BPH AND LOWER URINARY TRACT SYMPTOMS
Background
(AFP 2014;90:769; JAMA 2014;312:535; NEJM 2012;367:248)
- Lower urinary tract symptoms (LUTS): Storage: Frequency, nocturia, urgency, incontinence; Voiding: Incomplete emptying, intermittency, straining, dysuria, weak stream, hesitancy; Polyuria: ≥3 L UOP/24 h; nocturnal polyuria: ≥33% UOP at night
- Benign prostatic hyperplasia (BPH): Prostatic enlargement due to ↑ smooth muscle & epithelial cells within the prostatic transition zone, can lead to LUTS; complications include CKD, urinary retention, recurrent UTI, disturbed sleep, bladder stones, hematuria
- Acute urinary retention: Painful, palpable/percussible bladder in pt unable to void; may be caused by BPH, constipation, strictures, UTI, neuro d/o, overdistended bladder, medications (decongestants, opiates, antipsychotics, antihistamines); urgent catheterization for bladder decompression ± nontitratable a-blockers, laxatives, medication mgmt; ✓ renal function & monitor UOP for postobstruction diuresis
- Chronic urinary retention: Nonpainful bladder palpable/percussable after voiding, usually persistent PVR >300 mL
- Overactive bladder (OAB): Urinary urgency & frequency ± incontinence; may be 2/2 neurologic disorder (stroke, PD) or nonneurologic causes (BPH, bladder stones); storage sx are more prominent in OAB compared to voiding sx seen in BPH
- Epidemiology: ↑ w/ age; 25% in 40–49 y; >50% in 60–69 y; >80% in 70–79 y (J Urol 1984;132:474); accounts for 1.9 million PCP visits/y
- Differential dx: Prostate/bladder cancer, bladder stone, UTI, prostatitis, neurogenic bladder, urethral or bladder neck stricture
Evaluation and Prognosis
(J Urol 2009;181:1779; NEJM 2012;367:248)
- History: LUTS, pain, dysuria, hematuria, sexual function; ask which sx interfere most w/ QoL; fluid intake, caffeine intake. How many times each night do you wake up to urinate?
- PMHx/PSHx: Including neuro (stroke, PD, dementia, MS), DM (polyuria, polydipsia) Medications: Diuretics, antidepressants, bronchodilators, antihistamines, anticholinergics (↓ bladder function/ ↑ urinary sphincter tone), a-agonists (↑ prostatic smooth muscle tone) Frequency–volume chart: Record time/volume of every void for 72 h IPSS score: Quantitates LUTS sx at dx & in response to tx
| International Prostate Symptom Score (IPSS) (Adapted from J Urol 1992;148:1549) |
| Over the past month how often… |
| (1) Have you had a sensation of incomplete bladder emptying after urination? |
| (2) Have you had to urinate <2 h after you finished urinating? |
| (3) Have you stopped/started again several times when urinating? |
| (4) Have you found it difficult to postpone urination? |
| (5) Have you had a weak urinary stream? |
| (6) Have you had to push/strain to begin urination? |
| (7) Did you get up to urinate from the time you went to bed at night until waking in the morning (scored differently: 0 [0 pts], 1× [1 pt], 2× [2 pts], 3× [3 pts], 4× [4 pts], ≥5× [5 pts]) |
| Scoring (based on answers): Not at all (0 pts), <1 time in 5 (1 pt), <half the time (2 pts), about half the time (3 pts), >half the time (4 pts), almost always (5 pts); Mild sx: 0–7, Mod: 8–19, Severe: 20–35 |
- Exam: Suprapubic palpation (r/o bladder distention), overall motor/sensory function (r/o neuro disease, esp perineum/lower limbs), DRE (tone, prostate gland size, consistency, pain, shape abnormalities, nodules)
- Workup: Serum glucose, Cr, U/A; consider UCx (UTI sx), cytology (r/o cancer if hematuria/irritative sx); check serum PSA as a surrogate marker for prostate size & response to medical Rx (different than PSA screening for asx pt)
- Post-void residual: To r/o silent urinary retention (nl <100 mL) Uroflowmetry: Measures urine volume/time to quantify urine flow (can’t distinguish obstruction from decreased bladder contractility)
Treatment
(AFP 2008;77:1403; BJU Int 2004;94:738; NEJM 2012;367:248)
- Conservative management: Appropriate if mild sx or sx not bothersome to pt; adjust meds (avoid a-agonists, anticholinergics, diuretics), adjust fluid intake (UOP goal 1 L/24 h, ↓ intake in evening), lifestyle changes (wt loss, exercise), dietary advice (avoid caffeine, spicy/acidic foods, EtOH); pelvic floor relaxation, Valsalva voiding, crede voiding (manual bladder compression), double voiding; tx UTI before initiating further Rx (recurrent UTI warrants active tx)
- Medications: Indications for tx include adverse impact on pt QoL, recurrent UTI, renal insufficiency, hydronephrosis, urinary retention (may require surgical eval)
- α-Blockers: 1st-line tx of BPH; provide immediate benefit (in contrast to 5α-reductase inhibitors); most require dose titration;↓ smooth muscle contraction at bladder neck/prostate; reassess efficacy using IPSS 2–4 wk after initiating tx; meta-analysis of alfuzosin, doxazosin, tamsulosin, terazosin show equal efficacy (Eur Urol 1999;36:1); prazosin not commonly used due to short half-life & CV s/e Side effects: Dizziness, asthenia, orthostasis, rhinorrhea, HoTN, ↓ ejaculate volume/retrograde ejaculation; avoid in pts planning cataract surgery given risk of intraoperative floppy iris syndrome; use caution when combining with PDE5 inhibitors due to orthostasis; tamsulosin 0.4 mg/d preferred in men on sildenafil 5α-Reductase inhibitors: Block conversion of testosterone → dihydrotestosterone, ↓ prostate volume; dutasteride & finasteride equally effective in ↓ prostate volume & improving LUTS (EPICS, BJU Int 2011;108:388); benefit greater in men w/ larger prostate (>30 g, PSA ≥1.5); reassess efficacy using IPSS 3 mo after initiating tx; may take up to 1 y to show full efficacy
