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Is Erectile Dysfunction a Sign of Heart Disease?

Erectile dysfunction can be an early warning of heart and blood-vessel risk, but it doesn't prove heart disease. What the research shows and what to check.

12 min read · Longevity365 Editorial

A person in a white coat holds a gray blood-pressure cuff and a round gauge with black tubing.
Illustrative blood-pressure equipment. No measurement is being taken, and no person is identified as having erectile dysfunction or heart disease. Visible dial branding does not imply endorsement. Photo by Anna Tarazevich on Pexels.

Erectile dysfunction (ED)—difficulty getting or keeping an erection firm enough for sex—usually gets filed under sexual health, and ED medicine is now a few clicks away online. Cardiologists and urologists have spent more than two decades pointing out that the same symptom can also be an early message about the heart. Humanic Blue looks at that connection without treating every case of ED as heart disease.

Whether erectile dysfunction is a sign of heart disease depends on the man and the pattern. Erections rely on healthy blood vessels, and the American Urological Association (AUA) describes ED as a risk marker for underlying cardiovascular disease. Men with ED go on to have more heart attacks and strokes than men without it. But ED isn’t a diagnosis: medicines, hormones, nerve damage, stress and depression can cause it too. For anyone focused on living longer and better, the AUA frames a lasting change as a reason to look at heart health, not only to get a prescription.

In This Article

Key Takeaways

  • Observational studies link ED to more heart disease and strokes later, even after accounting for common risk factors. They cannot show that ED causes those events.
  • ED is a risk marker, not a diagnosis of heart disease. Medicines, hormones, nerve damage, stress and depression can cause it too.
  • Guidelines assess ordinary risk factors such as blood pressure, cholesterol and blood sugar first. Princeton IV experts suggest calcium scans for some men with ED; this is broader than the selective scanning in US cholesterol guidance.
  • The AUA warns that ED pills and nitrate heart medicines must not be combined because blood pressure can fall dangerously.
  • No study establishes that treating ED helps men live longer. Links between ED pills and fewer heart events come from observational research, which cannot separate drug effects from differences between users and nonusers.

Why does blood-vessel health matter for erections?

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, lists heart and blood vessel diseases among the most common causes of ED. Atherosclerosis (plaque buildup in arteries), high blood pressure and stroke are on that list. So is diabetes.

The American Urological Association’s ED guideline explains why. ED and heart disease share risk factors, including high blood pressure, smoking and diabetes. They also appear to share processes: inflammation, damage to the lining of blood vessels (the endothelium) and plaque buildup. Even ED pills work by relaxing the smooth muscle in the penis’s blood vessels, and the AUA notes they work in men whose blood vessels are still largely intact.

Why would the penis notice first? Italian cardiologist Piero Montorsi and colleagues at the University of Milan proposed what they called the artery size hypothesis. Penile arteries are smaller than the heart’s arteries, so the same amount of plaque may cause symptoms there sooner. It’s a plausible explanation, not a home test. Where the idea comes from

Men with ED have more heart problems later

A 2019 review by Binghao Zhao and colleagues at the Second Affiliated Hospital of Nanchang University in China pooled 25 studies covering about 155,000 men. Compared with men without ED, men with ED had about 43% higher risk of cardiovascular disease and about 59% higher risk of coronary heart disease, which affects the arteries supplying the heart. Their risk of stroke was about a third higher, and so was their risk of dying from any cause during the studies.

Those are relative numbers. A 43% higher risk doesn’t mean 43% of men with ED will develop heart disease. A man’s actual risk depends on his age, blood pressure, cholesterol, blood sugar, smoking and more. The studies were also observational, which the authors acknowledged could weaken the evidence: a link, not proof that ED causes heart disease.

A US study tested the link against the usual suspects. In the Multi-Ethnic Study of Atherosclerosis, researchers at Johns Hopkins’ Ciccarone Center followed about 1,750 men, average age 69, for nearly four years. Men with ED had nearly twice the rate of heart attacks, strokes and related deaths, even after accounting for traditional risk factors, depression and use of beta-blockers, medicines used for heart conditions and high blood pressure. Relatively few such events occurred, so the estimate is imprecise. See the numbers

The AUA tells clinicians to counsel men that ED is a risk marker for underlying cardiovascular disease and other health conditions that may need evaluation and treatment. Its guideline adds that those conditions, left untreated, shorten life and make it harder to live well. That is the connection to living longer: the AUA sees ED as a reason to evaluate potentially treatable conditions that can otherwise shorten life.

