Erectile Dysfunction May Predispose Older Men to Multiple Types of Substance Abuse

WASHINGTON — Older men with erectile dysfunction (ED) have an increased risk of substance abuse, including sedatives, opioids, and cocaine, according to a large retrospective study.

ED had the strongest association with sedative abuse, more than twice as likely as a matched cohort without ED. The risk was at least 50% greater for other psychoactive substances (such as ketamine), cocaine, and opioids. The risk of cannabis abuse was 45% greater in men with ED. An ED diagnosis was associated with a reduced risk of nicotine dependence in men of all ages. The analysis did not include alcohol abuse.

Surprisingly, the associations did not hold up in younger men with ED, who are known to have higher rates of depression, which can predispose to substance abuse, said Hossein Zolfaghari, a student at Rutgers New Jersey Medical School in Newark, at the American Urological Association meeting.

“What can explain these findings?” asked Zolfaghari. “There are a few things, the first being that elderly men are medically more complex. They have other prescriptions that can give them access to medications that have abuse potential, such as sedatives and opioids. Additionally, given this medical complexity, clinicians might be inclined to overlook some possible psychiatric causes of their erectile dysfunction.”

“We also know that erectile dysfunction medications, such as PDE5 [phosphodiesterase type 5] inhibitors [like sildenafil (Viagra)], decrease in efficacy as the patient gets older, which could also lead to an increased burden. There are also cultural factors. Specifically, there are outdated beliefs that some drugs might have aphrodisiac properties, and these outdated beliefs might be more prevalent in the elderly population.”

Session moderator Gregory Broderick, MD, of the Mayo Clinic in Jacksonville, Florida, asked whether substance abuse was based on prescriptions for specific types of drugs, such as sedatives. Zolfaghari said investigators identified substance abuse on the basis of ICD codes associated with abuse.

“That’s interesting,” said Broderick, “because you would think that elderly men have more sleep-architecture issues and would naturally be prescribed more sedatives. As always, the caveat here is that association does not mean causation.”

Adam Murphy, MD, of Northwestern University in Chicago, noted that some drugs have multiple effects and suggested a need for caution when interpreting associations.

“Some of them are stimulants, and when you want to have sex, they have aphrodisiac properties, but they can also cause vascular damage,” said Murphy. “Separating out the effects of the drugs from the statements might be useful. What do you think? Is the ED causing low dopamine, low pleasure, and the people are seeking certain drugs [that might be helpful]? What is your hypothesis about what is happening?”

Zolfaghari replied, “The hypothesis that we were working with is that erectile dysfunction can cause distress, and this can be self-medicated. Elderly men might have access to sedatives or opioids, based on their prescriptions, or they might have preconceived notions that amphetamines or cocaine or something else can help this problem. They might be at higher risk in the following 3 years to fall into abuse.”

By way of background, Zolfaghari pointed out that ED affects about a fourth of men 18 or older, including more than half of men older than 75. The condition shares certain risk factors with substance-use disorders, such as cardiovascular disease, diabetes, and depression. Previous studies have shown bi-directional relationships between ED and depression, and substance abuse is a recognized risk factor for ED.

“We asked whether there is a bi-directional relationship between erectile dysfunction and substance abuse risk,” he said. “Specifically, does an erectile dysfunction diagnosis predispose men to subsequent substance abuse?”

Investigators searched the TriNetX clinical data network for men with ED diagnoses and more than 3 years of follow-up. They used propensity matching to create two cohorts matched for age and race. Patients were excluded for prior substance abuse/dependence, psychiatric diagnoses, and prior nicotine dependence. The primary outcome was any substance/dependence over a 3-year period, as determined by diagnostic codes.

The analysis involved a total of 323,838 men, half with an ED diagnosis and half without. The study population included 176,960 men who were 65 or older. In that older subgroup, investigators found multiple statistically significant (P<0.05) associations between ED and substance abuse:

• Sedatives: HR 2.28
• Other psychoactive substances: HR 1.79
• Cocaine: HR 1.60
• Opioids: HR 1.58
• Cannabis: HR 1.45

ED was associated with a reduced risk of nicotine dependence (HR 0.71), which Zolfaghari described as a “protective effect.”

For the association with sedative abuse, exclusion of the first 90 days after ED diagnosis increased the hazard to 2.64, effectively ruling out detection bias.

In the 40-64 age group (n=133,292), ED had significant associations with cannabis (HR 1.32) and other psychoactive substances (HR 1.21) but a reduced risk of nicotine dependence (HR 0.90). In the youngest age group (20-39, n=13,586), the data showed “paradoxically protective” associations between ED and opioids (HR 0.53) and stimulants (HR 0.35).

Screening older men for substance abuse and reviewing their medication list for drugs with abuse potential are two actions that may help reduce the risk with ED.

“It’s important to address this holistically and look at psychiatric comorbidities that these patients may face, even though they’re elderly and might have heart disease or diabetes or something else more obvious,” said Zolfaghari. “It’s also important to educate patients on dispelling aphrodisiac myths. The fact that we found a protective association with nicotine dependence indicates to us that counseling may be helpful and actually result in decreased substance abuse later on.”

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