- Side effects: Gynecomastia, ED, ↓ libido; possible assoc w/ high- grade prostate cancer (NEJM 2011;365:97); ↓ PSA by 2–2.5-fold so caution must be used in interpreting PSA values in men on tx, ✓ PSA prior to initiation (J Urol 2005;174:877) Anticholinergics: Treat LUTS due to OAB; useful in BPH w/ irritative LUTS w/ nl PVR (J Urol 2011;185:1793); include tolterodine, oxybutynin, fesoterodine, darifenacin, solifenacin, fesoterodine, & trospium; monitor for urinary retention & ✓ PVR prior to initiation; may take 12 wk to work
- Side effects: Dry mouth, blurry vision, ↑ HR, drowsiness, constipation; contraindicated in gastroparesis, glaucoma; darifenacin, solifenacin more selective w/ ↓ s/e; trospium has ↓ ability to cross blood–brain barrier & has ↓ CNS effects (Urol Clin North Am 2006;33:465); ER versions better tolerated Combination therapy: Combinations more effective than monotherapy in the long-term; include doxazosin + finasteride (MTOPS, NEJM 2003;349:2387) & tamsulosin + dutasteride (J Urol 2008;179:616); tolterodine + tamsulosin effective in BPH + OAB sx (freq, urgency, incontinence) (JAMA 2006;296:2319) Phosphodiesterase inhibitors: Tadalafil FDA-approved for tx of LUTS 2/2 BPH; use caution in pts w/ CrCl <30 mL/min, or who are on a-blockers; may take up to 4 wk to work; contraindicated in pts on nitrates Saw palmetto: Approved in Germany & France for tx of BPH, despite placebo-controlled RCT showing no benefit (NEJM 2006;354:557) Desmopressin: May be used for refractory nocturnal polyuria
- Surgical treatment: Should be considered if medical therapy insufficient; Transurethral resection, laser ablation, simple prostatectomy, transurethral radiofrequency needle ablation, microwave tx, Uro-Lift; botulinum toxin injection (bladder overactivity)
| Commonly Used α-Adrenergic Receptor Antagonists | ||||
| Name | Selectivity | Titration | Starting Dose | Max Dose/d |
| Terazosin | Nonselective | Yes | 1 mg PO QHS | 10 mg |
| Doxazosin IR | Nonselective | IR: Yes ER: Maybe | IR: 1 mg PO daily ER: 4 mg PO
QDa |
8 mg |
| Alfuzosin | Nonselective | No | 10 mg PO dailyb | 10 mg |
| Tamsulosin | α-1A selective | Maybe | 0.4 mg PO dailyb | 0.8 mg |
| Silodosin | α-1A selective | No | 8 mg PO dailyc | 8 mg |
| Commonly Used 5α-Reductase Inhibitors | ||||
| Finasteride | Type 2 | No | 5 mg PO daily | 5 mg |
| Dutasteride | Type 1 & 2 | No | 0.5 mg PO daily | 0.5 mg |
aBefore breakfast. bAfter meal. cWith meal.
- Management of acute urinary retention: Urgent catheter placement; if unable in primary care setting → ED/same-day urology clinic for cath; may attempt trial without catheter after 2–3 d of a-blockade (BJU Int 2011;109:88)
- When to refer:
Complicated LUTS: Abnl DRE/PSA, hematuria, pain, infection (assess/tx prior to referral), palpable bladder, neuro disease, acute/chronic urinary retention Failure of conservative/medical mgmt
Pt desires surgical intervention, <45 y, or incontinent
Hx of prostate/bladder cancer
MALE SEXUAL DYSFUNCTION
Background
(Eur Urol 2010;57:804; Lancet 2013;381:153; NEJM 2007;357:2472)
- Erectile dysfunction: Inability to achieve/maintain erection sufficient for sexual activity
- Erectile function: Complex interplay between cardiovascular, metabolic/hormonal, psychological, & nervous systems Epidemiology: ↑ w/ age (5% complete ED in pts 40–49 y, 15% in pts 70–79 y) Risk factors: ↑ age, smoking, DM, CVD (HTN, PAD), neuro disease, endocrinopathy (metabolic syndrome, hypogonadism, hyperprolactinemia), obesity, pelvic/perineal/penile trauma/surgery, pelvic XRT, Peyronie disease (scar tissue → painful, abnl curvature of penis when erect), Rx/recreational drug use, EtOH
- Meds: Antihypertensives, sympatholytics, anticholinergics, antidepressants, anxiolytics, antipsychotics, antiepileptics, antiandrogens, ketoconazole, niacin, cimetidine, opiates Common comorbidities: Obesity, CVD, DM, depression, & EtOH abuse; mgmt of these conditions/risk factors may prevent/treat ED
- Psychogenic ED: Suggested by acute onset, preserved ability to obtain spontaneous erections (nocturnal/morning) & erections w/ masturbation
- ↓ libido: EtOH, depression, fatigue, stress, illicits, meds, relationship issues, ↓ T
- Premature ejaculation: (1) short ejaculatory latency, (2) lack of control of ejaculation, (3) distress due to premature ejaculation; prevalence 20–30%; multinational studies show average ejaculatory latency 5–6 min (J Sex Med 2010;7:2947); may be comorbid w/ ED; if present, tx ED first
- Priapism: Painful erection lasting >4 h; requires immediate tx (→ ED)
- Dyspareunia: Pain w/ intercourse for >3 mo; may be related to chronic pelvic pain syndrome, Peyronie disease, phimosis (inability to retract foreskin over glans), UTI/cystitis, psychological (h/o abuse)
- Hematospermia: Blood in ejaculate; usually benign; ✓ U/A, UCx, gonorrhea/chlamydia based on clinical suspicion; consider PSA, referral to Urology for reassurance; may be present for 4+ wk after prostate bx
Evaluation
(AFP 2016;94:820; J Urol 2005;174:230)
