Click any card to flip · 14 Step 1 high-yield concepts0 / 14 seen
Cryptorchidism
What is cryptorchidism, when is orchidopexy performed, and why does timing matter?
Answer
Cryptorchidism: failure of testicular descent through the inguinal canal (guided by gubernaculum, driven by T/DHT at ~wk 28).
Orchidopexy by 6 months (no later than 12 mo). Early surgery lowers risk of: • Seminoma (↑ 4–6× even after repair) • Infertility — heat-sensitive spermatogenesis • Inguinal hernia, testicular torsion
Labs: ↓ inhibin B (Sertoli damage first) + normal testosterone early (Leydig preserved); FSH rises.
Anatomic basis, classic exam findings, key differential, and management window?
Answer
Path: twisting of spermatic cord → cuts off arterial supply → ischemia. Most often due to bell-clapper deformity (tunica vaginalis inserts too high → free-rotating testis).
Presentation: Sudden severe unilateral scrotal pain ± abdominal pain + nausea; adolescent boy. Exam: high-riding testis, absent cremasteric reflex, horizontal lie; no relief with elevation (negative Prehn sign).
Ddx: Epididymitis (↑ w/ age; positive Prehn sign). US with Doppler can differentiate.
Surgical emergency — 6-hour window. Detorsion + bilateral orchiopexy (other side is at risk too).
Varicocele
What causes a varicocele, why is it usually left-sided, and why does it impair fertility?
Answer
Def: Dilation of the pampiniform plexus (testicular veins).
Why left > right: Left gonadal vein drains into the left renal vein at a 90° angle (↑ hydrostatic pressure); right gonadal vein drains directly into the IVC at an oblique angle. New-onset LEFT varicocele in an older man → think renal cell carcinoma invading renal vein. Sudden RIGHT-sided varicocele → IVC obstruction / retroperitoneal mass.
Presentation: "Bag of worms," enlarges with Valsalva, decompresses when supine. Dx: scrotal US with Doppler. Tx: surgical ligation or embolization if symptomatic/infertile.
Klinefelter Syndrome
Karyotype, body habitus, hormone pattern, fertility status, and key associated risks?
Answer
47 XXY (most common sex chromosome disorder in men).
Tx: Testosterone replacement at puberty (bone density, sexual development).
Testicular Germ Cell Tumors
Main categories, key markers, classic epidemiology, and which is radiosensitive?
Answer
Most common cancer in men 15–35. 95% are germ cell tumors.
Seminoma (40%): "fried egg" cells, homogeneous mass, radiosensitive, excellent prognosis, ↑ placental alkaline phosphatase (PLAP); ↑ hCG in some. β-hCG may be slightly elevated; AFP is NORMAL (key: seminomas never make AFP).
Non-seminomatous (NSGCT): 4 subtypes: • Embryonal carcinoma — ↑AFP, ↑hCG, aggressive • Yolk sac (endodermal sinus) — ↑↑AFP, Schiller-Duval bodies; most common in boys <3 • Choriocarcinoma — ↑↑hCG, hematogenous spread, hemorrhage • Teratoma — multiple germ layers; malignant in adult men
Risk factors: cryptorchidism, Klinefelter, family hx.
BPH — Pathophysiology & Treatment
Which prostate zone hypertrophies, what symptoms develop, and what are first-line drug classes?
Answer
Pathology: Nodular hyperplasia of the transitional (periurethral/central) zone of the prostate — surrounds urethra, causing obstructive symptoms. DHT-driven.
Marker:PSA (↑ in cancer, BPH, prostatitis); Free:Total PSA ratio ↑ risk if low.
Metastasis:OSTEOBLASTIC bone mets (classic pelvis, lumbar spine) — cause back pain + ↑ alk phos.
Treatment: Localized → surgery/radiation. Advanced → androgen deprivation therapy (ADT): GnRH agonists (leuprolide), antiandrogens (flutamide/bicalutamide), or orchiectomy. Prostate CA is androgen-sensitive.
