Transcript 1 - RCRMC Family Medicine Residency

Sexual Problems
Research on nitric oxide by
_______ led to the introduction
of the drug sildenafil (eg, Viagra)
in 1998.
(A) Ruth Westheimer
(B) Lou Ignarro
(C) Alfred Kinsey
(D) Richard von Krafft-Ebing
Answer
• (B) Lou Ignarro
All the following statements about
hypoactive sexual desire disorder are
correct, except:
(A) May be persistent or recurrent
(B) Must cause marked distress or
interpersonal difficulty
(C) May be generalized or
situational
(D) Medical and psychologic factors
are mutually exclusive
Answer
• (D) Medical and psychologic factors are
mutually exclusive
Which of the following therapies
was shown to improve desire in
33% of nondepressed women?
(A) Bupropion
(B) Oral contraceptives
(C) Topical testosterone
(D) Transdermal testosterone
Answer
• (A) Bupropion
Placebo-controlled studies show
improvement in lubrication and
arousal in women given _______,
but this effect was not
observed clinically.
(A) Sildenafil
(B) Estroge
(C) Bupropion
(D) Bestosterone
Answer
• (A) Sildenafil
Masters and Johnson claimed that
_______ exercises help 90% of
patients, including diabetics, with
erectile dysfunction.
(A) Sensate focus I
(B) Sensate focus II
(C) Sensate focus III
(D) None of the above
Answer
• (C) Sensate focus III
Estrogen exposure
followed by withdrawal
is sufficient to elicit
vasomotor symptoms in
women.
(A) True (B) False
Answer
• (B) false
Of the following, which is
considered the most likely
etiology of vasomotor symptoms
in menopausal women?
(A) Luteinizing hormone pulses
(B) Reduction in opioid levels
(C) Changes in serotonergic or
noradrenergic systems
(D) Gonadotropin deficiencies
Answer
• (C) Changes in serotonergic or
noradrenergic systems
When using selective serotonin
reuptake inhibitors (SSRIs) to
treat vasomotor symptoms in
women, common side effects
include all the following, except:
(A) Nausea
(B) Visual disturbances
(C) Sexual dysfunction
(D) Sleep disturbance
Answer
• (B) Visual disturbances
When treating vasomotor symptoms,
what factor(s) account(s) for the
differences in efficacy among patients
taking different
SSRIs and serotonin norepinephrine
reuptake inhibitors?
(A) Variation in effects on dopamine and
norepinephrine reuptake
(B) Variation in degree of
anticholinergic effects
(C) Variation in drug metabolism
(D) All the above
Answer
• (D) All the above
Which of the following are
recommended by the North American
Menopause Society for management of
vasomotor symptoms
in menopausal women?
1. Paroxetine
2. Venlafaxine
3. Gabapentin
4. Evening primrose oil
5. Black cohosh
(A) 1,2,3 (B) 1,3,4 (C) 1,2,3,5 (D)
1,2,3,4,5
Answer
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1. Paroxetine
2. Venlafaxine
3. Gabapentin
5. Black cohosh
(C) 1,2,3,5
Erectile dysfunction is most
common in men in which one of
the following age
groups? (check one)
A. Younger than 50 years.
B. 50 to 59 years.
C. 60 to 69 years.
D. Older than 69 years.
Answer
• D. Older than 69 years.
During the initial workup and
evaluation of erectile dysfunction,
which one of the following should
be done? (check one)
A. Penile duplex ultrasonography.
B. Testicular examination.
C. Nocturnal penile tumescence
assessment.
D. Neurophysiologic testing.
Answer
• B. Testicular examination.
Sildenafil (Viagra) has been shown
to be effective for the treatment of
erectile dysfunction in which of the
following
patients? (check all that apply)
A. A patient with diabetes mellitus.
B. A patient with hypogonadism.
C. A patient on antidepressant
therapy.
D. A patient with a spinal cord
injury.
Answer
• A. A patient with diabetes mellitus.
• C. A patient on antidepressant
therapy.
• D. A patient with a spinal cord
injury.
What is a low Total testosterone
level and how often do you find it
in men complaining of ED
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A. 200 ng/dL, 25%
B. 300 ng/dL, 5-10%
C. 400 ng/dL, 20%
D. 500 ng/dL, 20%
Answer
• B. 300 ng/dL, 5-10%
What % of Men with ED do not
repond to PDE5 inhibitors
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A. 20%
B. 25%
C. 33%
D. 40%
Answer
• C. 33%
Someone treated with testoterone
needs what tests monitored?
• A. hemoglobin, serum transaminase, and
prostate-specific antigen
• B. Glucose, serum transaminase and PSA
• C. Lipid profil, glucose, and PSA
• D. Lipid profil, Hemoglobin, and PSA
Answer
• A. hemoglobin, serum transaminase, and
prostate-specific antigen
If you prescribe testosterone
replacement the goal testosterone
level should be which of the
following?
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A. 350 to 500 ng/dL
B. 400 to 700 ng/dL
C. 500 to 800 ng/dL
D. 600 to 900 ng/dL
Answer
• B. 400 to 700 ng/dL
Testosterone replacement will
improve which of the following
• A. libido, lower voice, muscle strength
• B. libido, muscle strength, body
composition, and bone density.
• C. libido, muscle strength, muscle strength
duration in activities
Answer
• B. libido, muscle strength, body
composition, and bone density
What are the most common side
effects for PDE 5 inhibitors?
• A. sore throat, dizziness, abnormal vision
and headache
• B. headache, flushing, dyspepsia, rhinitis,
and abnormal vision.
• C. abdominal pain, diarrhea, vision changes,
rhinitis, sore throat
Answer
• B. headache, flushing, dyspepsia, rhinitis,
and abnormal vision.
• Headache is the most common up to 10%
Impotence is defined as the
inability to maintain erections
____ % of the time
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A. 50%
B. 60%
C. 75%
D. 90%
Answer
• C. 75%
Management of Erectile
Dysfunction
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Erectile dysfunction (ED) is the most common sexual problem in men.
The incidence increases with age and affects up to one third of men
throughout their lives.
It causes a substantial negative impact on intimate relationships, quality
of life, and self-esteem.
History and physical examination are sufficient to make a diagnosis of ED
in most cases, because there is no preferred, first-line diagnostic test.
Initial diagnostic workup should usually be limited to a fasting serum
glucose level and lipid panel, thyroid-stimulating hormone test, and
morning total testosterone level.
First-line therapy for ED consists of lifestyle changes, modifying drug
therapy that may cause ED, and pharmacotherapy with
phosphodiesterase type 5 inhibitors.
Obesity, sedentary lifestyle, and smoking greatly increase the risk of ED.
Phosphodiesterase type 5 inhibitors are the most effective oral drugs for
treatment of ED, including ED associated with diabetes mellitus, spinal
cord injury, and antidepressants.
Management of Erectile
Dysfunction
• Intraurethral and intracavernosal alprostadil, vacuum pump
devices, and surgically implanted penile prostheses are alternative
therapeutic options when phosphodiesterase type 5 inhibitors fail.
• Testosterone supplementation in men with hypogonadism
improves ED and libido, but requires interval monitoring of
hemoglobin, serum transaminase, and prostate-specific antigen
levels because of an increased risk of prostate adenocarcinoma.
• Cognitive behavior therapy and therapy aimed at improving
relationships may help to improve ED.
• Screening for cardiovascular risk factors should be considered in
men with ED, because symptoms of ED present on average three
years earlier than symptoms of coronary artery disease.
• Men with ED are at increased risk of coronary, cerebrovascular,
and peripheral vascular diseases.
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Clinical recommendationEvidence ratingReferencesDiagnostic testing for
erectile dysfunction should usually be limited to obtaining a fasting serum
glucose level and lipid panel, thyroid-stimulating hormone test, andmorning
total testosterone level.
C
First-line therapy for erectile dysfunction should consist of oral
phosphodiesterase type 5 inhibitors.
A
Phosphodiesterase type 5 inhibitors are most effective in the treatment of
erectile dysfunction associated with diabetes mellitus and spinal cord injury,
and of sexual dysfunction associated with antidepressants.
A
Additional therapy for erectile dysfunction may consist of psychosocial
therapy and testosterone supplementation in men with hypogonadism.
B
Testosterone supplementation in men with hypogonadism improves erectile
dysfunction and libido.
B
Screening for cardiovascular risk factors should be considered in men with
erectile dysfunction.
C
Male Sexual Dysfunction
• Hypogonadism in a male refers to a decrease in one or both of the two
major functions of the testes:
• sperm production ortestosterone production.
• These abnormalities can result from disease of the testes (primary
hypogonadism) or disease of the pituitary or hypothalamus (secondary
hypogonadism).
• The distinction between these disorders, is made by measurement of
the serum concentrations of luteinizing hormone (LH) and folliclestimulating hormone (FSH):
• The patient has primary hypogonadism if the
serumtestosterone concentration and/or the sperm count are below
normal and the serum LH and/or FSH concentrations are above
normal.
• The patient has secondary hypogonadism if the
serumtestosterone concentration and/or the sperm count are subnormal
and the serum LH and/or FSH concentrations are normal or reduced.
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Risk Factors for Erectile DysfunctionAdvancing age
Cardiovascular disease
Cigarette smoking
Diabetes mellitus
History of pelvic irradiation or surgery, including radical prostatectomy
Hormonal disorders (e.g., hypogonadism, hypothyroidism,
hyperprolactinemia)
Hypercholesterolemia
Hypertension
Illicit drug use (e.g., cocaine, methamphetamine)
Medications (e.g., antihistamines, benzodiazepines, selective serotonin
reuptake inhibitors)
Neurologic conditions (e.g., Alzheimer disease, multiple sclerosis, Parkinson
disease, paraplegia, quadriplegia, stroke)
Obesity
Peyronie disease
Psychological conditions (e.g., anxiety, depression, guilt, history of sexual
abuse, marital or relationship problems, stress)
Sedentary lifestyle
Venous leakage
Diagnosis and Evaluation
• There is no preferred, first-line diagnostic test for ED, and routine
screening is not recommended.