- History: Δ in desire, ejaculation, orgasm, penile curvature, genital pain; nocturnal/AM erections, ability to achieve erection/ejaculation from masturbation; distinguish complaints about ejaculation/orgasm from ED; ED severity (e.g., International Index of Erectile Function [IIEF-5]), chronology of sx; LUTS; Y hx, sexual orientation, hx of sexual abuse, relationship problems, partner’s sexual function; may be helpful to interview partner when feasible; screen for CV disease; EtOH/illicit use; presence of spontaneous erections suggests against a vascular or neurologic cause of ED
- Exam: Gen: 2° sexual characteristics; Neuro: Visual fields (pituitary tumor), genital/perianal sensation, LE sensation/strength; Chest: Gynecomastia, CV: Femoral/LE pulses; GU: Penis (phimosis, plaques); testicles (size, firmness), DRE (rectal tone, prostate size/consistency)
- Cremasteric reflex: Contraction of ipsilateral scrotum upon stroking inner thigh → assesses genitofemoral nerve and integrity of thoracolumbar erection center
- Workup: Comorbid conditions (e.g., HbA1c, serum lipids), AM testosterone (if ↓ see “Male Hypogonadism”); ✓ PSA if prostate pathology suspected (e.g., abnl DRE, LUTS) or plan for testosterone tx (need to discuss risks/benefits of prostate CA dx/tx [see “Prostate Cancer”])
Treatment
(AFP 2010;81:305; Ann Intern Med 2009;151:639; Eur Urol 2010;57:804; NEJM 2007;357:2472)
- General approach: Identify, treat, & optimize organic comorbidities & psychosexual dysfunction; avoid ED tx when sexual activity not recommended (i.e., in certain CAD pts, see “CAD”); involve partner when appropriate; counsel all pts re: ↑ risk of priapism w/ tx and requires immediate medical attention
- Stepwise progression of tx for ED: Oral type 5 phosphodiesterase inhibitors (PDE5i) → intraurethral alprostadil → intracavernous vasoactive drug injection → vacuum erection device (VED, can be trialed after PDE5i) → surgery (penile prosthesis)
- Lifestyle modification: Smoking cessation, diet, wt loss, ↑ exercise, ↓ EtOH, medication modification, psychotherapy
- SSRI-related ED: Usually causes delayed ejaculation, resulting in prolonged stimulation needed for orgasm; tx: ↓ dose, substitute another SSRI or non-SSRI (mirtazapine, bupropion), drug holidays, Rx PDE5i (below); Duloxetine and desvenlafaxine may be less commonly associated with male sexual dysfunction, and PCPs probably often consider SNRIs as next-line agents if SSRIs are causing sexual side effects
- PDE5i: 1st-line Rx; use does not result in spontaneous erection; requires sexual arousal, intact neural pathways/vasculature; no effect on libido; similar s/e & discontinuation among PDE inhibitors; insufficient evidence to recommend specific PDE5i (Ann Intern Med 2009;151:650); sildenafil & vardenafil should be taken on an empty stomach & not taken more than 1×/24 h; tadalafil may be taken w/ food
- Mechanism: ↑ NO → cavernosal smooth muscle relaxation → ↑ penile blood flow/erection in response to sexual stimuli; onset ~60 min, but as early as 20 min; may need to ↓ dose if liver disease, meds (esp CYP-450 3A4), age >65 y, CKD
- Side effects: Flushing, nasal congestion, HA, dyspepsia, hearing disturbances, back pain/myalgias (tadalafil, avanafil), ↑ QT (vardenafil), priapism (rare), vision loss (nonarteritic anterior ischemic neuropathy) & visual disturbance (blue hue; sildenafil, vardenafil) Cautions/Contraindications: Caution in pts on a- blockers (e.g., tamsulosin) antihypertensives, or EtOH use as may worsen orthostasis; concomitant use w/ organic nitrates is contraindicated (→ profound HoTN); wait 24 h (sildenafil) or 48 h (tadalafil) before administering nitrates in an emergency situation; contraindicated in pts w/ recent CV events & clinically hypotensive pts PDE5i failure: Determine if PDE inhibition was adequate; may try a different dose or drug w/in class; discuss risks/benefits of other therapies
| PDE5 Inhibitors | ||||||
|
Name |
Starting Dose | Dose Range |
Duration |
Notes |
||
| PRN | Daily | PRN | Daily | |||
| Sildenafil | 50 mg | N/A | 25–100 mg | N/A | 6–8 h | 1, 2 |
| Vardenafil | 10 mg | N/A | 5–20 mg | N/A | 6–8 h | 1, 2, 3 |
| Tadalafil | 10 mg | 2.5 mg | 5–20 mg | 2.5–5 mg | 24–36 h | 4 |
| Avanafil | 100 mg | N/A | 50–200 mg | N/A | >6 h | 1 |
| Rapid onset of action (~30 min): Avanafil, ODT vardenafil. Longest acting: Tadalafil No food interaction: Tadalafil, avanafil. Relieves LUTS due to BPH: Tadalafil Notes: (1) Absorption ↓ by fatty food; (2) May have visual s/e; (3) Avoid if hx/risk of ↑ QT. Also available as an orally disintegrating tablet; (4) May cause back pain & myalgia due to PDE11 inhibition. Most rapid onset of action. | ||||||
- Alprostadil: Prostaglandin that relaxes smooth muscle → vasodilatation & erection; available as an intraurethral pellet (insert 5– 10 min before sex, lasts 1 h) & penile injection (more effective than pellet, inject 10–20 min before sex, lasts ~1 h or more); s/e include priapism (more common than PDE5i), penile pain; also component of Trimix
- Yohimbine: ? placebo effect; not recommended by AUA due to concerns about effectiveness & safety (dizziness, HA, nausea, flushing, tachycardia, HTN)
- Vacuum erection device: Vacuum↓ intracavernosal pressure →↑ penile blood flow (maintained by elastic band)
- Penile prosthesis: Include semirigid, inflatable; high satisfaction rate, but tx of last resort as permanently destroys erectile tissue