Hypospadias vs Epispadias
Embryologic defect, location of opening, and which is associated with bladder exstrophy?
Answer
Hypospadias (common, 1 in 250 males): urethral (urogenital) folds fail to fuse ventrally under DHT → opening on VENTRAL surface. Most are distal (glanular, subcoronal); dorsally hooded foreskin.
Epispadias (rare): abnormal positioning of genital tubercle → opening on DORSAL surface. Classic association: bladder exstrophy.
Mnemonic: "Epi" = E on top (dorsal); "Hypo" = p below (ventral).
Management: Do NOT circumcise — foreskin used in urethroplasty. Repair by 6–12 months.
Erectile Dysfunction & PDE5 Inhibitors
Physiology of erection, how sildenafil works, main contraindication?
Ejaculate volume: essentially UNCHANGED — sperm are only ~5% of ejaculate (bulk from seminal vesicles + prostate).
Sperm fate: still produced; reabsorbed or phagocytosed in epididymis.
Anti-sperm antibody risk: Sperm antigens released into circulation (normally hidden by blood-testis barrier) → immune system can form anti-sperm Ab's. This is why vasectomy reversal often fails to restore fertility even when ducts are reconnected.
Efficacy: >99% after 2 negative post-op semen analyses (sperm clear over 2–3 months).
Hydrocele & Spermatocele
Differentiate these two scrotal fluid collections. Which is congenital vs acquired?
Answer
Hydrocele: Fluid collection between layers of the tunica vaginalis around the testis. • Communicating (congenital):patent processus vaginalis → peritoneal fluid enters scrotum; fluctuates w/ position; often resolves by age 1–2. • Non-communicating (acquired): obliterated processus + trauma/inflammation → no connection to peritoneum; stable size. • Transilluminates (classic sign).
Spermatocele:Epididymal cyst (usually head) filled with sperm-containing fluid. Distinct from the testis on palpation. Also transilluminates but more cystic feel. Usually asymptomatic.
Varicocele (for contrast): dilated pampiniform veins — does NOT transilluminate ("bag of worms").
Step 1-Style MCQs: Select the best answer for each question. Your choice locks in immediately and the explanation reveals automatically. Green = correct, Red = incorrect.
Question 1 of 6 — Testicular Torsion vs Epididymitis
A 16-year-old boy presents to the ED with sudden-onset severe left scrotal pain that began 3 hours ago while playing basketball. He is afebrile. On exam, the left testis is high-riding with a horizontal lie; the cremasteric reflex is absent on the left. Elevating the testis does NOT relieve pain. Which of the following is the most appropriate next step?
AOrder scrotal ultrasound with Doppler; treat empirically for epididymitis
BImmediate urologic consultation for surgical exploration + bilateral orchiopexy
CEmpiric ceftriaxone + doxycycline for STI coverage
DUrinalysis and discharge with analgesics
ECT abdomen/pelvis to rule out appendicitis
B — Immediate surgical exploration. Classic testicular torsion: sudden severe pain, adolescent, high-riding testis, horizontal lie, absent cremasteric reflex, NEGATIVE Prehn sign (no relief with elevation). Underlying defect is usually a bell-clapper deformity (the tunica vaginalis inserts too high on the cord, allowing free rotation). Surgical emergency — 6-hour window to save the testis. Do NOT delay for US if clinical suspicion is high. Bilateral orchiopexy is standard because the contralateral testis typically has the same deformity. Ischemia > 6 hrs → infarction + infertility. Epididymitis would show gradual onset + positive Prehn + preserved cremasteric reflex.
Question 2 of 6 — Varicocele + RCC
A 62-year-old man presents with a new-onset left-sided varicocele that does NOT decompress when he lies supine. He also reports flank pain + hematuria and 10 pounds of unintentional weight loss over the past 3 months. Which of the following is the most likely cause of the varicocele in this setting?
