Peyronie's Disease: First-Line Treatment

Overview of Disease Phases - Guides Treatment Timing

• Acute/active phase (first 6-18 months): penile pain, progressive curvature, growing plaques. Medical/nonsurgical treatment is appropriate here.
• Chronic/stable phase (after 12-24 months): pain resolves, deformity stabilizes. Surgery is considered if deformity prevents intercourse.

First-Line (Nonsurgical) Treatment - Acute Phase

1. Intralesional Collagenase Clostridium Histolyticum (CCH / Xiaflex) - Gold Standard

• The only FDA-approved pharmacological treatment for Peyronie's disease
• Directly injected into the plaque to enzymatically break down excess collagen
• Protocol: Multiple treatment cycles, each consisting of 2 injections separated by 1-3 days; cycles spaced at least 6 weeks apart
• Penile modeling (manual stretching/bending) is an essential component, starting 48 hours after the second injection of each cycle
• Restricted under a Risk Evaluation and Mitigation Strategy (REMS) program
• Adverse effects: Local pain, bruising, swelling, ecchymosis; rare but serious: penile fracture (corporal rupture) requiring surgical repair
• Best evidence in curvatures of 30-90 degrees with palpable, non-calcified plaque

2. Pentoxifylline (Oral) - First-Line Oral Agent

• Recommended as first-line oral therapy, used as a key component of multimodal treatment
• Nonspecific phosphodiesterase inhibitor; inhibits TGF-β1-mediated inflammation, prevents type 1 collagen deposition, and increases nitric oxide
• Best used in the active phase in combination with intralesional injection and penile traction
• Smith and Tanagho's General Urology, 19th Ed.

3. Penile Traction Therapy (PTT)

• A mechanical adjunct used alongside medical treatment
• Applies consistent tension to the penis to help counteract shortening and deformity
• Recommended as part of multimodal therapy during the acute phase

4. Other Intralesional Options (if CCH unavailable)

• Verapamil - calcium channel blocker; inhibits fibroblast proliferation and collagen synthesis
• Interferon-alpha-2b - inhibits fibroblast proliferation; shown efficacy in RCTs
• Both have evidence from randomized trials, though neither is FDA-approved specifically for PD

Agents with Limited/No Recommended Role

• Vitamin E, colchicine, tamoxifen, L-carnitine, potaba (potassium aminobenzoate), PDE5 inhibitors as monotherapy, omega-3 fatty acids, coenzyme Q10

• Iontophoresis, topical treatments, extracorporeal shockwave therapy (ESWT), radiation therapy

Surgery - Reserved for Stable Phase

• Disease has been stable for at least 12 months
• Penile deformity prevents satisfactory intercourse
• ED accompanies severe deformity

• Plication (Nesbit's procedure / 16-dot technique) - shortens the longer convex side; suitable when adequate penile length present
• Plaque incision/excision + grafting (bovine pericardial patch, vein graft, dermal graft) - for severe curvature or short penis
• Penile prosthesis implantation - preferred when concomitant ED is present; straightens the penis mechanically

2025 EAU Guideline Update

Summary Table

Dietary Instructions to Prevent Kidney Stone Formation

Guiding Principle

Universal Dietary Measures (All Stone Types)

1. High Fluid Intake - Most Important Intervention

• Target urine output: >2.0-2.5 L/day
• When urine output falls below 1 L/day, the risk of stone formation more than doubles
• A randomized controlled trial demonstrated that higher fluid intake significantly reduces stone recurrence
• Drink enough fluid in the evening to produce nocturia, then drink again before returning to sleep (nighttime = peak risk period due to physiologic urine concentration)
• Best beverages: Water, coffee, tea, beer, wine, orange juice - all associated with reduced stone risk in observational studies
• Avoid: Sugar-sweetened beverages (colas, fruit punch) and high-fructose drinks - increase risk, contribute to uric acid lithiasis, and cause weight gain

2. Restrict Dietary Sodium

• Target: <2 g sodium/day (87 mmol/day)
• Urine sodium excretion directly correlates with urine calcium excretion
• High sodium intake promotes hypercalciuria, increasing calcium oxalate and calcium phosphate supersaturation
• Salt restriction is one of the most effective ways to reduce urinary calcium

3. Moderate (Not Low) Dietary Calcium - Critical Counterintuitive Point

• Historically, calcium restriction was prescribed - this is now known to be harmful
• Multiple prospective studies and an RCT show that higher dietary calcium = lower stone risk
• Mechanism: dietary calcium binds intestinal oxalate, preventing its absorption and lowering urine oxalate
• Low-calcium diets are contraindicated - they increase stone risk and promote bone demineralization
• Target: age- and sex-appropriate intake (~1000-1200 mg/day)
• Landmark RCT: men on a normal-calcium, low-sodium, low-animal protein diet had 50% fewer recurrent stones over 5 years compared to men on a low-calcium diet

Calcium supplements vs. dietary calcium: Dietary calcium from dairy is preferred. Calcium supplements (especially taken away from meals) may paradoxically increase stone risk, as they do not bind intestinal oxalate effectively and may cause transient hypercalciuria.

