Wilhelm ED and Hypogonadism

Which chronic conditions are associated with ED?

lifestyle factors?

Hypertension, vascular disease, dyslipidemia, diabetes, endocrine, neurologic, renal, and liver disease.

Smoking, excessive alcohol, obesity, poor health, and reduced physical activity.

What are the two major erectile tissue components?

Corpus spongiosum and two corpora cavernosa.

What autonomic changes occur with sexual stimulation?

Sympathetic activity decreases and parasympathetic activity increases.

What is the NO cascade during an erection, and what does PDE5 do?

Sexual stimulation → NO release → ↑ cGMP → smooth muscle relaxation → ↑ penile blood flow.

PDE5 breaks down cGMP, causing detumescence (return to a flaccid penis)

What determines erection duration during the erectile process?

Reduced venous outflow from compression of subtunical venules.

What is testosterone's main role in erectile function?

Does normal or low testosterone strongly indicate ED?

It mainly affects libido and triggers the NO cascade.

No. It is not a strong indicator of ED.

What are the three ED classifications?

1) Organic: abnormalities in the vascular, hormonal, neurologic systems, or medication-induced.

2) Psychogenic: performance anxiety, relationship strain, low arousability, depression, and schizophrenia.

3) Mixed

Which drugs are major causes of ED?

Beta blockers (decreased perfusion)

Thiazides (decreased perfusion)

Finasteride/dutasteride (5α-reductase inhibitors)

SSRIs/SNRIs (decreased sexual arousal)

Opioids

Spironolactone (antiandrogen)

Why can ED be an early cardiovascular warning sign?

ED and cardiovascular disease share endothelial dysfunction and vascular risk factors.

Why are patients with diabetes at increased risk for ED?

Because of associated vascular disease and neuropathy.

What is an example of an intermediate-risk cardiovascular feature?

high-risk cardiovascular feature?

Recent MI within 2-8 weeks.

Recent MI within less than 2 weeks.

What should cardiovascular low-risk patients do before starting ED therapy?

intermediate-risk patients?

high-risk patients?

They can start ED therapy without further cardiovascular testing.

Complete an exercise stress test.

Defer sexual activity until cardiovascular risks are stabilized or controlled.

What is a vacuum erection device (VED)?

How long should the band be left in place at most?

Negative pressure draws blood into the penis and a constriction band reduces venous outflow.

No more than 30 minutes at a time.

How do PDE5 inhibitors work?

Can they initiate an erection without sexual stimulation?

They prevent cGMP breakdown and maintain erection longer. They are a first-line therapy.

No. Sexual stimulation is required to activate the NO/cGMP pathway.

What are the 4 PDE5 inhibitors and a key point for each?

Avanafil = fastest onset

Sildenafil = visual effects

Tadalafil = longest duration

Vardenafil = can cause QT prolongation

PDE5 inhibitor adverse effects?

What cardiovascular events within 6 months contraindicate PDE5 inhibitors?

What resting BP contraindicates PDE5 inhibitors?

Headache, flushing, nasal congestion, dizziness, dyspepsia, myalgia, priapism (erection lasting longer than four hours), and visual effects (nonselective PDE6 inhibition → altered retinal cGMP)

MI, stroke, or life-threatening arrhythmia.

Less than 90/50 mmHg.

Which drug class is absolutely contraindicated with PDE5 inhibitors?

Nitrates.

Which selective alpha-1 blockers can be used with PDE5 inhibitors?

What should be done when taking nonselective alpha-1 blockers (terazosin, doxazosin) and PDE5 inhibitors?

Alfuzosin, silodosin, and tamsulosin.

Use the lowest alpha-1 blocker dose and separate doses by 4-6 hours.

How many PDE5 inhibitor attempts should be tried before considering treatment failure?

About 6-8 attempts.

What is alprostadil injection?

What is MUSE?

A prostaglandin E1 that increases cAMP and relaxes cavernous smooth muscle. It is a second-line therapy because it is more invasive.

An intraurethral alprostadil insert.

What is combination ED therapy?

PDE5 inhibitor with VED and/or alprostadil.

