يئوخ ديمح ديس رت كد ينيلاب يزاسوراد هورگ نارهت يكشزپ مولع هاگشناد يزاسوراد هدكشناد

• Integral component of quality of life, well-being • Can impact treatment decisions and/or compliance with medical treatments • Sexual side effects of medications, illness

• Sexual behavior in males and females involves arousal of the

peripheral sex organs

, the

spinal cord

, and the

brain

.

– Factors that modulate activity within any of these regions can impair sexual function – Sexual arousal involves activity within the

parasympathetic nervous system

(allows for blood flow to the sex organs) – Sexual orgasm involves the activation of the

sympathetic nervous system

Erection Physiology

• Stimulation of penile shaft by the nervous system leads to the

secretion of nitric oxide (NO)

, causing the creation of

cyclic guanosine monophosphate

(cGMP) which functions to relax blood vessels ( vasodilatation ) so erectile tissues in the

corpus cavernosa

can fill with blood, and subsequently cause a penile erection. Phosphodiesterase type 5

(PDE5)

is always present in the penis and functions to destroy cyclic GMP, causing vasoconstriction of erectile tissues and resulting in the loss of erection. In normal males, the loss of an erection occurs after orgasm and ejaculation of sperm.

Medical History Illness/ Medications External Stressors Mental Health Sexual Function Cognitions/ Beliefs Family Beliefs Early Sexual Experiences Partner Relationship Partner’s Sexual Functioning

Masters & Johnson ’s Sexual Response Cycle •

4 Phase Sexual response cycle

–

Excitement phase

: erection, lubrication, muscular tension, ^ heart rate, sex flush –

Plateau phase

: advanced state of arousal, orgasmic platform builds, sex skin appears –

Orgasmic phase

: 3-15 contractions, rush, warmth, explosion, release –

Resolution phase

: return to prearoused state, men have refractory period unresponsive to stimulation, women may be rearoused to multiple orgasm

Kaplan ’s 3 Stages of Sexual Response

• Independent, variable sequence, integration of psychological and physiological • • •

Desire:

psychological cofactors

Excitement:

vasocongestion & myotonia

Orgasm

: pelvic muscular contractions

Zilbergeld & Ellison Sexual Response Process • Desire: cofactors make “normal” undefined • Arousal: subjective feeling of “turned on” • Physiological Readiness: vasocongestion and myotonia • Orgasm: reverses the physiological process of pleasurable buildup, “orgasmic fingerprinting ” • Satisfaction:

ultimate goal

Sexual Dysfunction

persistent and recurrent difficulties in becoming aroused or reaching orgasm

Epidmyology

• Sexual problems are

common

–43% women –31% men (Laumann et al., 1999)



Extremely prevalent in the general population ;Simons & Carey (2006)

   

3% orgasmic disorder 5% erectile disorder 3% hypoactive sexual desire disorder 5% premature ejaculation

• • •

Only 50% Women Experience Regular Orgasms During Intercourse

•

Premature Ejaculation Occurs in About 37% Young males

•

22% of women and 5% of men suffer from Hypoactive Sexual Desire Disorder 10% of males report panic attacks during attempted sexual activity Sexual Arousal Disorders affects about 5% of males, 14% of females

• •

21 percent of women aged 18 to 29 reporting physical pain with intercourse 27 percent reported experiencing non pleasurable sex, and 16 percent reported sexual anxiety.

Etiology

How do sexual problems develop?

