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324 Challenging Concepts in Urological Surgery
https://t.me/med1917
Clinical tip Laboratory
investigations
Laboratory investigations include
the following:
● Semen analysis.
● Microbiology analysis— sexually
transmitted diseases (Chlamydia
trachomatis/ Neisseria
gonorrhoeae), urinary tract
infection (coliforms, Klebsiella,
Pseudomonas), tuberculosis.
● Reproductive hormone levels:
– Follicle- stimulating
hormone (FSH).
– Luteinizing hormone (LH).
– Total testosterone.
– Prolactin.
● Leucocytospermia.
● Genetic screening.
● Sperm DNA damage or
fragmentation (e.g. COMET
test; sperm chromatin structure
assay).
Expert comment
Spermatozoa of infertile men
The spermatozoa of infertile
men show an increased rate
of aneuploidy, structural
chromosomal abnormalities, and
DNA damage, carrying the risk of
passing genetic abnormalities on to
the next generation. Positive testing
will require a formal referral for
genetic counselling and possibly
pre- implantation genetic diagnosis.
Learning point Genetic abnormalities
● Genetic abnormalities, such as numerical and structural chromosomal abnormalities, are found
more frequently in men with unexplained oligozoospermia/ azoospermia. These findings can be as
high as 13.7% in men with non- obstructive azoospermia (NOA) and 4.6% in oligozoospermia.
● A higher frequency of cytogenetic abnormalities and Y chromosome deletions are observed with
increasing severity of testicular dysfunction.
● Klinefelter syndrome (KS) is the most common chromosomal aneuploidy found in
azoospermic men.
● CFTR gene mutations (i.e. cystic fibrosis- associated genes) are the most common finding in
infertile couples. In MFI, it is often associated with congenital vas deferens abnormalities and
obstruction.
● Y- chromosome microdeletions are rarer but confer important diagnostic and prognostic information.
Y- chromosome deletions are inherited and will cause infertility in biological male offspring.
● Structural and numeric chromosomal anomalies can result in spontaneous abortions and multiple
congenital defects in the offspring.
This patient is diagnosed with azoospermia so it is important to perform further
investigations. The endocrinological tests required at this stage are FSH, LH, and testosterone levels. Our patient’s results can be seen in Table 33.4. A comprehensive
understanding of the normal functioning hypothalamic– pituitary– gonadal axis is important when interpreting these results (Figure 33.1).
Learning point Hypogonadism
Differentiating between hypergonadotropic hypogonadism (high FSH/ LH) and hypogonadotropic
hypogonadism (low FSH/ LH) is important.
Primary hypogonadism (aka hypergonadotropic hypogonadism) causes include testicular insufficiency,
disturbed spermatogenesis, KS, cryptorchidism, anorchia, testicular dysgenesis, history of orchitis or
testicular torsion, previous chemo/ radiotherapy, and testicular tumour.
Secondary hypogonadism (aka hypogonadotropic hypogonadism) causes include: hypothalamic- pituitary
dysfunction, Kallmann syndrome, idiopathic, pituitary tumours, anabolic steroid abuse, obesity. Patients
with hypogonadotropic hypogonadism require cranial imaging (computed tomography or magnetic
resonance imaging).
Differentiation can be made between NOA and obstructive azoospermia (OA) by reference to the
serum FSH levels. An elevated FSH level indicates an increased probability of diagnosing NOA.
Our patient suffers from hypergonadotropic hypogonadism, suggesting the primary
pathology lies at the testicular level. He has primary testicular deficiency. Our patient
undergoes a scrotal ultrasound scan which does not reveal any significant pathology
and despite there being no clinical evidence of OA, he also undergoes a screening
transrectal ultrasound scan. This was also normal.