• History and physical examination are sufficient in making an accurate
diagnosis of ED in most cases.
• Penile duplex ultrasonography is not a useful diagnostic test for
ED.7 The American Urological Association (AUA) recommends that
the initial evaluation of ED include a complete medical, sexual, and
psychosocial history.8
• The medical history may reveal comorbid conditions, risk factors
related to ED or medications that contribute to ED Sexual history
should focus on erection adequacy, altered libido, quality and timing of
orgasm, volume and appearance of ejaculate, presence of sexuallyinduced genital pain or penile curvature (Peyronie disease), and partner
sexual function.
• The five-item version of the International Index of Erectile Function
Questionnaire is a validated survey instrument that can be used to
assess the severity of ED symptoms
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Medications and Substances That May Cause or Contribute to Erectile DysfunctionMedication class or
substanceExamplesAnalgesics
Opiates
Anticholinergics
Tricyclic antidepressants
Anticonvulsants
Phenytoin (Dilantin), phenobarbital
Antidepressants
Lithium, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, tricyclic antidepressants
Antihistamines
Dimenhydrinate, diphenhydramine (Benadryl), hydroxyzine (Vistaril), meclizine (Antivert), promethazine
(Phenergan)
Antihypertensives
Alpha blockers, beta blockers, calcium channel blockers, clonidine (Catapres), methyldopa, reserpine
Anti-Parkinson agents
Bromocriptine (Parlodel), levodopa, trihexyphenidyl
Cardiovascular agents
Digoxin, disopyramide (Norpace), gemfibrozil (Lopid)
Cytotoxic agents
Methotrexate
Diuretics
Spironolactone (Aldactone), thiazides
Hormones
5-alpha reductase inhibitors, corticosteroids, estrogens, luteinizing hormone-releasing hormone agonists, progesterone
Illicit drugs, alcohol, and nicotine
Amphetamines, barbiturates, cocaine, heroin, marijuana
Immunomodulators
Interferon-alfa
Tranquilizers
Benzodiazepines, butyrophenones, phenothiazines
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Five-Item Version of the International Index of Erectile Function QuestionnaireScoresQuestions12345Over the past six months:
1. How do you rate your confidence that you could get and keep an erection?
Very low
Low
Moderate
High
Very high
2. When you had erections with sexual stimulation, how often were your erections hard enough for penetration?
Almost never or never
A few times*
Sometimes†
Most times‡
Almost always or always
3. During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner?
Almost never or never
A few times*
Sometimes†
Most times‡
Almost always or always
4. During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse?
Extremely difficult
Very difficult
Difficult
Slightly difficult
Not difficult
5. When you attempted sexual intercourse, how often was it satisfactory for you?
Almost never or never
A few times*
Sometimes†
Most times‡
Almost always or always
NOTE: The score is the sum of the above five question responses. Erectile dysfunction is classified based on these scores: 17 to 21 = mild; 12 to 16 = mild to
moderate; 8 to 11 = moderate; 5 to 7 = severe.
* —Much less than one half the time.
† —About one half the time.
‡ —Much more than one half the time.
Adapted with permission from Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Peña BM. Development and evaluation of an abridged, 5-item version of the
International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res. 1999;11:322.
The physical examination
• The physical examination should assess blood
pressure and heart rate; body habitus, for central
obesity; and cardiovascular, neurologic, and
genitourinary systems, including penile, testicular,
and digital rectal examinations
• The AUA and World Health Organization
recommend limited diagnostic testing in men with
ED. This may include a fasting serum glucose
level and lipid panel, thyroid-stimulating hormone
test, and morning total testosterone level.
• Additional diagnostic testing and urologic
evaluation may be warranted in cases of ED
refractory to standard therapies
Treatment
• LIFESTYLE MODIFICATIONS
• First-line therapy for ED is aimed at lifestyle changes and
modifying pharmacotherapy that may contribute to ED
• Sedentary lifestyle, a significant risk factor for
cardiovascular disease, may also be a modifiable risk
factor for ED.
• Obesity nearly doubles the risk of ED3; one study
determined that one third of men who were obese
improved their ED with moderate weight loss and an
increase in the amount and duration of regular exercise.
• The risk of moderate or total ED is almost double in men
who smoke compared with nonsmokers.
• Patient education should be aimed at increasing exercise,
losing weight to achieve a body mass index (BMI) less
than 30 kg per m2, and stopping smoking.
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Additional Testing in the Workup of Erectile DysfunctionOptional
diagnostic tests
Laboratory investigations (complete blood count; free testosterone, luteinizing
hormone, and prolactin levels; sex hormone-binding globulin test; urinalysis)
Psychological or psychiatric consultation
Specialized evaluation and diagnostic tests
In-depth psychosexual and relationship evaluation
Neurophysiologic testing (vibrometry; bulbocavernosus reflex latency;
cavernosal electromyography; somatosensory evoked potential test; pudendal
and sphincter electromyography)
Nocturnal penile tumescence and rigidity assessment
Psychiatric evaluation
Specialized endocrinologic testing (hypothalamic-pituitary-gonadal function
studies; magnetic resonance imaging of the sella turcica)
Vascular diagnostics (duplex ultrasonography; penile
pharmacocavernosometry and pharmacocavernosography; penile
arteriography; computed tomography or magnetic resonance imaging; nuclear
imaging)
Adapted with permission from Jardin A, Wagner G, Khoury S, et al.
Recommendations of the 1st International Consultation on Erectile
Dysfunction. In: Jardin A, Wagner G, Khoury S, et al., eds. Erectile
Dysfunction.Plymouth, U.K.: Health Publication Ltd, 2000:718–719.
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Clues to the Diagnosis of Erectile DysfunctionClinical clueSuggested diagnosisHistory
Altered or impaired partner sexual function
Psychological causes (e.g., anxiety, depression, guilt, history of sexual abuse, marital or relationship problems, stress)
Decreased appearance and volume of ejaculate
Chronic prostatitis, normal aging process, obstruction of ejaculatory duct(s), retrograde ejaculation
Decreased libido
Chronic fatigue syndrome, hypogonadism, hypothyroidism, psychological conditions
Impaired quality and timing of orgasm, including anorgasmia
Alcohol abuse, Cushing syndrome, hyper- or hypothyroidism, medications (e.g., antihistamines, antipsychotics, beta blockers,
selective serotonin reuptake inhibitors, thiazides, tricyclic antidepressants), psychological causes, surgery of the pelvis or prostate
Presence of sexually-induced genital pain
History of sexual abuse, genital piercings, sexually transmitted infections (e.g., genital herpes)
Physical examination
Assessment of body habitus for central obesity
Cushing syndrome, diabetes mellitus, metabolic syndrome
Decreased perineal sensation
Cauda equina syndrome, spinal stenosis, surgery of the pelvis or prostate, trauma
Decreased peripheral pulses
Atherosclerotic and peripheral vascular disease
Elevated blood pressure
Atherosclerotic vascular disease, cerebrovascular disease
Enlarged prostate on digital rectal examination
Benign prostatic hyperplasia, prostate cancer
Penile curvature
Peyronie disease, ruptured corpora cavernosum, venous leakage
Tachycardia
Anxiety, hyperthyroidism, stimulant abuse, underlying cardiovascular disease
Testicular abnormalities
Epididymitis, hypogonadism, testicular cancer, varicocele
Thyroid goiter
Hyper- or hypothyroidism
PHARMACOTHERAPY
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Phosphodiesterase type 5 (PDE5) inhibitors are the most effective oral drugs in the treatment of
ED,9,12and should be considered first-line therapy.
Retail sales of sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) approached $1.48 billion
in 2007.
Sildenafil has been found to be effective and safe in cases of ED associated with diabetes
mellitus and spinal cord injury, and in men with sexual dysfunction secondary to antidepressant
therapy
Compared with placebo, sildenafil has been shown to improve erections (74 versus 21 percent;
number needed to treat [NNT] = 2)22 and results in more frequent intercourse attempts (57 versus 21
percent; NNT = 3).
Approximately one third of men with ED do not respond to therapy with PDE5 inhibitors.
These agents are not effective for improving libido.24
The three PDE5 inhibitors are considered to be relatively similar in effectiveness, but there are
differences in dosing, onset of action, and duration of therapeutic effect
There are no rigorous data to suggest that one PDE5 inhibitor is superior to another.
An open-label trial found that patients preferred tadalafil and vardenafil over sildenafil, 26 yet most
evidence supports equal effectiveness between sildenafil and vardenafil.
PDE5 inhibitors are generally well tolerated, with mild transient adverse effects of headache,
flushing, dyspepsia, rhinitis, and abnormal vision. Headache is the most commonly reported adverse
effect, occurring in approximately 10 percent of patients.
Rare but important adverse effects include dizziness, syncope, and nonarteritic anterior optic
neuropathy (predominantly from crossover phosphodiesterase type 6 inhibition).
PDE5 inhibitors should not be taken concomitantly with nitrates because this may lead to a
synergistic effect, resulting in a potentially serious, even fatal, decrease in blood pressure. PDE5
inhibitors are metabolized by the cytochrome P450 3A4 and may affect metabolism of protease
inhibitors and antifungal medications.
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Phosphodiesterase Type 5 Inhibitors for Erectile DysfunctionDrugStandard
dose*Recommended time between dosing and intercourseOnset of
actionDuration †Sildenafil (Viagra)
50 to 100 mg
One hour
14 to 60 minutes
Up to four hours
Tadalafil (Cialis)
10 to 20 mg
One to 12 hours
16 to 45 minutes
Up to 36 hours
Vardenafil (Levitra)
10 to 20 mg
One hour
25 minutes
Up to four hours
*— Maximum recommended dose per 24 hours is the maximum strength dose for each
agent.
† — Duration during which successful erections may be achieved following a dose of
medication.
Information from reference
Testosterone
• Intracavernosal pressure and PDE5 activity are androgen-dependent.