Predisposing Factors Maintaining Factors

Early Development

Precipitating Factors

Current Functioning

• Predisposing – Childhood abuse or sexual assault – Early sexual experiences, messages about sex • Precipitating (onset) – Relationship distress – Major life changes (parenthood, retirement) – Menopause – Surgery, illness, medication • Perpetuating (maintaining) – Performance anxiety – Poor communication/lack of knowledge – Physical response (e.g., muscle tension)

• Organic causes • Psychosocial causes – Cultural influences and irrational beliefs – Psychosexual trauma – Sexual orientation – Ineffective or lack of sexual skills – Psychological conflicts – Performance anxiety – Problems in the relationship

Physical Causes of Sexual Dysfunctions

• • • • • •

Men:

Diabetes Alcoholism Lumbar-disc disease Atherosclerosis Spinal cord injuries Smoking

• • • • • •

Women:

Diabetes Heart disease Hormone deficiencies Neurological disorders Alcoholism Spinal cord injuries

Classifications

• • •

Lack of sexual desire disorder (HSD)

– Little or no interest in any sex activity – Common Presenting Problem – ; what is normal?

Hypogonadism

– Reduced output of testosterone

Sexual aversion disorder

– Irrational fears & phobia of sex, common cofactors are sexual abuse/trauma

• •

Male erectile disorder

– Persistent difficulty achieving or maintaining an erection, situational or generalized – Performance anxiety

Female arousal disorder

– persistent difficulty becoming sexually excited or adequately lubricated

• •

Male orgasmic disorder

– Premature ejaculation – Delayed ejaculation, retarded ejaculation, ejaculatory incompetence

Female orgasmic disorder

– Anorgasmic (preograsmic) – Rapid female orgasm: too quickly?

4.Sexual Pain Disorders

• •

Dyspareunia

– Persistent or recurrent pain during sexual intercourse in either gender; cofactors

Vaginismus

– Involuntary contraction of the muscle surrounding the vaginal barrel.

– Psychological fear of penile penetration often caused by sexual abuse/trauma.

Other Disorders

•

Peyronie’s disease - development of calcium deposits and fibrous tissue in the penis

•

Priapism - prolonged and painful erection

Erectile dysfunction

is

“The inability to obtain or sustain penile erection suitable for sexual intercourse or the completion of sexual activity ”

• Risk factors: age, smoking and obesity • Increase prevalence due to: DM, HTN, CVD, Anxiety + Depression

Erectile Dysfunction

 At least 3 million men in the UK are affected  prevalence of 53% in males with diabetes aged 18-75  39% of these had permanent ED (Hackett 1995)

Male Erectile Disorder (ED)

Top 12 causes of ED

Psychological Causes

 Loss of libido  Stress  Anxiety  Depression  Relationship problems  Embarrassment  Fear of failure (self fulfilling prophecy)  Sexual inhibition  Sexual abuse

Organic Causes



Penile Problems



Neurogenic



Vascular



Endocrine



Prescription Medication



Lifestyle

 Alcohol  Smoking

Lifestyle

 Recreational drugs  Cycling

Aetiology

Aetiology Multifactor, 80% organic cause • Vascular: - uncontrolled DM, cardiac, vascular disease - new or complicated anti-HTN Rx • Neurogenic: - Spinal cord injury - Neurological disease (e.g. MS) • Hormonal: ↓ testosterone, ↑ prolactin - TSH (rare cause hypothyroid) • Organic (focal): - BPH - liver/kidney disease

Aetiology contd. • Anatomical: excessive curvature (Peyronies Disease) • Psychogenic: - normal libido, sexual identity, recent life stresses, chronic EtOH - not hormonal • Medication: antidepressants, antihypertensives (ACE inhib + b-blocker)

–

vascular diseases

(most common cause), e.g., hardening of arteries, long term cigarette use –

diseases affecting the nervous system

, e.g., multiple sclerosis, alcoholism –

diseases affecting vascular and nervous system

, e.g., diabetes, hypothyroidism –

anything impairing penile vascular and/or nervous system:

• surgical or accidental injury • old age • pharmaceuticals

• Vasculogenic (arterial or cavernosal) • Psychogenic • Neurogenic • Hormonal • Drug induced • Other systemic diseases or aging

•          

Alcohol Estrogens Antiandrogens H 2 receptor blockers Anticholinergics Antihistamines Ketoconazole Antidepressants Antihypertensives Narcotics Sedative-Hypnotics

