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Opioid-Induced Androgen Deficiency

Dr. Anna Pickering

Medically reviewed by

Dr. Anna Pickering

April 2, 2019

Opioid-induced androgen deficiency is one negative side effect of long-term opioid abuse. Though managing pain with opioids is highly effective, it can result in hormone deficiencies.

What Is Opioid-Induced Androgen Deficiency?

Opioid-Induced Androgen Deficiency (OPIAD) was discovered to be a possible consequence of opioid use about four decades ago. OPIAD is a syndrome caused by prolonged overexposure to opioids. Despite how common OPIAD is, it is commonly under-diagnosed as a negative effect of chronic opioid use.

The Centers for Disease Control and Prevention estimates that 50 million American adults experience chronic pain. Opioids have been effective in treating chronic pain conditions. However, over time, opioids can modify the brain structures that contribute to the body’s production of testosterone and other sex hormones.

OPIAD syndrome happens when these modified structures can no longer effectively contribute to the gonad’s production of the required amount of testosterone and other hormones that the body needs to function properly. This is a condition called hypogonadism. Hypogonadism is frequently seen with chronic opioid use.

Opioid use can also affect the levels of adrenal hormone, which prevents other brain structures from producing more hormones and re-establishing a hormonal balance.

With the opioid crisis worsening in the U.S., OPIAD diagnosis is increasing. Untreated individuals suffering from OPIAD will experience lower quality of life, and other deficiencies that can develop into more problematic conditions.

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Signs And Symptoms Of Opioid-Induced Androgen Deficiency

It is possible for both men and women to experience OPIAD symptoms, as both need some level of testosterone hormone to function properly. It is also common for both genders to report low sex drive while taking opioids. Conditions like depression, low libido and erectile dysfunction are often chalked up to old age and OPIAD syndrome goes undiagnosed.

Possible symptoms of OPIAD include:

  • fatigue
  • hot flashes
  • depression and irritability
  • decreased sex drive
  • erectile dysfunction in men
  • testicular atrophy
  • irregular menstruation in females
  • reduced facial hair growth
  • decreased lean muscle mass
  • decreased bone density
  • anemia (lack of healthy red blood cells in the blood)
  • trouble concentrating or remembering
  • trouble sleeping
  • anemia (lack of red blood cells in the blood)

Signs of androgen deficiency may include low testosterone, which has also been associated with the metabolic syndrome, a set of risk factors for cardiovascular disease.

Why Is Opioid-Induced Androgen Deficiency Under-Diagnosed?

Some of the signs and symptoms of OPIAD can be difficult to identify, as they can easily be mistaken for negative side effects of opioids themselves. Studies report identifying OPIAD syndrome in men chronically abusing opioids 54 to 64 percent of the time.

Hypogonadism (teste/ovary failure) is dose dependent and happens fast. People taking 100 to 200 mg of morphine (or equivalent) for one month are 50 to 100 percent likely to develop some degree of OPIAD.

Even though OPIAD syndrome occurs about 50 percent of the time in people who abuse opioids over a long-period of time, it often goes under-diagnosed. If someone has abused high doses of opioids (100 mg or more) for more than three months then OPIAD syndrome should be suspected.

One study reports that hormone suppression occurred as soon as one week after opioid use and was present for twelve weeks. It is possible for people going through opioid addiction treatment to report continued symptoms like dizziness and fatigue. As these are common side effects of opioid use, OPIAD can easily be overlooked.

Short-Acting And Long-Acting Opioids And Androgen Deficiency

The risk of OPIAD depends, in part, on the opioid dose and formulation. There is some evidence to suggest that short-acting opioids have a lower risk of androgen deficiency when compared to long-acting opioids.

However, an increased risk of OPIAD was found with higher doses of short-acting opioids over larger doses of long-acting opioids. Individuals being treated with buprenorphine medication often have higher levels of testosterone and increased sex drive. This is thought to be because buprenorphine only partially acts like an opioid when compared to methadone.

Another thought is that buprenorphine also comes in a mixed formula with naloxone. Naloxone counteracts the effects of buprenorphine and may reopen channels for hormone development. However, more information is needed to prove this is the case.

Potential Dangers Of Opioid-Induced Androgen Deficiency

Though there is limited information on OPIAD, in most cases, OPIAD syndrome has been reversible. However, in a few other cases, hormone therapy was needed permanently, both men and women reported infertility and decreased hormone levels, which decreases total life expectancy.

Long-term opioid abuse can cause a domino effect of health concerns. OPIAD, causes decreased hormone levels, this affects bone density, which can eventually result in osteoporosis. Hyperlipidemia (high levels of fat in the blood) can also be a result of the hormone imbalance from OPIAD. This can cause weight gain, which can lead to metabolic syndrome and sleep apnea.

Currently, there is no evidence to prove that OPIAD improves by switching to another opioid or decreasing the dosage of the current opioid medication.

Treatment Options For Opioid-Induced Androgen Deficiency

Once diagnosed, treatment for OPIAD may be offered utilizing a number of androgen replacement therapy options including a variety of testosterone preparations and, for female patients with OPIAD, dehydroepiandrosterone (DHEA) supplementation.

Follow-up evaluation appointments for people receiving androgen replacement therapy should include a review of any unresolved symptoms of hypogonadism, laboratory evaluation, and surveillance for potential adverse effects of androgen replacement therapy, which includes prostate disease in males and infertility in males and females.

Anybody who receives long-term treatment with opioids is at risk for the development of OPIAD syndrome and should be monitored with attention to underlying symptoms and signs. Laboratory evaluation may be helpful in establishing this diagnosis once suspected.

People on androgen replacement therapy (ART) will require periodic follow-up including laboratory evaluation and surveillance for negative effects from androgen therapy, which can include polycythemia, reductions in HDL cholesterol, virilization in females, and prostate disease in males.

Do you still have questions about opioid-induced androgen deficiency or opioid addiction treatment? Contact us at, we are here to help.

National Center for Biotechnological Information - Opioid-Induced Androgen Deficiency (OPIAD): Diagnosis, Management, and Literature Review

National Center for Biotechnological Information - Opioid-induced androgen deficiency (OPIAD)

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