ABell-clapper deformity with torsion
BIdiopathic primary varicocele
CRenal cell carcinoma invading the left renal vein and obstructing gonadal venous drainage
DInguinal hernia compressing the testicular veins
EChronic prostatitis
C — Renal cell carcinoma invading left renal vein. A varicocele that fails to decompress when supine (does not empty with gravity) suggests venous obstruction — NOT the typical anatomic-angle varicocele. The left gonadal (testicular) vein drains into the left renal vein at 90°, so any process obstructing the left renal vein (RCC, tumor thrombus, retroperitoneal mass, nutcracker syndrome) can cause a left varicocele. The combination of flank pain + hematuria + weight loss + new varicocele in an older man is the classic RCC tetrad (though the full triad is flank pain + hematuria + palpable mass). Right-sided gonadal veins drain directly into the IVC — new right varicoceles suggest IVC obstruction. Always workup new/non-reducible varicoceles in older men.
Question 3 of 6 — BPH Pharmacology
A 68-year-old man with known BPH is started on combination therapy with tamsulosin and finasteride for moderate-severe LUTS. Six months later, his symptoms are improved and his PSA has decreased from 4.2 to 1.9 ng/mL. His internist is concerned about missing prostate cancer because of the PSA drop. What is the correct interpretation of this PSA change?
AThe PSA decrease is due to tamsulosin's effect on prostate smooth muscle
BFinasteride reduces PSA by approximately 50%, so the "corrected" PSA is ~3.8 ng/mL; continued monitoring is warranted
CThe PSA decrease rules out prostate cancer entirely
DPSA fluctuates randomly and this change is clinically meaningless
EA 50% drop in PSA warrants immediate prostate biopsy
B — Finasteride reduces PSA by ~50%.Finasteride (5α-reductase inhibitor) shrinks the prostate by blocking testosterone → DHT conversion. As the gland shrinks, PSA production drops predictably by about 50% over 6–12 months. To interpret PSA in men on finasteride, multiply the measured value by 2 (or compare relative changes). If PSA does NOT decrease, or rises on therapy, that is concerning for cancer. Tamsulosin (α1-blocker) relaxes smooth muscle but does not change prostate size or PSA production. Combination tamsulosin + finasteride (or dutasteride) is standard for moderate BPH with gland > 40g.
Question 4 of 6 — Seminoma vs NSGCT
A 28-year-old man feels a painless lump in his right testicle. Scrotal ultrasound confirms a 2.5-cm hypoechoic intratesticular mass. Radical inguinal orchiectomy reveals large clear "fried-egg" cells with central nuclei in sheets separated by fibrous septa infiltrated with lymphocytes. Tumor markers: β-hCG slightly elevated, AFP NORMAL, LDH elevated. Which of the following is the most likely diagnosis and optimal adjuvant therapy?
AYolk sac tumor; treat with BEP chemotherapy
BChoriocarcinoma; treat with methotrexate
CSeminoma; highly radiosensitive; consider surveillance, radiation, or single-agent carboplatin
C — Seminoma; radiosensitive."Fried-egg" cells (large clear cells with central nuclei) in sheets separated by fibrous septa with lymphocytes are classic for seminoma (most common testicular germ cell tumor). Markers: AFP is NEVER elevated in pure seminoma (if AFP is up, it's a mixed NSGCT). β-hCG may be slightly elevated (from syncytiotrophoblast-like cells). PLAP is often elevated. Seminomas are extraordinarily radiosensitive and chemosensitive — excellent prognosis even with metastases. Treatment options: inguinal orchiectomy + (surveillance / retroperitoneal radiation / single-agent carboplatin for stage I; BEP for advanced). Cryptorchidism, Klinefelter, and family history all ↑ risk. Ages 15–35 peak.
Question 5 of 6 — Klinefelter Hormone Pattern
A 21-year-old man presents to a fertility clinic with his partner after 18 months of unprotected intercourse without pregnancy. He is 6'4" tall with long arms and legs, mild gynecomastia, and small firm testes. Semen analysis shows azoospermia. Labs: testosterone 180 ng/dL (low), LH 31 mIU/mL (high), FSH 48 mIU/mL (very high), inhibin B undetectable, estradiol 58 pg/mL (elevated). Karyotype confirms 47,XXY. What is the best explanation for the elevated estradiol?