- Testosterone supplementation therapy: See “Male Hypogonadism”; contraindicated in hx prostate/breast CA; may be beneficial when combined w/ PDE5i; not indicated for tx of ED in setting of nl serum T; should NOT be used in men planning on having children as shuts down HPT axis and impairs spermatogenesis
- Premature ejaculation: Pause & squeeze technique, stop–start technique, masturbation prior to sex, desensitizing agents/topical anesthetics (lidocaine–prilocaine, condoms), low-dose SSRIs (sertraline 25–50 mg PO QD, paroxetine 5–20 mg PO QD; may also be taken as needed 3–4 h prior to intercourse), consideration of PDE5i if concomitant ED (tx ED first); consideration of psychotherapy/sex therapy if psychogenic component suspected
- Indications for referral: Priapism (ED referral), failure of PDE5i, hx pelvic/perineal trauma, significant penile deformity
- Information for patients: AFP 2010;81:313; Ann Intern Med 2009;151:1–44; JAMA 2016;316:1838
MALE HYPOGONADISM
Background
(JCEM 2010;95:2536; JCEM 2007;92:4241)
- Definition: Clinical syndrome resulting from failure of the testes to produce physiologic levels of testosterone (T) and/or a normal sperm count; due to disruption of the hypothalamic–pituitary–gonadal (HPG) axis
- Epidemiology: Hypogonadism affects 2–4 million men in US; serum testosterone levels typically decline 1–2%/y; normal, mild age-related decline in serum T of unclear significance (NEJM 2004;350:482; JCEM 2001;86:724)
- Physiology: (NEJM 2013;369:1011) Testosterone levels regulated by HPG axis; hypothalamus releases pulsatile GnRH → ⊕ anterior pituitary, which releases LH + FSH → ⊕ testes, which synthesize sperm & release testosterone; testosterone (& metabolite DHT) required for spermatogenesis, involved in libido, potency, muscle mass, & BMD (also prostate hypertrophy & ♂ pattern baldness)
- Pathophysiology: Leydig cell failure (“1° hypogonadism”) or inadequate LH/FSH due to hypothalamic or pituitary lesions (“2° hypogonadism,” more common); can → infertility & s/sx of low T (below)
| Selected Causes of Hypogonadism | |
| Cause | Example/Notes |
| Congenital | 1°: Klinefelter syndrome; 46,XY/XO; 47,XXY (common, 1 in 500 ♂), cryptorchidism, d/o of androgen biosynthesis; 2/2: LH, FSH, or GnRH receptor mutations; Kallmann, Prader–Willi |
| 1° acquired | Autoimmune; chemotherapy; medications (ketoconazole); infection (HIV, mumps); bilateral orchiectomy; radiation; torsion; trauma |
| 2° acquired | DM; obesity; medications (GnRH agonists, opioids); critical illness; ↑ PRL; CNS tumors; pituitary disease; TB; CNS XRT; trauma |
| Combined | Chronic systemic disease (cirrhosis, CKD), infiltrative disease (hemochromatosis, sarcoidosis), sickle cell disease, thalassemia, alcoholism, meds (glucocorticoids), DAX1 mutations, older age |
Evaluation
(JCEM 2010;95:2536; NEJM 2010;363:123)
- General approach: Hypogonadism should be considered as a potential dx in men with specific or multiple findings (below); if sx present, assess for potential etiology via hx/PE & lab testing; both hx & labs can be nonspecific → symptoms and lab abnormalities required to make a diagnosis
- Specific features: Highly suggestive of ↓ hypogonadism: Sexual: Incomplete or delayed sexual development, ↓ am erections, ↓ ejaculate volume, ↓ testicular size or volume, infertility; Chest: ↓ Body hair or shaving requirement; Endocrine: ↓ BMD, hot flashes
- Sensitive features: More common, less specific: Cognitive/Y; ↓ energy, depression, concentration/memory; sleep disturbances; Sexual: ↓ Libido, ED; MSK: ↓ Muscle bulk/strength, ↑ body fat, ↓ physical stamina; Heme: Mild normocytic anemia
- History: Also attempt to assess age of onset, fertility, & etiologic clues: medications, EtOH, PMHx of obesity, DM, OSA, or chemo/XRT hx (CCJM 2012;79:717)
- Physical: BMI, 2° sex characteristics (facial & body hair); testicular volume
- Lab: If suspect hypogonadism based on hx/PE, total AM testosterone is 1st-line; any ⊕ test should be confirmed as 30% of repeats will be nl; with repeat AM testosterone level, send LH/FSH, PRL, SHBG, iron studies, CBC/PSA, and ± estradiol
- Testosterone measurement: 98% of serum testosterone bound to SHBG or albumin; 2% of serum T is “free,” however, amount loosely bound to albumin also considered “bioavailable”; significant alterations in [SHBG] → total T being a less reliable marker → use free T values in these cases; sources of false ⊕ screening (low T) include acute illness; glucocorticoid use, hypothyroidism, obesity, DM
- Other studies: Semen fluid analysis if infertility, see “Infertility”; PRL, iron studies if 2° hypogonadism & no clear etiology (DM, obesity); pituitary MRI indicated if 2° hypogonadism & severe ↓ T (total T <150) or CNS sx; DXA (see “Osteoporosis”); further studies as per sx & in consultation w/ endocrinology
| Lab Testing for Hypoandrogenism (JCEM 2011;96:38) | |
| Screening Test | Mechanics/Interpretation |
| Total testosterone (1st-line) | Measured at 8–10 AM (values fluctuate during the d, AM values best standardized) Advantages: Standardized values, reflects free & “bioavailable” levels Disadvantages: More difficult to interpret in conditions which alter [SHBG], e.g., obesity, DM, aging, cirrhosis, ESLD, hypothyroidism, AEDs, HIV; if level low- nl → ✓ free T |
| Free testosterone | This should be calculated (requires simultaneous measurement of total T, SHBG, albumin); free T direct measurement often unstandardized/unreliable |
