Men with severe ED more than twice likely to have high ceramide levels

Andres Guillen, MD

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Serum ceramide testing may help patients with erectile dysfunction (ED) be identified and referred to relevant cardiac care that could better their condition, according to new study findings.¹

In data presented at the Sexual Medicine Society of North America (SMSNA) 2024 Fall Scientific Meeting in Scottsdale, AZ this week, a team of Mayo Clinic-based investigators reported that men with moderate to severe erectile dysfunction were more than twice likely to have actionable ceramide levels when assessed versus standard population. The research provides a further clinical bridge between cardiovascular disease risk and prevalence of ED, and provide rationale for further research into the benefit of ceramide testing.

Led by Andres Guillen, MD, a research fellow at the Mayo Clinic, investigators sought to analyze the utility of ceramide levels in patients with ED through self-reported erectile function results from the 6th edition of the International Index of Erectile Function (IIEF-6).

The association between cardiovascular disease and ED has been long established, with research showing the latter is a significant biomarker for risk of the former in young men in particular. Treating ED has been known to help reduce the risk of subsequent cardiovascular events. As Guillen and colleagues noted, American Urological Association (AUA) guidelines currently recommend evaluating serum lipids and using an ED diagnosis as “an opportunity to discuss and address cardiovascular risk.”

“Serum plasma ceramides are novel predictors of adverse cardiovascular events independent of traditional risk factors such as LDL and hsCRP levels,” investigators wrote. “Ceramide levels improve with lifestyle modification.”

Guillen and colleagues conducted ceramide testing, as well as lipid levels and HbgA1c, in all patients with ED and Peyronie’s disease during a period in late 2019. Ceramide levels were retrospectively analyzed with IIEF-6 results from electronic record data.

The team dichotomized the cohort by ED symptom severity—moderate to severe ED being defined as IIEF ≤17, and no to mild ED being defined as IIEF ≥18—and ceramide levels by the risk strata of cardiovascular disease.

The final analysis included 354 patients, of whom 253 (71.4%) had moderate or severe ED. Median patient age was 66 years old (IQR, 58.7 – 72.0), BMI was 28.7, and 70.8% reported alcohol intake at the time of assessment.

In total, 50 patients from the cohort developed a major adverse cardiac event (MACE). Investigators found that the difference in abnormal ceramide values were statistically significant between the ED severity cohorts. Based on IIEF scoring, the odds of reporting an abnormal ceramide test were significantly increased (odds ratio [OR], 2.3; 95% CI, 1.04 – 5.12; P = .034).

Based on MACE subtype, investigators also found that patients with moderate to severe ED who had a ceramide score of >6 were at higher risk of developing a transient ischemic attack.

The team concluded their findings show a link between elevated plasma ceramide levels and severity of symptoms in patients with ED. Patients undergoing treatment for ED may likely benefit from such testing going forward, and subsequent cardiac referral when needed, they wrote.

“In our cohort, men with moderate to severe ED were twice as likely to have actionable ceramide levels,” investigators wrote. “Further studies are warranted to optimize the utility of ceramide testing in men with ED and potentially drive lifestyle change.”

References

1. ^{Guillen A, Dumbrava M, Bonakdarhashemi M, Ziegelmann M,, et al. Ceramide Test in Patients With Erectile Disfunction to Assess Cardiovascular Risk. Paper presented at: Sexual Medicine Society of North America (SMSNA) 2024 Fall Scientific Meeting. Scottsdale, AZ. October 17 – 21, 2024.}
2. ^{Jackson G. Erectile dysfunction and cardiovascular disease. Arab J Urol. 2013 Sep;11(3):212-6. doi: 10.1016/j.aju.2013.03.003. Epub 2013 May 3. PMID: 26558084; PMCID: PMC4442980.}