AEctopic estradiol production by a gonadoblastoma
BSertoli cells directly producing estradiol via the 2-cell model
CPeripheral aromatization of the residual testosterone to estradiol
DEstrogen is not actually elevated in Klinefelter; this is a lab error
EExogenous estrogen administration
C — Peripheral aromatization of testosterone. In Klinefelter (47 XXY), seminiferous tubule dysgenesis → ↓ inhibin B → ↑ FSH (no feedback); Leydig hypofunction → ↓ T → ↑ LH (no feedback). But residual Leydig T is aromatized peripherally to estradiol (in adipose tissue, especially) — and this increased aromatization activity → ↑ E2 → gynecomastia. Tall stature is from ↑ adult height without the normal epiphyseal fusion driven by testosterone. Associated: ↑ breast cancer (male), ↑ extragonadal germ cell tumors, autoimmunity. Tx: testosterone replacement at puberty; sperm extraction + ICSI occasionally enables fertility.
Question 6 of 6 — Sildenafil + Nitrates
A 58-year-old man with CAD on chronic isosorbide mononitrate for angina presents to the ED 2 hours after taking a friend's sildenafil (Viagra) for erectile dysfunction. He reports severe headache, dizziness, and an episode of syncope. Exam: BP 72/40 mmHg, HR 102. Which of the following molecular mechanisms explains his presentation?
ESildenafil inhibits β-adrenergic receptors, and nitrates block muscarinic receptors
B — Synergistic cGMP accumulation. Normal erection: PNS (S2-S4, "Point") → NO from cavernous nerves → guanylyl cyclase → ↑ cGMP → smooth muscle relaxation in corpora cavernosa. Sildenafil (and tadalafil/vardenafil) is a PDE5 inhibitor — it blocks the enzyme that breaks down cGMP, sustaining smooth muscle relaxation. Nitrates (nitroglycerin, isosorbide) raise cGMP systemically via the same NO-GC pathway. Combined: massive cGMP accumulation → profound vasodilation → hypotension, reflex tachycardia, syncope, MI, potentially death. ABSOLUTE contraindication. Separate doses by at least 24h (sildenafil) or 48h (tadalafil). Treat acute hypotension with IV fluids, phenylephrine.
Ordering Drills: Arrange each sequence of steps in the correct physiologic or pathologic order. Drag items to reorder. Click "Check Order" to verify, or "Show Answer" to reveal the correct sequence.
Testicular Torsion — Clinical Cascade
Order the pathophysiology of testicular torsion from predisposition to infarction.
Severe scrotal pain; high-riding testis; absent cremasteric reflex
Seminiferous tubules degenerate during puberty → azoospermia
Tall eunuchoid stature + mild ID + ↑ breast/germ cell cancer risk
Nondisjunction at meiosis → 47 XXY karyotype
Leydig cell dysfunction → ↓ testosterone
Sertoli cell damage → ↓ inhibin B → ↑ FSH (no feedback)
Nondisjunction → 47 XXY karyotype
Seminiferous tubule degeneration at puberty
↓ inhibin B → ↑ FSH
↓ T → ↑ LH; peripheral aromatization → ↑ estradiol
Leydig cell dysfunction → ↓ testosterone
Tall eunuchoid + gynecomastia + azoospermia + ↑ cancer risk
Vignette MCQs: Clinical scenarios testing disease recognition and mechanisms. Select your best answer and the explanation appears automatically.
Vignette 1 of 4 — Epididymitis vs Torsion
A 23-year-old sexually active man presents with gradually worsening right scrotal pain and swelling over 3 days, along with dysuria and low-grade fever. Physical exam: tender, edematous right epididymis; normal testicular lie; cremasteric reflex PRESENT; pain improves when the testis is elevated (positive Prehn sign). Urinalysis shows pyuria. Urine NAAT is positive for Chlamydia trachomatis. Which of the following is the most appropriate treatment?
