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Delayed Ejaculation & Anorgasmia

Delayed Ejaculation & Anorgasmia

Delayed &

EMMANUELE A. JANNINI Chair of & Tor Vergata University of Rome, Italy It Soc Androl & Sex Med – President-elect Taxonomy of ejaculatory disorders

Epidemiology of ejaculatory disorders

25 a) timing 20 – 15 – 10

Percentage 5 b) modality 0 E N IA R PE DE IO M AS ‐ LAT G U R O JAC ‐ ANEJACULATION (impotentia ejaculationis) E AN AN Taxonomy of ejaculatory disorders

• EMISSION PHASE DISORDERS: – Retrograde ejaculation • EJACULATION PHASE DISORDERS: – Premature ejaculation – Deficient ejaculation: • Delayed ejaculation • Anejaculation • DISORDERS: – Anorgasmia – Postorgasmic illness syndrome Standard Operating Procedures (SOP) in Diagnosis and Treatment of Delayed Ejaculation/Anejaculation

ISSM Standards Committee Meeting June 23-25, 2010 Hotel Agneshof Nürnberg, Germany

Pierre Assalian Canada Emmanuele A. Jannini Italy Chris G McMahon (Chairman) Australia David Rowland USA Marcel Waldinger (Chairman) The Netherlands DELAYED EJACULATION Delayed ejaculation • Much less frequent than PE • A rare reason for medical help seeking

• Underdiagnosed • Undertreated Is DE a disease?

• girls are happy…

…where is the problem?

…but girls are not happy… Why so poor science?

• Low prevalence • Few studies • Classically considered A new psychogenic in nature • Classically treated with behavioral challenge • Definition(s) lacking • Etiologies largely unknown for • Pathogenesis obscure • Lack of awareness and Sexual acknowledgements of DE as a symptom of medical diseases • Low request of help by the medicine patients Delayed Ejaculation & Anejaculation

Confusing nomenclature Synonyms: delayed (DE), retarded (RE), or inhibited ejaculation (IE), inadequate ejaculation, idiopathic anejaculation, anorgasmia, primary impotentia , and psychogenic anejaculation No clear and evidence based definition DSM‐IV‐TR: Definition

“The persistent or recurrent delay in, or absence of, orgasm after a normal sexual excitement phase during sexual activity that the clinician, taking into account the person’s age, judges to be adequate in focus, intensity, and duration” “The disturbance causes marked distress or interpersonal difficulty…” “It should not be better accounted for by another Axis I (clinical) disorder or caused exclusively by the direct physiologic effects of a substance or a general medical condition” DSM‐V: Definition A. Either of the following symptoms must be experienced on almost all or all occasions (approximately 75%‐100%) of partnered sexual activity (in identified situational contexts or, if generalized, in all contexts), and without the individual desiring delay: 1. Marked delay in ejaculation. 2. Marked infrequency or absence of ejaculation. B. B. The symptoms in Criterion A have persisted for a minimum duration of approximately 6 months. C. C. The symptoms in Criterion A cause clinically significant distress in the individual. D. The is not better explained by a nonsexual or as a consequence of severe relationship distress or other significant stressors and is not attributable to the effects of a substance/ or another medical condition. Operationalisation Criteria of time‐to‐ejaculate, inability to ejaculate, distress, satisfaction … Lack of operationalized criteria Given that most sexually functional men ejaculate within about 4‐10 minutes following intromission [1], a clinician might assume that men with latencies beyond 25‐30 minutes (21‐23 min represents about two SD above the mean) who report distress or men who simply cease sexual activity due to exhaustion or irritation qualify for this diagnosis. 1. Patrick DL, Althof SE, Pryor JL, et al. Premature Ejaculation: An Observational Study of Men and Their Partners. J Sex Med. 2005: 2:58-367 Classification ‐ Specify whether:

• Lifelong: The disturbance has been present since the individual became sexually active. • Acquired: The disturbance began after a period of relatively normal sexual function. • Generalized: Not limited to certain types of stimulation, situations, or partners. • Situational: Only occurs with certain types of stimulation, situations, or partners. Classification ‐ Specify current severity:

• Mild: Evidence of mild distress over the symptoms in Criterion A. • Moderate: Evidence of moderate distress over the symptoms in Criterion A. • Severe: Evidence of severe or extreme distress over the symptoms in Criterion A. Prevalence of DE

Since the beginning of sex , DE was seen as a clinical rarity [1]: 17 cases. Apfelbaum [2]: 34 cases Kaplan [3]: 50 cases However, based on clinical experiences, some urologists and sex therapists are reporting an increasing prevalence of DE

1. Masters WH, Johnson VE. Human Sexual Inadequacy, Boston: Little Brown, 1970 2. Apfelbaum B. Retarded ejaculation: A much-misunderstood syndrome. In Lieblum, SR and Rosen, RC Eds, Principles and practice of : Update for the 1990's 2nd ed pp 168-206 New York: Guilford Press. 1989: 3. Kaplan H. The evaluation of sexual disorders: Psychological and medical aspects. New York: Brunner/Mazel. 1995: EPIDEMIOLOGY Epidemiology

