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Research · Medication

PDE5 inhibitors

In short trials, intercourse success was 69% on PDE5 inhibitors and 35% on placebo. In low-oxygen conditions, sildenafil raised maximum workload in one trial and cut time-trial time in another. A third altitude trial found no change. At sea level, sildenafil and tadalafil did not change performance. Combining these drugs with nitrates can drop blood pressure.

Add to Bio HackChecked 2026-11-09
Status
Prescription drugs in the US. Sildenafil is FDA-approved as Viagra for erectile dysfunction and as Revatio for pulmonary arterial hypertension. Tadalafil is FDA-approved as Cialis for erectile dysfunction and benign prostatic hyperplasia, and as Adcirca for pulmonary arterial hypertension.
Also called
sildenafil, Viagra, Revatio, tadalafil, Cialis, Adcirca, vardenafil, Levitra, avanafil, phosphodiesterase-5 inhibitors, PDE5i
Taken for
erectile dysfunction, sexual performance, exercise performance, endurance, altitude

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help3

Reported risks4

What people take it for, and what was found

Shown to help3

StrongStudied in menVery common

Erections and intercourse success

Shown to raise intercourse success to about 69% against 35% on placebo in men with erectile dysfunction, with no difference between sildenafil, vardenafil and tadalafil.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Intercourse success was 69.0% on PDE5 inhibitors and 35.0% on placebo. Improved erections were reported by 67% to 89% on treatment and 27% to 35% on placebo. In head-to-head trials, sildenafil, vardenafil and tadalafil did not differ [1]. A network meta-analysis found sildenafil 50 mg had the greatest efficacy of starting doses and tadalafil 10 mg had the lowest overall adverse event rate [2].
Population
RCTs of men with erectile dysfunction, mostly 12 weeks or shorter [1]; 82 trials with 47,626 men for efficacy [2].
Sources
[1], [2]
Caveats
Many trials were of low methodological quality and short [1]. [1] was funded by the Agency for Healthcare Research and Quality.
Limited

Exercise in low oxygen or at altitude

Small trials found sildenafil raised exercise capacity only at very low oxygen, about 3,900 m and above, with no change at lower altitudes.

The numbers and sources
Effect
Results differ by trial. Breathing 10% oxygen at low altitude, sildenafil 50 mg raised maximum workload to 172.5 W against 130.6 W on placebo. At Mount Everest base camp it also raised maximum workload and lowered pulmonary artery pressure [3]. At a simulated 3,874 m, sildenafil cut 6 km time-trial time by 15%. Responders improved 39% and nonresponders 1.0% [4]. At simulated altitudes of about 2,100 m and 3,900 m, sildenafil 50 mg did not change peak power or 15 km time-trial times, though oxygen saturation was 3% higher at the higher altitude [5].
Population
14 healthy mountaineers and trekkers [3]; 10 trained men [4]; 11 trained men and 10 trained women [5].
Sources
[3], [4], [5]
Caveats
Small crossover trials of single doses. The positive results came from very low oxygen levels (about 3,900 m and above). The authors of [5] state benefits are unlikely below 4,000 m.
Limited

Walking distance in pulmonary arterial hypertension

One trial found walking distance rose about 45 to 50 m more than placebo over 12 weeks in people with pulmonary arterial hypertension.

The numbers and sources
Effect
After 12 weeks, six-minute walk distance rose by 45 m, 46 m and 50 m more than placebo on 20, 40 and 80 mg three times daily. Mean pulmonary artery pressure fell and functional class improved. Clinical worsening did not differ from placebo [6].
Population
278 patients with symptomatic pulmonary arterial hypertension [6].
Sources
[6]
Caveats
One trial, not powered for mortality. It describes people with the disease, not healthy athletes.

Doses studied

The altitude and exercise trials used single doses of sildenafil 50 mg or 100 mg [3][4][5]. The pulmonary hypertension trial used sildenafil 20, 40 or 80 mg three times daily for 12 weeks [6]. The erectile dysfunction network meta-analysis compared starting doses of sildenafil 50 mg, tadalafil 10 mg, vardenafil 10 mg and avanafil 100 mg [2].

Risks

Reported risks3

StrongHow often is not known

Headache, flushing and other common effects

Shown to raise side effects such as headache and flushing, about 1.7 times placebo for sildenafil, with tadalafil 10 mg lowest among starting doses.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
PDE5 inhibitors raised the risk of any adverse event against placebo, for example RR 1.72 (95% CI 1.53 to 1.93) for sildenafil [1]. Among starting doses, sildenafil 50 mg had the highest overall adverse event rate and tadalafil 10 mg the lowest [2]. In pulmonary hypertension, flushing, dyspepsia and diarrhea were reported [6]. At altitude, sildenafil worsened existing headache in 2 of 14 participants [3]. The Cialis label lists headache, dyspepsia, back pain, muscle pain, nasal congestion and flushing as the most common reactions [7].
Population
Trial participants in [1], [2], [3] and [6]; label [7].
Sources
[1], [2], [6], [3], [7]
Caveats
Most trial data are short term [1].
LimitedHow often is not known

Low blood pressure with nitrates

The labels list use with nitrates as a contraindication, because blood pressure can drop, and warn of low blood pressure with alpha-blockers or heavy alcohol.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Both labels list use with organic nitrates as a contraindication, because the drugs potentiated the blood-pressure-lowering effect of nitrates in clinical pharmacology studies [8][7]. The Viagra label names nitrites in any form, and its patient information lists "poppers" such as amyl nitrite [8]. The Cialis label states that in a life-threatening situation, nitrates are considered only once at least 48 hours have passed since the last dose [7]. Both labels also warn of low blood pressure with alpha-blockers, other blood pressure drugs or large amounts of alcohol [8][7].
Population
Clinical pharmacology studies summarized in the labels [8][7].
Sources
[8], [7]
Caveats
Label statements, not trial rates.
LimitedHow often is not known