Table 33.4 Serum hormone levels for our patient
Parameter Patient’s results Reference range
FSH 40 1.5– 12.4 IU/ L
LH 18 1– 9 IU/ L
Testosterone 6.8 8– 30 nmol/ L
Hypothalamus
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325Case 33 Male factor infertility: management of the azoospermic patient
Selective oestrogen
receptor modulators
GnRH
GnIH
Anterior pituitary
FSH
Inhibin B
Activin
Testes
Sertoli cells
Figure 33.1 The hypothalamic– pituitary– gonadal axis. Secretion of the anterior pituitary luteinizing
hormone (LH) and follicle- stimulating hormone (FSH) are stimulated by the pulsatile release of
gonadotropin- releasing hormone (GnRH) and inhibited by the release of gonadotropin- inhibiting
hormone (GnIH) from the hypothalamus. Selective oestrogen receptor modulators (SERMs) competitively
inhibit hypothalamic oestrogen receptors, which leads to increased anterior pituitary gonadotropin
release and subsequent endogenous testosterone production. Inhibin B is secreted by the testicular
germinal epithelium (primarily Sertoli cells) in response to FSH and subsequently acts on the anterior
pituitary in a negative- feedback loop, inhibiting FSH production. Activin has an agonistic effect on the
pituitary secretion of FSH and its release is inhibited by inhibin B. Aromatase inhibitors are used to
correct a diminished testosterone:oestrogen ratio.
Reused with permission from Springer Nature. Kathrins M and Niederberger C. Nat Rev Urol. 2016;13(6):309– 23 (Figure 1).
LH
Testosterone
(~60,000 ng/dl)
Oestradiol
Aromatase
inhibitors
Aromatase
Testosterone
(serum ~500 ng/dl)
Leydig cells
Expert comment Hypergonadotropic hypogonadism
In men with testicular deficiency, hypergonadotropic hypogonadism (also called primary
hypogonadism) typically presents with higher levels of FSH and LH. Low testosterone levels may
or may not be observed. FSH levels often negatively correlate with the number of spermatogonia.
326 Challenging Concepts in Urological Surgery
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FSH levels are often elevated with absent or diminished spermatogonia. Occasionally it is possible
to observe normal FSH readings associated with a normal number of spermatogonia but no mature
spermatozoa are identified. This process is termed ‘maturation arrest’ with failure of spermatogenesis
at the spermatocyte/ spermatid level. Importantly, for patients undergoing sperm extraction, FSH
levels do not accurately predict the presence of spermatogenesis, as men with maturation arrest on
histology may have both normal FSH levels and testis volume. Furthermore, men with NOA and
high levels of FSH may still harbour focal areas of spermatogenesis which can be targeted using
microsurgical sperm extraction surgery.
The results of our patient’s genetic screening return 6 weeks after his initial assess-
ment. His chromosome analysis revealed 47,XXY— consistent with KS. Often patients
with this diagnosis are asymptomatic and go unrecognized until they try to conceive.
This is a common cause of NOA with one in eight azoospermic men (cf. 1 in 500
general population) diagnosed with classic meiotic disjunction on genetic testing.
Learning point Sex chromosome abnormalities (KS and variants (47,XXY; 46,XY/ 47,XXY
mosaicism))
KS is the most common sex chromosome abnormality. Adult males with KS often have small but firm
testes, along with features of primary hypogonadism. The overall phenotype of a patient is the final
result of genetic, hormonal, and age- related factors. The phenotype ranges from the characteristics of
a normally virilized male to the stigmata of androgen deficiency. In the majority of KS cases, infertility
and reduced testis volume are the only detectable clinical features.
Men with KS frequently have impaired Leydig cell function. This has a direct impact on testosterone
production, leading to testosterone deficiency when compared to the general population. More
obvious features of hypogonadism are infrequently displayed, along with cardiovascular and
renal problems. Sperm production and the presence of germ cells are variable in males with KS,
being more often observed in mosaicism, 46,XY/ 47,XXY. The production of 24,XY sperm has been
reported in 0.9– 7.0% of men with KS and in up to 25% of men with somatic karyotype 47,XXY. In
patients with azoospermia, open testicular sperm extraction (TESE) or microdissection testicular
sperm extraction (mTESE) are established therapeutic options, with spermatozoa being recovered
in up to 50% of cases. Some data suggest improved outcomes with sperm extraction performed
at a younger age; however, TESE in the peripubertal and prepubertal KS patient is still considered
experimental.
