alleviating the dysfunction in the short term
**Long-term outcome data are limited and suggest a significant relapse rate

==== Second-line: Pharmacologic treatment ====

===== Options =====

* '''<span style="color:#0000ff">PASTA (5):'''
# '''<span style="color:#0000ff">P<span style="color:#ff0000">DE5 inhibitors (only if comorbid erectile dysfunction)'''
# '''<span style="color:#0000ff">A<span style="color:#ff0000">nesthetic, topical'''
# '''<span style="color:#0000ff">S<span style="color:#ff0000">elective serotonin reuptake inhibitors (SSRIs)'''
# '''<span style="color:#0000ff">T<span style="color:#ff0000">ramadol'''
# '''<span style="color:#0000ff">A<span style="color:#ff0000">lpha-blockers'''

* All are considered off-label

====== Phosphodiesterase type 5 (PDE5) inhibitors ======
* '''<span style="color:#ff0000">In males with comorbid erectile dysfunction, erectile dysfunction pharmacotherapy alone or in combination with PE pharmacotherapy is recommended</span>''' for the treatment of lifelong PE or acquired PE
* '''In males with normal erectile dysfunction and''' 
**'''Lifelong PE, PDE5 inhibitors (off-label on-demand or daily dosing) are not recommended'''
** '''Acquired PE, most often secondary to comorbid ED, hyperthyroidism, chronic lower urogenital infection, prostatodynia, or CPPS, appropriate cause-specific treatment alone or in combination with an SSRI is recommended'''

====== Anesthetic, topical ======
* '''Efficacy'''
**'''Moderately effective in delaying ejaculation'''
*'''Drugs and Dosages'''
**'''Available as cream, gel, or spray'''
**'''2.5% lidocaine and/or 2.5% prilocaine'''
*Application
**Apply to penis 20 to 30 minutes pre-intercourse
**Wipe off penile cream before engaging in vaginal penetration

====== Selective serotonin reuptake inhibitors (SSRIs) ======
* '''Mechanism of Action: block pre-synaptic axonal reuptake of serotonin''' from the synaptic cleft of central serotonergic neurons by 5-HT transporters, resulting in enhanced 5-HT neurotransmission and stimulation of postsynaptic membrane 5-HT receptors.
* '''Ejaculation delay usually occurs within 5-10 days of starting treatment, but the full therapeutic effect may require 2-3 weeks of treatment''' and usually is sustained during long-term use.
*'''<span style="color:#ff0000">Drugs and Dosages'''
**'''<span style="color:#ff0000">Daily dosing'''
***'''<span style="color:#ff0000">Options: paroxetine, clomipramine, sertraline, fluoxetine, or citalopram.'''
**** '''<span style="color:#ff0000">Paroxetine'''
*****10-40mg daily
*****'''<span style="color:#ff0000">Exerts the strongest ejaculation delay</span>''', increasing IELT approximately 8.8x over baseline
**'''On-demand'''
***'''Options: dapoxetine (not available in Canada) or off-label paroxetine, clomipramine, sertraline, and fluoxetine'''
**** '''On-demand administration''' 3-6 hours before intercourse is modestly efficacious and well tolerated but is '''associated with substantially less ejaculatory delay than daily treatment'''
* '''<span style="color:#ff0000">Adverse effects'''
** Usually minor, start in the first week of treatment, and may gradually disappear within 2-3 weeks.
** '''<span style="color:#ff0000">Includes'''
***'''<span style="color:#ff0000">Fatigue'''
***'''<span style="color:#ff0000">Yawning'''
***'''<span style="color:#ff0000">Mild nausea'''
***'''<span style="color:#ff0000">Diarrhea'''
***'''<span style="color:#ff0000">Perspiration'''
*** '''<span style="color:#ff0000">Hypomania''' 
****'''Can occur infrequently; treatment with SSRIs should be avoided in men with a history of bipolar depression'''
***** '''SSRIs are associated with a small increase in the risk for suicidal ideation or suicide attempts in youth but not adults.'''
****** '''Caution is suggested in prescribing SSRIs to young adolescents with PE age ≤ 18 years, and to males with PE and a comorbid depressive disorder, particularly when associated with suicidal ideation.'''
*** '''<span style="color:#ff0000">Weight gain and increased risk of type 2 diabetes</span>''' associated with long-term SSRI use
***'''<span style="color:#ff0000">Priapism</span>'''; rare potential adverse effect of SSRIs
***'''Upper GI bleeding'''
****Platelet serotonin release has an important role in hemostasis and SSRIs, especially with concurrent use of aspirin and NSAIDs, may be associated with increased risk for upper GI bleeding
*** '''Abnormal semen parameters'''
****In males with normal semen parameters, paroxetine has been reported to induce '''abnormal sperm DNA fragmentation''' in a significant proportion of patients, without a measurable effect on other semen parameters. 
*****Fertility potential of a substantial number of men on paroxetine may be adversely affected by these changes in sperm DNA integrity
* '''Patients should be advised to avoid sudden cessation or rapid dose reduction of daily dosed SSRIs, which may be associated with an SSRI withdrawal syndrome'''

====== Tramadol ======

====== Alpha-blockers ======