AUrgent surgical exploration for suspected torsion
BIM ceftriaxone + oral doxycycline (for C. trachomatis + N. gonorrhoeae)
CCiprofloxacin alone (enteric coverage)
DReassurance and discharge with analgesics only
EHigh-dose corticosteroids for suspected autoimmune orchitis
B — Ceftriaxone + doxycycline. Classic acute epididymitis in a sexually active man < 35. Key features distinguishing from torsion: gradual onset, dysuria/urethritis, fever, preserved cremasteric reflex, POSITIVE Prehn sign, normal lie. Pathogens by age: <35 yo: N. gonorrhoeae + C. trachomatis (cover both with ceftriaxone + doxycycline); >35 yo: E. coli/Pseudomonas (cover with fluoroquinolone). Sexual partners should be treated + tested. Mumps orchitis (different) — post-pubertal males 5–10 days after parotitis.
Vignette 2 of 4 — Nonseminomatous Germ Cell Tumor
A 22-year-old man feels a painless right testicular lump. On exam, the right testis is firm and irregular. Scrotal US shows a 3-cm heterogeneous mass. Tumor markers: AFP 1,820 ng/mL (markedly elevated), β-hCG 240 mIU/mL (elevated), LDH 420. Radical inguinal orchiectomy reveals tumor cells with glandular arrangements and Schiller-Duval bodies (perivascular glomeruloid structures). Which of the following is the most likely diagnosis?
ASeminoma
BYolk sac (endodermal sinus) tumor — NSGCT
CLeydig cell tumor
DSertoli cell tumor
ETeratoma (mature)
B — Yolk sac tumor. Buzzwords: elevated AFP (pathognomonic — AFP is NEVER elevated in seminoma), Schiller-Duval bodies (glomeruloid perivascular structures, classic histologic feature). Yolk sac tumor is the most common testicular tumor in boys <3 years old, but also occurs in young adults as part of mixed NSGCTs. Markers for testicular tumors: • Seminoma: PLAP ↑, β-hCG slightly ↑, AFP NORMAL. • Yolk sac: ↑↑ AFP. • Choriocarcinoma: ↑↑ β-hCG; hemorrhagic. • Embryonal carcinoma: ↑ AFP + ↑ β-hCG. • Teratoma: multiple germ layers; malignant in adult men. Tx: inguinal orchiectomy + BEP chemotherapy (bleomycin, etoposide, cisplatin).
Vignette 3 of 4 — BPH with Acute Urinary Retention
A 72-year-old man presents with sudden inability to urinate over the past 8 hours. He has had progressive urinary hesitancy and weak stream for 2 years. After starting diphenhydramine for allergic rhinitis yesterday, he now cannot void. He has suprapubic pain and bladder distention on exam. DRE shows a symmetrically enlarged, smooth, rubbery prostate. Which of the following best explains the acute worsening?
AProstate cancer with urethral invasion
BUTI-induced bladder wall edema
CAnticholinergic effect of diphenhydramine + α1-adrenergic activity at bladder neck ↑ prostatic smooth muscle tone
DBladder rupture from chronic retention
EPrimary bladder outlet obstruction due to urethral stricture
C — Anticholinergic + α-adrenergic exacerbation.Anticholinergics (diphenhydramine, oxybutynin, TCAs) block M3 muscarinic receptors on bladder detrusor muscle → ↓ detrusor contraction → retention. Men with underlying BPH have marginal function — anticholinergics tip them into acute urinary retention. Another common precipitant: sympathomimetic decongestants (pseudoephedrine) activate α1 receptors on prostate/bladder neck → ↑ smooth muscle tone → outlet obstruction. Tx: catheter decompression + α1-blocker (tamsulosin). Add 5α-reductase inhibitor (finasteride) for large glands or recurrent retention. DRE reveals symmetric smooth BPH; prostate cancer would feel nodular/hard.
