Sexual Dysfunction

Integrated Pharmacotherapy III (PHRC 501)

Dr. Maha AlDoughaim

Dr. Abdulmajeed AlShehri
Assistant Professor
Department of Pharmacy Practice
College of Pharmacy, KSAU-HS

PHRC 501
1 Lecture 6: Sexual Dysfunction
Dr. Abdulmajeed AlShehri / Dr. Maha AlDoughaim
 Lectures’ Learning Outcomes
At the end of the lectures, the students should be able to:

1. List medications which may cause sexual dysfunction

2. Given a patient case, recommend appropriate therapy for female sexual
disorders, and male hypogonadism
3. Discuss side effects, monitoring, advantages/disadvantages, and drug
interactions associated with drug therapy for the treatment of sexual
dysfunction

PHRC 501
2 Lecture 6: Sexual Dysfunction
Dr. Abdulmajeed AlShehri / Dr. Maha AlDoughaim
 Introduction
• Sexual disorders are common

• Sexual dysfunction is characterized by a clinically significant

disturbance in the ability to respond sexually or to experience
sexual pleasure
• Estimated that 43% of women and 31% of men in the US suffer
from sexual dysfunction
• Lack of sexual satisfaction is associated with significant emotional
distress (e.g., depression, marital conflict) and physical problems
(e.g., cardiovascular disease, diabetes mellitus)
• Classified as:
– Lifelong or acquired
– Situational or generalized
PHRC 501
3 Lecture 6: Sexual Dysfunction
Dr. Abdulmajeed AlShehri / Dr. Maha AlDoughaim
 Introduction
• Male sexual dysfunction:
– Increases with aging and is often associated with underlying
disorders such as diabetes mellitus or cardiovascular disease
– Most commonly manifest as erectile dysfunction (ED)
• Female sexual dysfunction:
– Probably underdiagnosed and includes emotional and
relationship factors as well as responses to external cognitive
sexual stimuli

• The sexual response cycle concept is useful in understanding

sexual problems

PHRC 501
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 Classification of Sexual Dysfunctions

Impaired Sexual
Response Phase
Female Male
Female sexual interest/ Male hypoactive sexual
arousal disorder desire disorder
Desire Other specified sexual Other specified sexual
dysfunction: sexual dysfunction: sexual aversion
aversion
Excitement (arousal, Female sexual interest/ Erectile disorder
vascular) arousal disorder
Female orgasmic disorder Delayed ejaculation
Orgasm (muscular)
Premature ejaculation
Genito-pelvic pain/ Other specified or
Sexual pain penetration disorder unspecified sexual
dysfunction
Guidelines: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
PHRC 501
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Models of Human
Sexual Response
• Female (A) and male (B) sexual
response cycles
• Desire precedes both cycles in
this model
• Women may have a brief
plateau followed by orgasm
(cycle C) or a long plateau with
no orgasm (cycle B)
• Women may have multiple
orgasms before resolution,
although many do not (cycle A)
• For men with premature
ejaculation, the plateau phase
is brief. After ejaculation, men
enter a refractory period lasting
minutes to hours during which
they are unable to ejaculate.

PHRC 501
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 Male Sexual
Dysfunction

PHRC 501
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 Types of Sexual Dysfunction in Men
Type of Definition
Dysfunction
Decreased libido Decreased sexual drive or desire

Increased libido Inappropriate and excessive sexual drive or desire

Erectile dysfunction Failure to achieve a penile erection suitable for satisfactory
(impotence) sexual intercourse
Commonly referred to as “dry sex”; ejaculation is delayed or
Delayed ejaculation
absent
Retrograde Ejaculate passes retrograde into the bladder, instead of toward
ejaculation the anterior urethra (antegrade) and out of the penis
Sperm are insufficient in number, have abnormal morphology,
Infertility
or have inadequate motility, and fail to fertilize the ovum

PHRC 501
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 Erectile Dysfunction-
Treatment

Phosphodiesterase Alprostadil Other

(PDE-5) Inhibitors (prostaglandin E1) therapy

PHRC 501
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 Erectile Dysfunction Treatment
Phospho-diesterase inhibitors (PDE-5 inhibitors):
• First line pharmacotherapy for management of erectile dysfunction
• MOA:
– Bind to PDE5 enzyme and inhibit cGMP hydrolysis smooth-muscle relaxation
in the corpus cavernosum and increased blood flow to the penis
• Common adverse reactions:
– Headache, flushing, dyspepsia, nasal congestion, nasopharyngitis, visual
abnormalities
• Drug-drug interaction:
– CYP3A4 inhibitors and inducers (erythromycin, ketoconazole, ritonavir )
– Alpha Blockers: decrease BP
– Nitrates (e.g. nitroglycerin): significant increase in cGMP, resulting in a
synergistic reduction in BP
• The use of PDE5 inhibitors with any form of organic nitrates is
contraindicated