• The prevalence of hypogonadism (defined as a morning serum total
testosterone level less than 300 ng per dL [10.41 nmol per L]) in men
with ED is estimated to be 5 to 10 percent.
• In men with hypogonadism, testosterone supplementation is superior
to placebo in improving erections and sexual function.
• Response rates are higher in primary versus secondary testicular
failure, and with transdermal versus oral or intramuscular testosterone.
• 3Supplementation is also associated with improved satisfaction with
erectile function and sexual desire.29Men with hypogonadism who
failed a trial of sildenafil were found to have significant improvement
in erectile function with the addition of testosterone supplementation.
• Testosterone supplementation may result in erythrocytosis, elevated
serum trans-aminase levels, exacerbation of untreated sleep apnea,
benign prostatic hyperplasia, and an increased risk of adenocarcinoma
of the prostate.
• Men receiving testosterone supplementation require more frequent
monitoring of hemoglobin, serum transaminase, and prostate-specific
antigen levels, and prostate examinations.31
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SURGICAL AND PROCEDURAL
THERAPY
Alprostadil (Caverject) is a viable second-line therapeutic option for the
treatment of ED.
It should initially be administered in the physician's office at the lowest dose
and sequentially titrated to an adequate erectile response while monitoring for
syncope.
The physicians should also provide education on self-administration.8 Intracavernosal alprostadil is more effective, better tolerated, and preferred by men
over the intraurethral form.
Common adverse effects of intraurethral alprostadil include local penile pain,
urethral bleeding, dizziness, and dysuria.
Common adverse effects of intracavernosal alprostadil include penile pain,
edema and hematoma, palpable nodules or plaques, and priapism.
Patients should be informed about the potential for occurrence of prolonged
erections and should seek emergent medical evaluation for rigid erections
lasting longer than four hours.
Priapism is most commonly treated with aspiration of blood from the corpus
cavernosum under local anesthetic.
If this treatment is insufficient, then intra-cavernosal injections of
phenylephrine should be performed with hemodynamic monitoring to watch
for severe hypertension, tachycardia, or arrhythmia.
Vacuum pump devices
• Vacuum pump devices are a noninvasive second-line option
• They are contraindicated in men with sickle cell anemia or blood
dyscrasias, and in those taking anticoagulants.
• If used properly, adverse effects and potential risks are negligible, yet
there may be a substantial learning curve.
• When first- and second-line therapies have failed, surgical
implantation of an inflatable penile prosthesis can be considered in
consultation with a urologist
• Patients should be counseled regarding risks, benefits, and
expectations of this procedure.
• The AUA does not endorse penile venous reconstructive surgery or
surgeries to limit venous outflow from the penis.
• Penile arterial reconstructive surgery is controversial and more
rigorous trials are needed to prove short- and long-term effectiveness.
ALTERNATIVE THERAPIES
• Korean red ginseng (Panax ginseng) at 900 mg three times
daily has been reported to improve erections but not
overall sexual experience.
• Yohimbine has shown superiority over placebo for
treatment of ED with limited adverse effects,34 but is not
recommended by the AUA because of questions about its
safety and effectiveness.
• Some dietary supplements marketed for treatment of ED
obtainable via the Internet (e.g., Super X, Stamina-Rx)
contain PDE5 inhibitors (sildenafil 30 mg and tadalafil 20
mg, respectively).
• Although these and other similar products claim to be free
of any adverse effects, they have the same risks as PDE5
inhibitors
BEHAVIOR THERAPY
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When there is no obvious medical etiology for ED, psychosocial factors
should be explored.
The potential clue that psychosocial factors may be a cause is that a man is
able to achieve normal erections and orgasm through masturbation or sex with
a partner other than the “index case” partner with whom he has erectile
dysfunction (e.g., a spouse with whom there is substantial conflict).
Group or individual cognitive behavior therapy; psychosexual therapy,
including sensate focus technique; and therapy aimed at improving
relationship difficulties may help to improve sexual dysfunction in men.
A 2007 Cochrane review found that men who received group therapy plus
sildenafil had more successful intercourse and were less likely to drop out of
the study compared with those who received only sildenafil.36
When comparing psychosocial interventions versus alprostadil injections and
vacuum pump devices, no differences in effectiveness were found.36
In some cases, education about medical and psychosocial etiologies of ED in
conjunction with physician reassurance may prove adequate to restore normal
male sexual function.
Male Sexual Dysfunction
• The sexually competent male must have desire for
his sexual partner (libido), divert blood from the
iliac artery into the corpora cavernosa to achieve
penile tumescence and rigidity (erection) adequate
for penetration, then discharge sperm, and
prostatic and seminal vesicle fluid through the
urethra (ejaculation), and experience a sense of
pleasure (orgasm).
• Impotence is defined as the inability to develop or
sustain erection 75 percent of the time.
• It is a common abnormality and may be due to
psychological causes, medications, hormonal
abnormalities, neurologic, or vascular problems.
Male Sexual Dysfunction
• The following include some of the mechanisms that may be
responsible for sexual dysfunction in men:
• Libido declines with androgen deficiency, depression, and in
association with the use of prescription and recreational drugs.
• Erectile dysfunction may reflect either inadequate arterial blood flow
into (failure to fill) or accelerated venous drainage out of (failure to
store) the corpora cavernosae.
• Disorders of ejaculation occur if the bladder neck sphincter is damaged
during prostate surgery, or if alpha adrenergic impulses responsible for
clamping down the bladder neck sphincter to facilitate antegrade
ejaculation fail, resulting in retrograde ejaculation. Failure to ejaculate
in men with adequate erectile function is also a common side effect of
antidepressant medication or a reflection of an unresolved
patient/partner conflict. Male sexual dysfunction associated with
antidepressant use is discussed elsewhere.
SEXUAL HISTORY
• Important information in the history
includes
• determination of the rapidity of onset
• evaluation of erectile reserve
• assessment of risk factors for impotence.
• This information plus nocturnal penile
tumescence testing often points toward the
cause of the sexual dysfunction
Rapidity of onset
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Sexually competent men who had no sexual problems
until "one night when they could not perform" and
thereafter become impotent invariably have psychogenic
impotence.
This problem may be caused by performance anxiety,
disaffection with the current sexual partner, or some other
emotional problem
psychologic counseling is the preferred therapy in this
setting.
Only radical prostatectomy or other overt genital tract
trauma causes a sudden loss of male sexual function.
In comparison, men suffering from impotence of any other
cause complain that sexual function failed sporadically at
first, then more consistently.
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Erectile reserve
In men presenting with a complaint of inability to develop erections, the
presence or absence of spontaneous erections is an important clue to diagnosis.
Most men experience spontaneous erections during REM sleep, and often
wake up with an erection, attesting to the integrity of neurogenic reflexes and
corpora cavernosae blood flow.
Information regarding nocturnal or early morning erections can be elicited by
history from patient and/or partner, but proof may require nocturnal penile
tumescence testing.
Complete loss of nocturnal erections is present in men with neurologic or
vascular disease.
Nonsustained erection with detumescence after penetration is most commonly
due to anxiety or the vascular steal syndrome.
With anxiety, a conscious or subconscious concern about maintaining erectile
rigidity activates an adrenergic hormone release, which is inimical to
maintaining erectile turgor and rigidity.
Sensate focus exercises are effective in restoring erectile confidence and
competence in this setting.
In the vascular steal syndrome, blood is diverted from the engorged corpora
cavernosae to accommodate the oxygen requirements of the thrusting pelvis.
Vascular surgery to ensure equitable genital and pelvic arterial inflow is
obligatory
PHYSICAL EXAMINATION
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In addition to the basic physical examination, the evaluation of the
sexually dysfunctional male should include the following:
A careful assessment of femoral and peripheral pulses as a clue to the
presence of vasculogenic impotence. If pulses are normal, the presence
of femoral bruits implies possible pelvic blood occlusion.
A search for visual field defects, present in hypogonadal men with
pituitary tumors. (See "Causes of secondary hypogonadism in males".)
A breast examination to detect gynecomastia, often present in
Klinefelter's syndrome. (See "Causes and evaluation of
gynecomastia".)
A search for penile placques indicative of Peyronie's disease.
(See"Miscellaneous benign diseases affecting soft tissue and bone",
section on 'Peyronie's disease'.)
Examination of the testicles looking for atrophy, asymmetry or masses.
Evaluation of the cremasteric reflex, an index of the integrity of the
thoracolumbar erection center. This is elicited by stroking the inner
thighs and observing ipsilateral contraction of the scrotum.
Hormonal testing
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The value of routine measurements of serumtestosterone, prolactin and
thyroid function tests in men with erectile dysfunction is no longer a subject of
debate.
The only way to know if a man with complaints of sexual dysfunction has
testosterone deficiency is to measure his serum testosterone level.
Although the frequency of abnormalities detected in different studies has
varied substantially, the author feels that measurement of these parameters is
warranted.
In one series, 29 percent of 422 impotent men had hormonal disorders
including hypogonadism in 19 percent, hyperprolactinemia in 4 percent, and
either hypothyroidism or hyperthyroidism in 6 percent [7]. We found similar
results in another report, with 34 percent of 105 men with impotence
had testosterone deficiency, hyperprolactinemia, or thyroid dysfunction [8].
In a study of 1022 men with erectile dysfunction, persistently low
serum testosterone (less than 300 ng/mL [10.4 nmol/L]) was found in only 4
percent of men under age 50, and 9 percent of those over age 50 [9]. However,
if testing had been restricted to those men with symptoms of low sexual desire
or signs of hypoandrogenism, 40 percent of cases would have been missed,
including 37 percent of who responded to treatment with testosterone. One
percent had hyperprolactinemia. Similar results were seen in a study of 1455
men
Nocturnal penile tumescence testing
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NPT testing, once a tedious, laborious and expensive process
performed only in a hospital sleep laboratory, has been simplified.
Devices such as the Rigi-Scan monitor provide accurate, reproducible
information quantifying the number, tumescence and rigidity of
erectile episodes a man experiences as he sleeps in the comfort of his
own bed [11]. The data generated can be downloaded to provide a
graphic index quantifying erectile activity as either normal or impaired
(graph 1).