What separates an ED-related risk association from a diagnosis of heart disease?

Is every case of ED about the heart?

The AUA lists vascular disease, tobacco use, nerve disease, hormone problems, medication side effects and psychological issues as common contributors. Several can overlap in one man. The pattern helps a clinician sort them out:

  • Gradual and getting worse. According to the AUA, worsening symptoms may point to underlying conditions that are progressing, especially cardiovascular ones.
  • Morning or night erections still happen. The AUA says this suggests, but doesn’t confirm, a psychological component. Medical causes can still be present.
  • A new medicine. NIDDK lists antidepressants, some blood pressure medicines and water pills, antihistamines, sedatives and some pain relievers, including codeine and oxycodone. Don’t stop a prescribed medicine without talking to the prescriber.
  • After pelvic surgery or a spinal injury. NIDDK lists nerve damage from these among the causes.
  • Low desire and weaker morning erections. The AUA recommends a morning testosterone test for every man with ED. The Endocrine Society’s 2026 statement says diagnosing low testosterone takes symptoms plus at least two early-morning, fasting blood tests.
  • Pain or a curve. NIDDK lists penile curvature, called Peyronie’s disease, among the causes. A urologist can evaluate that problem; curvature does not by itself identify a cardiovascular cause of ED.

NIDDK also says anxiety, depression and stress can cause ED or make it worse. The full picture keeps a heart message from turning into a one-cause story.

How does considering several possible contributors change the meaning of ED as a warning signal?

What a heart-risk check can include

One detailed approach comes from Princeton IV, a 2024 consensus from 16 US scientists and clinicians in cardiology, urology, sexual medicine and related fields. It describes ED as both a risk marker and a risk-enhancing factor for atherosclerotic disease: information that may lead clinicians to judge risk higher than a standard calculator suggests. The meeting was paid for by an unrestricted grant from Sanofi, whose consumer-health business was later cleared by the FDA to start a trial toward selling the ED drug Cialis without a prescription. The paper says Sanofi staff had no role in its content.

For men without heart symptoms, the check starts with ordinary risk factors: blood pressure, cholesterol, blood sugar, smoking and family history. The 2026 American College of Cardiology (ACC) and American Heart Association (AHA) cholesterol guideline estimates risk with a calculator called PREVENT, built for adults ages 30 to 79.

Princeton IV goes a step further. In an ACC summary, Johns Hopkins cardiologist Michael Blaha and three colleagues explain that men at low estimated risk whose ED stems from blood-vessel problems should be given strong consideration for a coronary artery calcium scan. The scan uses computed tomography (CT), a type of X-ray imaging, to spot calcified plaque in the heart’s arteries. Blaha co-wrote Princeton IV and was senior author of the Hopkins study above, so this summary is the consensus explaining itself rather than an outside review.

That suggestion hasn’t become standard US guidance. The 2026 cholesterol guideline recommends calcium scans selectively, for men 40 and older at borderline or intermediate risk, when the result would change a decision about statins, medicines that lower cholesterol. Researchers at Erasmus MC in Rotterdam note that the scan involves a small radiation dose, about 1.5 millisieverts, below a typical year of natural background radiation. Because it images part of the lungs and liver, it can also turn up incidental findings—unexpected changes unrelated to the reason for the scan. How the consensus works

For men who already have heart disease, the questions change: how well they handle exercise, whether symptoms are stable, and which medicines they take. The ACC summary puts sex at roughly 2 to 3 METs, a measure of effort. It compares that effort with climbing two flights of stairs or walking a mile in 20 minutes without symptoms. The comparison describes exertion, rather than giving personal clearance for sex. For men with symptoms at that level, the summary describes clinical evaluation, which may include a stress test to assess the heart during exercise. The exertion details

ED pills, nitrates and “natural” enhancers

The AUA recommends discussing oral PDE5 inhibitors, including sildenafil (Viagra) and tadalafil (Cialis), with men who have ED unless a medical reason makes their use unsafe. These drugs help sustain the blood-vessel relaxation needed for an erection. An improved erection does not establish that underlying blood pressure, blood sugar or cholesterol problems have been addressed. The AUA describes an ED diagnosis as an opportunity to address a man’s general health.