PHRC 501
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 Phospho-diesterase inhibitors (PDE-5
inhibitors)
Sildenafil Vardenafil Tadalafil Avanafil
(Viagra) (Levitra) (Cialis) (Stendra)
Half-life 4 hours 4-5 hours 17.5 hours 5 hours
Metabolism Major: CYP3A4 Major: CYP3A4 CYP3A4 Major: CYP3A4
Minor: CYP2C9 Minor: Minor: CYP2C
CYP3A5, CYP2C
Usual dosage 25–100 mg/day 5–20 mg/day 5–20 mg/day 50–200 mg/day
Administration 1 hour before 1 hour before 0.5 hours 0.5 hours
time sexual activity sexual activity before sexual before sexual
activity activity
Time required 24 hours 24 hours 48 hours 12 hours
from last dose to
administration of
a nitrate (e.g.,
nitroglycerin)

PHRC 501
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 Erectile Dysfunction Treatment
Alprostadil:
• Synthetic analog of prostaglandin E1 (PGE1)
• MOA:
– Binding to PGE1 receptors localized on the surface of smooth
muscle cells, thus activating cAMP which in turn induces penile
vascular smooth muscle relaxation to provide penile erection
• Available as injection, cream

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 Algorithm for selecting treatment for
Erectile Dysfunction

PHRC 501
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 Premature (early) Ejaculation (PE)

• Common type of male sexual dysfunction ~ 1 - 30% !

• Definition: (according to DSM-5)

‒ Ejaculation that occurs before or shortly after vaginal
penetration
‒ Studies suggest a 60-second or less intravaginal ejaculatory
latency to define PE

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 Treatment
• SSRI’s can cause prolongation of the pre-orgasmic
plateau and thus may delay ejaculation
– Dapoxetine is a short-acting SSRI that can be taken 30 mg
and 60 mg as needed and is approved by the FDA

– Paroxetine creates strongest ejaculatory delay, taken as 20

mg/d or situational (20 mg 3-4 hours before sexual
activity), Effects usually within 5-10 days of initiation

PHRC 501
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 Treatment
• PDE-5 inhibitors added to SSRIs may further improve PE
– Study showed SSRI+PDE5-Is vs SSRI alone resulted in better latency
time, satisfaction with sexual intercourse, and reduced anxiety
compared to SSRIs alone, however the number of adverse events are
slightly increased
• Topical
– Local Anesthetics topical e.g. Lidocaine and prilocaine cream
– Decreases penile sensation
– Don’t recommend as safety profile not established, and may result in
loss of erection, penile & partner numbness, local burning, irritation,
and allergic reaction
• Psychological

PHRC 501
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 Androgen Deficiency
• If the patient is young, deficient in secondary sexual
characteristics, or has other signs of hypogonadism, a
testosterone level should be determined
• Low testosterone concentrations secreted from testes
• Prevalence
– 7% prevalence in men < 50 yrs
– 20% prevalence in men > 50 yrs
Androgen Deficiency Symptoms
Loss of energy Depression
Decreased libido Irritability
Erectile dysfunction (ED) Decreased sprematgenesis
Decreased axillary and pubic hair Anemia
Loss of muscle mass Osteoporosis
Decreased mental acuity

PHRC 501
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 Treatment
• Testosterone affects erectile function at three levels
1. At CNS, it increases the release of stimulatory (proerectile)
neurotransmitters such as dopamine, oxytocin, and nitric oxide
2. Modulates neuronal nitric oxide synthase activity and pelvic
ganglionic activity
3. Regulate the sensitivity of the target tissues to adrenergic and
noncholinergic/nonadrenergic nerve signals

• Indicated in symptomatic patients with primary or secondary

hypogonadism, as confirmed by both the presence of a
decreased libido and low serum concentrations of testosterone

