Evidence memo / Anabolic androgens & PEDs

Tadalafil (off-label performance use)

Also: Cialis · tadalafil daily · Adcirca

An approved PDE5 inhibitor with genuine evidence in erectile dysfunction, prostate symptoms and pulmonary hypertension, taken daily in the strength world for blood flow and pumps on evidence that mostly is not about performance at all.

Approved for specific usesPost-market evidenceInvestigationalSafety / regulatory watch

The verdict

Our read at a glance.

Whether daily vasodilation produces a training or body-composition benefit beyond the approved indications.

The signal
The approved evidence is strong across three separate indications - erectile dysfunction, the lower urinary tract symptoms of benign prostatic hyperplasia, and pulmonary arterial hypertension - with labelled products and large trial programmes, including a daily low-dose regimen. Research has also examined its endothelial and metabolic effects, which is where the performance rationale comes from. What is missing is a demonstration that any of that translates into training adaptation, strength or body composition in healthy people; the pump is real vasodilation and has not been shown to produce a downstream benefit.
The unknown
Whether chronic PDE5 inhibition in healthy young men does anything useful or anything harmful over years, since the long-term data come from older men with the approved conditions.
Our read
A well-evidenced drug being used for something it has never been tested for. The vasodilation is real and immediately noticeable, which is exactly why people conclude it is doing more than it has been shown to do. The nitrate and stacked-vasodilator interaction is the part that actually matters.

The mechanism

How it works.

Nitric oxide released in vascular tissue activates guanylate cyclase, producing cyclic GMP, which relaxes smooth muscle and dilates vessels. Phosphodiesterase type 5 is the enzyme that degrades cyclic GMP and ends that signal. Tadalafil inhibits PDE5, so cyclic GMP persists and vasodilation is sustained - in the corpus cavernosum, which is the erectile indication, in prostatic and bladder smooth muscle, which is the BPH indication, and in pulmonary vasculature, which is the pulmonary hypertension indication. Its long half-life is what makes daily dosing practical and produces continuous rather than episodic effect. The performance rationale extends this to skeletal muscle: more blood flow means more oxygen and nutrient delivery, and the visible pump is that mechanism working. Whether sustained vasodilation improves training adaptation is a separate question, and it has not been answered.

Safety & regulatory boundary

The consequential part.

Approved for the indications above; daily use for pumps or performance is off-label. The critical interaction is with nitrates, where the combination can cause profound and dangerous hypotension, and it should be used cautiously with alpha-blockers and other vasodilators - including the citrulline and nitric-oxide precursors common in this population. Rare but serious reported events include non-arteritic anterior ischaemic optic neuropathy and sudden hearing loss. Prohibited in some sporting contexts.

What's next

What we're watching.

Any trial with training or body-composition endpoints, and long-term data in young healthy users.

Context

Why this is discussed.

It is prescribed daily at low dose legitimately, it improves the pump noticeably, and it is used to offset the sexual side effects of other compounds.

The evidence base

23 cited references.

Regulatory & labels3

DailyMed label: tadalafil

A-S Medication Solutions (FDA label) · 2024

DailyMed label: Tadalafil

Aurobindo Pharma Limited (FDA label) · 2024

DailyMed label: TADALAFIL

Solco Healthcare US, LLC (FDA label) · 2025

Indexed literature (PubMed)12

Benign prostatic hyperplasia

Infante Hernández S et al. · Med Clin (Barc) · 2024

Benign Prostatic Hyperplasia

Langan RC · Prim Care · 2019

Benign prostatic hyperplasia - what do we know?

Devlin CM et al. · BJU Int · 2021

Benign Prostatic Hyperplasia

Am Fam Physician · Am Fam Physician · 2023

Benign Prostatic Hyperplasia

Kaplan SA · J Urol · 2023

Benign Prostatic Hyperplasia

Kaplan SA · J Urol · 2023

Benign Prostatic Hyperplasia

Kaplan SA · J Urol · 2023

Benign prostatic hyperplasia

Bruskewitz R · J Urol · 1997

Benign Prostatic Hyperplasia

Kaplan SA · J Urol · 2023

Keep reading

Related published memos.