Module 3

Question 1

Erectile dysfunction -“The inability to attain or sustain an erection adequate for sexual stimulation”:

Answer 1

Can be the result of age related changes (e.g.
diminished testosterone, altered response to NO, etc), comorbidities (e.g. DM,
BPH, depression, etc .. Table 51-1), and medications (e.g. 5-alpha reductase
inhibitors, beta-blockers, TCAs, etc. .. Table 51-2)

Question 2

Before initiating treatment for ED:

Answer 2

a physical examination and thorough
medical, social, and medication histories with emphasis on cardiac disease must
be taken to assess for ability to safely perform sexual activity and to assess for
possible drug interactions
Diagnosis should include PE (including a check for signs of hypogonadism),
medication review, Hx, and labs ( HbA1C, PSA, FLP, testosterone)

Question 3

ED treatment should include:

Answer 3

Non-pharmacological interventions
Reduce fat and cholesterol in diet
Decrease or limit alcohol consumption
Eliminate tobacco use and substance abuse
Weight loss if appropriate
Regular exercise
Co-morbidity (DM, HTN, etc.) management - including (if possible) removal of
causal medications

Question 4

In general, If a medication is removed, consider that it probably will have to be
replaced with a reasonable alternative:

Answer 4

Examples:
SSRIs are a potential cause of ED. A reasonable replacement might be bupropion
(assuming no contraindications)
Dutasteride (for BPH) is a common cause of ED. Tardenafil as a replacement for
or in combination with a 5-alpha reductase might be reasonable

Question 5

PDE5Is - Often considered drug of choice when pharmacotherapy is
necessary. There is no convincing evidence that one agent in this class
is superior to another. Choice may be based on patient preference, cost,
and formularies:

Answer 5

There is no drug effect without some type of sexual stimulation
because these drugs do not cause penile erections; they only provide the ability of
the penis to respond to sexual stimulation.
Varying duration of action (most 4-5 h, tadalafil 36h).
Headache and flushing most common ADRs. Serious cardiac events possible

Question 6

Significant DIs exist with some ED meds that are a safety alert

Answer 6

nitrates - severe hypotension
In an emergent situation,
a patient who has taken sildenafil may be given a nitrate after 24 hours; for tadalafil,
after 48 hours.
Vardenafil does not have a suggested time interval, but blood pressure and heart
rate did not change when the drug was taken 24 hours before nitrate administration.
These suggested intervals are a direct correlation to half-life and duration of action
Prolonging of QT interval
Serious cardiovascular events have been associated with PDE5 inhibitors; therefore, they should not be used in patients in whom sexual intercourse is inadvisable
because of poor cardiac status.

Question 7

Testosterone replacement (Low-T):

Answer 7

Testosterone replacement regimens
should never be administered to men with normal serum testosterone levels, or
in patients with isolated erectile dysfunction as the only sign of hypogonadism.
Before initiating any testosterone replacement regimen in patients 40 years and
older, patients should be screened for breast cancer, benign prostatic hyperplasia,
and prostate cancer. All are testosterone-dependent conditions and theoretically
could be worsened by exogenous administration of testosterone

Question 8

Alprostadil - PgE1 analog administered by intracavernosal injection &
intraurethral inserts:

Answer 8

Because PGs bypass many steps in the erectile cascade,
they are quite effective at producing an erection, even in cases where PDE5 inhibitors cannot do so.
Most invasive and low patient acceptance. Reserved as second or third line alternatives

Question 9

BPH:

Answer 9

BPH increases urethral resistance, resulting in compensatory changes
in bladder function. Obstruction-induced changes in detrusor function, including
smooth muscle hypertrophy, compounded by age-related changes in the functioning of the bladder, lead to urinary frequency, urgency, and nocturia, the most
bothersome BPH-related complaints. Not all patients with LUTS have BPH and not
all men with BPH have LUTS.

Question 10

BPH diagnosis:

Answer 10

Diagnosis includes components such as symptom assessment (AUA score), PE and PSA
PSA is present in small quantities in the serum of men with healthy prostates, but
is often elevated in the presence of prostate cancer or other prostate disorders.
PSA is not uniquely an indicator of prostate cancer, but may also detect prostatitis
or BPH. PSA correlates with prostate size and can be used as a prognostic marker

Question 11

Non-pharmacologic interventions for BPH:

Answer 11

Lifestyle modification - limiting
EToH, caffeine, avoid certain medications (Table 52-4)(e.g. decongestants, androgens, etc) as well as addressing co-morbidities (weight loss, etc)
Watchful waiting is the most conservative approach for patients with mild symptoms or those with moderate symptoms without bother.
Appropriate option for patients with mild symptoms (AUA-SI score d 7), and for manywith moderate to severe symptoms (AUA-SI e 8) if they are not bothered
Behavior modification includes restricting fluids close to bedtime, minimizing caffeine, sweetened drinks and alcohol intake, frequent emptying of the bladder during
waking hours (to avoid overflow incontinence and urgency), and avoiding drugs
that could exacerbate voiding symptoms (e.g. antihistamines, decongestants).
At each visit, assess the patient’s risk of developing acute urinary retention by
evaluating the patient’s prostate size or using PSA as a surrogate marker of
prostate enlargement
The level of symptom distress that individual men are able to tolerate is variable

Question 12

Alpha-blockers:

Answer 12

fairly rapid onset (2-4 weeks) with relatively rapid symptom
resolution , durable effect (years) with AUA symptom index (AUASI) improving
30-45%. No effect on prostate size (PSA) or disease progression.
Relax smooth muscle in bladder neck, urethra & prostate(Blue dots indicate the
distribution of alpha receptors surrounding the bladder and prostate). It is clear
why these agents would provide rapid relief of symptoms
New second generation (alfuzosin) and third generation (tamsulosin and silodosin) agents are preferred because of uroselectivity, no need for dose titration and limited
orthostasis

Question 13

Alpha-blockers:

Answer 13

Older agents also have an indication for hypertension and
have more CV ADRs (e.g. orthostasis, reflex tachycardia, etc).
e.g. terazosin. doxazosin
dose titration should follow the “start low, go slow” paradigm
Most guidelines advocate for the individual management of BPH and hypertension
Note that the ACC / AHA recommends that that for those with the comorbidities of
hypertension and BPH, each of those conditions should be treated independently
based on GDMT. For those with persistent HTN on maximized first line therapies,
alpha-blockers with vascular effects may provide benefit in terms of additional BP
lowering

Question 14

5 alpha reductase inhibitors:

Answer 14

Management of moderate to severe BPH in
patients with enlarged prostate glands.
Management of patients who desire medical therapy but cannot tolerate alpha-1-adrenergic antagonists and do not have predominately irritant symptoms or
concomitant erectile dysfunction (Symptoms are non-bothersome, so the delay in
onset would not interfere with Qol)
Reduce prostate size (and PSA) and thus outlet obstruction
Reverse / Slow disease progression
Decrease the risk of disease complications
Note: although dutasteride blocks both the Type I and Type II iso-enzymes of
5-alpha reductase while finasteride only blocks Type II, there is not a clinically
significant difference in outcomes when either is used
Peak effect 6-12 months, effect is only durable as long as drug is continued
(prostate will return to pre-treatment size (or larger) when / if 5ARIs are stopped
Finasteride & Dutasteride reduces, but does not stop the prostate from producing
PSA
If PSA fails to decline by 50% after 6-12 months or an increase of 0.3 ng/L or more
above the baseline nadir level, patient should be evaluated for prostate cancer.
May also indicate worsening condition or non-compliance with 5 a-reductase inhibitors

Question 15

PDE5Is (tadalafil):