| Bioavailable testosterone | Measures free + albumin-bound T; similar to free T, measured if suspect altered [SHBG]; many assays unstandardized/unreliable |
Figure 16-1. Testing algorithm
Management
(NEJM 2004;350:482)
- Comorbidities: In pts w/ diseases known to lead to low testosterone (obesity, DM), should also treat underlying condition which may be contributing (CCJM 2012;79:717)
- Testosterone replacement therapy: Indicated for pts w/ sx hypogonadism; contraindicated in pts w/ breast or prostate CA; use w/ caution in pts w/ ↑ risk of prostate CA (↑ PSA, prostate nodule on exam, ⊕ FHx, poorly controlled BPH/LUTS–see “BPH & LUTS”), CHF, untreated OSA, HCT >50; S/e: Acne, ↑ HCT, ↑ OSA, ↓ sperm count, ± gynecomastia, ♂ pattern baldness (JCEM 2011;96:38)
- Preparations
- Gel (Testim, AndroGel; Axiron): 5 g TOP QD typical starting dose; apply to shoulder, upper arm or abdomen; s/e: transfer to others; skin irritation; odor IM (testosterone enanthate/cypionate): 100– 300 mg q2–3wk; s/e: fluctuating levels → fluctuating sx; injection site pain Patch (Androderm): 5 mg TD QD to back, abdomen, upper arm, thigh; dose 2.5–10 mg
- Serum testosterone levels: Only useful to check if symptoms fail to improve on therapy
- Monitoring: At 1–2 mo, then q6mo × 2, then yearly: Assess response to tx, perform DRE; Labs: check HCT q6mo then annually, PSA; if baseline >0.6 ng/mL, check at 3 & 6 mo, then annually; BMD at baseline and if low, then 1–2 y after initiating tx (NEJM 2004;350:482)
- When to refer: Dx uncertain, labs difficult to interpret; suspect pituitary pathology; fertility desired (↑ chance of success if 2° hypogonadism; → hCG injections) → endocrinology
MALE INFERTILITY
Background
(Lancet 1997;349:787)
- Definition: Failure to conceive after 12 mo of unprotected intercourse (6 mo if ♀ partner >35 y); affects 15% of couples; ~20% d/t ♂ only, 30- 40% d/t both ♂ and ♀; also eval ♀ partner, see “Women’s Health.” ♂ infertility assoc w/ ↑ rate of genetic abn, CA, other serious medical conditions in the ♂ himself; ∴eval ♂ even if known ♀ factor or planned IVF, as may improve health/identify heritable conditions (Fertil Steril 2013;100:681)
- Indications for evaluation: Infertility or concerns for ♂ fertility/future fertility (e.g., h/o cryptorchidism, varicocele)
- Causes: Unknown (40–50%), testicular dz (30–40%, i.e., hypogonadism, primary spermatogenesis failure), defective sperm transport (10–20%, i.e., retrograde ejaculation, epidiymal obstruction), endocrine (1–2%, secondary hypogonadism); spermatogenesis takes ~72–81 d;∴events (e.g., febrile illness) w/in previous 3 mo can impact sperm production; changes may take >2–3 mo before reflected in semen parameters. Exogenous testosterone, testosterone-like products/anabolic steroids can shut down HPT axis for mo/y following discontinuation
Evaluation
| Basic Reproductive Hx Detailed Medical Hx | |
| Coital frequency/timing
Duration of infertility/prior fertility Childhood illnesses/development Systemic medical illnesses Prior surgeries Sexual hx (incl sexual function, STI) Gonadal toxin exposure (e.g., heat, chemo) (Andrology 2016;4:648) |
Basic reproductive history Complete ROS Medication use
Family reproductive history Detailed social history (incl tobacco, EtOH and anabolic steroid/illicit drug use)
(Adapted from Fertil Steril 2015;103:e18) |
- Exam: Habitus, secondary sexual characteristics (body hair distribution, gynecomastia), genital exam (penis, location of meatus, testicle location/consistency/size, epididymides, vasa deferentia, varicocele), DRE as indicated
- Varicocele: Present in 15% of ♂ population, ~40% of infertile ♂; subclinical (detectable on u/s but not physical exam) not clinically relevant (Fertil Steril 2014;102:1556)
- Workup: Basic reproductive hx and semen analysis (2 if 1st semen analysis abn); refer to urologist or specialist in ♂ infertility if abnl
- Semen analysis (SA): Generally ♂ infertility associated with abnl SA; nl SA doesn’t r/o ♂ factor/guarantee fertility, abnl SA doesn’t guarantee infertility; performed after 2–5 d abstinence, by masturbation in clinic where it will be analyzed; can collect at home (masturbation or collection condom) and transport at body temp to lab w/in 1 h but less reliable; frequent ejaculation (q1–2d) doesn’t ↓sperm concentration, can ↓ ejaculatory volume, may ↑sperm quality; abstinence >10 d assoc w/ ↓ quality/motility Endocrine: Usually NOT the cause of ♂ infertility; eval indicated if abn SA, impaired sexual function; Screening: AM testosterone, FSH; abn T should prompt further eval, see “Hypogonadism”; Do NOT give T to pts interested in fertility → suppresses HPT axis/↓ spermatogenesis; ↑ FSH suggests testicular failure Specialized testing: Limited clinical utility, defer to urologist or ♂ infertility specialist; defer genetic testing (e.g., karyotype, CFTR mutation, Y-chromosome microdeletion testing) to specialist Imaging: Generally not indicated; scrotal u/s if irregular testes/concern for mass or if congenital bilateral absence of vas deferens/varicocele are being considered
| Semen Analysis Reference Values (WHO 2010) | |
| Volume | >1.5 mL |
| pH | >7.2 |
| Sperm concentration | >15 × 106/mL |
| Total sperm count | >39 × 106/ejaculate |
| Percent motility | >40% |
| Forward motility | >32% |
| Normal morphology* | >4% |
*Based on Krueger strict morphology.