There is limited published information regarding the prevalence of aneuploidies in children of KS
fathers being conceived by intracytoplasmic sperm injection (ICSI) versus the general population.
However, contemporary European guidelines support the role of in- depth counselling regarding
potential genetic abnormalities in any biological offspring. The role of pre- implantation genetic
diagnosis remains unclear. Close follow- up of men with KS is advocated, with androgen replacement
to be considered if levels are found to be hypogonadal. Men with KS are at greater risk of
cardiovascular disease and metabolic syndrome.
The final investigation in the patient pathway is a testicular biopsy. This should
also be considered a therapeutic procedure in nearly all cases, as sperm may be harvested for in vitro fertilization. European Association of Urology guidelines support
the role of testicular biopsy in unexplained NOA. A truly diagnostic testicular biopsy is
reserved for confirmation of patients with OA in patients with normal sized testes and
normal gonadotropin levels.
Learning point Testicular biopsy
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Approximately 50% of men with NOA will have spermatozoa that can be used for ICSI identified
within focally, active testicular tissue. A good correlation exists between histology at biopsy and
the likelihood of finding mature sperm cells at sperm retrieval and ICSI. Currently there is no role
for testicular fine- needle aspirate mapping outside of a research setting. However, the greater the
number of testicular biopsies performed, the higher the chance of a successful retrieval. Microsurgical
techniques allow identification of focal areas of potential spermatogenesis by targeting fuller and
dilated tubules at ×200 magnification. Currently, ICSI outcomes appear to be poorer for patients with
NOA versus OA (live birth rates 19% vs 28%, respectively).
Our patient undergoes a combined procedure for testicular biopsy and sperm harvesting for ICSI. The procedure of choice in this situation is mTESE. This procedure
offers a 50– 54% success rate of harvesting testicular sperm, with reported 61% fertilization rates and a cumulative pregnancy rate of nearly 30% per ICSI cycle. Success
rates in KS are likely to be much lower but published figures suggest that performing
TESE/ mTESE in subjects with KS results in sperm retrieval rates of close to 50%, with
pregnancy rates and live birth rates approaching 50%, with the results being independent of any clinical or biochemical parameters tested.
Our patient went on to have spermatozoa successfully harvested by mTESE but unfortunately the subsequent treatment cycle of ICSI was unsuccessful. Further sperm retrieval and ICSI are planned. Pre- implant genetic diagnosis could be offered, following
appropriate counselling, to this patient to avoid the risk of implanting an embryo with
a known severe genetic disorder that may end in an unsuccessful pregnancy.
Clinical tip Role of adjuvant therapies to improve sperm retrieval in NOA
No randomized controlled trials exist supporting the role of endocrine therapies to potentiate
spermatogenesis in NOA. However, studies evaluating their empirical use appear to demonstrate
improved sperm quality and output. Endogenous FSH and testosterone levels, both of which are
required for spermatogenesis, have been shown to be increased by human chorionic gonadotropin,
human menopausal gonadotropin, and clomiphene citrate. Evidence has shown that these treatments
prior to mTESE increased the sperm in ejaculate, thus obviating the need for surgical sperm retrieval
and a greater likelihood of a successful sperm retrieval in persistently azoospermic men (57% vs 33.6%)
when compared to a control group.