Could the pills protect the heart? A study of insurance claims from about 72,500 US men with ED, led by cardiovascular researcher Robert Kloner at the Huntington Medical Research Institutes in Pasadena, found PDE5 users had about 13% fewer major heart events and about 25% fewer deaths over roughly three years. Kloner also led Princeton IV, and the study was funded by Sanofi. The ACC summary says studies like this have limitations “including indication bias, not providing causality”: men prescribed these pills may have been healthier to begin with. The study details

The firm safety rule is nitrates, heart medicines such as nitroglycerin. The AUA warns that combining nitrates with a PDE5 inhibitor can make blood pressure drop sharply, and men who take nitrates regularly shouldn’t use these pills. Princeton IV describes minimum nitrate-avoidance intervals of 24 hours for sildenafil, vardenafil or avanafil and 48 hours for tadalafil. Those intervals are clinical safety guidance, not permission to time the medicines yourself or stop a nitrate; any change belongs with the prescribing clinician.

Over-the-counter “enhancement” products add a wrinkle. The FDA says many products sold for sexual enhancement “are likely to be contaminated with dangerous hidden ingredients.” In a May 2026 warning about one supplement, it said hidden sildenafil and tadalafil “may interact with nitrates found in some prescription drugs, such as nitroglycerin, and may lower blood pressure to dangerous levels.” A bottle labeled “natural” can contain the same prescription drugs sold at the pharmacy counter. The NIDDK treatment guide advises talking with a health professional before using supplements, and before ordering ED medicine online.

When do symptoms need urgent care?

ED alone does not diagnose a heart attack. Accompanying heart attack warning signs need urgent action. The American Heart Association lists chest discomfort; discomfort in one or both arms, the back, neck, jaw or stomach; shortness of breath; a cold sweat; nausea; and lightheadedness. It advises calling 911.

Princeton IV says sex should wait until the heart is stabilized for men with unstable angina (new or worsening chest discomfort from inadequate blood flow to the heart), uncontrolled high blood pressure, severe heart failure, a recent untreated heart attack or high-risk heart rhythm problems. For men with stable heart disease, the ACC summary says that men with an active lifestyle who tolerate exercise without symptoms can have sex safely. A heart diagnosis doesn’t automatically end the conversation about sex or ED treatment.

What’s Interesting

One of the body’s early heart clues shows up in a place few people mention at a cardiology appointment. The ACC summary’s authors say clinicians should ask about sexual activity in every man, whether or not he has heart symptoms.

Britain’s risk calculator already counts it. QRISK3, developed at the University of Nottingham from the health records of about 7.9 million patients in England, includes an ED diagnosis or treatment among its inputs. In the US, the ACC summary notes that the 2019 prevention guideline listed risk-enhancing factors specific to women, such as early menopause, but none specific to men. Researchers still have to show that adding ED to a calculator, and acting on it, prevents more heart attacks than current care.

What This Means in Practice

The AUA frames persistent ED as a chance to look at a man’s wider health. Its guideline and the cardiovascular guidance above describe several distinct parts of that evaluation:

  • The symptom history. The AUA asks when ED began, whether it is worsening, whether morning erections still occur and whether desire has changed. Medicines, supplements and symptoms during exertion also matter to the evaluation.
  • Basic risk assessment. Blood pressure, cholesterol and blood sugar help describe cardiovascular risk. A1C is a blood test reflecting average blood sugar over roughly three months. The AUA also recommends morning testosterone measurement in men with ED; a low result alone does not establish a diagnosis.
  • A reason for imaging. The 2026 cholesterol guideline reserves calcium scanning for selected risk groups when the result would affect a statin decision. Princeton IV proposes wider consideration for some men whose ED has a blood-vessel cause.
  • Medication compatibility. The AUA’s nitrate warning makes use of nitrates, ED pills and enhancement supplements important information for every prescriber.

Primary care clinicians and urologists evaluate ED; the cardiovascular guidance describes further heart evaluation for men with heart disease or concerning symptoms.

These findings are averages across large groups of men. Your own risk depends on your age, health history and the pattern of your symptoms. No ED treatment has been shown to help men live longer. What the AUA points to is the chance to find conditions, such as undiagnosed diabetes or heart disease, that shorten lives when left untreated.

For the decade-level prevention context around that cardiovascular signal, Healthy Aging for Men in Their 50s brings the relevant screening and risk questions together.

