Anorgasmia and delayed orgasm46th Annual UCLA State-of-the-Art Urology ConferenceMarch 5, 2021

Sriram Eleswarapu, MD, PhDHealth Sciences Assistant Clinical ProfessorDivision of AndrologyDepartment of UrologyDavid Geffen School of Medicine at UCLASEleswarapu@mednet.ucla.edu

@eleswarapu

Disclosure

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• No current commercial relationships.• This presentation includes discussion of off-label uses of medications.

A man walks into your office…• “I’m having trouble reaching climax.”• “I haven’t been able to orgasm in months.”• “I can’t seem to come. I lose my erection after 20 minutes.” • “My wife/husband/partner gets tired and we both lose interest.”

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A man walks into your office…• “I’m having trouble reaching climax.”• “I haven’t been able to orgasm in months.”• “I can’t seem to come. I lose my erection after 20 minutes.” • “My wife/husband/partner gets tired and we both lose interest.”

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Learning objectives

•To review the physiology and neurochemistry of ejaculation

•To understand the definitions of delayed orgasm and anorgasmia

•To understand how to evaluate delayed orgasm and anorgasmia

•To establish a clear pathway for managing men with these problems

• To arm yourself with “just enough” neurochemistry to guide pharmacology

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Sexual response•4 stages of sexual response: Desire, Arousal, Orgasm, Resolution• Increasing levels of sexual arousal reach a threshold triggers the

ejaculatory response

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Sensory input

• Primarily from the glans

• Dorsal nerve Pudendal nerve S2-S4

7Image: Public domain from Mikael Häggström (2014)

Ejaculation and orgasm• Emission + Expulsion (Ejection) + Orgasm

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Emission• Emission + Expulsion (Ejection) + Orgasm• Sympathetic nervous system

• T10-L2 pelvic plexus • Epididymis: Contracts (oxytocin)

• Vas deferens: Sperm moves to posterior urethra

• Prostate/seminal vesicles: Semen is expressed

• Bladder neck: Closes

9Image: Goodin DS, in Aminoff’s Neurology and General Medicine (5th Ed.), 2014

Emission

10Image: Goodin DS, in Aminoff’s Neurology and General Medicine (5th Ed.), 2014

• Emission + Expulsion (Ejection) + Orgasm• Sympathetic nervous system

• T10-L2 pelvic plexus • Epididymis: Contracts (oxytocin)

• Vas deferens: Sperm moves to posterior urethra

• Prostate/seminal vesicles: Semen is expressed

• Bladder neck: Closes

Ejection• Emission + Expulsion (Ejection) + Orgasm• Somatic innervation of striated pelviperineal muscles

• S2-S4 perineal branch of pudendal nerve• Ischiocavernosus muscle: Rhythmic contraction

• Bulbospongiosus muscle: Rhythmic contraction

11Image: Gray’s Anatomy (public domain)

Orgasm• Emission + Expulsion (Ejection) + Orgasm• Pleasurable result of cerebral processing of

sensory nerve input from pelvic muscle contraction and ejection of seminal fluid

12Image: American Pie (Universal Pictures, 1999)

Cerebral control• Complex interplay of regions of the brain to process,

regulate, and inhibit orgasm• Medial preoptic area (MPOA) and medial amygdala are

sensitive to testosterone (hormonal input)• Pons (nucleus paragigantocellularis)• Key neurotransmitters

• Serotonin (5-HT)

• Norepinephrine

• Dopamine

• Prolactin

• Oxytocin

13Image: Clement & Guiliano, Basic Clin Pharmacol Toxicol 2016

Keeping it simple• Serotonin (in general) inhibits ejaculation

• “Serotonin suppresses”

• Dopamine elicits ejaculation• “Dopamine drives”

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Keeping it simple• Serotonin (in general) inhibits ejaculation

• “Serotonin suppresses”

• Dopamine elicits ejaculation• “Dopamine drives”

• Prolactin suppresses ejaculation counterbalanced by dopamine

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What’s normal?