• 1632 patients studied at the Unit of the Univ. of Florence

• 82 (5.0%) with DE – of those, 62 reported mild DE – and 20 reported severe DE or anejaculation Prevalence of Delayed Ejaculation

Prevalence is unclear DE is reported at low rates in the literature, rarely Prevalence isexceeding unclear because 3% [1of ‐the3] lack of a Limitedprecise normative definition data of this for syndrome. defining Itthe is the duration of “normal”least ejaculatory common male latency, sexual complaint. particularly Only regarding75% the right “tail” of menthe reportIELT distribution always ejaculating (i.e., during beyond the mean sexual activity, and less than 1% of men will complain of problemslatency with to orgasm)reaching ejaculation Epidemiologicthat last studies more than have 6 months. not distinguished (DSM V) delayed ejaculation vs. anejaculation

1. Perelman M. Curr Sex Hlth Rep. 2004: 1:95-101 2. Laumann EO, Paik A, Rosen RC. JAMA. 1999 Feb 10: 281:537-44 3. Simons JS, Carey MP. Arch Sex Behav. 2001: 30:177-219. Characteristics

• High levels of relationship distress, sexual dissatisfaction, about their sexual performance, and general health issues • Lower frequencies of coital activity [Rowland 2005] • A distinguishing characteristic: men with DE have little or no difficulty attaining or keeping their ‐in fact they are often able to maintain erections for prolonged periods of time • Despite their good erections, they report low levels of subjective , at least compared with sexually functional men [Rowland 2004] CLINICAL ASPECTS Assalian Jannini McMahon Rowland Waldinger

Evaluation of men presenting with DE should include a full medical/sexual history, a focused physical examination and any investigations suggested by these findings

Recommendation Pathophysiology

Psychogenic Inhibited EjaculationNEUROGENICInfective DE Urethritis Congenital Mullerian duct cyst Genitourinary tuberculosis interruptionWolfian duct abnormaility of the nerve supply to the Schistosomiasisgenitals • traumaticPrune surgicalbelly syndrome to the lumbarEndocrine sympatheticHypogonadism ganglia Neurogenic Diabetic autonomic • abdominoperitoneal Causes neuropathy Medication Alpha-methyl Dopa injury• lumbar sympathectomy. diuretics Radical Tricyclic and SSRI ProctocolectomyNeurodegenerative Diseases Bilateral sympathectomy• Phenothiazine Abdominal aortic• Alcohol abuse aneurysmectomy • alcoholic neuropathy Para-aortic lympthadenectomy Etiologies and risk factors of deficient ejaculation • NON‐ORGANIC • ORGANIC  Repressive sexual  education  Retroperitoneal lymph  in childhood node dissection  Deep psychological  mellitus conflicts  Transverse myelitis  Multiple sclerosis  Neuroleptic drugs • higher frequency of masturbatory activity • lower night emissions • longer IELT • higher anxiety and states • higher mean penile shaft sensory threshold values • Longer mean latencies of dorsal nerve somatosensory evoked potential • penile shaft hyposensitivity and hypoexcitability • adaptation to a certain masturbatory technique Psychoanalytic theories on DE

• “Anal” block. • Sperm retention. • Heavy misogyny. • ‘Autosexual’, rather than heterosexual, or homosexual, orientation. (Apfelbaum, 2000) Personality characteristics of delayed ejaculators • Overcontrolled, or paltry, poor, week personalities. • Obsessive‐compulsive need for control over the body. • Obstinate. A clinical continuum

Premature ejaculation

Delayed ejaculation Mild Moderate Severe

Anejaculation Lifelong DE, like lifelong PE, is considered to be a primarily a neurobiological variant, which may or may not secondarily lead to psychological or psychosocial distress. Aging

• seminal volume ? • levels ? • contractility ? • vescicle contractility ? • deferentes contractility ? Variation in ability to reach orgasm and orgams‐related concern as a function of the aging process (EMAS and ED Florentine centre data)

Corona et al., Best Pract Res Clin Endocrinol Metab. 2013;27:581 “Lost ” Syndrome

• Extended (multipara) Drugs affecting ejaculation

• Alprazolam • Aloperidol • Iproniazide • Aminocaproico Acid • Isocarbossazide • Amitriptiline • Labetanolo • • Lorazepam • Butaperazine • Mebanizine • Clorpromazine • Mesoridazine • • Metildopa • Desmetilimipramine • Pargiline • Fenelzine • • Fenossibenzamine • Perfenazine • • Prazosine • • • Guanadrel • Tioridazine • Guanetidine • • Imipramine • Trifluoperazine Comparison between different therapies affecting ejaculation15