Bottom Line

Erectile dysfunction can be an early marker of heart and blood-vessel risk. Large observational studies link it to more heart attacks and strokes, but it doesn’t prove heart disease, and many other causes exist. Experts still disagree about how far testing should go, and nobody has shown that treating ED extends life. The AUA recommends evaluating ED in the context of wider health, including ordinary cardiovascular risk factors. Its warning about nitrates makes medication compatibility a separate safety question.

A NOTE FROM LONGEVITY365

We read research, consult expert perspectives and work to make complicated health information easier to understand. What you’re reading here reflects how we’ve interpreted and organized that information. It is educational content—not personal medical advice, diagnosis or treatment guidance.

We’re not perfect, and neither is the available research. Evidence changes, new studies emerge and what’s appropriate for one person may not be appropriate for another.

Use this article as a starting point for your own research and conversations with qualified professionals. Always talk with your doctor or another trusted healthcare professional before making decisions that could affect your health, particularly if you take medications, are receiving treatment, have existing health conditions, are pregnant or have other circumstances that could affect what’s appropriate for you.

Extra Insights & Sources

Reader Questions

A few questions to carry into the comments or your next conversation. Please leave out identifying or personal medical details.

  • 01How does separating a risk marker from a diagnosis change the way you understand the ED–heart connection?
  • 02What would you want to know about a proposed calcium scan: the risk estimate, the harms, or what its result would change?
  • 03What distinction between treating erections and evaluating wider health deserves more explanation?

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Extra Insights & Sources

For readers who want the details behind each claim above.

What We Know

  • ED is associated with higher future risk of cardiovascular events across large cohort studies. Supported (observational).
  • Vascular disease, diabetes and high blood pressure can contribute to ED. Established.
  • ED has several non-cardiac causes, and history plus examination guide the workup. Established.
  • PDE5 inhibitors must not be combined with nitrates because of the risk of a severe drop in blood pressure. Established.

What We Don’t Know

  • Whether heart disease caused any one man’s ED, without a clinical evaluation. Unknown from the symptom alone.
  • Whether routine coronary calcium scanning benefits every man with ED. Not established; depends on risk.
  • Whether PDE5 inhibitors prevent heart attacks or extend life. Preliminary: observational associations only.
  • Whether treating ED by itself reduces cardiovascular events. Not established.
  • Whether adding ED to US risk calculators would prevent more events than current care. Unknown.

The ED and heart-disease studies

In the statistics below, relative risk (RR) and hazard ratio (HR) compare groups. Values above 1 indicate a higher risk or rate over time; below 1 a lower one. An HR of 1.9 means an estimated 90% higher rate, not a 90% chance of an event. Confidence intervals (CI) describe uncertainty; P values describe how compatible the results are with a statistical model of no difference, not whether ED caused the outcome. Adjusting for measured risk factors cannot rule out unmeasured differences between groups.

Zhao et al., 2019 meta-analysis. The review in The Journal of Sexual Medicine included 25 studies with 154,794 individuals. Compared with men without ED, relative risks were 1.43 for cardiovascular disease, 1.59 for coronary heart disease, 1.34 for stroke and 1.33 for all-cause mortality (all P < .001). Men 55 and older, men with ED of shorter duration (under 7 years), and study populations with higher rates of diabetes (20% or more) and smoking (40% or more) were more prone to cardiovascular disease, and severe ED predicted higher cardiovascular and all-cause mortality risk. The authors noted that not all the included studies were randomized controlled trials, which might downgrade the evidence, and that retrospective and cross-sectional studies were included. The authors reported no conflicts of interest, and funding came from the National Natural Science Foundation of China, with no commercial entity involved.

Multi-Ethnic Study of Atherosclerosis (MESA), 2018. Researchers at the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease (first author S M Iftekhar Uddin; senior author Michael J. Blaha) published this research letter in Circulation. Of 1,914 men (mean age 69 ± 9.2 years, where 9.2 is the standard deviation describing the spread of ages, not the age range), 877 (45.8%) reported ED; 1,757 were followed for a median 3.8 years (IQR, or middle half of follow-up times, 3.5 to 4.2), with 75 hard cardiovascular events (heart attack, resuscitated cardiac arrest, coronary death, stroke and stroke death). In the fully adjusted model, ED was associated with hard cardiovascular events (HR 1.9; 95% CI 1.1 to 3.4), adjusting for age, race and ethnicity, education, smoking, diabetes, family history of coronary disease, cholesterol ratio, systolic blood pressure, blood-pressure and lipid medication, beta-blocker use and depression score. The authors concluded that “ED was found to be a significant predictor of hard CVD events after adjustment for traditional CVD risk factors, depression, and beta-blocker use.” Funding came from the National Heart, Lung, and Blood Institute; the authors reported “no disclosures pertinent to this work.”

American Urological Association guideline (approved April 2018). Paraphrased here. Guideline Statement 3 (a Clinical Principle) says men should be counseled that ED is a risk marker for underlying cardiovascular disease and other health conditions that may need evaluation and treatment. The guideline defines risk markers as characteristics that predict a higher probability of disease without being part of its cause. It says ample evidence shows ED marks treatable underlying conditions, such as undiagnosed diabetes and cardiovascular disease, that reduce quality and length of life if left untreated. It cites Prostate Cancer Prevention Trial data indicating that ED predicted future cardiac events as strongly as smoking or a family history of heart attack, and the QRISK group’s model, in which ED was associated with about a 25% higher relative cardiovascular event rate at the study’s mean age. That is a relative comparison with men without ED, not an extra 25 percentage points of personal risk. The association varied with age and does not show that ED causes cardiovascular disease. It does not recommend cardiac imaging for every man with ED.

QRISK3, 2017. Julia Hippisley-Cox and colleagues at the University of Nottingham developed QRISK3 (BMJ) from 7.89 million patients aged 25 to 84 in English general practices, validating it in 2.67 million more. “Erectile dysfunction diagnosis or treatment in men” was among the new risk factors that met the model’s inclusion criteria. Disclosure: Hippisley-Cox is a paid director of ClinRisk, which produces software implementing clinical risk algorithms, and co-author Carol Coupland is a paid consultant statistician for ClinRisk.

Princeton IV and the risk check

ASCVD means atherosclerotic cardiovascular disease: heart and blood-vessel disease related to artery plaque. CVD is the broader term cardiovascular disease. CAC means coronary artery calcium. A 10-year risk estimate is a predicted chance of an event during the next decade, not a diagnosis. Risk categories below belong to the guidance and calculator described; they are not interchangeable personal test results.

The consensus. Princeton IV (Kloner RA et al., The Journal of Sexual Medicine, 2024) came from a March 2023 meeting at the Huntington Medical Research Institutes in Pasadena, California, using expert lectures and Delphi-type discussion, a structured process for developing expert agreement. Its authors listed as a limitation that all the participants at this meeting came from the United States. It integrated coronary artery calcium scoring into an algorithm based on ACC and AHA recommendations. It describes ED as both a risk marker and a risk-enhancing factor for atherosclerotic disease, and says that a diagnosis must include a serious investigation into whether the patient has underlying vascular risk factors or outright CVD. For calcium scoring, it states that men with a borderline to intermediate risk score (a 5% to 20% 10-year risk of ASCVD) should have coronary artery CT calcium scoring.

Funding. The paper states that the meeting was funded by an unrestricted educational grant from Sanofi, and that Sanofi staff played no part in choosing speakers or topics or in any aspect of the meeting’s content. The consensus also discussed the pros and cons of over-the-counter PDE5 inhibitors. In January 2025, Sanofi announced that the FDA had lifted a clinical hold on the actual-use trial run by Opella, Sanofi’s consumer-healthcare business, to support switching Cialis (tadalafil) from prescription to over-the-counter status. As of September 25, 2026, no US over-the-counter approval for Cialis had been announced. The paper’s conflict-of-interest statement lists Sanofi ties for three authors: Kloner has received grant funds from Sanofi and been a paid consultant for the company, unrelated to the manuscript; Kevin McVary has consulted for Sanofi; and Raymond Rosen has been a paid consultant for Sanofi Pharmaceuticals. Several other authors report ties to drug and device companies; Blaha is among those listed as disclosing no conflicts.

The ACC summary (September 23, 2024). Leonardo Lima, Michael J. Blaha, Roger S. Blumenthal and Raul Santos wrote that ED “should be considered a risk-enhancing factor when considering the intensity of risk-factor reduction.” They noted that the ACC/AHA prevention guidelines then in use (2019) estimated 10-year risk “primarily in people 40-79 years of age,” that “The guidelines include specific risk-enhancing factors for women, such as early menopause and pre-eclampsia, but not a specific risk factor for men, such as ED,” and that Princeton IV urges future ACC/AHA guidelines to treat ED as a risk-enhancing factor and recommends that men at low 10-year ASCVD risk with vasculogenic ED also be given strong consideration for CAC scoring. They also wrote that ED “symptoms may precede clinically evident CVD by several years,” that “Clinicians should inquire about sexual activity in every man, independently of CVD symptoms or established disease,” and that evaluating cardiovascular risk in men with ED “seems to be cost-effective regardless of ED severity.”

