Erectile dysfunction
Persistent inability to achieve or maintain an erection sufficient for intercourse. AUA 2018 and EAU 2023 list PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) as first-line. Cardiovascular risk and testosterone level should be assessed. International guidelines do not include herbal preparations or supplements.
ICD-10 N52.911 drugs
Also known as: ED, Impotence
Drugs used for this condition
- ASildenafilFirst line · Phosphodiesterase type 5 inhibitors (PDE5)First-line for erectile dysfunction per AUA 2018 and EAU 2024. Standard dose 50 mg taken 30–60 minutes before intercourse; titrate up to 100 mg or down to 25 mg. Not more than once daily. Effect lasts up to 4 hours and requires sexual stimulation. In diabetes, post-prostatectomy, or on antihypertensives – usually maximum dose is needed.
- ATadalafilFirst line · Phosphodiesterase type 5 (PDE-5) inhibitorTadalafil is first-line PDE-5 inhibitor for erectile dysfunction. AEMPS approved two regimens: on-demand (10–20 mg 30 minutes before intercourse) and daily (2.5–5 mg). Long half-life is the main advantage over sildenafil – effect up to 36 hours (the 'weekend pill'). Also approved for pulmonary arterial hypertension (Adcirca 40 mg/day).
- AVardenafilFirst line · Phosphodiesterase type 5 (PDE-5) inhibitorVardenafil is first-line PDE-5 inhibitor for erectile dysfunction. AEMPS approved 5, 10 and 20 mg doses 25–60 minutes before intercourse. Alternative to sildenafil or tadalafil when one is not tolerated. Not used for pulmonary hypertension (only tadalafil and sildenafil).
Marketing claims without evidence base
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
- DL-arginineNot recommended · Conditionally essential amino acid, NO precursor. Sport and cardio-biohacking supplement. AEMPS does not register as medicineL-arginine is sold to men with ED as «natural Viagra» on the NO-mediated cavernosal vasodilation hypothesis. The Rhim 2019 (Sex Med Rev) meta-analysis in mild-to-moderate ED found a positive signal (OR 3.37; 95% CI 1.29–8.77): arginine improved erection more often than placebo. The data are low quality: small heterogeneous RCTs (I2=44%), part of the effect from combinations, and no head-to-head against PDE-5 inhibitors. Use caution with nitrates and PDE-5 inhibitors due to additive hypotension. AUA 2018 lists PDE-5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil), vacuum devices and psychotherapy for psychogenic ED first-line; L-arginine is not mentioned in main international guidelines. If L-arginine was recommended for ED instead of standard therapy, consider seeking a second opinion from a urologist.
- DL-citrulline (free form and L-citrulline malate for sports formulas)Not recommended · Non-essential amino acid and urea-cycle intermediate. Normally produced in liver and gut from glutamine and converted in plasma to L-arginine and then nitric oxide (NO). Supplements market it as a «natural Viagra alternative», a «pump» agent for bodybuilders (vasodilation and muscle blood flow), and a remedy for blood pressure and cardiovascular health. Neither AEMPS nor EMA register it as a medicine; a specialty product (citrulline malate) exists for mitochondrial disorders and urea-cycle defects, but it is a specialised drug, not a supplement. AESAN classifies regular L-citrulline supplements as complementos alimenticios. FDA has issued no supplement approval.L-citrulline is marketed as a «natural Viagra», especially to men who avoid the doctor or urologist. A small single-blind non-randomized study (Cormio, Urology 2011, 24 men, mild ED, crossover design: one month placebo then one month citrulline) reported improvement in 50% on citrulline 1.5 g/day versus 8% during the placebo period. The sample is small, duration short, and the result is not reproduced in larger RCTs. In men with moderate or severe ED, citrulline does not work: the AUA Guideline 2024 recommends phosphodiesterase-5 inhibitors as first-line (sildenafil 25–100 mg, tadalafil 5–20 mg on demand or 2.5–5 mg daily, vardenafil, avanafil); for contraindications or intolerance – vacuum devices, intracavernous alprostadil injections, implants. The Spanish AEU follows the same algorithm. Citrulline is not in these recommendations. A proper ED workup in a man over 40 includes cardiovascular-risk assessment (ED is an early atherosclerosis marker), diabetes screening, testosterone, and psychogenic factors. If citrulline was bought instead of evaluation, consider seeking a second opinion – ED after 50 deserves cardiology and endocrinology assessment, not a packet of powder.