Sudden vision or hearing loss

The label warns of sudden vision loss from NAION and sudden hearing loss. Case reports describe 54 people with hearing loss, and of 7 followed, 4 did not improve.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The Cialis label warns that sudden loss of vision in one or both eyes could be non-arteritic anterior ischemic optic neuropathy (NAION), and notes higher risk with a prior NAION or a crowded optic disc. It also warns of sudden decrease or loss of hearing [7]. A systematic review of published cases found 54 people with moderate to profound sensorineural hearing loss while using PDE5 inhibitors, most often sildenafil, vardenafil or tadalafil. Of 7 with follow-up after stopping, 4 did not improve, 2 recovered fully and 1 partly [9].
Population
Postmarketing reports summarized in the label [7]; 54 patients aged 37 to 62 in 6 studies [9].
Sources
[7], [9]
Caveats
Postmarketing reports and case series cannot give a rate or establish cause. [9] had no control group.

Mixed results1

ModerateStudied in menHow often is not known

Melanoma

Mixed results: one cohort linked sildenafil to melanoma, while a meta-analysis found a small link it judged not causal, likely from sun exposure.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In a cohort of US men, recent sildenafil use was associated with melanoma (HR 1.84, 95% CI 1.04 to 3.22), while squamous and basal cell skin cancers were not raised [10]. A meta-analysis of 5 observational studies found a relative risk of 1.11 (95% CI 1.02 to 1.22). The association appeared only with low exposure and early-stage melanoma, and PDE5 inhibitor use was also linked to basal cell cancer. The authors concluded it did not meet criteria for a causal link, pointing to sun exposure as a likely confounder [11].
Population
25,848 men in the Health Professionals Follow-up Study, 142 melanomas [10]; 866,049 men in 5 studies [11].
Sources
[10], [11]
Caveats
Both sources are observational. They disagree on interpretation. [10] reports a signal, while [11] judges it not causal.

Claims tested and not found

  1. That PDE5 inhibitors improve exercise performance at sea level. At sea level, sildenafil 50 or 100 mg had no effect on any cardiovascular or performance measure in trained cyclists [4]. Tadalafil 20 mg did not change VO2max or ventilatory and anaerobic thresholds in athletes, and lowered systolic blood pressure [12].

Sources

  1. Tsertsvadze A, Fink HA, Yazdi F, et al. Oral Phosphodiesterase-5 Inhibitors and Hormonal Treatments for Erectile Dysfunction: A Systematic Review and Meta-analysis. Annals of Internal Medicine. 2009. https://doi.org/10.7326/0003-4819-151-9-200911030-00150
  2. Chen L, Staubli SE, Schneider MP, et al. Phosphodiesterase 5 Inhibitors for the Treatment of Erectile Dysfunction: A Trade-off Network Meta-analysis. European Urology. 2015. https://doi.org/10.1016/j.eururo.2015.03.031
  3. Ghofrani HA, Reichenberger F, Kohstall MG, et al. Sildenafil Increased Exercise Capacity during Hypoxia at Low Altitudes and at Mount Everest Base Camp. Annals of Internal Medicine. 2004. https://doi.org/10.7326/0003-4819-141-3-200408030-00005
  4. Hsu AR, Barnholt KE, Grundmann NK, et al. Sildenafil improves cardiac output and exercise performance during acute hypoxia, but not normoxia. Journal of Applied Physiology. 2006. https://doi.org/10.1152/japplphysiol.00806.2005
  5. Kressler J, Stoutenberg M, Roos BA, et al. Sildenafil does not improve steady state cardiovascular hemodynamics, peak power, or 15-km time trial cycling performance at simulated moderate or high altitudes in men and women. European Journal of Applied Physiology. 2011. https://doi.org/10.1007/s00421-011-1930-3
  6. Galiè N, Ghofrani HA, Torbicki A, et al. Sildenafil Citrate Therapy for Pulmonary Arterial Hypertension. New England Journal of Medicine. 2005. https://doi.org/10.1056/NEJMoa050010
  7. U.S. Food and Drug Administration. CIALIS (tadalafil) tablets, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcd8f8ab-81a2-4891-83db-24a0b0e25895
  8. U.S. Food and Drug Administration. VIAGRA (sildenafil citrate) tablets, prescribing information. 2023. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d905dc8d-917f-4ea3-a4ee-a1ecf6967d4e
  9. Pinkus P, Farsi S, Strickland WD, et al. Sensorineural Hearing Loss and Phosphodiesterase-5 Inhibitors: A Systematic Review. International Archives of Otorhinolaryngology. 2026. https://doi.org/10.1055/s-0046-1820094
  10. Li WQ, Qureshi AA, Robinson KC, Han J. Sildenafil Use and Increased Risk of Incident Melanoma in US Men. JAMA Internal Medicine. 2014. https://doi.org/10.1001/jamainternmed.2014.594
  11. Loeb S, Ventimiglia E, Salonia A, et al. Meta-Analysis of the Association Between Phosphodiesterase Inhibitors (PDE5Is) and Risk of Melanoma. Journal of the National Cancer Institute. 2017. https://doi.org/10.1093/jnci/djx086
  12. Di Luigi L, Baldari C, Pigozzi F, et al. The Long-Acting Phosphodiesterase Inhibitor Tadalafil does not Influence Athletes' VO2max, Aerobic, and Anaerobic Thresholds in Normoxia. International Journal of Sports Medicine. 2008. https://doi.org/10.1055/s-2007-965131

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