The 2026 ACC/AHA cholesterol guideline. Published March 13, 2026, it recommends the PREVENT-ASCVD equations, “designed for adults ages 30-79 years without known ASCVD or subclinical atherosclerosis,” and “selective use of a non-contrast coronary artery calcium (CAC) scan” for men 40 and older and women 45 and older at borderline or intermediate risk when the result would influence statin decisions, according to the ACC’s announcement.

Calcium-scan radiation and incidental findings. Daniel Bos and Maarten Leening of Erasmus MC, Rotterdam, wrote in European Radiology (2018) that radiation exposure from a prospective ECG-gated calcium scan “approximates 1.5 mSv,” compared with annual background radiation of 2 to 5 mSv. They noted that “A downside of this wider field-of-view is the greater probability of detecting incidental findings,” which may especially turn up in the liver and lungs. The authors declared no relevant relationships with companies.

Sex and heart disease

METs compare an activity’s energy demand with resting: 2 to 3 METs means about two to three times resting demand. Ischemia means insufficient blood flow to heart muscle. Revascularization restores blood flow, for example through a stent or bypass. TIA means transient ischemic attack, a temporary interruption of blood flow to the brain; peripheral artery disease affects arteries outside the heart and brain. The New York Heart Association (NYHA) heart-failure classes below describe increasing symptom limitation: I means no limitation with ordinary activity, II slight limitation, III marked limitation and IV symptoms at rest. Arrhythmias are abnormal heart rhythms. Angina is chest discomfort from insufficient blood flow; unstable or refractory angina is new, worsening or persistent despite treatment. These categories guide clinical assessment; a home exertion comparison does not establish clearance.

Princeton IV restates the first Princeton panel’s conclusion that about 30 minutes of sexual intercourse or activity with a usual partner in a long-standing relationship corresponds to a workload of roughly 2 to 3 metabolic equivalents of task (METs). The ACC summary adds that this probably poses no greater risk than climbing two flights of stairs or walking 1.6 km (1 mile) in 20 minutes without cardiac symptoms, and that men who reach 5 to 6 METs on a treadmill test (about 4 minutes of the standard Bruce protocol) without signs of ischemia can generally have sex safely.

The ACC summary groups men with heart disease by risk:

  • Low risk: 5 METs without ischemia on a recent exercise test, controlled blood pressure, mild heart-failure symptoms (NYHA class I or II), successful revascularization or mild valve disease.
  • Intermediate risk: moderate angina, a heart attack within 2 to 8 weeks without intervention, NYHA class III heart failure, prior stroke or TIA, or peripheral artery disease. These men should be evaluated further before resuming sex.
  • High risk: NYHA class IV heart failure, uncontrolled hypertension, unstable or refractory angina, recent heart attack without treatment (Princeton IV: under 2 weeks), or high-risk arrhythmias. Sex should be deferred until the condition stabilizes, with cardiology referral.

PDE5 inhibitors, nitrates and hidden ingredients

How the pills work. The AUA guideline lists sildenafil, tadalafil, vardenafil and avanafil as the FDA-approved oral PDE5 inhibitors and recommends informing men with ED about them (Strong Recommendation; Evidence Level: Grade B). PDE5 is phosphodiesterase type 5, an enzyme. These medicines block the breakdown of cGMP, a chemical messenger, which relaxes smooth muscle in the penis’s erectile tissue (the corpus cavernosum) and makes erections harder and longer-lasting in men with ED whose blood vessels are sufficiently intact. The guideline notes that an ED diagnosis is therefore an opportunity to address several issues affecting a man’s general health.

Nitrates. The AUA warns that nitrate medicines combined with a PDE5 inhibitor can cause a sudden, steep drop in blood pressure, and that men who take nitrates regularly should not use PDE5 inhibitors. Princeton IV recommends avoiding a shorter-acting PDE5 inhibitor (such as sildenafil, vardenafil or avanafil) within 24 hours of a nitrate-containing substance, and a longer-acting one (such as tadalafil) within 48 hours. The ACC summary adds that most patients with atherosclerotic heart disease in the modern era don’t need nitrates or use them very rarely, and that any conversation about stopping nitrates should be centered on the patient.