Answer 15

Treatment of the signs and symptoms of benign prostatic
hyperplasia +/- ED
Relaxes smooth muscle of urethra, prostate and bladder neck
Tadalafil may be prescribed alone, or along with an ±1-adrenergic antagonist and/or
5±-reductase inhibitor. Although other phosphodiesterase type 5 inhibitors share the same mechanism of action as tadalafil and can improve the AUA Symptom
Score, tadalafil (which is the only PDE5I approved by the FDA for this indication)
is preferred because of its longer plasma half-life, which is theoretically beneficial
in the management of BPH, a chronic disease.
Comparable efficacy to alpha-blockers for LUTS, but does not increase flow rate
or reduce PVR
Peak onset 1-4 weeks

Question 16

Tadalafil adverse reactions:

Answer 16

Use with alpha-blockers, antihypertensives or
substantial amounts of alcohol may lead to hypotension
headache, dizziness, flushing, back pain, myalgia, and cyanopsia
Precautions: Unstable angina, uncontrolled or high-risk arrhythmias, persistent hypotension,
poorly controlled hypertension, or New York Heart Association Classification IV
congestive heart failure
Contraindication: Current use of nitrates

Question 17

BPH combination therapy:

Answer 17

alpha-blocker and anticholinergic (or ²3 agonist)
For men with low post-void residual urine volumes and irritative symptoms (e.g.,
frequency, urgency) that persist during treatment with an alpha-adrenergic antagonist, combination treatment with an anticholinergic agent can be tried
Improved storage voiding parameters and frequency compared with alpha-1-adrenergic antagonist therapy alone
For patients who poorly tolerate anticholinergic adverse effects, an alternative is
Mirabegron
The risk of side effects, increased post-void residual urine volume, decreased
maximal urinary flow rate, or acute urinary retention is low a-blocker and PDE-5Is.

For men with moderate symptoms of BPH and erectile dysfunction, treatment with
daily tadalafil (5 mg/day) alone or in combination with tamsulosin (0.4 mg/day) can
be considered
Addition of PDE-5Is to alpha blockers may improve lower urinary tract symptoms
PDE-5i and 5a-RIs
Addition of PDE-5i to 5a-RIs can offset erectile dysfunction commonly seen with
5a-RIs

Question 18

BPH combination therapy:

Answer 18

Alpha-blocker offer immediate relief; 5 alpha-RIs
reduce prostate enlargement over time In patients with an enlarged prostate gland and an elevated PSA e1.4 ng/mL,
combination drug therapy with an ±1-adrenergic antagonist and a 5±-reductase
inhibitor is more beneficial than single drug therapy. Rationale
a-blocker offer immediate relief
5a-RIs reduce prostate enlargement
Works better for those with obstructive symptoms
May consider stopping a-blocker after 6-12 months, but should continue in those
patients with severe symptoms as long as they are responding

Question 19

Red Flag medications in pregnancy
Commonly used / teratogenic:

Answer 19

Warfarin, Phenytoin, Valproic Acid, Carbamazepine, Lithium, ACE inhibitors/ARBs, Thalidomide, Ethanol, statins

Considerations must be given to not only those who ARE pregnant, but all women
of child bearing years where pregnancy is possible (planned or un-planned)

Question 20

Combined Oral Contraceptives:

Answer 20

Risks can include, but not limited to cancers,
CV events/HTN, VTE, drug interactions
Concomitant use of broad spectrum antibiotics and combination contraceptives
may result in decreased contraceptive efficacy; however this is Category 1 under US MEC

If a typical failure rate of 1% to 3% is a concern for the patient, consider additional
or alternative forms of birth control
Concomitant use of P450 enzyme inducers (rifampin, phenytoin, carbamazepine,
phenobarbital) may result in decreased contraceptive efficacy
If use COC - use higher doses (at least 35 mcg EE) + high progestin, shorten
hormone free interval to 4 days or less
Avoid low progestin - the patch, POP
Consider additional or alternative forms of birth control
Concomitant use of Anti-HIV protease inhibitors can either increase or decrease
serum levels of estrogens and progestins - may need backup method

Question 21

Managing hormone concerns:

Answer 21

Estrogen
Excess - N/V, cervical mucorrhea, hypertension, headache, breast tenderness,
edema, melasma, bloating
Deficiency - Early or mid-cycle breakthrough bleeding, increased spotting, hypomenorrhea, vasomotor symptoms
Progestin
Excess - breast tenderness, headache, fatigue, changes in mood
Deficiency - Late break through bleeding, hypermenorrhea, dysmenorrhea
Androgen
Excess - increased appetite, weight gain, acne, oily skin, hirsutism, decreased
libido, increased breast size, breast tenderness, increased LDL, decreased HDL
Amenorrhea - rule out other causes. Can increase to more estrogenic formulation
or to triphasic formulation to decrease amenorrhea. Not a concern if patient is
happy.
Acne/ oily skin/ hirsutism - Rule out other causes. Switch to less androgenic formulation of progestin (or decrease progestin content)3rd generation Desogestrel,
norgestimate4th generation drospirenone
Dienogest

Question 22

More about managing hormone concerns:

Answer 22

GI- typically resolves in 1-3 months. Decrease
estrogen component will help with nausea. Decrease progestin component to help
with bloating and constipation
Bleeding /spotting - Common (30-50%) when first initiated. Often resolves by 3rd
or 4th cycle
Other manipulations of estrogen and progestin depend at the point of the cycle
bleeding / spotting occurs
First rule out other causes including medications (eg. Medications that increase
metabolism)If spotting or bleeding before completing active pills (late cycle
(days10-21)) - increase progestin to enhance endometrial support
Monophasic with higher progestin or triphasic with progestin
If spotting after withdrawal bleeding (early cycle (days 1-9))- increase estrogen
or decrease progestin in the early pills(triphasic)If mid-cycle spotting/bleeding -
increase both estrogen/progestin midcycle
Headaches - If headaches start or worsen after starting OC, need to rule out other
causes (take BP, ask about headache, any focal neurologic symptoms)If related
to OC use and are not serious - Discontinue OC, Lower estrogen dose, Lower progestin, Eliminate pill free interval (only if HA occur during pill free interval)
Decreased Libido
Ask about depression
If due to decrease in vaginal lubrication, switch to vaginal ring contraception
Increase estrogen
Hypertension - COCs can cause small increases (i.e., 6 to 8 mm Hg) in blood
pressure, regardless of estrogen dosage
Low -dose COCs is acceptable in women younger than 35 years with well-controlled and frequently monitored hypertension
Discontinuing the COC usually restores blood pressure to pretreatment values
within 3 to 6 months
VTE / Thromboembolism
Estrogens - increase hepatic production of factor VII, factor X, and fibrinogen in the
coagulation cascade, therefore increasing the risk of thromboembolic events
Progestins
Newer 3rd and 4th generation progestins - greater effect on procoagulant, anticoagulant, and fibrinolytic pathways
Increased resistance to the anticoagulant effect of activated protein C by some
progestins
Higher levels of sex hormone binding globulin
For women who are at an increased risk of thromboembolism - Consider low-dose oral estrogen contraceptives containing older progestins or Progestin only pills

Question 23

Progestin Only oral contraceptives:

Answer 23

Indicated in Breastfeeding (post-partum phase), older women, women who cannot take estrogen
The failure rate is higher than other progestin-only methods or COCs
Effectiveness is lowered when taken as little as a few hours late

Question 24

DM I/II/GDM in pregnancy:

Answer 24

TreatmentADA diet
Insulin - drug of choice
Regular insulin or NPH
Insulin lispro (Humalog)
Insulin aspart (Novolog) Insulin requirements will increase beginning around 28weeks gestation and continue to increase due to placental hormones
Increasing data on safety of insulin glargine in pregnancy
Oral agents (metformin / glyburide) 2nd line. Reasonable alternative for women
who decline to take, or are unable to comply with, insulin therapy.