PHRC 501
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 Treatment
Drug Initial Dose Usual Range Other
Testosterone 4 mg as a 2-6 mg as a - Recommended application
transdermal single dose at single dose at sites: upper arm, back,
patch bedtime bedtime abdomen, and thigh. Rotate
sites.
- Avoid swimming, showering,
or washing administration site
for 3 hours after patch
application
Testosterone 5-10 g 5-10 g - Cover application site to avoid
gel (equivalent to (equivalent to transfer to others
50-100 mg 50-100 mg - Avoid swimming, showering or
testosterne) testosterne) washing administration site for
gel as a single gel as a single 2 hours after gel application
dose in the dose in the - Recommended application
morning morning sites: shoulders, upper arms,
abdomen
PHRC 501
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 Treatment
Drug Initial Dose Usual Range Other
Oral, Testosterone 120-240 mg 2 120-240 mg 2 Serum testosterone levels
undecanoate to 3 times to 3 times vary
daily daily
Testosterone 30 mg every 30 mg every Place buccal system just
buccal system 12 hours 12 hours above incisor tooth on both
morning and morning and sides of the mouth. To remove
evening evening slide buccal system down
toward the tooth
Testosterone 200-400 mg 200-400 mg - Contraindicated in
cyponate IM every 2-4 every 2-4 patients with severe
injection weeks weeks heaptic/renal impairment
- Supra-physiologic serum
concentrations of
testosterone linked to mood
swings
PHRC 501
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 Treatment
Testosterone side effects
• Increased prostate size and PSA level • Gum/mouth irritation, tenderness,
• Patch adhesive may cause skin irritation edema, and taste perversion with buccal
• Alopecia, increased hematocrit tablet
• Acne, weight gain, hypertension, CHF
• Oral testosterone replacement may
cause hepatotoxicity

Testosterone Monitoring
• Symptom score assessment at baseline and every 6-12 months while on
therapy
• PSA should be monitored at baseline and yearly thereafter
• Hematocrit at baseline and every 6 months for the first 18 months of
therapy, then yearly

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 Female Sexual
Dysfunction

PHRC 501
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 Female Sexual Dysfunction
• According to the DSM 5, symptoms should persist for at
least 6 months and be associated with personal distress or
affecting relationships
• Hypoactive Sexual Desire Disorder (HSDD) is central to
female dysfunction as decrease in sexual desire leads to the
other sexual disorders
• The most significant factor in increasing sexual dysfunction
is aging

PHRC 501
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 Categories for Female Sexual
Dysfunction
DSM-5 Categories:
A- Female sexual interest/arousal disorder

B- Orgasmic disorder

C- Genito-pelvic pain/penetration disorder

PHRC 501
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 Causes of Female Sexual Disorders

1-Endocrinological 2-Gynecological
Diabetes, hypothyroidism Surgically or naturally postmenopausal,
atrophic vaginitis
3-Neurological 4-Psychological
CVA, Parkinsons, MS Depression, Sexual abuse
5-Cardiovascular 6-Medications
Hypertension, Hypercholesterolemia SSRI antidepressants, Antihypertensive,
Spironolactone, Antipsychotics,
Narcotics, Benzodiazepines, Tricyclic
antidepressants, Barbiturates ,
Hormonal preparations (e.g. Danazol,
GnRH agonists).

PHRC 501
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 Female sexual interest/arousal disorder

• Absent/reduced interest in sexual activity, erotic thoughts,

sexual excitement, arousal, and/or genital sensation and lack
of initiation of sexual activity

• The most frequently reported sexual problem

– 4 in 10 women state they have low sexual desire

• Female sexual desire is a complex interaction among biologic,

psychological, social, interpersonal, and environmental
components

PHRC 501
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 Treatment

• Pharmacological
– Hormonal Therapy: (Estrogen, and Testosterone)
– Bupropion
– Sildenafil
– Flibanserin
• Non-pharmacological
– Psychological therapy
– Eros Clitoral Therapy Device

PHRC 501
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 Treatment
Hormonal Therapy
• Estrogen for Menopause:
– Topical estrogen (intra-vaginal):
• Indicated if loss of genital arousal is identified to be due to
vulvovaginal atrophy
– Systemic estrogen (Patch or oral):
• Only indicated if loss of genital congestion is identified to be due
to vulvovaginal atrophy and systemic estrogen is preferred
because of other menopausal health considerations
– Side effect: Increased rate of CVD, blood clots, breast and ovarian
cancers
– Contraindicated in estrogen-receptor positive breast cancer

PHRC 501
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 Treatment
Testosterone
– There are ongoing trials of a low-dose testosterone gel,
brand name LibiGel, designed for use in women.

– Use of products designed for use in men would clearly be

off-label and should be done with caution

– Transdermal patches designed for men contains higher

doses than those designed for women.