The Kloner claims study (2023). Robert A. Kloner (Huntington Medical Research Institutes and Keck School of Medicine of USC) and colleagues, including HealthCore/Anthem researchers, analyzed US claims data (The Journal of Sexual Medicine) for men with ED from 2006 to 2020: 23,816 exposed to PDE5 inhibitors and 48,682 unexposed, matched on baseline risk, with mean follow-up of 37 and 29 months. Major adverse cardiovascular events were 13% lower with exposure (HR 0.87; 95% CI 0.79 to 0.95), all-cause mortality 25% lower (HR 0.75; 95% CI 0.65 to 0.87) and cardiovascular death 39% lower (HR 0.61; 95% CI 0.41 to 0.90). The authors listed the study’s retrospective design (looking back at existing records) and unknown confounders (other differences between users and nonusers that could affect outcomes) as limitations. Europe PMC lists the funding as a grant from Sanofi to the Huntington Medical Research Institutes.

The ACC summary describes the follow-up as “a 15-year period”; the paper’s enrollment window spanned 2006 to 2020, but mean follow-up was about 2.5 to 3 years.

Hidden ingredients. The FDA’s sexual-enhancement notification list states: “Many products that claim to help with sexual enhancement or treat sexual dysfunction—such as male enhancement supplements, erectile dysfunction treatments, male energy pills and stamina pills—are likely to be contaminated with dangerous hidden ingredients.” Its May 29, 2026 warning about X10 Natural Enhancement Supplement reported undeclared sildenafil and tadalafil and said they “may interact with nitrates found in some prescription drugs, such as nitroglycerin, and may lower blood pressure to dangerous levels.” NIDDK’s treatment page says: “Do not order an ED medicine online before talking with a health care professional.”

Other causes, testosterone and the artery size hypothesis

NIDDK’s list of causes (last reviewed October 2024). Diseases and conditions: diabetes; chronic conditions such as chronic kidney disease, obesity and COPD (chronic obstructive pulmonary disease, a long-term lung condition); heart and blood vessel diseases such as atherosclerosis, high blood pressure and stroke; hormone issues such as low testosterone and thyroid imbalance; nerve damage from multiple sclerosis, spinal cord injury or pelvic surgery; and reproductive problems such as enlarged prostate and Peyronie’s disease. Medicines: antidepressants, appetite suppressants, antihistamines, blood pressure medicines and diuretics, chemotherapy and hormone medicines, some pain relievers (NSAIDs, or nonsteroidal anti-inflammatory drugs, codeine, oxycodone), sedatives and ulcer medicines. Mental and emotional factors: anxiety, depression, stress, loneliness and low self-esteem. Lifestyle: too little physical activity, heavy drinking, smoking and drug use. NIDDK defines ED as trouble “getting or keeping an erection that is firm enough for sex,” and says ED becomes more common with age but “is not a routine part of aging.”

The AUA’s history questions. Key questions include onset, severity, whether the problem is getting or keeping an erection, situational factors, whether night or morning erections still happen, and whether symptoms are stable or getting worse. Worsening symptoms, it says, may suggest progressing underlying conditions, especially cardiovascular ones. The AUA recommends measuring morning total testosterone in men with ED (Moderate Recommendation; Evidence Level: Grade C).

Testosterone diagnosis. Hypogonadism means insufficient testosterone production; ng/dL means nanograms per deciliter, the concentration unit in the statement below. The Endocrine Society’s July 2026 statement says “Hypogonadism diagnosis should be made by a healthcare provider based on at least two early-morning, fasting testosterone tests,” with a “common clinical threshold near 300 ng/dL.”

The artery size hypothesis. Piero Montorsi and colleagues at the University of Milan’s Centro Cardiologico Monzino described it in The American Journal of Cardiology (2005): because atherosclerosis is systemic (it affects arteries throughout the body), all major vascular beds (groups of blood vessels supplying different organs) should be affected to the same degree, but because penile arteries are narrower than coronary arteries, men with ED will seldom have symptoms of coronary artery disease at the same time, whereas men with coronary artery disease will often report ED. The team wrote that the available clinical evidence appeared to support the hypothesis. It remains a proposed mechanism.

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