10 •31 patients with PE (1 minute). 5 •4‐weeks treatment Minutes 0 • Crossover e in am ne r li e ip ra in m rt et il lo Se x af l C ro en ra •2‐week washout Pa ld o Si avi eh Abdel‐Hamid et al.: Int JB Imp Res, 2001 Salonia J Urol 2002; Chen 2003 Mitka JAMA 2003; Mondaini Int J Impot Res 2003; Abdel‐Hamid Drugs 2004

HYPOTHYROIDISM

Nature Rev Urol 2012;9:508 THERAPY Aims of DE therapy

1. To cure the disease (i.e. hypothyroidism). 2. To cure the couple. 3. To eliminate the symptom. 4. To create a “positive memory” of sexual success. Assalian Jannini McMahon Rowland Waldinger Treatment of DE should be etiology specific, and may include patient/couple psycho-education and/or psychosexual therapy, pharmacotherapy or integrated treatment.

Men/partners of reproductive age may require pre- operative sperm cryo-storage, sperm harvesting and assisted reproductive techniques Recommendation Assalian Jannini McMahon Rowland Waldinger

Recommendation Patients with psychogenic inhibited ejaculation (IE) are a challenging to treat population All require patient/couple psycho-education and/or psychosexual therapy which may be long term Behavioral therapy of DE

• Progressive desensitization – Non‐genital sexual activities minimizing performance pressure and maximizing focus on pleasure. • Stimulation and temporary inattention – Patient is stimulated to orgasm when inattentive. Dynamic‐behavioral therapies of DE

• Systematic analysis of marital problems and intrapsychic inhibition. • Use of fantasies to distract from hypercontrol and from the ‘spectator’ role. • Favor the insight of: • dynamics of symptom maintenance • irrational fears • traumatic memories Behavioral therapy of anejaculation

Obtain the ejaculation – Non coital (manual/oral stimulation) – (alone, then with the partner) Relaxation techniques Hypnosis Game theory (Apfelbaum) – Teach to , to lose rigidity, stimulating fantasies Comparative studies on sex therapy

• Couples with different types of sexual dysfunction. • No matching for type of dysfunction across treatment groups. • Poor outcome criteria. • Lacking of long‐term outcome data. Humans are not animals…

• Oxytocin with PGF2 induces ejaculation in dog and bull, but not in humans, both i.v. and nasal spray. • , provokes in rats premature ejaculation, but not in humans treated with 2‐3 mg sublingual. Off‐label pharmacological approaches NO EBM !!! Drug Treatment

Virtually all drug studies have been performed on men with SSRI induced ejaculatory dysfunction Alpha‐1 Agonists Cyproheptadine Amantadine Apomorphine Quinelorane Oxytocin Reboxetine may induce , seminal emission and ejaculation during defecation and micturition. • O'Flynn et al.: Reboxetine‐induced spontaneous ejaculation. Br J . 2000 • Haberfellner et al.: Sexual dysfunction caused by reboxetine. Pharmacopsychiatry. 2002 • Clayton et al.: Lack of sexual dysfunction with the selective noradrenaline reuptake inhibitor reboxetine during treatment for major depressive disorder. Int Clin Psychopharmacol. 2003 • Sivrioglu et al.: Reboxetine induced erectile dysfunction and spontaneous ejaculation during defecation and micturition. Prog Neuropsychopharm, 2007 Midocrine

Alpha‐1 adrenergic receptor agonist Less frequent and less severe adrenergic effects Safarinejad recently reported that midocrine reverses organic anejaculation in non‐SCI subjects in more than 50% of patients [1] In a RCT of 128 patients, stepwise titration of oral midodrine 7.5–15mg/day resulted in antegrade, retrograde and combined antegrade/retrograde ejaculation occurred in 18 (29.5%), 8 (13.1%) and 9 (14.8%) patients respectively

1. Safarinejad MR. Midodrine for the treatment of organic anejaculation but not spinal cord injury: a prospective randomized placebo-controlled double-blind clinical study. Int J Impot Res. 2009 Jul-Aug: 21:213-20 Recommendation

Level 4 evidence to support the treatment of delayed ejaculation with pharmacotherapy Grade D i.e. NO Recommendation FAILURE OF EMISSION DELAYED EJACULATION Neurogenic ANEJACULATION Metabolic ANORGASMIA Drug Disease Specific Management NEVER INHIBITED MALE ORGASM Psychosexual Therapy

INHIBITED MALE ORGASM Nocturnal/ Emissions IS THERE ORGASM? SOMETIMES Psychosexual Therapy AGE RELATED DEGENERATION Reassure/alter sexual technique

ALWAYS IS THERE EJACULATION?

conclusion YES NO

ARE SPERM PRESENT IN URINE AFTER ORGASM?

NO YES

ASPERMIA RETROGRADE Ejac.Duct Obstruction EJACULATION Reassure/Educate Pharmacotherapy Surgery

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