Management
(Fertil Steril 2013;100:631)
- Indications for referral: Abn reproductive hx, abn SA, abn endocrine profile, persistent infertility despite neg ♀ eval/tx, clinical varicocele assoc w/ abn SA or future interest in fertility, concern for genetic abn; treatment options include intrauterine insemination (i.e., injection of washed sperm into the uterus), IVF, removal of sperm from testes by microdissection, correction of hormonal problems
- Recs for ↑ chances of conception while awaiting referral (Fertil Steril 2013;100:631)
- Education: Intercourse frequency (q1–2d) and timing (6 d leading up to ovulation, see “Women’s Health”), avoid lubricants (incl olive oil, saliva; can use canola/mineral oil, hydroxyethylcellulose-based products, if needed), avoid gonadotoxins/heat exposure Lifestyle: Heart-healthy diet, moderate exercise, weight loss, ↓ EtOH, stop tobacco/marijuana/illicit drug use, ↓ stress Supplements: Limited evidence supporting use; daily MVI/? CoQ10 may have benefit; stop testosterone-like products Optimize chronic medical conditions (e.g., diabetes), sexual function
- Patient information: JAMA 2015;313:320;1770
PROSTATITIS
BACTERIAL PROSTATITIS
(AFP 2010;82:397; JAMA 1999;282:236; NEJM 2006;355:1690)
- Prostatitis: Acute or chronic (>3 mo) prostate inflammation, most commonly caused by bacteria; E. coli most common followed by other GNRs (Klebsiella, Proteus, Pseudomonas) & Enterococcus (Am J Med 1999;106:327); GC/CT can infect the prostate
- Complications: Bacteremia, pelvic abscess, metastatic infection, epididymitis Risk factors: Prostate biopsy, immunocompromise, anatomic abnormalities, urinary catheters/instrumentation, sexual activity Ddx: UTI, cystitis, urethritis, BPH, chronic pelvic pain syndrome, epididymoorchitis
| Acute Bacterial Prostatitis Chronic Bacterial Prostatitis | ||
| Symptoms | Sudden onset: fevers, chills, pelvic/perineal pain, dysuria, urgency, freq, hesitancy, weak stream, cloudy urine | May be subtle or asx: urgency, freq, hesitancy, weak stream, pain w/ ejaculation; consider in pts w/ recurrent UTIs |
| Exam (DRE) | Swollen, warm, tender prostate | Swollen, warm, tender prostate, or normal exam |
| Workup | U/A, UCx, urine gram stain; avoid prostatic massage (may lead to bacteremia); ✓ GC/CT | Compare midstream U/A, UCx, gram stain before & after 1 min prostate massage (⊕ if bacteria only in post, or post >10x pre-massage Ucx); ✓ GC/CT |
| Therapy | Empiric Tx (IV abx if acutely ill):
Gram ⊖ organisms: Ciprofloxacin 500 mg PO BID, levofloxacin 500 mg PO QD, or TMP-SMX DS PO BID; Gram ⊕: Cephalexin 500 mg PO q6h; GC/CT: see “STI” Tx 4–6 wk, adjust abx based on culture; β-lactams & nitrofurantoin have poor prostate penetration; for recurrent infections, treat w/ longer course (3 mo) w/ different abx |
|
| Referral indications: Urinary retention, severe sx, suspicion for prostatic abscess (e.g., fever for >36 h after appropriate abx tx initiated) | ||
- Patient information: JAMA 2012;307:527
CHRONIC PROSTATITIS / CHRONIC PELVIC PAIN SYNDROME
- Chronic pelvic pain for ≥3 of 6 mo; may be inflammatory or noninflammatory w/o infection; unclear if related to h/o bacterial or ongoing cryptic infection; usually dx of exclusion, so likely heterogeneous group of disorders rather than a single disorder
- Ddx: BPH, urethral stricture, prostatic abscess, prostate cancer, urethritis, epididymoorchitis, cystitis, proctitis, IBS, lumbar radiculopathy
- History: Pain in abdomen, rectum, prostate, perineum, penis, and/or testicles, dysuria, hesitancy, weak stream; similar presentation to chronic bacterial prostatitis, but negative UCx & no h/o UTIs; screen for sexual dysfunction, h/o abuse, depression/Ψ; ± pain w/ erections/ejaculation; consider UPOINT classification to guide dx/tx (www.upointmd.com)
- Exam: Abdomen, back/spine, rectal exam (prostate/pelvic muscle tenderness), detailed genital exam; ✓ for hernias, scrotal masses, hemorrhoids
- Workup: U/A, UCx (pre-and postprostate massage), STI testing; imaging guided by sx; prostate massage is typically done in a urologist’s office
- Treatment (AFP 2010;82:397; NEJM 2006;355:1690): Difficult to tx as likely a collection of different disorders; UPOINT classification can help guide tx (www.upointmd.com)
- Symptomatic treatment: NSAIDs or celecoxib useful if pain is primary symptom Antibiotics: Controversial but commonly used; RCT fail to show benefit, & no clear guidelines exist (often used >1 mo), may improve pain if bacterial source α–blockers é 5α- reductase inhibitors: Controversial but commonly used (JAMA 2011;305:78); RCT of alfuzosin failed to show benefit (NEJM 2008;359:2663); however, α-blockers ± 5α-reductase often trialed at least 3 mo, may be used w/ or w/o abx Other: Quercetin, pregabalin, gabapentin, nortriptyline; pelvic floor physical therapy; psychotherapy; referral to chronic pain specialist Urology referral: Persistent or severe pain/LUTS
SCROTAL & TESTICULAR LESIONS
Background
(AFP 2014;89:273)
- Any skin lesion (dermatitis, neoplasm, benign growth) can occur on scrotum & cause sx
- History: Onset, duration, severity, location, referral of pain, prior tx, exacerbating/ameliorating factors (voiding, BMs), assoc sx (fevers, chills, night sweats, wt loss), sexual hx, surgical hx, trauma, STI
- Workup: Color duplex U/S is imaging modality of choice when dx unclear
- Indications for referral: Surgical emergencies (→ ED immediately) for painful/ edematous scrotum in setting of injury, torsion, strangulated inguinal hernia