• Impotent men with normal NPT are considered to have psychogenic
impotence whereas those with impaired NPT are considered to have
"organic" impotence usually due to vascular or neurologic disease. In
comparison, testosterone deficient hypogonadal men are still capable
of exhibiting some erectile activity during nocturnal penile tumescence
studies
• In the past, third party payers demanded proof of "organic" impotence
before they would approve payment for penile prosthesis surgery. Now
NPT results are used to identify men with underlying arterial or venous
disorders who might benefit from corrective vascular surgery.
Testosterone Replacement
• Testosterone should be administered only to a man who is
hypogonadal, as evidenced by clinical symptoms and signs consistent
with androgen deficiency and a distinctly subnormal serum
testosterone concentration. In comparison, increasing the serum
testosterone concentration in a man who has symptoms suggestive of
hypogonadism but whose testosterone concentration is already normal
will not relieve those symptoms.
• Testosterone can be replaced satisfactorily whether the testosterone
deficiency is due to primary or secondary hypogonadism.
• The principal goal of testosterone therapy is to restore the serum
testosterone concentration to the normal range. It is not yet known if
restoring the normal circadian rhythm of testosterone is important.
• The role of testosterone replacement to treat the decline in serum
testosterone concentration that occurs with increasing frequency above
age 60 in the absence identifiable pituitary or hypothalamic disease is
uncertain.
TESTOSTERONE PREPARATIONS
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Choosing among the differenttestosterone preparations requires an
understanding of their pharmacokinetics. Native testosterone is absorbed well
from the intestine, but it is metabolized so rapidly by the liver that it is
virtually impossible to maintain a normal serum testosterone concentration in a
hypogonadal man with oral testosterone. The solutions to this problem that
have been developed over many years involve modifying the testosterone
molecule, changing the method of testosterone delivery, or both. The
following testosterone preparations are currently available or are under
development for treating testosterone deficiency:
Alkylated androgens — Decades ago, investigators discovered that adding an
alkyl group in the 17-alpha position of thetestosterone molecule retarded its
catabolism by the liver. Since that time, several 17-alkylated androgens
(eg, methyltestosterone) have been available for oral use. Many
endocrinologists who treat male hypogonadism think that these preparations
are not fully effective in producing virilization, although no studies have tested
these observations. In addition, several reports have described hepatic side
effects with these preparations, including cholestatic jaundice, a hepatic cystic
disease called peliosis hepatis, and hepatoma. For both of these reasons, and
because better preparations are available, the 17-alkylated androgens should
generally not be used to treat testosterone deficiency.
Testosterone esters
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Testosterone enanthate and testosterone cypionate are esters of testosterone that have been used for many years for
the treatment of testosterone deficiency. The rationale for their use is that esterification of a lipophilic fatty acid to the
17-beta hydroxyl group of testosterone (algorithm 1) makes testosterone even more lipophilic than the native
molecule. Intramuscular injection of testosterone esters results in their storage in and gradual release from the oilbased vehicle in which they are administered, thereby prolonging the presence of testosterone in the blood [6,7].
The therapeutic characteristics of testosterone enanthate are relatively well described. In one report, for example, 100
mg of testosterone enanthate was administered once a week for 12 weeks to 12 men with primary hypogonadism [8].
The mean serum testosterone concentration increased to slightly higher than the upper limit of normal one to two days
after the injection and gradually decreased to the mid-normal range by the time of the next injection (graph 1).
When the dose of testosterone was increased to 200 mg in an attempt to prolong the dosing interval to every two
weeks, the peak serum testosterone concentration increased further, and the nadir, just before the next injection,
decreased to the low-normal range. Regimens of 300 mg every three weeks and 400 mg every four weeks increased
the peaks and decreased the nadirs further.
The serum concentrations of luteinizing hormone (LH), which were initially above normal in all the men, decreased
gradually after initiation of the 100 mg/week regimen, reaching the normal range by six to eight weeks and remaining
in the normal range thereafter. Serum LH concentrations also decreased to normal with the 200 mg per two week
regimen, barely to normal with the 300 mg per three week regimen, and remained supranormal with the 400 mg per
four week regimen [8].
These data suggest that testosterone enanthate doses from 100 mg per week to 300 mg per three weeks are
biologically effective, but that 400 mg per four weeks is not. Less information is available for testosterone cypionate,
but the few studies that have been performed suggest that its characteristics are similar to those of testosterone
enanthate.
An advantage of testosterone enanthate and cypionate over other testosterone preparations is that they are biologically
effective in initiating and maintaining normal virilization in all hypogonadal men. Another advantage to some men is
freedom from daily administration. The disadvantages are the need for deep intramuscular administration of an oily
solution every one to three weeks and fluctuations in the serum testosterone concentration, which result in
fluctuations in energy, mood, and libido in many patients. These fluctuations are more pronounced as the dosing
interval is increased.
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Transdermal delivery
Transdermal delivery of testosterone first became available in 1994 with the introduction of a scrotal
patch. Since then, body patches and gels have also become available, but the scrotal patch is no
longer available in the United States. The major advantage of transdermal administration is
maintenance of relatively stable serum testosterone concentrations, resulting in maintenance of
relatively stable energy, mood, and libido.
Patch — One patch, Androderm, is currently available. Androderm relies upon chemical means to
increase the absorption of testosterone across nongenital skin, and it is meant to be worn on the arm
or torso. It delivers approximately 5 mg of testosterone per 24 hours and results in normal serum
testosterone concentrations in the majority of hypogonadal men. Anecdotal reports suggest that as
many as one third of men who try this preparation cannot continue it because of severe skin rash.
Testosterone gels — Two testosterone gels are available, AndroGel and Testim. AndroGel is
supplied in 2.5 g and 5.0 g packets, which contain 25 mg and 50 mg of testosterone, respectively, and
a metered-dose pump that delivers 1.25 g of gel (containing 12.5 mg of testosterone) per pump
depression. When this preparation is applied to the skin once a day in doses of 5 to 10 g (delivering
50 to 100 mg of testosterone), the serum testosterone concentrations usually reach the normal male
range within a month and remain steady throughout 24 hours. The serum concentrations of
testosterone throughout the 24 hours from one application to the next are similar at one, three, and six
months. Occasional local skin irritation occurs but usually does not necessitate discontinuation of
therapy. Testim is supplied in doses of 5 and 10 g, which contain 50 and 100 mg of testosterone,
respectively, and, when applied daily, usually result in normal serum concentrations of testosterone.
Anecdotal reports suggest that this preparation gives an odor.
Buccal tablet — A buccal tablet (Striant), 30 mg, is applied twice a day and adheres to a depression
in the gum above the upper incisors. It releases testosterone across the buccal mucosa into the
systemic circulation.
Human chorionic gonadotropin (hCG) — This preparation, while not an androgen, stimulates the
testes to make testosterone and is especially useful in stimulating both testosterone and sperm
production.
MONITORING
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Patients who are treated with testosterone should be monitored to determine
that normal serum testosterone concentrations are being achieved. They should
also be monitored for both desirable and undesirable effects.
Serum testosterone concentration — The timing of
serumtestosterone measurements varies with the preparation that is used.
The serum testosterone should be measured midway between injections in men
who are receiving testosterone enanthate, and the value should be mid-normal,
eg, 500 to 600 ng/dL (20.8 to 24.3 nmol/L). The dose should be reduced if
higher values are obtained.
The serum testosterone can be measured at any time in men who are using any
of the transdermal preparations, with the recognition that the peak values occur
six to eight hours after application of the patch. The concentrations fluctuate
when a gel is used, but not in a predictable way, so at least two measurements
should be made at any dose of gel; the time of measurement does not appear to
matter. The value should be well within the normal range (400 to 700 ng/dL
[13.9 to 27.7 nmol/L]).
If the patient has primary hypogonadism, normalization of the serum LH
concentration should also be used to judge the adequacy of
thetestosterone dose, no matter which testosterone preparation is used.
OUTCOMES
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The desirable effects of testosterone administration include the development or
maintentance of secondary sexual characteristics, and increases in libido, muscle
strength, body composition, and bone density. Undesirable effects related directly to
testosterone include acne, prostate disorders such as benign prostatic hyperplasia
symptoms, sleep apnea, and erythrocytosis.
Virilization/sexual function — Normalization of the serumtestosterone concentration
should lead to normal virilization in men who are not virilized and maintenance of
virilization in those who already are. Men who become hypogonadal in adulthood and
are still normally virilized but whose hypogonadism is manifested by a decrease in
libido and energy should note a marked improvement in these symptoms. Failure of
improvement when the serum testosterone concentration has been restored to normal
suggests another cause of the symptoms.
Muscle strength/fat-free mass — Testosterone replacement also leads to substantial
improvements in muscle strength and fat-free mass in hypogonadal men. In one report,
for example, the administration of 100 mg of testosterone enanthate once a week for 10
weeks to hypogonadal men increased their strength in the bench press by 22 percent,
their squat strength by 45 percent, and fat-free mass by 5 percent.
Bone density — Testosterone replacement improves bone density in male
hypogonadism as illustrated in a study of 72 such men recievingtestosterone replacment
therapy. The increase in bone density averaged 39 percent in the first year of
testosterone replacement and eventually reached and was maintained in the normal
range. The response was greatest in the first year in previously untreated patients and
was most pronounced in those with lowest bone density measurements at baseline.
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Undesirable effects
Testosterone enanthate and thetestosterone patch and gels
have few side effects unrelated to the action of
testosterone.
Some of the actions of testosterone itself, while not side
effects, are undesirable.
Puberty-related
During the first few months after the initiation
oftestosterone replacement, some of the undesirable effects
of normal puberty, such as acne and gynecomastia, can be
seen
When testosterone is first administered to hypogonadal
adolescent boys, physically aggressive behavior may
increase
Overtreatment of a boy whose epiphyses have not yet
closed can cause premature closure and permanent short
stature
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Prostate
Prostate volumes and serum prostate specific antigen (PSA) increase in response
to testosterone treatment. On average, values increase to those of age-matched eugonadal men.