4. Restrict Animal Protein

• Target: moderate intake (avoid excess meat, poultry, fish, shellfish)
• Animal protein increases stone risk via multiple mechanisms:
  • Generates sulfate ions that reduce calcium solubility
  • Causes metabolic acidosis → calcium release from bone → hypercalciuria
  • Acidosis reduces tubular calcium reabsorption (more calcium in urine)
  • Acidosis decreases urinary citrate excretion (citrate is a key inhibitor)
  • Increases urinary uric acid excretion
• Net effect: higher urine calcium + lower citrate = markedly increased lithogenesis

5. Reduce Oxalate-Rich Foods (Especially in Calcium Oxalate Stone Formers)

• Urine oxalate is a strong independent risk factor for calcium oxalate stone formation
• Foods high in oxalate to limit:
  • Spinach (very high - a single serving can significantly raise urine oxalate)
  • Rhubarb, beets, Swiss chard
  • Nuts and nut butters (peanuts, almonds)
  • Chocolate and cocoa
  • Tea (especially black tea in large quantities)
  • Wheat bran, soy products
• Consuming adequate dietary calcium WITH oxalate-rich foods helps bind oxalate in the gut before absorption

6. Increase Potassium and Plant-Based Foods

• Higher potassium intake decreases urine calcium excretion
• Potassium-rich foods (fruits, vegetables, legumes) raise urine pH and citrate excretion due to their alkali content
• Citrate is the most important natural inhibitor of calcium stone formation
• A diet rich in fruits and vegetables (DASH-style diet) is protective

7. Avoid High-Dose Vitamin C Supplements

• Vitamin C (ascorbic acid) is metabolized to oxalate
• High-dose vitamin C supplements (>1000 mg/day) are associated with increased calcium oxalate stone risk in men
• Stop vitamin C or multivitamins >100 mg ascorbic acid at least 5 days before any 24-hour urine collection

Stone-Type Specific Dietary Advice

Calcium Oxalate Stones (Most Common ~80%)

Uric Acid Stones

• Restrict purines: organ meats (liver, kidney), anchovies, sardines, herring, red meat, shellfish
• Restrict animal protein broadly (raises urine uric acid + lowers urine pH)
• Avoid fructose/sugar-sweetened beverages (increase uric acid production)
• Increase alkaline foods (fruits, vegetables) - uric acid crystallizes at low pH; raising urine pH to 6.0-6.5 dissolves uric acid stones
• High fluid intake mandatory

Struvite (Infection/Magnesium Ammonium Phosphate) Stones

• Dietary measures have limited direct impact
• Primary prevention is treating and preventing UTI with urease-producing bacteria
• Adequate fluid intake remains important

Cystine Stones

• Very high fluid intake is the cornerstone: target urine output >3 L/day
• Restrict sodium and animal protein (methionine from animal protein is a cystine precursor)
• Alkalinizing foods (fruits/vegetables) help increase urine pH, raising cystine solubility
• Dietary restriction alone is usually insufficient; pharmacologic therapy (D-penicillamine, tiopronin) is generally also needed

Summary Table

• Comprehensive Clinical Nephrology, 7th Ed.
• Harrison's Principles of Internal Medicine, 22nd Ed.
• National Kidney Foundation Primer on Kidney Diseases, 8th Ed.

Safety of Lidocaine/Prilocaine Spray for Premature Ejaculation

Important Terminology Clarification First

What the Product Is

Overall Safety Profile: Generally Well Tolerated

• Mild to moderate local numbness occurred in only 3 of 25 (12%) treated men
• None discontinued due to adverse effects
• The spray was considered easy to use by 83% of participants

• Treatment-emergent adverse events (TEAEs) occurred in 38.9% of men (vs. 50% placebo) - most mild
• No grade ≥3 adverse events, no serious adverse events, no withdrawals due to adverse effects
• Plasma concentrations of lidocaine and prilocaine were far below anticipated minimum toxic concentrations
• Both drugs cleared rapidly after application with no clinically significant accumulation even with repeated dosing (21 days)
• Area under the curve of metabolites was ≤20% of parent drugs

Local (Topical) Side Effects

Systemic Safety

• Lidocaine and prilocaine plasma levels remain well below toxic thresholds
• Rapid clearance, no accumulation with regular use
• No cardiovascular or CNS toxicity reported in trials

• This risk is dose-dependent and relevant at large doses (e.g., prolonged EMLA over large skin areas in infants)
• At the tiny doses used for penile application (2.5-5 mg prilocaine per application), clinically significant methemoglobinemia has not been reported
• Higher risk in patients with G6PD deficiency, congenital methemoglobinemia, or those taking oxidizing drugs (sulfonamides, metoclopramide, nitrates)

Who Should Use With Caution or Avoid

Efficacy Summary (Context for Risk-Benefit)

• TEMPE/PSD502 increased mean intravaginal ejaculatory latency time (IELT) from baseline by 3.8 min vs. 0.7 min for placebo in the pivotal RCT
• Adjusted improvement: IELT 2.4x longer than placebo (p<0.01)
• Ejaculatory control and sexual quality of life scores improved for both men and their partners

Practical Safety Instructions

1. Apply 3 sprays to the glans 5-15 minutes before intercourse
2. Wipe off excess or use a condom before penetration to protect partner
3. Titrate dose - start with fewer sprays and increase if needed; avoid over-anesthesia that impairs erection
4. Do not use with damaged or inflamed penile skin
5. Avoid in men with known amide local anesthetic allergy

Bottom Line

1. Local penile numbness (dose-dependent, manageable by dose titration)
2. Partner vaginal numbness if a condom is not used
3. Rare risk of methemoglobinemia in susceptible individuals (G6PD deficiency)

• Kaplan & Sadock's Comprehensive Textbook of Psychiatry
• Smith & Tanagho's General Urology, 19th Ed.
• Campbell-Walsh-Wein Urology
• PMID: 17129234 | PMID: 37380910 | PMID: 30057136