           

ß-blockers Phenothiazines Metoclopramide Cigarettes Cocaine Spironolactone Lipid-lowering agents NSAIDs Cytotoxic drugs Diuretics Marijuana Digoxin

(and some possible alternatives)

 b -blockers  Thiazide diuretics  Hydralazine  a -blockers  ACE inhibitors  Ca channel blockers  K channel blockers

o Thiazides o K-sparing diuretics o Carbonic anhydrase inhibitors o Loop diuretics



SSRI



TCA



MAOI

 ??

 Newer agents thought to have lower risk

  

Phenothiazines Carbamazepine Risperidone

 ??

 Newer agents thought to have lower risk



Cyproterone acetate



LHRH analogues



Oestrogens



none



Gemfibrozil



Clofibrate



Statins



Carbamazepine



Phenytoin



Refer neurology



Levo-dopa



Refer neurology



H 2 -antagonists



PPI



Allopurinol



Indomethacin



Disulfiram



Phenothiazine antihistamines



Phenothiazine antiemetics



Other antihistamines



Cyclizine, Ondansetron

Assessment

Initial Assessment

• Take your time!

• Assured privacy • (Comfortable surroundings) • Carried out by competent individual (GP, urologist, specialist nurse practitioner) • Must be aware of local specialist facilities (ED clinics, protocols for referrals, psychosexual services, etc)

Also

• Why seeking help now?

• What does he think the cause is?

• What has he tried?

• Does partner know?!

• What is partner’s attitude?

 History  Physical Examination  Investigations  Treatment

History

• Ask patient to describe the problem in detail • Exclude other problems such as premature ejaculation • Clues to psychogenic vs organic origin

History

 Patients Description of Problem  Duration of Problem  Medical History  Prescription Medication  Sexual History  Social History  Psychological  Lifestyle  Include Partner

Physical Examination

 External Genitalia  Rectal Examination of Prostate  Secondary Sexual Characteristics  Gynecomastia  Peripheral Pulses  Blood Pressure

Investigations

• Testosterone (Hx suggests hypogonadism) • LH (if T low) • Prolactin (if T low ± low libido) • Urinalysis (DM) • Haemoglobinopathy screen (afro-caribbean) • U&E (renal problems associated with ED) • LFT (liver problems associated with ED)

Investigations

 Serum Testosterone  Serum Prolactin  Serum Follicle Stimulating Hormone  Serum Leutenising Hormone  Thyroid function tests  PSA  HbA1c  Blood Glucose

• • • • • •

Sudden onset Early collapse of erection Good quality ( “better”) self-stimulated or early morning erections Premature ejaculation or anorgasmia Relationship issues Major life events

• • • • • •

Generalised anxiety states Depressive illness Psychosis Body Dysmorphic Disorder Gender identity problems Alcoholism

• • • • •

Gradual onset Lack of tumescence Normal ejaculation Normal libido (except hypogonadal men) Risk factor in PMHx (esp cardiovascular, endocrine and neurological systems)

•

Surgery, DXT or trauma to genitalia

Organic origin

• • • •

Drug associated with ED Smoking High alcohol consumption Use of recreational or body-building drugs

Psychological Organic

 Sudden onset  Gradual onset ( unless surgery or trauma)  Presence of early morning and nocturnal erections  Absence of morning or nocturnal erections  Response to stimulation Inconsistent erections  No response to sexual stimulation  Decreased libido   Relationship problems Change in life events  Aged under 55  Normal libido and ejaculation  Underlying medical condition  Aged over 55

Treatments

• Some unpleasant administration methods or adverse effects, so unbiased, informed patient choice important • Address both organic and psychological elements • ? Involve partners • Agree “treatment goals” before starting