- Fournier gangrene (Emergent): Necrotizing fasciitis of perineum; painful/swelling/ induration of penis/scrotum/perineum, cellulitis/edema, ± crepitus, fever → ED
- Testicular torsion (Emergent): Testis twists around spermatic cord → hypoxia → ED
- Suspected cancer (Urgent): Intratesticular masses are CA until proven o/w → urology
ACUTE EPIDIDYMOORCHITIS
- Most common cause of scrotal pain; usually d/t infection (spread from urinary tract) or ischemia; orchitis alone rare unless viral
- Causes: Infectious: Bacterial (<35 y: STI; >35 y: E. coli), viral (mumps, coxsackie), granulomatous (TB); Noninfectious: Behçet syndrome (oral/genital ulcers, uveitis), amiodarone (pain at head of epididymis), tumor, prolonged sitting, heavy lifting
| Features of Acute Epididymitis | ||
| Acute Epididymitis | Testicular Torsion | |
| History | Acute or gradual onset, fever present | Sudden onset, fever absent, ± N/V |
| Exam | Testicle in nl position; pain in epididymis | Testicle may be “high riding” or horizontal; pain in testicle |
| Cremaster reflex | Present | Ipsilateral reflex may be absent |
| Scrotal U/S | ↑ blood flow | ↓ blood flow |
- Risk factors: Sexual activity, bladder outlet obstruction, urogenital malformation
- Exam: Swollen/tender spermatic cord ± testicle, ± urethral discharge
- Cremasteric reflex: Contraction of ipsilateral scrotum upon stroking inner thigh → assesses genitofemoral nerve; may be absent in torsion
- Workup: H&P, midstream U/A, UCx, STI testing (if at risk); urethral swab cx/GS if d/c
- Scrotal U/S: Usually not necessary (recommended for orchitis, r/o tumor/torsion)
- Treatment: Scrotal support, analgesics (NSAIDS, ± opiates), ice, empiric abx
- GC/CT suspected: Ceftriaxone + azithromycin/doxycycline, see “STI”
- If STI unlikely: Levofloxacin 500 mg PO QD × 10 d, tailor based on cx results
- Follow-up: Pain/fever usually resolves within 3 d, induration may last wk/mo; if no improvement: Re-evaluate, repeat cx, scrotal U/S; if STI, tx sexual partners, see “STI”
CHRONIC EPIDIDYMOORCHITIS – ORCHALGIA – EPIDIDYMALGIA
(Rev Urol 2003;5:209)
- Definition: Scrotal pain >3 mo; may be intermittent, bilateral, mild– severe pain, often part of chronic prostatitis/CPPS, see “Chronic Prostatitis/Chronic Pelvic Pain Syndrome”
- Risk factors: ? STI; often dx of exclusion so likely heterogeneous group of problems
- Exam: Epididymal tenderness (up to 50% will have nl exam); check external genitals, DRE (prostate/muscle tenderness), inguinal/lower abdomen, back/spine
- Workup: Assess LUTS, midstream U/A, UCx, STI testing; urethral swab cx/GS if d/c
- Scrotal ultrasound: Esp if indurated epididymis or difficult exam 2/2 pain/habitus
- Treatment: Typically self-limited, may take mo/y to resolve, very difficult to tx (limited data d/t heterogeneity); consider UPOINT classification to guide tx (www.upointmd.com)
- Conservative mgmt: NSAIDs, scrotal support, avoid painful activities, warm compresses, pelvic floor PT (if pelvic muscle tenderness) Opiates: Avoid d/t chronic nature of pain, strongly consider referral to pain specialist Empiric abx: 4–6 wk; evidence lacking for effectiveness/regimen Referral: For consideration of spermatic cord block (can repeat every couple of mo if effective); surgery (epididymectomy/orchiectomy) may not ↓ pain∴last resort
SPERMATOCELE/EPIDIDYMAL CYST
- Definition: Retention cyst of epididymal head; contain spermatozoa; found in 30% of ♂
- Exam: Nontender swelling behind/above (i.e., separate) from testicle, compression → pain
- Workup: U/S if dx in question
- Treatment: Typically asx → reassurance (may continue to grow); If sx → urology referral
HYDROCELE
- Definition: Fluid collection within tunica vaginalis; often present at birth, most resolve by 1 y; can spontaneously occur/recur/↑ size
- Risk factors: Scrotal trauma, scrotal infection, STI
- Exam: Painless swelling involving testicles, transilluminates
- Workup: U/S if doesn’t fully transilluminate, can’t assess testicle or other scrotal contents
- Treatment: Generally asx, no tx required; if pain or size limit activity → urology referral
VARICOCELE
- Definition: Dilation of testicular veins; very common, majority L side or b/l; unilateral R side rare; may be associated with infertility
- Exam: “Bag of worms” in scrotum, ↑ size w/ standing/Valsalva; may c/o dull pain/heaviness
- Workup: Consider abdominal CT or U/S to r/o retroperitoneal mass if unilateral R side or sudden onset/worsening
- Treatment: Generally asx; refer to urologist if painful, assoc w/ infertility or discrepant testicular size prior to attempting to conceive
TESTICULAR CANCER
(AFP 2008;77:469; NEJM 2014;371:2005)
- Pathology: Germ cell tumors (95%, seminoma/nonseminoma), sex cord stromal tumors
- Epidemiology: Most common tumor in ♂ 15–35 y; 8000 cases/y in US, 400 deaths/y (CA Cancer J Clin 2013;63:11)
- Risk factors: Cryptorchidism (surgery ↓ CA risk & facilitates monitoring), testicular dysgenesis, FHx, HIV (seminoma) (JCO 2003;21:1922)
- Screening: USPSTF recommends against routine screening in asx pts (Ann Intern Med 2011;154:483) d/t high cure rate and unclear mortality benefit (Cochrane Database Syst Rev 2011:CD007853); consider screening in pts w/ risk factors
- Exam: Intratesticular mass ± pain/swelling/hardness; does not transilluminate; usually unilateral, R > L; bilateral likely lymphoma; ✓ for gynecomastia
- Workup: Assume testicular mass CA until proven o/w → Color duplex U/S, ✓ tumor markers (AFP, LDH, β-hCG) → urgent urology referral
OTHER CAUSES OF SCROTAL PAIN/MASSES
- Strangulated inguinal hernia: Surgical emergency → ED