Question 25

HTN in pregnancy:

Answer 25

HTN
when SBP reaches 160 or DBP reaches 110
Continue treatment when multiple hypertensive’s were required before pregnancy
or when end organ damage is present
methyldopa / labatolol / nifedipine ER 1st line is first line therapy

Question 26

Hypothyroidism in pregnancy:

Answer 26

hypothyroidism
Levothyroxine - goal is to
attain normal thyrotropin concentrations

Women who received thyroid replacement prior to pregnancy can expect an
increased dosage requirement of 25-50% during pregnancy

Question 27

Depression in pregnancy:

Answer 27

Pregnant patients with severe unipolar major depression who were successfully
treated with antidepressants prior to pregnancy should generally receive the same
drug during pregnancy. For patients who have not been treated with antidepressants in the past, we suggest selective serotonin reuptake inhibitors (SSRIs) as
initial treatment, rather than other antidepressants
No psychotropic drugs with labeling approved by the FDA for use during pregnancy
and lactation
1st line - psychotherapy, but not always an option
SSRI’s
Avoid paroxetine (D) during first trimester
CV malformations
Fluoxetine (C) citalopram (C) sertraline (C) –>Literature is reassuring, best data
for use during pregnancy
Risk of PPHTN after 20 weeks gestation with SSRI’s
Risk of neonatal withdrawal or adaptation syndrome1
d/c 2 weeks before term

TCA’s
Literature is reassuring
Possible withdrawal symptoms

Atypical antidepressants
Limited data

Question 28

Menopause nonpharmacological interventions:

Answer 28

Goals - Alleviate or reduce symptoms, Improve QOL, Minimize ADRs
Non-pharmacological interventions - avoid vasomotor triggers (hot beverage, spicy
food, EToh, etc), exercise, water based lubricants

Question 29

Pharmacotherapy menopause:

Answer 29

Pharmacotherapy - hormone therapy remains the most effective treatment for vasomotor symptoms and vulvovaginal
atrophy, especially in women with moderate to severe symptoms, provided there
is not CHD, significant CHD risk factors or history of breast cancer

Question 30

Oral Estrogens:

Answer 30

FDA approved for moderate to severe vasomotor symptoms,
vulvovaginal atrophy and prevention of post-menopausal osteoporosis.
Note, oral estrogens should NOT be used for osteoporosis prevention in the absence of vasomotor symptoms of menopause or for patients with local symptoms
ONLY
The HOPE trial demonstrated low dose provided equivalent efficacy relief as
standard doses

Question 31

Oral progestins:

Answer 31

Used in women with an intact uterus to reduce endometrial
hyperplasia and endometrial cancer with estrogen monotherapy.
Must be taken minimum of 12-14 days/month
NOT necessary s/p hysterectomy .. so check surgical history

Question 32

Length of menopause pharmacological therapy:

Answer 32

: Length of therapy - The
benefit to risk ratio appears to be best if HT is started close to the time of
menopause. Typically can stop 2-3 years after starting. Longer durations may be
associated with CHD, stroke, VTE, various cancers etc.
Can abruptly stop hormone therapy or can taper. No evidence that tapering of HRT
reduces the recurrence of hot flushes compared with sudden discontinuation1 out
of every 4 will need to be re-initiated due to bothersome vasomotor symptoms
Strong consideration for tapering in those on higher doses of estrogen or long
duration.
Tapering options
Dose taper - Progressively decrease dose of estrogen
May require 3-6 months in some women
Do not decrease again until symptoms are tolerable and improve
Day taper
Decrease the number of days per week HRT is taken
Do not decrease again until symptoms are tolerable and improve
Combination of dose and day tapering
Note- progesterone is not tapered, only the estrogen component is. Progesterone
is stopped at the end of the taper when completely stopping HRT

Question 33

Vulvovaginal complications during menopause:

Answer 33

symtoms can range from vaginal
dryness to atrophy , dyspareunia (painful coitus) and lower urinary tract symptoms
(urge incontinence / OAB)
Local or systemic estrogen therapy for symptom relief
Estrogen can help to restore thickness, elasticity, and lubrication
Estrogen can help reduce the risk of recurrent urinary tract infections
In the absence of vasomotor symptoms, local/ topical (vaginal) estrogen therapy
should be used. There is minimal systemic absorption (with exceptions) and does
not require the concomitant administration of a progestin