Some men, especially those over the age of 50, experience an exacerbation of benign prostatic
hyperplasia (BPH), a testosterone-dependent disease. Symptoms, predominantly lower urinary tract
symptoms (LUTS) due to urinary outflow obstruction, may increase.
Because prostate cancer is, at least to some degree,testosterone dependent, it seems theoretically
likely that the risk of prostate cancer is less in hypogonadal men than eugonadal men and the risk
increases to normal, but not above, when testosterone is replaced. However, no data are available to
support or refute this assumption. It seems prudent, nonetheless, to screen hypogonadal men for
prostate cancer before beginning testosterone replacement and to monitor them for prostate cancer
during treatment, just as one would monitor a eugonadal man.
There is no reason to think that men who rely on medication to maintain a normal
serum testosterone concentration are more likely to develop these conditions than men who produce
their own testosterone. Nevertheless, the physician who prescribes testosterone for a man over age 50
should monitor him as follows:
For BPH, lower urinary tract symptoms should be assessed by the International Prostate Symptom
Score (IPSS). If warranted by symptoms, the urine flow rate and post-void residual urine in the
bladder by ultrasonography should be measured before beginning treatment. If the diagnosis of
moderate or severe LUTS due to BPH is made, treatment of that condition should be considered
before beginningtestosterone replacement.
For prostate cancer, digital rectal examination and measurement of serum PSA should be performed
before initiatingtestosterone replacement, three months after initiation of treatment, and then in
accordance with evidence-based guidelines for prostate cancer screening, depending on the age and
race of the patient. The patient should be referred for prostate biopsy if a prostate nodule is palpated
at any time or if the serum PSA concentration, confirmed by a repeat value, is above 4.0 ng/mL
initially or if it rises by more than 1.4 ng/mL in any one-year period or, if data are available for two
or more years, a PSA velocity of >0.4 ng/mL per year, beginning six months after initiation of
testosterone therapy. The latter recommendations assume that the patient does not have prostatitis
and that the values are confirmed by repeat measurement.
Sleep apnea Erythrocytosis
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Sleep apnea may be worsened [33]; the physician should
inquire about symptoms, such as excessive daytime
sleepiness and witnessed apnea during sleep by a partner.
If indicated, polysomnography should be performed.
• Erythrocytosis is common adverse effect
oftestosterone administration. The hemoglobin and
hematocrit should be measured initially, after three
months, and then yearly.
• Skin irritation — The patch, Androderm, often causes
skin rashes, some very mild and others quite severe,
requiring discontinuation of this treatment. The rash may
sometimes be prevented by pretreatment of the skin with a
corticosteroid cream. Local skin irritation occasionally
occurs with testosterone gels (AndroGel and Testim), but
usually is not severe and does not necessitate
discontinuation of therapy.
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Secondary exposure
With testosterone gels, the possibility of skin transfer to another person is low
if the patient follows the package insert directions which include:
Wash hands thoroughly after application.
Avoid skin contact until the gel has dried completely.
Keep the application site covered.
In a study of healthy male volunteers receiving testosterone gel, intense skin
contact with a second male volunteer (pretreated with norethisterone [400 mg
IM] to suppress endogenous testosterone) did not result in an increase in serum
testosterone concentrations.
However, the US Food and Drug Administration added a boxed warning to
both testosterone gel products after receiving reports of secondary exposure in
eight children ages nine months to five years. Exposure resulted in penile or
clitoral enlargement, premature development of pubic hair, advanced bone
age, increased libido, and aggressive behavior, most of which regressed when
the child was no longer exposed to testosterone (with the exception of
penile/clitoral enlargement).
These complications are extremely rare (8 cases/1.8 million prescriptions), and
therefore, testosterone gel use should still be considered safe. However, it is
extremely important to take precautions to avoid contact transfer of
testosterone, eg, by washing hands after application and keeping the
application site covered with clothing.
Time course of effects
• The time course of the effects
oftestosterone replacement is variable. This
was illustrated in a three-year study of
physiological transdermal testosterone
replacement in 18 previously untreated
hypogonadal men. Increases in fat-free
mass, prostate volume, erythropoiesis,
energy, and sexual function occurred within
the first three to six months.
• In contrast, the full effect on bone mineral
density did not occur until 24 months.
RECOMMENDATIONS
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The following recommendations are consistent with the Endocrine Society Clinical
Practice Guidelines:
We recommend testosterone therapy for symptomatic men with hypogonadism. We
usually recommend transdermal testosterone to most hypogonadal men, especially a gel,
because it usually produces normal serum testosterone concentrations, and most patients
find it the most convenient. Some men, however, prefer injections of testosterone
enanthate because of the freedom from daily application.
For some patients, cost may be an issue. In general, the newest preparations, the gels,
cost the most; patches, somewhat less; and injectable esters, the least.
Men who begin using a transdermal preparation need to be seen two to three months
after the initiation of therapy to measure the serumtestosterone concentration and
evaluate the possibility of undesirable effects. Men who use the body patch or a 5 g dose
of the gel (containing 50 mg of testosterone), but whose serum testosterone
concentration is not high enough, can try wearing two patches or applying 7.5 or 10 g of
the gel (containing 75 or 100 mg of testosterone, respectively).
The initial regimen of testosterone enanthate should be 200 mg every two weeks, which
can be administered either by the patient himself or by someone in the patient's
household. The patient should be seen approximately two to three months later and, if he
is bothered by fluctuations in energy, mood, or libido, the regimen can be changed to
100 mg once a week or transdermal testosterone can be offered again.
Historical milestones
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Sigmund Freud—first to talk about sexual issues and drive and first known sex
therapist
Richard von Krafft-Ebing—wrote book on sexual disorders (Psychopathia Sexualis);
treatment with sex hormones and concept
of synthetic hormones developed between World War I and II
Alfred Kinsey—professor who performed survey of sexual habits
Masters and Johnson—witnessed 11,000 live sexual encounters in laboratory
examined physiologic and psychologic impact of sexual intercourse
Established that vaginal and clitoral orgasm physiologically identical
introduced sexual response cycle (arousal, plateau, orgasm, and resolution)
developed intervention of sexual therapy
Helen Kaplan Singer—introduced desire as first phase of sexual response cycle
trained therapists who educated and brought patients to treatment
Ruth Westheimer ("Dr. Ruth")—sex education
Lou Ignarro—published research on nitric oxide, which led to introduction of sildenafil
(eg, Viagra) in 1998
Berman sisters—focus on education and women’s health
Rosemary Basson—showed that male model of sexual response cycle not applicable to
women (for women, desire and arousal intermix)
Biopsychosocial model
• evaluation of biologic, psychologic, and
social factors
• biologic factors—genetic loading
• Impact of substances (eg, recreational
drugs, alcohol, prescription
• drugs, over-the-counter drugs, herbal
preparations)
• medical conditions; genetic predisposition;
• evaluation of couple—infrequently done,
but necessary for full evaluation of sexual
disorders
Bringing up sexual issues
• Journal of American Medical Association
(Marwick 1999) survey—71% of patients
thought physician would dismiss concerns
• 68% afraid of embarrassing physician
• ask patients about sexual history;
• move into questions about sexual function
• can take direct approach, or ask first how
patient feels about answering such questions
Overview
• include disorders of sexual response cycle
• pain (dyspareunia and vaginismus)
• each element interacts with all others
Biologic interventions
• thorough physical examination and laboratory
tests to rule out underlying medical conditions (eg,
diabetes, hormonal imbalances)
• effect of substances—eg, selective serotonin
reuptake inhibitors (SSRIs) widely prescribed, and
shown to reduce desire by 60% (paroxetine [eg,
Paxil] up to 85%)
• administration of medications, hormones, or
devices—use hormones with great caution to
correct deficiency or boost borderline values
reflected in symptoms (can inhibit natural
production)
Hypoactive sexual
desire disorder
• persistent or recurrent deficiency or absence of sexual
fantasies or desire for sexual activity
• must cause marked distress or interpersonal difficulty
• rule out drug use or medical issues
• distinctions—lifelong vs acquired generalized vs
situational
• psychologic vs combination of causes (medical and
psychologic factors not mutually exclusive)
• Chicago study—33% of women have hypoactive desire
• Can improve with age
Treatment
• phosphodiestrase-5 inhibitors with SSRIs seem to improve desire, (but
not first choice of treatmentfor SSRI-related sexual dysfunction)
• Bupropion (eg, Wellbutrin) study—nondepressed women given
bupropion
• (150 mg twice daily)
• within 2 wk, desire improved in 29% (due to dopaminergic effect)
• Oral contraceptives (OCs)—studies suggest improvement in desire
with discontinuation of mono- or biphasic OCs or switch to triphasic
• perimenopausal patients—efficacy seen with hormone therapy using
patches
• testosterone—via patch or topical ointment
• monitor dosing carefully
• patch not yet approved by United States Food and Drug
Administration (FDA)
• examine woman’s relationship with partner before prescribing biologic
intervention
Female arousal disorders
• persistent or recurrent inability to attain
or maintain adequate lubrication or swelling
• Understand nature of stimulation, age of
patient, and relationship with partner (ie,
distinguish between situational and
generalized dysfunction)
• prevalence—20% of women (vs 43% for
overall sexual dysfunction)
Therapy
• hormone replacement
• topical estrogen—used to increase clitoral
sensitivity
• testosterone alone or in combination with estrogen
(eg, Estratest)
• sildenafil—placebocontrolled studies show
improvement in lubrication and arousal
• not yet reproduced clinically; second choice to
hormone therapy
• clitoral vacuum devices (eg, EROSCTD)—appear
to improve genital sensation, vaginal lubrication,
orgasmic abilities, and sexual satisfaction
Female orgasmic
disorder
• persistent recurrent delay or absence of
