According to a recent study, long-acting opioids are nearly five times more likely to suppress testosterone levels than short-acting opioids.
Over the last few years, we’ve seen a surge in data that couples opioid use with lowered male testosterone levels. We know the use of opioids can lead to hypogonadism, a condition of lowered sex hormone production. In males, lowered testosterone levels can lead to fatigue, depression, and even osteoporosis and obesity. Some studies suggest this hypogonadism is also associated with lowered pain tolerance.
In previous studies, opioid users were lumped together, but this recent study compared the testosterone levels of patients taking long-acting opioids with patients taking short acting opioids.
Dr. Andrea Rubinstein presented data at the annual American Academy of Pain Medicine meeting. Her study compared 81 male patients taking opioids for at least three months. Those in the long-acting opioid group included patients prescribed methadone, buprenorphine (Subutex, Suboxone), sustained-release medications in patch form, such as morphine and fentanyl, and sustained-release medications like OxyContin (taken whole as intended with the coating not removed). These patients were compared with those on short acting opioid like immediate-release oxycodone and hydrocodone.
The patients on the long acting opioid were nearly five times more likely to have low testosterone levels than patients on the short acting opioids. The age of the patient and the total daily dose did not appear to affect the risk of low testosterone.
It’s possible that short acting opioids give more fluctuation in serum opioid levels, and thus less likely to suppress hormonal function.
This is not great news for those of us who treat opioid addiction. We use long-acting opioids like methadone and buprenorphine precisely because they are long-acting, and give a steady blood levels. Their long action in the body means they can be dosed once a day (usually) and still relieve all opioid withdrawal symptoms. The relief from opioid withdrawal frees the patient to focus on making important life changes. With short-acting opioids, most addicts feel a euphoric high, followed several hours later by withdrawal. This drives them to seek opioid drugs as often as every six hours. It’s hard to maintain a normal life when seeking pursuing opioids three or four times per day. Simply staying out of withdrawal becomes the opioid addict’s full time job. Short acting opioids may be better for my patients’ testosterone levels, but not good for their disease off addiction.
So what should I do with this data about hypogonadism in my practice?
I think I should be more diligent about monitoring my patients for symptoms of low libido. It’s important to ask male patients about sexual difficulties because sometimes they are embarrassed to mention them. If patients have no symptoms of hypogonadism, they probably don’t need further testing. If patients do have symptoms, I’ll ask them to see their family doctors for a work-up, because that’s something that can’t be treated at the opioid treatment programs where I work. Testosterone can be supplemented with gel or intramuscular injections, and testosterone levels need to be monitored, as well as cholesterol levels.
I’ve had previous patients who object to testosterone supplementation because they felt they were treating a side effect from one medication with a second medication. While this is true, the only other option is tapering off methadone or buprenorphine, or cutting down their dose. This also has risks, as opioid addiction is a life-threatening illness. If a patient wants completely off medication, he should have an inpatient treatment lined up as soon as his dose is low enough for admission.
What about women on medication-assisted treatments with low sex drive? Women weren’t included in this study, but yes, we know their hormones are also affected by opioids. Testosterone may help women recover their sex drive, but it has serious side effects and hasn’t been proven to be safe in the long term for women. For females who report sexual dysfunction on long-acting opioids, I will continue to refer them to their gynecologists.
As usual, the benefits of long-acting opioids must be balanced against their risks.