PHRC 501
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 Treatment
Bupropion
– Antidepressant that act on the dopamine and noradrenergic receptors, is
not commonly associated with high rates of sexual side effects
– Improves sexual interest and arousal in premenopausal women and
women taking SSRIs
– Several studies have found a reduction in SSRI-related sexual side effects
with the addition of bupropion
• Use of sustained release 150 mg twice daily, but no statistically significant
improvement with sustained release 150 mg once daily
– There is some evidence to support the use of bupropion for treatment of
HSDD even in the absence of depression or SSRI therapy
• Bupropion sustained release 150 mg daily and 300 to 400 mg daily; both
studies found benefit
• Common side effects included headache, insomnia, dry mouth, and nausea

PHRC 501
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 Treatment
Sildenafil

– Management of SSRI-induced FSD

– In a randomized, double-blinded, placebo-controlled trial
of 49 premenopausal women with SSRI-induced sexual
dysfunction
• Patients treated with sildenafil 50 to 100 mg as needed before
sexual activity
• Improved global sexual function score

PHRC 501
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 Strategies for managing FSD in the setting of depression and
SSRI therapy
 Continue SSRI, add bupropion sustained release 150 mg
twice a day
 Continue SSRI, prescribe sildenafil 50–100 mg as needed
before sexual activity
 Reduce dose of SSRI if possible, OR drug holiday
 Switch antidepressant classes from SSRI to bupropion
• It is important to investigate the onset of a patient’s sexual dysfunction
• Depression itself may lead to sexual dysfunction, and treatment with an
SSRI may actually be helpful, although this may take weeks of therapy
• It is also possible that the symptom will resolve spontaneously

PHRC 501
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 Treatment
Flibanserin “Addyi®”
– Intended for pre-menopause women diagnosed with HSDD
– FDA approval (18 Aug, 2015)
– MOA: serotonin 1A receptor agonist and a serotonin 2A
receptor antagonist
– After 4 weeks of using flibanserin 100 mg Qhs , the women
reporting “satisfying sexual events”
– Side effects are Hypotension, syncope, dizziness, nausea,
fatigue, sleepiness, and trouble sleeping
• Drinking alcohol while on flibanserin may result in severely
low blood pressure and syncope
– CYP3A4 substrate

PHRC 501
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 Orgasmic Disorder
• Defined as a marked delay in, or infrequency or lack of intensity of, orgasm
occurring in 75%–100% of occasions of sexual activity
• Prevalence of female orgasmic problems ranges from 10% - 42%, but only a
fraction of women report associated distress
• Premature ejaculation in the male may contribute to female orgasmic
dysfunction
• Treat underlying cause and Psychological therapy may be helpful

• Primary • Secondary
‒ Never had orgasm (~10 ‒ Currently anorgasmic
-15% of population) ‒ Due to surgery,
‒ Associated with physical trauma,
medications, or
medical/physical factors; hormonal deficiencies
or emotional trauma

PHRC 501
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 Genito-Pelvic Pain/Penetration Disorder

• Symptoms of genito-pelvic pain/penetration disorder consist of

persistent or recurrent difficulties with vulvovaginal pain or fear
of pain during intercourse or penetration
• Genito-pelvic pain/penetration disorder refers to four
commonly comorbid symptoms:
1. Difficulty having intercourse
2. Genito-pelvic pain
3. Fear of pain or vaginal pain
4. Tension of the pelvic floor muscles

PHRC 501
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 Genito-Pelvic Pain/Penetration Disorder

• Causes:
– Pelvic trauma or surgery
– childhood or adolescent sexual abuse or assault
– Infections (STD, candidiasis)
– atrophic vaginitis

• Atrophic vaginitis is most common in menopausal women

– Hypoestrogenic states also can occur in the postpartum period, during
lactation, and in premenopausal women with the administration of
antiestrogenic drugs (tamoxifen, aromatase inhibitors e.g letrozole, and
medroxyprogesterone) may cause vaginal atrophy

PHRC 501
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 Treatment
• Treatment is directed to the underlying cause:
– Psychological therapy
– Vulvar dermatoses (e.g. Lichen sclerosis)
• Topical steroid treatment e.g. clobetasol or halobetasol propionate
– Vulvodynia
• Topical lidocaine 5% ointment or EMLA (lidocaine/prilocaine) cream applied
to the painful areas 10 minutes before intercourse
– Atrophic vaginitis
• Over-the-counter vaginal lubricants and moisturizers
• Topical estrogen therapy
• Selective estrogen receptor modulator (Ospemifene 60 mg/day)

PHRC 501
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 PHRC 501
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