orgasm
• assess nature of stimulation
• Clinician must judge adequacy of sexual
stimulation in context of patient’s sexual
experience and age
• only 30% of women able to reach orgasm
through intercourse
• 40% of women have difficulty achieving
orgasm through intercourse alone
Therapy
• vacuum device—helpful in premenopausal
and postmenopausal women
• sacral nerve stimulation (eg, InterStim)—
observed to improve orgasmic dysfunctio;
• option for highly motivated treatmentresistant patients
• Kegel exercises—recommended by speaker
• drugs— little evidence of efficacy
• cabergoline (eg, Dostinex)
• shows some promise ( patent pending for
precoital use)
Dyspareunia
• look for organic causes
• can be psychologic pain during intercourse,
especially in patients exposed to sexual
intrusions early in life (psychotherapy
required)
• treatment—Kegel exercises
• topical nitroglycerin appears effective
Vaginismus
• introitus blocked
• spasm in muscles of pelvic floor rather
than upper vagina
• caused by early sexual trauma, conflict with
partner, or uncomfortable sexual position
Treatments
• systemic desensitization using progressive
• dilation—not effective in speaker’s
experience
• Intravenous diazepam abreaction—no
longer used
• Botulinum toxin injections (University of
Tehran study)—effective within 1 wk in 18
of 23 women given injections to sides
• of vagina
• effects disappear in about 4 to 5 mo
Psychologic and Alternative
Interventions
Masters and Johnson's prescribed exercises
•
• sensate focus I—pleasurable touching, excluding genitalia and breasts
• partners take turns; patients return to therapy and relate details of
touching (to desensitize about verbalizing, encourage dialogue, and
foster understanding of how
• to please partner)
• sensate focus II—includes breasts and genitalia
• sexual intercourse forbidden
• teach hand-guiding (allows one partner to show mate nonverbally
which kinds of touching most pleasurable)
• if patients have sexual intercourse, evaluate whether appropriate to
proceed or return to sensate focus I or II
• sensate focus III— genital-to-genital touching
• Masters and Johnson claimed technique helps 90% of patients with
erectile dysfunction, including diabetic patients
Sexual positions
• no single optimal sexual position
• Stimulation of anterior vaginal wall—rear
entry position
• Clitoral stimulation—missionary position
with woman’s pelvis elevated
• Gräfenberg spot—some reports suggest
evidence insufficient
• other reports describe anatomic location
Alternative therapies
• eg, acupuncture, herbs, aromatherapy
• Investigational treatments
• apomorphine (eg, Uprima)— central agent
that stimulates desire; side effect of
vomiting
• flibanserin—in phase III trials
• alprostadil—not successful in women;
placebo response—50% for treatment of
sexual disorders (confounds research)
Alternative Therapies For
Menopause
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Risk factors for vasomotor symptoms
lower body weight;
Smoking
ethnicity (Asian women less likely to
complain of hot flushes than white women
• in United States, black women more likely
to report symptoms than white women)
Overview
• results from narrowing of hypothalamic
thermoregulatory set point
• increases chance of heat sensation in response to
internal and external triggers
• role of estrogen—acts at hypothalamus
• exposure followed by withdrawal necessary, but
not sufficient to elicit vasomotor symptoms
• severity of symptoms does not correlate with
estrogen levels
• hot flushes do not occur in all conditions
• associated with low estradiol levels
Proposed mechanisms
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luteinizing hormone (LH) pulses or gonadotropins—do not mediate symptoms
eg, women with hypothalamic amenorrhea with LH pulses do not experience vasomotor
symptoms
isolated gonadotropin deficiency does cause vasomotor symptoms
treatment with gonadotropin-releasing hormone agonists (which eliminate LH pulses)
does produce vasomotor symptoms;
opioids—do not play major role; eg naloxone infusion reduces hot flushes and LH pulse
frequency in some symptomatic menopausal women
decreased plasma endorphin levels before hot flushes demonstrated in some but not all
studies
estrogen-mediated change in serotonergic or noradrenergic systems—likely
evidence for norepinephrine—injection into hypothalamus causes peripheral
vasodilation
gonadal steroids modulate adrenergic activity
baseline norepinephrine metabolites increase in symptomatic women with hot flushes
levels increase further after episode;
clonidine ( 2-receptor agonist) ameliorates hot flushes in some women
yohimbine ( 2-receptor antagonist) increases flushing
evidence for serotonin— receptors for 5-HT1A and 2A important in thermoregulation
receptor expression and activity modulated by gonadal steroids
association between serotonin levels and severity of menopausal symptoms
exact relationship between serotonin and estrogen in thermoregulation unknown
Estrogens
• 80% to 90% effective (placebo response
20%- 50%)
• dose-dependent; all routes of administration
effective
• FDA-approved for treatment of vasomotor
symptoms
• studies show decreases in hot flush scores
• some concerns about safety, thus
alternatives increasingly important
• No single agent addresses all symptoms
Progestins
• effective at higher doses
• side effects—fairly common
• significant concern about effects on breasts
and vasculature
• higher rates of breast cancer in women
using progestin vs estrogen alone
• contraindications in menopausal patient
similar to those for estrogen
SSRI therapy
• efficacy differs with drug and with patient population
• side effects—nausea, weight gain, sexual dysfunction, and
sleep disturbance;
• fluoxetine (eg, Prozac) study in breast cancer patients—8
wk of drug (20 mg) vs placebo
• 50% decrease in hot flush score in both groups
• some statistically significant benefit noted in crossover
• paroxetine—studies show benefit for healthy women as
well as those with breast cancer
• side effects may limit use
• controversy remains as to whether responses modified by
breast cancer
• meta-analyses—suggest some improvement in non-breast
cancer population
Serotonin norepinephrine
reuptake inhibitors (SNRIs)
• venlafaxine (eg, Effexor)—crossover phase
of studies shows reduction in hot flush
scores in women with and without history
of breast cancer
• side effects may limit use
• desvenlafaxine—shown to be beneficial
Variation within and among
SSRIs and SNRIs
• causes—effects on dopamine and
norepinephrine reuptake
• Degreem of anticholinergic effect
• drug metabolism (eg, paroxetinem and
fluoxetine inhibit cytochrome P450
[involved with activation or metabolism of
tamoxifen]
• may decrease hot flushes in women taking
tamoxifen, but may reduce efficacy of
breast cancer treatment)
Other neuroactive agents
• gabapentin—effective at higher doses in women with
breast cancer and general population
• side effects may limit acceptance
• 80% decrease in hot flush scores (40%-50% in placebo)
• clonidine—use established for treating flushes
• minimal to modest efficacy
• 40% discontinuation rate due to side effects
• tibolone—not available in United States; effective for hot
flushes
• Studied extensively in Europe, but safety questionable
(increased risk for breast cancer and endometrial
hyperplasia reported in some studies)
Nonprescription
remedies
lifestyle changes—lower ambient temperature
•
• avoidance of hot beverages
• Paced respiration—somewhat effective
• exercise—does not reduce symptoms, and strenuous activity can
trigger symptoms symptoms
• phytoestrogens or isoflavones—soy and red clover sources; some
studies show benefit (40-80 mg daily)
• But majority show no significant difference from placebo
• fairly safe; increased risk for adverse estrogenic effects
• short-term studies do not show change in endometrial thickness
• black cohosh—herbal preparation
• Mechanism of action unknown
• some studies show decrease in vasomotor symptoms with minimal
risks
• long-term studies lacking
• additional herbs and interventions—evening
• primrose oil, ginseng, licorice, vitamin E, topical progesterone, and
acupuncture; none shown effective
Bioidentical hormones
• require prescription, but not approved by
FDA; data on efficacy, side effects, and
longterm safety lacking
• North American Menopause Society NAMS)
statement—preparations presumed to carry
known risks and benefits of standard
hormone therapy
• Inform patient about lack of regulatory
oversight
Dosing recommendations
(NAMS)
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paroxetine—12.5 to 25 mg daily fluoxetine—20 mg daily;
venlafaxine—37.5 to 75 mg daily
can increase dose on weekly basis
gabapentin— 300 mg daily
increasing to 300 mg tid
better to use at night due to sedative effect
clonidine—0.05 to 0.1 mg bid, or 0.1 mg daily patch
nonprescription alternatives—isoflavones and black
cohosh with limit to 6-mo trial
Management
• minimal symptoms—lifestyle modification
• moderate to severe symptoms—estrogen
with or without progestin if risk for breast
cancer or thromboembolic disease minimal
(SSRI or SNRI for women with higher risk)
• add topical vaginal preparation for vaginal
symptoms
• Gabapentin with or without vaginal
estrogen
• isoflavone or black cohosh
A 65-year-old male patient presents for the
first time to you in consultation of his
concerns about “male menopause” that he has
read about in a recent popular entertainment
magazine. In particular, he relates that he is
recently married and they are considering
having children. Of the following changes,
which is mostly likely to naturally happen as
he ages?
1.higher morning testosterone levels
2.increased testosterone bioavailability
3. androgen production declines
4.cessation of spermatogenesis
3. androgen production declines
• While normal spermatogenesis is androgendependent, this capacity is largely preserved
throughout life. Androgen production and
bioavailability do undergo age-related changes.
There is a reduction in the frequency of the large
morning luteinizing hormone pulses, and both
total testosterone secretion and morning peaks are
diminished. There is also an increase in the
binding of testosterone that results in reduced
bioavailability. Reduced androgen bioavailability
contributes to the observed reduction in libido and
to the decline in frequency of spontaneous
nocturnal erections. The ability to achieve an
erection with appropriate stimulation is, however,
relatively preserved.
A 64-year-old male complains of decreased
libido and a reduction in frequency of
morning erections. On physical exam the
testicles are small and the consistency is
relatively soft. A total testosterone level is 103
ng/dL. Your working diagnosis is
hypogonadism. What medical conditions are
associated with male hypogonadism?
1.alcoholism
2.myotonic dystrophy
3. multiple sclerosis
4.proton pump inhibitor use
1.alcoholism
A 58-year-old male patient presents with a 2-month
history of worsening erectile dysfunction. His past
medical history is significant for impaired fasting
glucose, hypertension treated with a thiazide
diuretic, and hypercholesterolemia treated with a
statin. Erectile dysfunction is defined as an inability
to develop or sustain an erection satisfactory for
intercourse. What is the most likely cause of this
patient’s erectile dysfunction?
1.excessive venous outflow
2.antihypertensive medications
3.unrecognized alcoholism
4.age-elevated fasting glucose
age-elevated fasting glucose
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mpotence is a common problem that increases with age, affecting up to 25% of 65-yearolds and 50% of 80-year-olds.
Diabetes is the most common neurologic contributor to impotence, and results from the
peripheral neuropathy or coexisting vascular disease. Alcoholism can also contribute to
impotence, both through the peripheral neuropathy and by inducing hypogonadism.
Other neurologic causes include trauma (especially surgical), and multiple sclerosis.
Vascular causes are common and may result from an arterial occlusion reducing inflow
or from excess venous leakage. Excess venous leakage accounts for 75% of cases of
impotence in the subset of patients, in whom no hormonal and neurologic cause for
impotence can be found.
Medications are a common cause of impotence, accounting for an estimated 25% of
cases of erectile dysfunction. Classes of medicines associated with erectile dysfunction
include anticonvulsants, antibiotics, antiarrhythmics, antihypertensives, antidepressants,
antipsychotics, hypnotics, gastrointestinal antacids, and miscellaneous drugs including
clofibrate, naproxen, and interferon.
Psychologic causes such as depressive and anxiety disorders should not be overlooked.
Reference:
Kronenberg HM, Melmed S (eds). Williams Textbook of Endocrinology (11th ed.).
Saunders Elsevier, 2008.
A 68-year-old African-American male patient with a
history of morbid obesity, hypertension, diabetes
mellitus, and hypercholesterolemia presents to you
for evaluation of recent onset erectile dysfunction.
Of the following lab sets, which would provide the
most helpful information in determining his
etiology?
1.morning total testosterone, fasting glucose, and
lipid profile
2. sex hormone binding globulin, albumin, free
testosterone, LH, and FSH
3. morning cortisol, LH, and FSH
4morning TSH, ACTH, LH, and FSH
1.morning total testosterone,
fasting glucose, and lipid profile
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The evaluation of erectile dysfunction begins by providing a comfortable environment. Providers should solicit
information about a patient's sexual activity, performance, and satisfaction during the routine review of symptoms.
Historical information includes an evaluation of libido, erectile function, and soliciting signs and symptoms of
commonly related problems including diabetes, vascular disease, and surgery. Also included is a complete review of
both prescription and over-the-counter medicines.
Physical exam is often unrevealing, but signs of hypogonadism, vascular insufficiency, and peripheral neuropathy
should be sought.
Diagnostic evaluation should further include a fasting glucose, TSH, and testosterone level to identify diabetes,
thyroid dysfunction, or hypogonadism. Nocturnal penile tumescence can assist in ascertaining the presence or absence
of spontaneous erections. Postage stamps are placed in a ring around the flaccid penis at night. Disruption of the ring
suggestions the occurrence of an erection. Portable computerized units may be more sensitive and reliable.
Finally, evaluation of erectile potential can be performed by injecting vasoactive agents into the corpus cavernosum.
Failure to achieve an erection after intracavernous injection of papaverine or phentolamine suggests venous leakage.
Formal vascular testing including duplex ultrasound or arteriography may be indicated in selected cases.
Laboratory evaluation of erectile dysfunction can be fairly limited. Assessment of the seriousness of comorbidities
such as diabetes, hypertension, and hypercholesterolemia can be very helpful. Thyroid dysfunction can be helpful as
hypothyroidism is a common etiology.
Evaluation of the pituitary-gonadal axis and the factors involved in transport of the sex hormones can be the most
valuable laboratory information. Assessment of testosterone levels starting typically with total testosterone. Free
testosterone can be a useful number but there are limitations concerning the type of assay used. Knowledge of sex
hormone binding globlin and albumin levels are helpful to calculate the free testosterone levels from the total level.
LH and FSH levels can be used to look for secondary hypogonadism.
A 62-year-old male patient presents with
diminished libido and erectile
dysfunction. His evaluation reveals a
total testosterone level of 158 ng/dL.
What is the best initial treatment for this
patient?
1.sildenafil citrate
2.intracavernous injections
3.counseling with a sexual therapist
4.weekly testosterone injections
4.weekly testosterone injections
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Initial treatment of erectile dysfunction and hypogonadism should be directed at the
underlying cause whenever possible.
If impotence is the result of psychosocial issues, referral to and counseling by a
professional with experience in treating sexual disorders may be most helpful.
Depression should be treated with counseling and medications either alone or in
combination.
Hypogonadism, when established by a reduced free testosterone level of less than 67
ng/dl, should initially be treated with testosterone replacement, usually in the form of
intramuscular injections. Total testosterone levels less than 300 ng/dL should be
worrisome. Age-related testosterone levels should be used for assessment and total
testosterone is a better assessment than free testosterone.
Vacuum devices and bindings are useful for vascular disorders. Vacuums facilitate
vascular in-flow and binding devices slow venous outflow. Intracavernous self-injection
of papaverine, phentolamine, or prostaglandin E1 is usually effective in mild to
moderate vascular disease.
Penile prostheses offer an approach to patients who have not responded to other
treatments, especially those with diabetic neuropathy or severe vascular disease.
Sildenafil causes the release of nitrous oxide, which increases smooth muscle relaxation
by inhibiting phosphodiesterase, which results in elevation of cyclic GMP. It has been
shown to be useful in all forms of erectile dysfunction (organic, psychogenic and
mixed).
Reference:
Wein: Campbell-Walsh Urology, 9th ed. Copyright © 2007 Saunders, An Imprint of
Elsevier
A 48-year-old male patient presents to you with
complaints of erectile dysfunction. He inquires about
therapies for this problem and the risks associated
with each. Most importantly, he is concerned about
priapism. Priapism is a sustained, painful erection
that exceeds 4 hours. If not treated, priapism may
result in permanent damage. Priapism is a
complication of some treatments for impotence.
Which treatment carries the LEAST risk of causing
priapism?
1.transurethral alprostadil
2.intracavernous injections
3.oral sildenafil
4.penile binding devices
4. penile binding devices
• Intracavernous injections, oral sildenafil, and
transurethral alprostadil have all been associated
with priapism.
• The goal of treatment of priapism is to achieve
detumescence with preservation of potency. This
can be attempted in multiple ways, including an
intracorporal injection of dilute epinephrine (20
mcg) or phenylephrine (100-200 mcg).
• Reference:
• Wein: Campbell-Walsh Urology, 9th ed.
Copyright © 2007 Saunders, An Imprint of
Elsevier
A 37-year-old woman complains of gaining 10 pounds in the
last 6 months. She had been stable at a weight of 150 pounds
for the past 5 years. Her past medical history is notable for
epilepsy, depression, hypertension, GERD, and gout. She has
no allergies. She takes valproic acid, fluoxetine,
chlorthalidone, esomeprazole, and allopurinol. All of these
medications were started about 1 year ago when her insurance
formulary changed. She does not smoke, drink, or use drugs.
She goes to the gym twice a week for 30 minutes and has
done so for the past 5 years. She is a concert pianist.
Her physical exam, CBC, and CMP are normal.
What is the next step in her management?
1. Change chlorthalidone to atenolol.
2.Change esomeprazole to ranitidine.
3.Change valproic acid to topiramate.
4.Change fluoxetine to paroxetine. Begin orlistat.
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3.Change valproic acid to
topiramate.
Medications that can increase weight include tricyclic antidepressants, most
atypical antipsychotics, lithium, and some SSRIs including paroxetine, insulin,
thiazolodinediones, glucocorticoids, and beta blockers. Drugs that are
associated with weight loss include the antiepileptics topiramate and
zonisamide, the antidepressants fluoxetine and bupropion, sympathomimetics
sibutramine and phentermine, and the lipoprotein lipase inhibitor orlistat.
Drug therapy with orlistat, sibutramine, or phentermine is indicated when
weight loss attempts with diet and exercise alone have failed, but only after
considering the side effects (mainly GI with orlistat and cardiovascular with
sibutramine and phentermine) and the lack of long-term safety or efficacy
data. Sympathomimetics are contraindicated in people with heart disease or
people taking MAOIs or cytochrome p450 3A4 modifying drugs. Orlistat may
cause deficiencies in the fat-soluble vitamins A, D, E, and K.
Allison, DB, Mentore, JL, Heo, M, et al. Antipsychotic-induced weight gain: a
comprehensive research synthesis. Am J Psychiatry 1999; 156:1686.
Fava, M. Weight gain and antidepressants. J Clin Psychiatry 2000; 61 Suppl
11:37.
Li, Z, Maglione, M, Tu, W, et al. Meta-analysis: pharmacologic treatment of
obesity. Ann Intern Med 2005; 142:532.
Which of the following health benefits can be
expected when a 100kg person loses 5 kg
using diet and exercise?
1.reduction in cardiovascular mortality by
50%
2.reduction in gallstones by 50%
3.reduction in blood pressure by 5mmHg
4. reduction in diabetes risk by 10%
5.reduction in osteoarthritis by 10%
3.reduction in blood pressure by
5mmHg
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n the DPPP study, lifestyle interventions led to a 6.8kg weight loss and a 50% reduction
in the risk of developing diabetes. Meta-analyses have suggested that blood pressure
decreases by about 1 mm Hg for each kilogram of weight lost. Although obesity is
associated with gallstones, weight loss can also be associated with increased gallstone
formation. A loss of ~10kg may be associated with a 25% decrease in cardiovascular,
cancer, and all-cause mortality. A 2kg/m2 decrease in weight is associated with a 50%
decrease in osteoarthritis.
Other benefits of weight loss with lifestyle modification include decreased risk of colon,
breast, and hepatobiliary cancer; decreased NAFLD; decreased kidney disease; and
decreased dementia.
Hamman, RF, Wing, RR, Edelstein, SL, et al. Effect of weight loss with lifestyle
intervention on risk of diabetes. Diabetes Care 2006; 29:2102.