327Case 33 Male factor infertility: management of the azoospermic patient
Expert comment mTESE
Unadjusted sperm retrieval rate
after mTESE are reported to be
52% in a pooled data analysis of
studies comparing conventional
TESE with mTESE. mTESE appears
to offer a 1.5× improvement in
sperm retrieval versus TESE. Salvage
mTESE after failed TESE/ TESA has
also resulted in 46.5% published
successful sperm retrieval rate.
mTESE is associated with a lower
complication rate in relation to
haematoma and fibrosis formation.
Equivalence is observed on
recovery to baseline testosterone
level during long- term follow- up.
Summary
The causes of MFI are varied and in part poorly understood. Our case highlights the optimal assessment of male patients who have been unable to conceive after 12 months
of regular, unprotected intercourse. This case focuses on the implications of genetic abnormalities (specifically KS) but other factors should always be considered, including
testicular insufficiency, hypogonadotropic hypogonadism, anatomical obstructions of
the seminal tract, urogenital infections, ejaculatory dysfunction, and idiopathic male
infertility (30– 40% of MFI cases).
Patients should always be assessed simultaneously alongside their partner in a
dedicated fertility clinic setting as part of a specialist multidisciplinary team approach.
328 Challenging Concepts in Urological Surgery
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Future directions
Men with infertility are vulnerable to being under- investigated and inappropriately counselled
regarding their chances and options for becoming a father. An expanding portfolio of diagnostic
testing is opening the door for men who suffer permanent infertility following chemotherapy,
radiation, and other medical treatments. Currently, sperm freezing is the standard of care method to
preserve male fertility. Testicular tissue freezing is an experimental option to preserve the fertility of
prepubertal boys and others who cannot produce sperm. Testicular tissues contain spermatogonial
stem cells (SCC) and new SCC- based techniques currently in the research pipeline may be available
in the male fertility clinic of the future. Alongside a better understanding of the role of oxidative stress
and improved molecular prognostic biomarkers, these scientific advances will hopefully translate to
better patient selection and novel targeting for innovative therapeutics in the future.
A final word from the expert
MFI affects up to 50% of infertile couples and management is dependent on careful assessment
and understanding of the primary reproductive abnormality. Men with azoospermia represent
approximately 10– 15% of men referred for fertility investigations. Men with OA benefit from
microsurgical reconstruction, endoscopic treatment, or advanced sperm retrieval and ICSI
techniques. Conversely, men with NOA represent a greater diagnostic and therapeutic challenge.
The advent of improved in vitro fertilization methods has allowed a larger proportion of these
men to father their own biological offspring using modern assisted conception procedures
rather than being confined to donor insemination programmes. Multidisciplinary teams
involving a urologist with a specialist MFI interest are strongly recommended.
Further reading
Ashraf CM, Dharmaraj P, Sankalp S, et al. Microdissection testicular sperm extraction (micro-
TESE): results of a large series from India. Andrology. 2014;3:113.
Baazeem A, Belzile E, Ciampi A, et al. Varicocele and male factor infertility treatment: a new
meta- analysis and review of the role of varicocele repair. Eur Urol. 2011;60(4):796– 808.
Corona G, Pizzocaro A, Lanfranco F, et al. Sperm recovery and ICSI outcomes in Klinefelter
syndrome: a systematic review and meta- analysis. Hum Reprod Update. 2017;23(3):265– 275.
De Braekleer M, Ferec C. Mutations in the cystic fibrosis gene in men with congenital bilateral
absence of the vas deferens. Mol Hum Reprod. 1996;2(9):669– 677.
Dohle GR. Inflammatory- associated obstructions of the male reproductive tract. Andrologia.
2003;35(5):321– 324.
Hamdy FC, Eardley I. Section 7. In: Oxford Textbook of Urological Surgery. 1st ed. Oxford:
Oxford University Press; 2017:839– 942.
Hussein A, Ozgok Y, Ross L, Niederberger C. Clomiphene administration for cases of non-
obstructive azoospermia: a multicenter study. J Androl. 2005;26(6):787– 791.