Vignette 4 of 4 — Prostate Cancer with Bone Mets
A 71-year-old man presents with 4 weeks of lower back pain unresponsive to NSAIDs, 12 pounds of unintentional weight loss, and new lower extremity weakness. PSA is 82 ng/mL (markedly elevated). DRE reveals a hard nodule in the posterior prostate. MRI spine shows multiple osteoblastic lesions in the lumbar vertebrae with epidural cord compression at L3. Alkaline phosphatase is 520 U/L (elevated). Which of the following treatments BEST addresses both the tumor and the hormonal driver?
C — ADT + corticosteroids + spinal radiation. Classic metastatic prostate cancer with epidural cord compression — an oncologic emergency. Clues: elderly man, PSA > 80, hard posterior prostate nodule (peripheral zone), osteoBLASTIC bone mets (prostate CA uniquely → blastic; most others → lytic), ↑ alk phos (bone turnover), cord compression signs (weakness, back pain). Treatment of choice: • ADT: GnRH agonist (leuprolide) + antiandrogen (bicalutamide/flutamide) to block "flare." • Emergent radiation + high-dose steroids for cord compression (within hours). Prostate CA is androgen-dependent so ADT provides durable response. Bisphosphonates/denosumab for bone protection.
Step 1 Traps: Common false statements that appear plausible but are incorrect. Choose the correct answer to reveal the trap explanation.
Trap 1 of 7
Testosterone binds the androgen receptor with greater affinity than DHT, making it the primary mediator of male external genital development.
Reversed. DHT binds the androgen receptor with ~50× higher affinity than testosterone. DHT is responsible for external genitalia development in utero, prostate growth, and male-pattern hair. Testosterone maintains internal (Wolffian) ducts — epididymis, vas, seminal vesicles. This is why 5α-reductase deficiency produces a 46 XY with normal internal male structures but female-appearing external genitalia at birth (virilizes at puberty).
Trap 2 of 7
Prostate cancer typically causes osteolytic bone metastases with hypercalcemia.
Reversed. Prostate cancer uniquely causes OSTEOBLASTIC bone mets (blastic = bone-forming → appear white/dense on X-ray; ↑ alkaline phosphatase). Most other cancers (breast, lung, kidney, multiple myeloma) cause OSTEOLYTIC mets (lytic lesions + hypercalcemia). Classic finding: axial skeleton mets (pelvis, lumbar spine, femur) → back pain in elderly man = consider prostate cancer. Tx: bisphosphonates or denosumab for bone support + ADT.
Trap 3 of 7
The pampiniform plexus is an arterial network that delivers oxygenated blood to the testes and requires precise temperature regulation.
False. The pampiniform plexus is a VENOUS plexus (not arterial) that COOLS arterial blood heading to the testis via countercurrent heat exchange — the artery is surrounded by the venous plexus, which has already lost heat on its way back from the cooler scrotum. This keeps testicular temp ~2°C below core body. Dilation = varicocele (L > R due to left gonadal vein → left renal vein at 90°). Twisting = testicular torsion.
Trap 4 of 7
Sperm are primarily stored in the seminal vesicles before ejaculation.
False — sperm are NOT stored in seminal vesicles. The name is misleading. Sperm are stored in the tail (cauda) of the epididymis, where the lumen widens and flow slows, allowing storage up to ~1 month. Seminal vesicles contribute ~70% of ejaculate volume (fructose, prostaglandins, alkaline fluid, clotting proteins) that joins sperm at the ejaculatory duct during emission.
Trap 5 of 7
In testicular torsion, elevating the testis relieves pain (positive Prehn sign).
False — reversed. In testicular torsion, Prehn sign is NEGATIVE (elevation does NOT relieve pain). In epididymitis, Prehn sign is POSITIVE (elevation DOES relieve pain). Other key differences: torsion has absent cremasteric reflex, high-riding testis, horizontal lie, sudden onset, adolescent boys. Epididymitis: present cremasteric, normal lie, gradual onset, fever, dysuria.
Trap 6 of 7
BPH causes cancer of the peripheral prostate zone and frequently progresses to prostate adenocarcinoma.