Treatment Options



Education



Lifestyle Modification



Glycaemic Control



Psychosexual counselling



Drug Therapy



Mechanical Devices



Surgery

• Success depends on patient motivation • Patient works with therapist • Explore reasons why he is not experiencing normal sexual arrousal • 50% - 80% success rate

Routes Of Administration

• Oral • Topical • Intramuscular • Intraurethral • Intracavernosal

Oral

• PDE-5 Inhibitors • Apomorphine (uprima) • Yohimbine • Methyltestosterone • Trazadone (deseryl)

Topical

• Testosterone pach (Testoderm) • Testosterone Gel (androgel 1%)

Intramuscular

• Testosterone cypionate • Testosterone enantate • Testosterone propionate

Intraurethral

• Alprostadyl (muse) • Prostaglandin tab placed into urethra • Diffuses to corpora cavernosa • 65% effective

Intraurethral Therapy

 Prostaglandin E1 (Alprostadil)  Muse  Intraurethral Pellet  Risk of Priapism  May affect partner  Training to self administer  Manual dexterity  Test dose given in clinic

Intracavernosal

• Alprostadyl (Caverject , Edex) • Papaverine • Phentolamine • 94% effective !

Intracavernosal Therapy

 Prostaglandin E1 (Alprostadil)  E.g. Viridal,Caverject  Naturally occurring  Vaso-active properties  73-90% effective  No stimulation required  Effective within 5-15 minutes

Intracavernosal Therapy Cautions

 Training to self inject  Manual dexterity  Test dose given in clinic  Priapism  Haematoma  Irritation  Infection  Fibrosis (Peyronies & Angulation )

• • •

Topical Nitroglycerin

: Perpheral vasodilator,probably increases cGMP

Topical Aminopylline:

probably increases cGMP PDE inhibitor,

Topical Minoxidil:

vasodilator Peripheral

Other Medications ……

•

Bromocriptine:

Reduces elevated prolactin levels, wich can cause decreased libido • •

Levodopa Pentoxyphlline:

Improves RBC flow through arteriols •

Zinc:

Correct Zn dificiency,wich has been linked to ED in patients with CRF •

Vasoactive Intestinal Polypeptide

: Increases cAMP synthesis •

Vitamin E

• Aphrodisiacs – Myths abound and drugs or other agents can be toxic – Safest method to ^ drive is exercise • Psychoactive drugs – Alcohol – Hallucinogens – Stimulants

Oral PDE-5 Inhibitors

• • •

Sildenafil, vardenafil, tadalafil Current standard of care for ED Not as effective in patients who have undergone radical prostatectomy or have severe vascular disease

• •

High rate of discontinuation Sexual stimulation required

• Probably the best marketed drug ever!

• Erection improved in 50 - 80% cases • Clinically safe

Sildenafil

• • • • • •

Brand name: Viagra 25, 50, 100 mg Take 1 hour before sexual activity; effects last for up to 4 hours Absorption may be delayed by high-fat meal Side effects: headache, flushing, dyspepsia Contraindication: use of nitrates

Tadalafil

• • • • • •

Brand name: Cialis 5, 10, 20 mg Improves erectile function for up to 36 hours Can be taken with food but no alcohol consumption Side effects: headache, dyspepsia, back pain, myalgia Contraindications: use of nitrates, alpha blockers (except tamsulosin)

Vardenafil

• • • • •

Brand name: Levitra 2.5, 5, 10, 20 mg Administration 60 minutes before sexual activity; absorption may be delayed by high-fat meal Side effects: headache, flushing, rhinitis, dyspepsia Contraindications: use of nitrates, alpha blockers

Comparison

• they all are all PDE5 inhibitors with the same mechanism of action and similar adverse effects. • They all require sexual stimulation as a prerequisite and are effective regardless of the cause of erectile dysfunction. • Viagra has been around the longest and thus has the benefit of having long-term safety data. It also has the highest use and lowest discontinuity of the three drugs. However, Viagra is also administered in higher doses than the others. • Tadalafil has the longest period of onset ( administration. others, thus it has a potential time of 2 hours ) and lasts up to 36 hours, whereas as sildenafil is effective up to 12 hours and vardenafil is only effective 4-5 hours after • Vardenafil, however, is the most potent (lowest maximal concentration) and binds to PDE5 more rapidly than the onset of 10 minutes .