Junwirth A, Diemer T, Kopa Z, Krausz C, Minhas S, Tournaye H. European Association of
Urology guidelines on male infertility. European Association of Urology. 2019. https://
uroweb.org/ wp- content/ uploads/ EAU- Guidelines- on- Male- Infertility- 2019.pdf
Lamfranco F, Kamischke A, Zitzmann M, et al. Klinefelter’s syndrome. Lancet
2004;364(9430):273– 283.
Nieschlag E, Behre HM, Nieschlag S, eds. Andrology: Male Reproductive Health and
Dysfunction. Berlin: Springer Verlag; 2010.
Pierik FH, Dohle GR, van Muiswinkel JM, Vreeburg JT, Weber RFA. Is routine scrotal ultra-
sound in infertile men advantageous? J Urol. 1999;162(5):1618– 1620.
Rowe, T. Fertility and a woman’s age. J Reprod Med. 2006;51:157.
https://t.me/med1917
van Assche E, Bonduelle M, Tournaye H, et al. Cytogenetics of infertile men. Hum Reprod.
1996;11(Suppl 4):1– 24.
World Health Organization. WHO Laboratory Manual for the Examination of Human Semen and
Sperm- Cervical Mucus Interaction. 5th ed. Cambridge: Cambridge University Press; 2010.
World Health Organization. WHO Manual for the Standardized Investigation and Diagnosis of
the Infertile Couple. Cambridge: Cambridge University Press; 2000.
Weidner W, Krause W, Ludwig M. Relevance of male accessory gland infection for subsequent
fertility with special focus on prostatitis. Hum Reprod Update. 1999;5(5):421– 432.
329Case 33 Male factor infertility: management of the azoospermic patient
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34
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CASE
Erectile dysfunction
James Tracey and Majid Shabbir
Expert commentary Majid Shabbir
Case history
A 46- year- old male was referred for a 6- month history of erectile dysfunction (ED).
His primary issue is maintaining a firm erection long enough for sexual intercourse.
Previously, erections were satisfactory. He has a stable, supportive partner but now
lacks confidence and is avoiding intercourse. He does not have morning erections anymore, has smoked daily since the age of 18 years, and has a family history of coronary
artery disease (CAD).
Clinical tip History
● The goal in the history is to discover the 4 Cs: Causes, Comorbidities, Complicating factors, and
Contraindications to treatment.
● Identifying potential causes helps determine if the ED is psychogenic, organic, or mixed. Ask about
duration of onset, situational ED, morning or night erections, genital trauma, penile curvature, and
priapism events.
● Important comorbidities include CAD, hypertension, hyperlipidaemia, diabetes, peripheral vascular
disease, prostate diseases, pelvic floor pain, pelvic surgery, psychiatric health, and smoking. It is
important to ask about medications and, specifically, recreational drug use as the patient rarely
offers this information without prompting.
● Complicating factors include lack of desire, premature or anejaculation, anorgasmia, pain with
intercourse, sexual orientation issues, psychosocial stresses, partner age, and health. All may lead
to significant changes in sexual function that can cause or contribute to ED and should be clearly
defined to obtain the best result from treatment. Including partners in the consultation can impact
decisions in up to 58% of cases.
● Contraindications can include use of oral nitrates or alpha blockers and fitness for intercourse.
5
The patient’s ED is not situational. He has no penile curvature or history of pri-
apism. He denies any lower urinary tract symptoms (LUTS), pelvic discomfort, or any
past medical history. He takes no medications and does not use recreational drugs.
He has never had concerns of a lack of desire, ejaculation, orgasm, or pain with
intercourse. He has minimal stress but leads a sedentary lifestyle. He can walk up
two flights of stairs briskly; his partner is 39 years old and healthy. On examination
he has normal external genitalia, a small, non- tender prostate and palpable lower extremity pulses. His blood pressure is 128/ 84 mmHg. His body mass index (BMI) is 32
kg/ m2. His sexual health index for men score is 17/ 25. Initial testing sent includes a
urinalysis, full blood count, basic metabolic panel, morning total testosterone, fasting
blood glucose, glycated haemoglobin (HbA1c), and lipid profile. All testing returned
Learning point
Epidemiology of ED
● ED prevalence is as high as 52%
in men 40– 70 years old with
10% exhibiting severe ED.
