Sildenafil
Sildenafil is the prototype PDE5 inhibitor, originally developed as an antianginal and repurposed as the first oral erectile-dysfunction drug. In the PED context it is used both for erectile function (androgen users on heavily suppressive cycles or 19-nor compounds frequently report ED) and as a peripheral vasodilator for the training 'pump'. It is fast-acting and short-lived, with a large clinical safety database, but is dangerous when combined with nitrates.
01 Overview
Sildenafil inhibits phosphodiesterase type 5, the enzyme that degrades cyclic GMP in vascular smooth muscle. Higher cGMP prolongs nitric-oxide-mediated smooth-muscle relaxation, increasing blood flow into the corpus cavernosum during sexual stimulation. It requires sexual arousal to work — it does not by itself initiate an erection. Onset is roughly 30-60 minutes and duration around 4 hours.
Among androgen users it addresses erectile dysfunction that arises from crashed oestradiol, elevated prolactin (notably on nandrolone/trenbolone), or blood-pressure medication. It is also taken pre-workout as a vasodilator to enhance the muscle pump. The main hazards are a profound, potentially fatal drop in blood pressure with any nitrate, and additive hypotension with other vasodilators and alpha-blockers.
02 Mechanism
Selective, reversible inhibition of phosphodiesterase type 5 (PDE5), raising cGMP in vascular and cavernosal smooth muscle and potentiating nitric-oxide-mediated vasodilation.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Pulmonary hypertension (label) | 20 mg/day | Oral | Revatio dosing, three times daily; not for ED use. |
| Low | 25 mg | Oral | Starting dose for the ED-naive, elderly, or those on interacting drugs. |
| Erectile function | 50–100 mg | Oral | Taken ~30-60 min before activity; max one dose per day. 100 mg is the label ceiling. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Improved erectile functionReliably restores erection sufficient for intercourse in most men with organic or drug-induced ED. | ~70-80% responder rate | Clinical | |
| Peripheral vasodilation ('pump')Increased skeletal-muscle blood flow reported pre-workout; supported by some exercise-performance data at altitude. | modest | Observational |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Headache and facial flushingVasodilatory headache, flushing and nasal congestion are the most frequent complaints. | Mild | Very common | Clinical | |
| Visual disturbanceTransient blue-tinged vision, light sensitivity or blurring from weak PDE6 cross-inhibition in the retina. | Mild | Common at higher doses | Clinical | |
| Nitrate interaction (severe hypotension)Combined with organic nitrates or nitric-oxide donors, cGMP potentiation causes a catastrophic drop in blood pressure. | Life-threatening | Rare but potentially fatal | Clinical |