The data reported within this study highlight significant age-related differences in substance misuse risk following ED diagnosis. Most notably, elderly men (≥65 years) with ED demonstrated significantly elevated risk for sedative (HR 2.28), opioid (HR 1.58), cocaine (HR 1.60), cannabis (HR 1.45), and other psychoactive substance abuse (HR 1.79) over the 3-year follow-up period. This contrasts sharply with younger men (20-39 years), who showed protective associations for opioid (HR 0.53) and stimulant abuse (HR 0.35). Men in the middle-aged cohort (40-64 years) demonstrated intermediate findings with modest elevations in cannabis (HR 1.32) and other psychoactive substances (HR 1.21).

This age-dependent pattern presents a notable paradox. Younger men with ED experience higher rates of mood disorders following diagnosis—with men under 45 years having a 40% risk of depressive symptoms compared with less than 20% in men over 65 years with similar ED severity.^17,18 Given the established association between mood disorders and substance use, one would expect younger cohorts to demonstrate elevated substance abuse risk.¹⁹ However, our findings reveal the opposite pattern, suggesting that mechanisms beyond simple mood disorder pathways must be operative.

Younger men with ED may initially turn to opioids or stimulants in an attempt to enhance sexual performance or alleviate ED-related psychological distress. However, as these substances are well-documented to worsen erectile function,^20,21 their negative impact may create a deterrent effect, discouraging continued use. This negative feedback loop would likely be less operative in elderly men, whose greater average baseline ED severity may render the incremental worsening caused by substance use relatively less perceptible. Furthermore, elderly men with ED face distress not only from ED itself but also from its associated comorbidities, generating a heavier psychological burden that may increase vulnerability to substance abuse beyond what mood disorder pathways alone would predict.

Several hypotheses may explain the elevated substance abuse risk in older men with ED. Prescribing patterns represent one possible mechanism for the elevated sedative and opioid abuse risk in older men. Polypharmacy is common in elderly populations, and sedatives are frequently prescribed for anxiety and insomnia—conditions that may be exacerbated by ED-related distress.²² Similarly, opioids are commonly prescribed for chronic pain conditions prevalent in this age group. This increased access to prescription medications with abuse potential may create opportunities for misuse in the setting of ED diagnosis. The strong association with sedatives (HR 2.28) and opioids (HR 1.58) supports this hypothesis, and the strengthened sedative association after excluding diagnoses within the first 90 days (HR 2.64) suggests true increased risk rather than mere detection bias.

Gaps in mental health care could also contribute as older men are significantly less likely to receive treatment for mental health disorders compared with younger cohorts.²³ This treatment gap may leave elderly men with ED-related psychological distress without adequate psychiatric care, potentially increasing susceptibility to self-medication behaviors. Additionally, the higher prevalence of medical comorbidities in elderly populations may serve as diagnostic distractors, making psychiatric etiologies less apparent to clinicians focused on managing multiple chronic conditions.

Age-related differences in treatment response may play a role, as treatment success for ED generally increases with decreasing age, with younger men exhibiting improved response rates to phosphodiesterase-5 inhibitors (PDE5i).²⁴ As younger men achieve greater psychological relief through effective ED treatment, this may attenuate risks associated with mood disorders. Conversely, older men with less responsive ED may experience persistent psychological distress, potentially creating vulnerability to substance misuse.

Finally, it is important to consider the role of historical and cultural factors surrounding the role of substances in ED diagnosis. Older men grew up in an era with different attitudes toward discussing sexual health and seeking legitimate medical help, potentially making them more likely to explore alternative solutions. Substances including cocaine, cannabis, and opioids have historically been associated with myths regarding aphrodisiac properties, despite scientific evidence demonstrating their detrimental effects on sexual function.^20,21 Older generations may be more susceptible to these persistent cultural beliefs, leading to experimentation with illicit substances in hopes of improving sexual function, which may subsequently progress to dependence.

In contrast to the elevated risks for most substances, both middle-aged and elderly cohorts demonstrated protective associations for nicotine dependence (HR 0.90 and 0.71, respectively). Tobacco use demonstrates a well-established unidirectional, dose-dependent relationship with ED, with each additional 10 years of smoking raising ED risk by 15% and each additional 10 cigarettes per day raising risk by 14%.²⁵ Smoking cessation is frequently emphasized as part of standard counseling for newly diagnosed ED patients, and the protective effect observed suggests this counseling may be effective in motivating behavior change.^26–28