● ED increases progressively after
the age of 40 years.
● The degree of bother is
inversely related to age.
● The rate of progression,
remission, and stability is near
equivalent.
4
1
2
3
332 Challenging Concepts in Urological Surgery
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within normal limits except an elevated glucose and HbA1c of 75 mmol/ mol indicating
a type 2 diabetes mellitus (DM) diagnosis.
Expert comment Metabolic equivalents of the task
Intercourse is equivalent to mild to moderate non- sexual activity or 3– 4 metabolic equivalents
of the task (METS) at orgasm. This is equivalent to walking 1 mile on level ground in 20 minutes,
briskly climbing two flights of steps in 10 seconds, or being able to golf (4– 5 METs). However, this
generalization does not cover all situations as intercourse in the older, the less fit, an extramarital
setting with an unfamiliar person and location, or after excessive alcohol intake may raise the METS
Evidence base Risk factors
that predict ED
The risk factors that predict ED are
shown in Table 34.1.
are displayed with diabetes being
the prominent risk factor.
7– 9
Odd ratios
Table 34.1 Risk factors for ED
Risk factor Odds
ratio
Diabetes mellitus
4.1
(DM)
Prostate disease 2.9
Peripheral vascular
2.6
disease
Cardiac disease 1.8
Hyperlipidaemia 1.7
Hypertension (HTN) 1.6
Major depressive
1.7
disorder
Smoking 1.5
Expert comment Intercourse
and risk of MI
There is a >2 relative risk of
non- fatal MI in the 2 hours after
intercourse, with an absolute risk of
roughly 20 events per million.
17
requirement. Completing 4 minutes on a standard treadmill stress test without concerns is more
indicative of a safe level (5– 6 METS).
Learning point ED and CAD risk
● ED occurs in up to 71% of DM.
● CAD and ED are both commonly caused by endothelial dysfunction.
● ED is an independent risk factor and early marker for the development of CAD with a lead-
time of 2– 5 years prior to a coronary event. This has been established across continents and held
true over time.
11– 13
It is imperative to assess a new ED patient’s cardiac risk.
● Both the Princeton Consensus Panel and UK Guidelines identify three risk levels:
1. Low- risk patients can be cleared for treatment and include asymptomatic CAD and fewer
than three risk factors (excluding sex) of CAD. Risk factors are controlled HTN, DM, smoking,
hyperlipidaemia, sedentary lifestyle, family history or early CAD, mild, stable angina, previous
revascularization, uncomplicated past myocardial infarction (MI), mild valvular disease, or chronic heart
failure New York Heart Association (CHF NYHA) class I/ left ventricular dysfunction.
2. Intermediate risk requires further evaluation with a stress test prior to treatment to reclassify
as high or low risk.
3. High- risk patients should not receive treatment for ED and include unstable/ refractory angina,
uncontrolled HTN, CHF NYHA class III/ IV, MI or cerebrovascular accident within 2 weeks, high- risk
arrhythmias, hypertrophic obstructive cardiomyopathy, and moderate– severe valve disease.
With his new diagnosis of ED and diabetes, he has more than three risk factors for
CAD (DM, family history of CAD, smoking, sedentary lifestyle) and so is classified as
‘intermediate’ risk. He was referred for a stress test which reclassified him as low risk.
He was started on metformin, an exercise and weight loss regimen, and a smoking
cessation programme. Evidence has shown modification of lifestyle risk factors can
improve sexual function.18 He was offered sildenafil and sexual health counselling.
He declined the latter. At 3- month follow- up he did not feel the sildenafil was helping
enough and was experiencing mild gastric reflux and flushing during use.
