These prescription oral medications, best known for erectile problems, relax blood vessels. Controlled trials support benefits for erections, enlarged-prostate urinary symptoms and high blood pressure in the lungs. Health records link use to fewer heart attacks and longer survival, size unknown; Alzheimer's findings conflict. Common side effects are usually mild; with nitroglycerin-type heart medications or "poppers", blood pressure can drop severely. Daily use against blood-vessel aging is plausible but unproven. (Full Review)

Protocol

Daily low-dose tadalafil

2.5–5 mg once daily

Labeled regimen for daily erectile use and enlarged-prostate urinary symptoms

On-demand sildenafil

25–100 mg (commonly 50 mg)

30–60 minutes before sexual activity; at most once daily

On-demand tadalafil

10–20 mg

At least 30 minutes before activity; at most once daily; effect lasts up to 36 hours

Time to effect

Erections (on demand)

30–120 minutes

Sildenafil 30–60 minutes; tadalafil 30–120 minutes

Urinary benefit (daily tadalafil)

1–4 weeks

Steady state in about 5 days

Vascular effects

Months to years

If real, would accrue over this span

Benefits

High: Improved erectile function; relief of enlarged-prostate urinary symptoms; better exercise capacity and survival with high blood pressure in the lung arteries; fewer Raynaud's attacks; lower blood pressure and improved vascular function; heart failure exercise capacity

Medium: Fewer cardiovascular events and lower all-cause mortality; sexual function in women with antidepressant-associated dysfunction

Low: Lower Alzheimer's disease risk; improved insulin sensitivity; sperm motility in infertile men

Speculative: Increased brain blood flow in small vessel disease; browning of white fat

Contraindications

Organic nitrates and nitric oxide donors (nitroglycerin, isosorbide mononitrate, nicorandil; withheld 24 hours after sildenafil or vardenafil, 48 hours after tadalafil)

Alkyl nitrite inhalants ("poppers", amyl nitrite) or riociguat

Resting hypotension (below 90/50 mmHg) or uncontrolled hypertension (above 170/110 mmHg)

Heart attack, stroke or life-threatening arrhythmia within the past 6 months

Unstable angina or angina during sexual intercourse

Advanced heart failure (New York Heart Association Class III–IV)

Severe aortic stenosis or hypertrophic obstructive cardiomyopathy

Severe liver impairment (Child-Pugh Class C) or creatinine clearance below 30 mL/min (daily tadalafil)

Hereditary retinal degeneration, including retinitis pigmentosa, or prior NAION (sudden optic-nerve vision loss) in either eye

Sickle cell disease with pulmonary hypertension; pregnancy (erectile or longevity use)

Key Interactions

Soluble guanylate cyclase stimulators (vericiguat; not recommended)

Alpha-blockers (doxazosin, tamsulosin)

Strong CYP3A4 inhibitors (ritonavir, clarithromycin)

CYP3A4 inducers (rifampin, carbamazepine) and St. John's wort

Antihypertensives (amlodipine, losartan, lisinopril)

QT-prolonging antiarrhythmics with vardenafil (amiodarone, sotalol)

Cimetidine; grapefruit juice; alcohol (heavy intake)

L-arginine, L-citrulline, horny goat weed (Epimedium, icariin) and yohimbe

Sexual enhancement supplements

Blood-pressure-lowering supplements (beetroot nitrate, garlic, hibiscus)

Penile injection therapy (alprostadil) or other erectile treatments

Sauna and hot-tub exposure

Risk & Side Effects

High: Headache, flushing and nasal congestion; indigestion and reflux; back pain and muscle aches; blood-pressure drop with nitrates or alpha-blockers; transient visual disturbances

Medium: Sudden hearing loss

Low: Sudden optic-nerve vision loss; melanoma; prolonged erection

Speculative: Retinal harm in carriers of retinal degeneration mutations

Monitoring

Marker	Target	Why
Blood pressure (seated and standing)	Below 120/80 mmHg seated; standing drop under 20/10 mmHg	Hypotension risk; vascular effect
ApoB	Below 80 mg/dL (below 60 mg/dL at high risk)	Atherosclerosis driving erectile dysfunction
HbA1c	4.8–5.4%	Sugar damage to vessels and nerves
Total testosterone (morning)	500–900 ng/dL	Low levels blunt response
eGFR	Above 90 mL/min/1.73 m²	Guides tadalafil dosing
ALT	Below 25 U/L	Liver clears all agents
hs-CRP	Below 1.0 mg/L	Vascular inflammation
IIEF-5 score	22–25	Erectile response
IPSS	0–7	Urinary benefit of daily tadalafil
Eye examination (acuity, optic disc)	No established target; track change from own baseline	Optic-nerve risk

Cadence: Blood pressure at 1–2 weeks and after dose changes; symptom scores at 4–12 weeks; then blood pressure, lipids, HbA1c and kidney function every 6–12 months; annual skin examination for those with melanoma risk factors; immediate evaluation for sudden vision or hearing change

Qualitative Assessment

Erection firmness, reliability and confidence during sexual activity
Frequency of spontaneous morning erections
Night-time urination frequency and urinary stream strength
Exercise tolerance and energy during daily activities
Side-effect diary: headache, flushing, reflux, back pain, dizziness on standing
Any change in color vision, visual field or hearing
Sexual and relationship satisfaction

PDE5 Inhibitors for Health & Longevity

Protocol

Benefits

Risk & Side Effects

Monitoring

Qualitative Assessment