- Cutaneous scrotal abscess, infection of scrotal skin: I&D, abx rarely needed
- Pyocele: Infected hydrocele, 2° to scrotal/abdominal infection
- Torsion of testicular appendix: Must r/o testicular torsion; sudden onset pain often localized to superior aspect of testicle ± “blue dot sign” (40%), cremasteric reflex intact; Tx: Self-limited, none
- Mumps orchitis: Fever, HA, myalgia, parotid swelling
PROSTATE CANCER
Background
(JAMA 2014;311:1143; 2015;314:825; 2073; NEJM 2011;365:2013)
- Clinical heterogeneity: Varies from indolent (majority) to aggressive, rapidly lethal disease
- Epidemiology: Annually 240,000 US men dx, 30,000 deaths; 1 in 6 lifetime risk of dx, but 30% men >50 & 70–90% >80 y have prostate CA on autopsy; only ~3% die from prostate CA (CA Cancer J Clin 1997;47:273)
- Presentation: Most cases asx, detected by abnl PSA or DRE; urinary sx are usually a late finding ∴ LUTS usually not d/t prostate CA
- Risk factors:↑ age, African ancestry (earlier onset/more aggressive), obesity, family hx (1° >2° relative (esp if dx <65 y), BRCA1/2 carrier, Lynch syndrome
- Prevention: No recommended tx; 5a-reductase inhibitors (off label) ↓ incidence low grade but slight ↑ in high-grade CA, unclear benefit (NEJM 2011;365:97); vitamins do not ↓ risk (SELECT, JAMA 2009;301:39; 52)
- PSA: Secreted by nl prostate cells, good surrogate for prostate size; prostate CA, inflammation, trauma disrupt normal architecture → ↑ PSA; if ↑ PSA r/o benign causes repeat several wk later; 5a-reductase inhibitors ↓ PSA by ~50% and should be taken into account when interpreting PSA (J Urol 2005;174:877); role of PSA velocity, density, fractionation in detection of prostate CA unclear (Cancer 2007;109:1689)
- Factors that alter PSA: Increase: Age; ejaculation (up to 0.8 ng/mL for 48 h), prostatitis (PSA returns to baseline after 6–8 wk), prostate biopsy or TURP (levels may take 2–4 wk to normalize), acute urinary retention; DRE may increase PSA by 0.26–0.4 ng/mL; Decrease: Finasteride, dutasteride Interpretation: Cut-off for upper limit of normal controversial, and a value of 4.0 ng/mL typically used (Se 21%, Sp 91%, PPV 30%) (CA Cancer J Clin 2010;60:70); NPV 85% if PSA ≤4.0 (NEJM 2004;350:2239); role of PSA velocity, density, fractionation in detection of prostate CA unclear (Cancer 2007;109:1689)
- Digital rectal exam: Detects peripheral zone tumors, but ~30% of tumors arise in other parts of prostate; prostate CA may manifest as induration, a nodule, or asymmetry; Se 59%, Sp 94%, PPV 28%, NPV 99% (Fam Pract 1999;16:621)
- PSA/DRE are not diagnostic: CA found in 22% of PSA btw 2.6–9.9 ng/mL, 67% >10 ng/mL (JAMA 1997;277:1452; NEJM 1991;324:1156); no PSA completely r/o CA
| Benefits of Screening (Ann Int Med 2015;163:ITC1; NEJM 2011;365:2013) |
| Early detection & tx, some studies show CA-specific survival benefit, esp in pts at ↑ risk |
| ⊖ Results may provide reassurance |
| Risks of Screening |
| Bx and tx of tumors assoc with low but nonzero rates of impotence, incontinence, bowel problems, infection, pain, & mortality. Tumors might not have caused clinical problems |
| Cost & pt anxiety |
| Shared Decision-Making (Adapted from Ann Intern Med 2013;158:761; CA Cancer J Clin 2010;60:70) |
| (1) Inform pt prostate CA can be a serious problem that screening may detect at earlier stage |
| (2) Invite pt to participate in deciding whether or not to be screened; point out that pt may change his mind & decision is not urgent |
| (3) Inform pt that some trials found a mortality benefit w/ screening; discuss that evidence is mixed w/ some experts in favor & some against; review major society guidelines |
| (4) Inform pt that many prostate CA detected by screening might never have caused problems if left undetected & that these pts would likely have died of other causes |
| (5) Even if the PSA & DRE are nl, a pt may still have prostate CA; if the PSA or DRE are abnl a bx may be necessary & even this may not conclusively r/o cancer; PSA may be elevated for other reasons |
| (6) Tx of prostate CA, even if detected early, may entail surgery or radiation, which have significant s/e |
- Documentation: Discussion of risks/benefits of screening & shared decision-making esp if pt declines screening
- Refer for biopsy: Abnl DRE and/or PSA (usually ≥4 ng/mL, or significant ↑); consider referral to urologist if strong family hx or high risk
- Patient information: cancer.org/prostatemd (American Cancer Society, links to video for pts on risks/benefits of screening); www.prosdex.com/index_content.htm; uspreventiveservicestaskforce.org/prostatecancerscreening/prostatecan (USPSTF); http://www.mayoclinic.com/health/prostatecancer/HQ01273 (Mayo Clinic)
|
Prostate CA Screening Guidelines |
||||
| Recommendation | USPSTF | AUA | ACP | ACS |
| Shared decision- making | On pt request (Ann Intern Med 2012;157:120) | Yes (J Urol
2013;190:419) |
Yes | Yes |
| Age to discuss screening | Recommends against screening | 55–69 y; discuss w/ men <55 y if high risk† | 50–69 y unless high risk† | 50 y if avg-risk, 40–45 y if high riska |
| Stop screening | N/A | 70 y or life expectancy
<10–15 y |
<50 y, >69 y, life
expect <10–15 y |
Life expectancy
<10 y |
| Screening tests | N/A | PSA | PSA + DRE | PSA ± DRE |
| Freq of screening | N/A | q1–2 y | PSA >2.5 q1 y | PSA >2.5 q1 y PSA <2.5 q2 y |
| Criteria for bx referral | N/A | Consider age, FHx, race, DRE, PSA
(total, free, velocity, density), prior bx, PMHx |
PSA ≥4, abnl DRE
PSA 2.5–4, individualized risk eval |
|
aAfrican-American pts & those w/ 1st-degree relatives w/ prostate cancer diagnosed before 65 y.