Sildenafil, Tadalafil, Vardenafil

• • Phosphodiesterase (PDE)-5 inhibitors cGMP NO in the corpus cavernosum (and elsewhere - SE) • Contraindicated in patients on nitrates, hypotension, recent stroke / MI or in whom sexual activity is inadvisable • Caution if CV disease, penile deformity or risk of priapism (multiple myeloma, leukaemia, sickle cell disease)

PDE-5 inhibitors

Adverse effects: • Nasal congestion • Dyspepsia, vomiting, headache • Flushing, dizziness, visual disturbance • Raised IOP (v painful red eyes) • (rash) • Priapism (medical emergency - refer)

• Alph-2 receptor blocker • Oral agent. 3-36 mg per day • Mostly ineffective except in some patients with psychogenic impotence • May increses BP and sympathetic outflow in hypertensive patients and those taking TCAs • May be effective in treating SSRI-induced sexual dysfunctions

• Apomorphine is a centrally acting drug that improves erectile dysfunction by enhancing the central natural erectile signals that normally occur in the brain during sexual stimulation. • It is a non-selective dopamine receptor agonist and acts mainly on dopamine D2 like receptors in the brain.

Sublingual Apomorphine

• • • • •

2 mg and 3 mg doses Erection usually achieved within 20 minutes of administration if adequate sexual stimulation No interaction with food or alcohol Tolerable side effects

–

Concerns about hypotension No contraindications

• Similar adverse effect profile but also vasovagal syndrome (nausea, sweating and syncope)

• • • •

Intracavernosal Injections and Suppositories

Utilize prostaglandins Result in relaxation of the sinusoidal smooth muscle Injection: minimal discomfort Intraurethral suppositories: less effective method of delivery delivery

Topical Alprostadil

• Alternative to PDE-5 inhibitors • Clinical trials show efficacious and well tolerated in ED patients with mild to moderate symptoms • Effective in patients with CVD, diabetes • Side effects: genital pain, tenderness, erythema – 2% of partners report mild vaginal burning

           

Mechanical Devices

Vacuum therapy Constriction rings Erection differs physiologically from normal or pharmacologically induced erection Numerous choice Recent addition to FP10 Cost effective Lack of spontaneity Cold blue penis (75%) Penis may pivot at base Altered Sensation / discomfort of Orgasm (25%) Haematoma (15%) Manual dexterity

• • • • • •

External cylinder with pump Constriction ring Suitable for wide range of patients 90% success rate 80% patients continue with device One-off cost, but cumbersome

External Vacuum Devices

• • • •

Least expensive method of restoring sexual function Vacuum chamber draws blood into the penis Effective in 95% of men Drawbacks: interruption of spontaneity; need for personal instruction in use; initial cost

Priapism

 Erection lasting longer than 4 hours  Action to be taken by the patient  Sexual intercourse and ejaculation  Exercise  Cold shower / bath  Ice packs  Attend A&E or Urology ward

Surgical Treatment

Reserved for patients in whom conservative treatment has failed

Surgical Options

 Implantation of penile prosthesis  Ligation for venous incompetence  Vascular bypass surgery

Summary

 ED is a common problem in men with diabetes  Multiple risk factors  Should be dealt with sensitively and in a matter of fact manner  Variety of treatments available  Treatment plan guided by patient choice  Most patients can be treated successfully

• Treatment – Pharmaceutical • SSRIs • anti-anxiety • lidocaine – Psychological

• Extasy : Love drug • Marijuana • Alcohol • Cocaine • Quatt • Amphetamies : Crstal amphetamine • Ephedrine • Amyl nitrite