16Figure: Waldinger et al., J Sex Med 2005

• Numerous “stop-watch” studies of ejaculatory latency time (ELT) since the 1960s

• Large variability in stop-watch studies versus patient self-report

• ELT median = 5.4 min• ELT range = 0.5 to 44 min• ELT decreases with age

Delayed orgasm and anorgasmia• DSM-V: Delayed or inhibited ejaculation following normal sexual arousal and adequate

sexual stimulation• Requires personal distress

• Ejaculation that takes > 2 standard deviations above the mean ELT• Approximately 22-30 min

• Exhaustion prior to orgasm leading to cessation of sexual activity in otherwise healthy individuals

• 8-14% of adult men• More common with increasing age

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Causes of DO/AO• Medications (SSRI, opioids, and many others)• Hormonal

• Hypothyroidism

• Low testosterone

• Elevated prolactin

• Increasing age• Comorbidities (metabolic syndrome)• Neurologic disorders• Psychosocial or relationship factors• Diminished penile sensitivity

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Diagnosis of DO/AO• History

• Thorough medication review

• Opioid medications

• Substance abuse discussion

• Sudden versus progressive onset

• Physical exam (including focused neurological assessment)• Laboratory testing

• Testosterone, prolactin, LH, FSH, estradiol

• TSH, reflex T4

• Hemoglobin A1c

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Treatment pathways

• Psychosocial contributors and no identifiable medical cause? sex therapy• Concomitant ED? PDE-5 inhibitor• Hypogonadism? testosterone replacement therapy (TRT) • Hypothyroidism? replace (levothyroxine)• Opioid use? wean• Penile sensitivity problem? consider penile vibratory stimulation (PVS)• SSRI? make switch to bupropion / consider cyproheptadine on-demand• High / normal prolactin? cabergoline• Low / normal prolactin? oxytocin (intranasal)

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Pharmacology• Bupropion (75 mg bid)

• NDRI (norepinephrine-dopamine reuptake inhibitor), has dopaminergic effect

• Bupropion’s prosexual association is largely based on one study, 66% effective Ashton & Rosen, J Clin Psychiatry 1998

• One follow-on study showed bupropion superior to sertraline Coleman et al., Ann Clin Psychiatry 1999

• Survey study showed higher libido, orgasm intensity, duration with bupropion Modell et al., Clin Pharmacol Ther 1997

• Cyproheptadine (4-12 mg, 4 h before sex)• Antihistamine; antagonist of serotonin and acetylcholine receptors Arnott & Nutt, Br J Psychiatry 1994

• Cabergoline (0.5-1 mg, twice a week)• Dopamine (D2) receptor agonist; counteracts prolactin; 66% improvement Hollander et al., Sex Med 2016

• Oxytocin (24 IU intranasal, 5-20 min before sex)• Limited data showing efficacy (10-person study) Burri et al., Psychoneuroendocrinology 2008

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Summary• Ejaculatory response

• Sensation: Dorsal nerve pudendal nerve S2-S4

• Emission: T10-L2 sympathetic pelvic plexus emission/bladder neck closure

• Ejection: S2-S4 somatic perineal branch of pudendal nerve bulbospongiosus/ischiocavernosus contractions

• Neurotransmitters and hormones• Serotonin (and norepinephrine) = “suppresses”

• Dopamine = “drives”

• High prolactin delayed orgasm

• Oxytocin surge of arousal

• Testosterone = plays a role in the MPOA, medial amygdala, and elsewhere (e.g., pelvic floor)

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Summary• Delayed orgasm / anorgasmia

• ~22+ minutes and bother

• Medications (SSRI), hormones, age, comorbidities

• Bupropion, cyproheptadine, cabergoline, oxytocin

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Anorgasmia and delayed orgasm46th Annual UCLA State-of-the-Art Urology ConferenceMarch 5, 2021

Sriram Eleswarapu, MD, PhDHealth Sciences Assistant Clinical ProfessorDivision of AndrologyDepartment of UrologyDavid Geffen School of Medicine at UCLASEleswarapu@mednet.ucla.edu

@eleswarapu