sexual-dysfunctions4

Report
‫دكتر سيد حميد خوئي‬
‫گروه داروسازي باليني‬
‫دانشكده داروسازي دانشگاه علوم پزشكي تهران‬
• 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
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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 nonpleasurable sex, and 16 percent
reported sexual anxiety.
Etiology
How do sexual problems
develop?
Predisposing
Factors
Maintaining
Factors
Early
Development
Current
Functioning
Precipitating
Factors
• 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:
Women:
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Diabetes
Alcoholism
Lumbar-disc disease
Atherosclerosis
Spinal cord injuries
Smoking
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
Lifestyle
Alcohol
Smoking
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
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•
Vasculogenic (arterial or cavernosal)
Psychogenic
Neurogenic
Hormonal
Drug induced
Other systemic diseases or aging
•
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Alcohol
Estrogens
Antiandrogens
H2 receptor blockers
Anticholinergics
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Antihistamines
Ketoconazole
Antidepressants
Antihypertensives
Narcotics
Sedative-Hypnotics
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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
H2-antagonists
PPI
Allopurinol
Indomethacin
Disulfiram
Phenothiazine
antihistamines
Phenothiazine
antiemetics
Other antihistamines
Cyclizine, Ondansetron
Assessment
Initial Assessment
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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
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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
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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
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Generalised anxiety states
Depressive illness
Psychosis
Body Dysmorphic Disorder
Gender identity problems
Alcoholism
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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
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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

Normal libido and ejaculation


Underlying medical condition

Relationship problems
Change in life events

Aged under 55

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
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Oral
Topical
Intramuscular
Intraurethral
Intracavernosal
Oral
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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
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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: PDE inhibitor,
probably increases cGMP
• Topical Minoxidil: Peripheral
vasodilator
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
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•
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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 (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
administration.
• Vardenafil, however, is the most potent (lowest maximal
concentration) and binds to PDE5 more rapidly than the
others, thus it has a potential time of 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 D2like 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 welltolerated 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
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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
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Extasy : Love drug
Marijuana
Alcohol
Cocaine
Quatt
Amphetamies : Crstal amphetamine
Ephedrine
Amyl nitrite

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