Two errors. BPH involves the CENTRAL/TRANSITIONAL (periurethral) zone — that's why it causes obstructive urinary symptoms. Prostate CANCER arises from the PERIPHERAL (posterior) zone — palpable on DRE. And BPH is NOT a precursor to prostate cancer (they involve different zones). BPH ↑ PSA modestly (mild, diffuse); cancer ↑ PSA more and gives a hard nodule on DRE. Men can have both simultaneously (unrelated).
Trap 7 of 7
Seminomas always elevate both AFP and β-hCG, which distinguishes them from non-seminomatous germ cell tumors.
False — critical distinction. SEMINOMAS NEVER ELEVATE AFP. If AFP is elevated, the tumor is a non-seminomatous germ cell tumor (NSGCT), even if histology looks "seminoma-like." Seminoma may modestly elevate β-hCG (from syncytiotrophoblast-like cells) and PLAP. Pure seminoma markers: PLAP+, LDH+, β-hCG slight↑, AFP NORMAL. NSGCT markers: ↑AFP (yolk sac, embryonal) or ↑↑β-hCG (choriocarcinoma). Treatment differs: seminoma is radiosensitive; NSGCT requires BEP chemotherapy.
Reference Tables: Quick-lookup tables for scrotal pathology, prostate conditions, and male reproductive pharmacology. Print-friendly format.
The highest-yield concept in male endocrinology: LH stimulates Leydig cells (in the interstitium) to produce testosterone. FSH stimulates Sertoli cells (inside the tubules) to support germ cells, produce ABP (androgen-binding protein) + inhibin B. Feedback: testosterone → ↓ GnRH + ↓ LH; inhibin B → ↓ FSH selectively. Clinical pattern recognition: ↑ FSH + normal T → Sertoli dysfunction (↓ inhibin B, as in Klinefelter). ↓ T + ↑ LH/FSH → primary hypogonadism. ↓ T + ↓ LH/FSH → secondary (central) hypogonadism.
TRAP Testosterone vs DHT — Where Each Acts
Key USMLE distinction: Testosterone maintains INTERNAL structures (Wolffian → SEED: Seminal vesicles, Epididymis, Ejaculatory duct, vas Deferens). DHT masculinizes EXTERNAL structures (penis, scrotum, prostate). DHT binds the androgen receptor ~50× more potently than T. Enzyme: 5α-reductase. Clinical: finasteride (5α-reductase inhibitor) → ↓ DHT → treats BPH + pattern baldness, but preserves testosterone functions (libido, fertility mostly intact).
USMLE pattern: painless testicular mass in a man 15–35 = germ cell tumor until proven otherwise. 95% of testicular cancers are germ cell origin. Always radical inguinal orchiectomy — do NOT biopsy transscrotally (seeding risk). Markers guide classification: • ↑ AFP → NSGCT (yolk sac, embryonal); pure seminoma NEVER has ↑ AFP • ↑↑ β-hCG → choriocarcinoma (or elevated slightly in seminoma) • ↑ PLAP → seminoma • ↑ LDH → tumor burden marker Risk factors: cryptorchidism (↑ 4–6× even after repair), Klinefelter, family Hx.
TESTING Torsion vs Epididymitis — Differential
Common USMLE side-by-side:
Torsion: sudden onset, adolescent, high-riding testis, absent cremasteric reflex, NEGATIVE Prehn sign, horizontal lie, no fever/dysuria. Emergency surgery within 6h.
Epididymitis: gradual onset, any age but peak <35 (STI) or >35 (E. coli), normal lie, present cremasteric, POSITIVE Prehn sign, fever/dysuria. Treat with antibiotics.
Ultrasound with Doppler confirms if unsure — no flow = torsion. Never delay surgery for imaging if clinical suspicion is high.
TRAP BPH Zone vs Prostate Cancer Zone
Two different zones, two different diseases — easy trap: BPH = TRANSITIONAL (central/periurethral) zone. Why symptomatic? The gland surrounds the urethra → bulk obstruction → LUTS. Tx: α-blockers + 5α-reductase inhibitors.