Neter, JE, Stam, BE, Kok, FJ, Grobbee, DE. Influence of weight reduction on blood
pressure: a meta-analysis of randomized controlled trials. Hypertension 2003; 42:878.
Williamson, DF, Pamuk, E, Thun, M, et al. Prospective study of intentional weight-loss
and mortality in never-smoking overweight US white women aged 40-64. Am J
Epidemiol 1995; 141:1128.
Felson, DT, Zhang, Y, Anthony, JM, et al. Weight loss reduces the risk for symptomatic
knee osteoarthritis in women. The Framingham Study. Ann Intern Med 1992; 116:535.
A 55-year-old man is evaluated prior to elective knee replacement. He has
had knee osteoarthritis for over 5 years and has activity-limiting pain and
knee buckling despite NAIDS, steroid injections, and arthroscopy. His
past medical history includes cholelithiasis and diverticulosis. He has no
allergies, and he takes only a fiber supplement, zinc, and vitamin C. He
has never smoked, drinks 1 brandy per week, and does not use drugs. He
works as a wedding photographer and videographer. He has 1 sister, who
is healthy. Except for pain, he is able to walk up a flight of stairs without
stopping.
His height is 5'5", and his weight is 250 pounds. His physical examination
is normal.
His EKG and a chest x-ray are normal.
What is the next step in his management?
1.Stop fiber supplement 1 week prior to surgery.
2.Perform pulmonary function tests prior to surgery.
3.Advise that the rate of operative complications is too high unless he
loses weight so that his BMI is less than 35 kg/m2.
4. Perform treadmill stress test prior to surgery.
Proceed with surgery.
Proceed with surgery.
• Obesity is not a risk factor for most major perioperative
complications, including cardiac or pulmonary
complications. Therefore, no additional testing is necessary
prior to surgery simply because of obesity, and surgery
need not be delayed for weight loss. Obesity is clearly
related to DVT risk during surgery so aggressive and
appropriate DVT prophylaxis during and after surgery
should be given.
• Dindo, D, Muller, MK, Weber, M, Clavien, PA. Obesity in
general elective surgery. Lancet 2003; 361:2032.
• Smetana, GW, Lawrence, VA, Cornell, JE. Preoperative
pulmonary risk stratification for noncardiothoracic surgery:
systematic review for the American College of Physicians.
Ann Intern Med 2006; 144:581.
A 57-year-old woman is evaluated for weakness, episodes of crampy
abdominal pain, and extreme dyspnea at rest that has been progressive
over the last 2 weeks. She has also noticed some red-tinged urine. Her past
medical history is notable for a Roux-en-Y gastric bypass 1 month ago
and gallstones. She has lost 3 kilograms since the surgery. She has no
allergies. She takes omperazole, propanolol, and lisinopril. She worked as
a truck driver. She does not smoke, drink, or use drugs.
Her temperature is 36.8° Celsius, heart rate 88, blood pressure 190/100,
respiratory rate 18, and saturation 98% on room air. Her exam was normal
except for surgical scars and 4/5 weakness in all 4 extremities with normal
reflexes.
Her CBC and CMP are normal. A urinalysis shows trace protein, 1+
blood, 0-2 WBCs, 0-2 RBCs, and no casts.
Her weakness worsens rapidly over the next few days, and she has a
seizure requiring intubation.
What test is most likely to reveal the diagnosis?
1. blood culture
2.methylmalonic acid
3.urine porphobilinogen
4.CT scan of the abdomen and pelvis
5.lumbar puncture
3.urine porphobilinogen
• The combination of abdominal pain, progressive
neurologic symptoms, and hematuria without RBCs
suggests an acute porphyric attack, particularly in the
setting of the negative carbohydrate balance following a
bariatric operation. Pophryria is diagnosed by
measurement of urinary porphyrins, most easily
porphobilinogen. The time course is too rapid for vitamin
B12 deficiency, which would cause an elevated
methylmalonic acid. Surgical complications such as
abscess or bleeding would show up on CT or blood
cultures but would not explain the neurologic problems or
hematuria. Demyelinating processes that could be found on
lumbar puncture cannot explain the abdominal pain or
hematuria.
• Bonkovsky et al., N Engl J Med 358(26):2813-2825 June
26, 2008.
A 47-year-old woman is seen for bilateral hand and foot numbness that has been
progressing over the past 2 months. Her past medical history is notable for
hypertension, a roux-en-y gastric bypass 5 years ago after which she lost 60
pounds, and kidney stones. She has no allergies. She takes no medications. She
doesn't smoke, drinks 1 glass of wine per week, and does not use drugs. She is a
legislative aide.
Her temperature is 37.2° Celsius, heart rate 79, blood pressure 121/78, respiratory
rate 16, and oxygen saturation is 98% on room air. She is 5'5" tall and weighs 170
pounds. Her physical examination is normal except for decreased pinprick,
position, and vibration sense in her hands and feet as well as upgoing toes
bilaterally.
A CBC shows a WBC count of 6,500 per microliter, a hemoglobin of 12 mg/dL, a
hematocrit of 37%, a mean corpuscular volume of 102 fentoliters, and a platelet
count of 235,000 per microliter. Her sodium is 140 meq/L, potassium is 3.9
meq/L, chloride is 110 meq/L, CO2 is 24 meq/L, BUN is 12 mg/dL, creatinine is
1.1 mg/dL, and glucose is 110 mg/dL.
What management is most likely to prevent further neurologic deficits?
1. cessation of alcohol 2.use metformin
3.cobalamin injections
4.spinal stimulation
5.plasmapheresis
3.cobalamin injections
• Long-term complications of malabsorptive bariatric
surgery include deficiencies in folate, iron, vitamin B12,
calcium, vitamin D, and copper; hyperoxaluria leading to
kidney stones; dumping syndrome; postprandial
hypoglycemia; abdominal wall hernias; gallstones; and
anastomotic stenosis. In this case, the combination of
neuropathy with posterior column signs and a macrocytic
anemia suggests vitamin B12 deficiency. Vitamin B12 is
absorbed in the terminal ileum but requires intrinsic factor
from the gastric antrum to be absorbed.
• Shah M, Simha V, Garg A. Review: long-term impact of
bariatric surgery on body weight, comorbidities, and
nutritional status. J Clin Endocrinol Metab. 2006
Nov;91(11):4223-31. Epub 2006 Sep 5.
A 35-year-old male is seen for management of his diabetes. His past
medical history is notable for diabetes for 5 years, with blood sugars
averaging 180-220 mg/dL and osteoarthritis. He has tried 3 diets and 2
exercise programs in the last year. Each time he lost about 5 pounds but
quickly gained it back. He is allergic to penicllin. He takes metformin,
glipizide, and celecoxib. He does not smoke, drink, or use drugs. He is an
administrator at a food bank. His parents are both deceased from coronary
artery disease.
His temperature is 36.8° Celsius, heart rate 60, blood pressure 115/76,
respiratory rate 14, and oxygen saturation 98% on room air. He is 5'2" tall
and weighs 240 pounds. He is alert and in no distress. His HEENT, heart,
lung, abdominal, and neurologic exams are normal.
What is the next step in management of his weight?
1. referral to nutritionist for low fat diet 2.referral to nutritionist for low
carbohydrate diet
3.prescription for Bupropion
4.referral for physical therapy
5.referral to bariatric surgeon for education on gastric bypass procedures
5.referral to bariatric surgeon for
education on gastric bypass procedures
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BMI is calculated as weight in kilograms divided by height in meters squared. Weight in
kilograms is equal to the weight in pounds divided by 2.2. Height in meters is equal to
the height in inches multiplied by 2.54 and then divided by 100.
A 1991 NIH consensus panel recommended consideration of surgical treatment of
obesity for patients who are well-informed and motivated, have an acceptable surgical
risk, have failed to lose weight with previous non-surgical attempts, and have either a
BMI greater than 40 kg/m2 or a BMI greater than 35 kg/m2 and serious comorbidities,
including diabetes, sleep apnea, cardiomyopathy, or joint disease. A 2005 ACP
guideline recommended considering surgical treatment of obesity for patients with BMI
> 40 kg/m2 who have failed to lose weight on medical management and who have
comorbid conditions related to obesity. Meta-analysis concluded that bariatric surgery
results in the loss of 20-30 kg, which is maintained for up to 10 years. Randomized and
observational studies support the superiority of bariatric surgery over diet and exercise
alone in the severely obese. Bupropion is not FDA-approved for weight loss.
Maggard MA, Shugarman LR, Suttorp M, Maglione M, Sugerman HJ, Livingston EH,
Nguyen NT, Li Z, Mojica WA, Hilton L, Rhodes S, Morton SC, Shekelle PG. Metaanalysis: surgical treatment of obesity. Ann Intern Med. 2005 Apr 5;142(7):547-59.
A 19-year-old man with type I diabetes complains of
frequent vivid dreams, nightmares, and headaches on
waking in the morning. He takes 20 units of glargine
at night and uses a carb counting sliding scale of
humalog with meals. He has no known
complications of his diabetes. Which of the
following is most likely to help with his symptoms?
1.conversion to NPH from glargine
2.drinking a caffeine free soda before bedtime
3.conversion to an insulin pump with programmable
basal rates
4.use of continuous positive airway pressure (CPAP)
3.conversion to an insulin pump
with programmable basal rates
• Nocturnal hypoglycemia may present with vivid dreams,
nightmares, daytime somnolence, or morning headaches,
or it may be asymptomatic. Following nocturnal
hypoglycemia, the morning blood sugar may be high due
to either carbohydrate intake to treat the hypoglycemia or
counterregulatory hormones, the Somogyi effect.
• Although eating a snack with complex carbohydrates
and/or proteins makes intuitive sense for prevention of
nocturnal hypoglycemia, studies have been inconsistent.
Simple carbohydrates at bedtime will not provide lasting
protection against hypoglycemia. Long acting basal
insulins, such as glargine, may provide protection from
nocturnal hypoglycemia in some cases.
•