6
10
14– 16
Learning point Physiology of erections
Erection begins with sexual stimulation (thoughts or physical contact) causing the parasympathetic
nervous system to release nitric oxide (NO) from sinusoidal endothelium. NO causes the activation
of guanylyl cyclase, thus converting guanosine triphosphate guanosine triphosphate (GTP) to cyclic
guanosine monophosphate (cGMP) in smooth muscle cells. cGMP accumulation activates K+ and Ca
channels causing a decrease in intracellular calcium thereby allowing smooth muscle fibres to relax.
The helicine arteries then dilate increasing blood flow to the corpus cavernosa. Phosphodiesterase
type 5 (PDE5) breaks down cGMP (into 5′- GMP) and inhibitors (PDE5is) of this enzyme bolster
erections by blocking cGMP degradation. The first PDE5i was sildenafil citrate, which was originally
synthesized in England, and while studied for hypertension and angina was found to have extensive
erectogenic properties.
19
2+
Learning point Comparison of PDE5is
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See Table 34.2.
● There are no randomized- controlled trials comparing the efficacy of PDE5i directly. However, rates
of successful erections were relatively similar for each when compared to placebo.
● PDE5i are affected by meals (fatty) with tadalafil being minimally affected.
● All are contraindicated with organic nitrates for 24 hours except tadalafil for 48 hours.
20,21
● Vardenafil is contraindicated with alpha blockers, the remaining can be administered with caution
with a 6- hour window of separation recommended.
● All have side effects of facial flushing (4– 12%), nasal congestion (1– 10%), headache (13– 16%), and
dyspepsia (4– 12%).
22– 24
Table 34.2 Comparison of PDE5 inhibitors
333Case 34 Erectile dysfunction
Drug Dosage Half- life
(T
)
1/ 2
Peak plasma
conc.
Cross- reactivity Side effects
Sildenafil 25– 100 mg 4 h 60 min PDE6 Blue- green visual change
Vardenafil 5– 20 mg 4 h 60 min PDE6 Visual changes and QT
prolongation
Tadalafil 10– 20 mg on
17.5 h 120 min PDE11 Muscle aches
demand or
2.5– 5 mg daily
Avanafil 50– 200 mg 5 h 30 min Limited PDE6 Visual change
Clinical tip How to assess for sildenafil failure
● Ask what dose was tried, how it was taken, was there sexual stimulation after, did they have side
effects, and how many attempts were tried?
● Sildenafil dosages are 25– 100 mg. Only two of three patients met success in completing intercourse
on the starting dose.
22
● It should be taken on an empty stomach. High- fat meals cause a reduction in plasma concentration
while alcohol delays gastric emptying and absorption. If food or alcohol has been had, the patient
should wait 2– 3 hours before taking the dose.
● PDE5is require sexual stimulation to have an effect.
● On average, it can take up to six attempts to get everything right.
● Prior to second- line therapy being initiated, one should determine whether the trial was adequate,
re- educate, and ensure dose titration was performed.
● Consider switching to a different PDE5i if side effects are an issue, a partial response is obtained, or
one medication offers a lifestyle advantage over another.
The patient was taking the 100 mg dose but usually just after a meal with wine.
Otherwise, he had appropriate sexual stimulation within 1– 4 hours and tried the medication several times. He was re- educated but due to side effects was switched to tadalafil.
Learning point Use of PDE5Is
● PDE5is are not associated with MI, stroke, or mortality in patients with stable angina, CAD, HTN,
DM, or heart failure.
● Though more common, side effects cause discontinuation in <5% of patients.
● There is little to no harm in starting at the highest dose and decreasing if need be.
● PDE5is have been shown to increase not only penile rigidity but improve orgasmic function, patient
and partner satisfaction, quality of life, and even depressive symptoms.
● Given the ease of use they should be offered as first- line therapy.
25
26
27,28
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