Prostate cancer = PERIPHERAL (posterior) zone. Why DRE matters? Posterior zone is palpable through rectum → feel hard nodules. BPH does NOT predispose to cancer — they are distinct in zone, pathogenesis, and location. Men can have both simultaneously.
BUZZWORD PSA + Osteoblastic Bone Mets → Prostate CA
Classic vignette cluster for metastatic prostate cancer: elderly man + back/hip pain + ↑↑ PSA (> 10) + hard posterior prostate nodule on DRE + osteoblastic (sclerotic) bone lesions on imaging + ↑ alkaline phosphatase. Most common cancer in men (3rd deadliest). Osteoblastic bone mets are virtually pathognomonic (vs. osteolytic mets in breast, lung, kidney, myeloma). Treatment = androgen deprivation (leuprolide + antiandrogen); prostate CA is androgen-sensitive. Bone-directed agents: bisphosphonates or denosumab.
TESTING Sildenafil + Nitrates = Fatal Hypotension
HY pharmacology: PDE5 inhibitors (sildenafil, tadalafil, vardenafil) and nitrates (nitroglycerin, isosorbide) BOTH elevate cGMP (via complementary mechanisms). Nitrates → NO → ↑ cGMP; PDE5 inhibitor → blocks cGMP breakdown → prolonged elevation. Combined: massive systemic vasodilation → profound hypotension, syncope, MI, death. ABSOLUTE contraindication. Separate by 24h (sildenafil) or 48h (tadalafil). Treat acute hypotension with IV fluids + phenylephrine. Also caution with α-blockers (additive hypotension).
Clinical Correlates: Review key disease profiles and clinical connections. Click "Show" to reveal comparison details.
Acute Scrotum Workup
Testicular Torsion vs Epididymitis vs Fournier's Gangrene
Three entities to differentiate in a man with acute scrotal pain:
Controlling the Male HPG Axis — ADT, Finasteride, PDE5i
The male HPG axis can be targeted at several levels for therapy:
GnRH agonists (leuprolide):CONTINUOUS dosing desensitizes the pituitary → ↓ LH/FSH → ↓ testosterone → medical castration. Uses: prostate cancer (metastatic). Initial "FLARE" of T requires concurrent antiandrogen for 2 weeks.
Androgen receptor antagonists (flutamide, bicalutamide, enzalutamide): Block testosterone/DHT at target tissue. Combined with leuprolide for full ADT.
5α-reductase inhibitors (finasteride, dutasteride): Block T → DHT conversion. Uses: BPH, male-pattern alopecia. Reduce PSA by ~50% (interpret labs with caution).
α1-blockers (tamsulosin): Relax prostate smooth muscle → fast relief of BPH symptoms. Orthostatic hypotension is key AE.
Sertoli-only syndrome: Isolated ↑ FSH + normal T + low inhibin B. Azoospermia from absent germ cells.
Obstructive azoospermia: Normal hormones + normal testicular biopsy + azoospermia. Think vas deferens absence (CFTR mutation/CBAVD) or prior vasectomy.
Reversible causes of male infertility:
• Varicocele (#1 treatable cause) → varicocelectomy
• Heat exposure (hot tubs, laptops on lap, tight underwear) → avoidance
• Anabolic steroid abuse → discontinuation; may need hCG/clomiphene to restart axis
• Obstructive azoospermia (CBAVD, post-vasectomy, infection) → surgical reconnection, TESE + ICSI
• Medications: testosterone supplementation (!), opioids, SSRIs, antipsychotics
• Klinefelter: rare pregnancies via TESE + ICSI
• Hyperprolactinemia: cabergoline/bromocriptine
Male Repro Histology Synthesis
Key Histology-Clinical Correlations
Histology directly informs clinical pathology:
Sertoli cells: Form blood-testis barrier (tight junctions); produce inhibin B (↓FSH), ABP (concentrates T locally), MIS (fetal). Dysfunction → azoospermia + ↑ FSH (Klinefelter, cryptorchidism).
Leydig cells: Interstitial, Reinke crystals, tubular cristae; produce testosterone under LH. Dysfunction → ↓ T + ↑ LH (primary hypogonadism).