What are at-home measures mentioned for priapism?

Attempt ejaculation; if unsuccessful, pseudoephedrine and an ice pack.

Which PDE5 inhibitor has an onset around 36 hours?

Which have onset around 60 minutes?

onset around 15 minutes?

Tadalafil.

Sildenafil and vardenafil.

Avanafil.

Which PDE5 inhibitor can prolong the QT interval?

Vardenafil.

What is the Hypothalamic-Pituitary-Gonadal axis pathway in males?

Hypothalamus

→ GnRH →

Anterior pituitary

→ LH + FSH

LH → Leydig cells → Testosterone

FSH → Sertoli cells → Spermatogenesis + inhibin B

What provides negative feedback on GnRH?

What provides negative feedback on FSH?

Testosterone.

Inhibin B.

What enzyme converts testosterone to DHT (dihydrotestosterone)?

What is the role of DHT?

5α-reductase.

DHT = stronger androgen → prostate function + male pattern baldness

What enzyme converts testosterone to estradiol?

What is the role of estradiol?

Aromatase.

Estradiol is important for: Bone density, Sexual function/libido, Brain function

Which testosterone fractions are bioavailable?

What testosterone fraction is not bioavailable?

Why does it matter clinically?

Unbound and albumin-bound testosterone.

Testosterone bound to SHBG (Steroid Hormone Binding Globulin)

Helps interpret testosterone levels when SHBG varies.

What is hypogonadism?

primary hypogonadism?

secondary hypogonadism?

late-onset/functional hypogonadism?

A decrease in sperm production, testosterone production, or both.

Disease of the testes.

Disease of the hypothalamus or pituitary.

Reduced free testosterone from increased SHBG.

What is the typical lab pattern in primary hypogonadism?

secondary hypogonadism?

Low testosterone, low sperm count, high LH, and high FSH (high because only the testes are the problem, not the brain)

Low testosterone, low sperm count, and low or normal LH/FSH. (all low because the brain causes downstream effects)

What genetic condition can cause primary hypogonadism?

Klinefelter syndrome (XXY)

What medications can cause secondary hypogonadism?

All can suppress GnRH: Opioids, glucocorticoids, and marijuana.

Negative feedback from: Anabolic steroids

What are specific clinical features of hypogonadism?

nonspecific clinical features?

Reduced libido, decreased spontaneous erections, ED, gynecomastia, and decreased testicular volume.

Low energy, reduced strength, depressed mood, increased body fat, hair loss (body/face), and infertility.

When should testosterone be measured for diagnosis?

Between 8 and 10 AM while fasting.

When is measuring free testosterone concentration useful?

When testosterone protein binding may be altered, such as with obesity or aging.

What should be checked with a repeat testosterone below 300 ng/dL?

LH and hematocrit (normally, testosterone stimulates erythropoiesis. So low testosterone can cause low hematocrit)

Why should TRT (testosterone replacement therapy) be avoided when fertility is a concern?

What alternatives can be considered?

Negative feedback suppresses GnRH and further impairs spermatogenesis.

Aromatase inhibitors, human chorionic gonadotropin (mimics LH), clomiphene (estrogen antagonist that blocks negative feedback of GnRH, so GnRH increases)

What clinical abnormalities make TRT contraindicated?

Prostate cancer, high prostate-specific antigen levels (testosterone can stimulate prostate tissue).

High hematocrit levels or MI/stroke within 6 months (testosterone can increase hematocrit and cause thrombosis).

When do many TRT effects begin to appear?

During the first 3-6 months.

Which testosterone formulation is often first-line?

Transdermal gel. Counseling point: Risk of transfer to other people or pets.

How often is nasal testosterone administered?

Three times daily.

What are testosterone pellets?

How often are they replaced?

Testosterone pellets are rice-sized implants placed under the skin to release steady levels of testosterone.

Every 5-6 months.

What is a key administration feature of the oral testosterone undecanoate?

It is taken with food containing fat (it's a lipophilic drug).

When should patients be monitored after starting TRT?

Evaluate shortly after initiation; at 3-6 months; then annually.