- DMacaNot recommended · Botanical supplement, Peruvian maca root (Lepidium meyenii), marketed for male and female sexual functionMaca is an over-the-counter supplement. The Shin systematic review (BMC Complement Altern Med 2010) pooled 4 RCTs with 131 participants: at 1.5–3 g/day for 12 weeks in men with mild erectile dysfunction, maca gave a small improvement on the IIEF questionnaire versus placebo. Effect size was small, methodology weak and investigator funding by Peruvian maca producers not fully disclosed. Current AUA 2018 and EAU 2024 ED guidelines recommend PDE-5 inhibitors (sildenafil, tadalafil) as first line, testosterone screening, cardiovascular risk assessment and lifestyle factors. Maca is not in international guidelines. If maca was bought instead of seeing a urologist for persistent erectile problems, discuss with a doctor; ED can be the first sign of occult coronary disease and type 2 diabetes.
- DPanax ginseng (Korean/Chinese ginseng)Not recommended · Plant adaptogen, supplement. In EU – traditional herbal medicinal product (EMA HMPC); OTC tincture in RussiaKorean ginseng (Panax ginseng) is sold as «natural Viagra» for erectile dysfunction. Several small RCTs in Korean patients with mild-to-moderate ED showed moderate IIEF (International Index of Erectile Function) improvement at 900–1000 mg three times daily of standardised Korean Red Ginseng extract. AUA 2018 lists PDE-5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil), vacuum devices and psychotherapy for psychogenic ED first-line; Korean ginseng is mentioned as complementary therapy with «evidence limited» caveat. ESC 2022 for ED in patients with cardiovascular disease lists PDE-5 and risk factor management. If ginseng was recommended as a PDE-5 substitute or without workup (testosterone, HbA1c, lipid panel, TSH), consider seeking a second opinion from a urologist.
- DTongkat ali (Eurycoma longifolia)Not recommended · Botanical supplement, Eurycoma longifolia root, traditional Malaysian and Indonesian medicine; sold on iHerb and Amazon as a «natural testosterone booster», adaptogen and aphrodisiac. NOTE: in 2016-2019 the FDA recalled tongkat ali products for lead contamination and adulteration with synthetic PDE-5 inhibitorsTongkat ali is actively marketed as a «natural aphrodisiac» and a «safe alternative to Viagra». No evidence base supports these claims: RCTs are small, some are manufacturer-sponsored, and placebo-controlled data on erectile function (IIEF score) are weak. Erectile dysfunction requires cardiovascular and endocrine workup: 50–60% of cases in men over 40 relate to atherosclerosis, diabetes or hypogonadism, and these diagnoses need targeted treatment. IMPORTANT: in 2016–2019 the FDA recalled tongkat ali products for adulteration with undeclared sildenafil or tadalafil. This means some users of a «natural» supplement actually receive a PDE-5 inhibitor in an unknown dose – dangerous with nitrates (severe hypotension risk), cardiovascular disease and alpha-blocker interactions. Endocrine Society 2018 and AUA recommend, for erectile dysfunction, PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) at known doses with cardiovascular monitoring. If erectile dysfunction is being treated with tongkat ali, seek a second opinion from a urologist or endocrinologist. The risk of heavy-metal contamination and adulteration is high – choose certified manufacturers.
- FGinkgo biloba extractNot recommended · Herbal agents for cognitive disordersAUA 2018 and EAU 2023 list PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) as first-line for erectile dysfunction. Ginkgo biloba is not included in clinical guidelines. Small studies in antidepressant-induced ED yielded mixed results, and no large independent RCTs exist.
- FMucuna pruriens (velvet bean)Not recommended · Plant source of L-DOPA. Used in Ayurveda for Parkinson disease; in the West – biohacking supplementMucuna is sold in the biohacking segment as «natural Viagra» on the dopaminergic libido modulation hypothesis. No evidence base in erectile dysfunction: no significant RCTs with IIEF or sexual function scale endpoints. AUA 2018 lists PDE-5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) first-line for ED; mucuna is not mentioned. If mucuna was recommended for ED instead of workup (testosterone, HbA1c, lipid panel, TSH) and standard therapy, consider seeking a second opinion from a urologist.
- FTribulus terrestris (puncture vine)Not recommended · Plant «testosterone booster» and aphrodisiac of Bulgarian folk medicine, supplement. AEMPS does not register as medicineTribulus is sold as «natural Viagra» for erectile dysfunction. Evidence base is minimal: small Bulgarian and Indian RCTs showed heterogeneous IIEF scale results; no large international RCTs. AUA 2018 lists PDE-5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) first-line for ED; tribulus is not mentioned. If tribulus was recommended for ED instead of workup (testosterone, HbA1c, lipid panel, TSH) and standard therapy, consider seeking a second opinion from a urologist.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit