Breaking the Habit: Opioid-Induced Endocrinopathies

Aside from the chances of becoming addicted or even dying from an overdose, opioids have also proven damaging to the endocrine system. An awareness by both patients and physicians is a much-needed first step to combatting these often severe conditions.

Opioids have been grabbing headlines for the past couple of years. They’ve become an epidemic, and the U.S. is right in the center of it. In 2014, the U.S. used almost 70% of the world’s opioids. Vicodin is the most prescribed drug in the U.S.

And it’s not just pain management physicians prescribing these drugs. Family practitioners, cardiologists, neurologists, nephrologists, and so on, are all prescribing opioids to their patients for acute and chronic pain. These drugs grab headlines because they can lead to addiction and death — according to the American Society of Addiction Medicine, of the 52,000 lethal drug overdoses in 2015, 20,000 of those deaths were from prescription painkillers, while about 13,000 of those fatalities were from heroin. (Most heroin users started out by abusing prescription opioids.) These are probably well-known statistics, but what’s often overlooked are these drugs’ multiple effects on the endocrine system.

Niki Karavitaki, MSc, PhD, FRCP, of the University of Birmingham, United Kingdom, gave a Meet-the-Professor talk at ENDO 2018 in Chicago on how chronic use of opioids can lead to multiple endocrinopathies. She says that currently there is a lack of data on the prevalence of opioid-induced endocrinopathies and on predictive factors for who will develop them. “It seems that awareness of the endocrine effects of opioids amongst healthcare professionals prescribing or looking after patients on these agents is rather limited and possibly this is one of the reasons the problem has not been addressed in an effective way in clinical practice,” she says.

Admitting There’s a Problem

The first step to solving any problem is admitting there is one, and in this case, that can go for the patients as well as the physicians who treat them. Karavitaki says that one of the contributing factors for this so-called “opioid crisis” is the inappropriate prescribing of these drugs. She writes in her Meet-the-Professor Clinical Case Management piece “Opiate-Induced Endocrinopathies” that prescribing of opioids has increased fourfold in the U.S. since the mid-1990s, and from 2003 to 2013, opioid prescribing nearly doubled. In her clinical practice, she was seeing a number of patients on various types and doses of opioids who had hypogonadism.

“It seems that awareness of the endocrine effects of opioids amongst healthcare professionals prescribing or looking after patients on these agents is rather limited and possibly this is one of the reasons the problem has not been addressed in an effective way in clinical practice.” – Niki Karavitaki, MSc, PhD, FRCP, University of Birmingham, United Kingdom

According to Karavitaki, opioids can suppress the hypothalamo/pituitary/gonadal system and in the long term, can reduce bone mineral density. These drugs also suppress the hypothalamo/pituitary/adrenal system and reduce glucocorticoid secretion.

But there remains a lack of awareness or appreciation for how opioids affect the endocrine system. “Apart from the gonadal axis, robust data on the impact of opioids on other parts of the endocrine system and its clinical significance are lacking,” Karavitaki says. “One of the main reasons for this is the under-recognition of the problem and its consequences, thereby attracting limited attention at a research level. The first steps for improving the landscape of opioid-induced endocrinopathy is provision of adequate funding for research and engaging the endocrine academic community on this hot topic.”

Making the Connection

And patients may not be making the connection between the opioids they’re taking and these endocrinopathies. Or they may be hesitant to bring up the manifestations of an endocrinopathy like hypogonadism with their physician. Opioid-induced hypogonadism remains under-diagnosed partly because men may be embarrassed to tell their doctors they’re suffering from lower libido or ability to perform, and partly because there is an under-appreciation for this connection among physicians.

“Hypogonadism in males manifests with erectile dysfunction and reduced libido,” Karavitaki says. “The patients may feel uncomfortable to discuss these manifestations with their physician or may relate them with other factors like aging, presence of other comorbidities, or pain and not raise them during clinic consultation. On the other hand, the clinicians may lack awareness of these sequelae or under-appreciate their significance, missing, unfortunately, a significant clinical problem.”

Karavitaki argues that doctors treating men on opioids need to think about testing testosterone levels, as well as the need for more studies and the development of guidelines, since these drugs are so prevalent. Other effective measures in solving this problem would be enhancing patient awareness and warning them about the possibility of these adverse effects before opioid initiation and encouraging them to report relevant manifestations should any develop.

“From the clinician’s perspective,” Karavitaki says, “given that these agents are prescribed by a wide range of health professionals (who may not necessarily have good endocrine background), vital points are educating and alerting them for actively enquiring about clinical manifestations and for monitoring for endocrinopathy during opioid treatment.”

An Elegant Solution?

The opioid epidemic doesn’t seem to be going away any time soon. Steps to address the overall problem are sometimes met with criticism and pushback from patients’ groups who cry foul at more extreme measures like severely limiting who can receive opioids for their legitimate chronic pain. Meetings among physicians’ groups and associations are held. Plans are laid out. Prescription drug monitoring programs have been developed, but they have barriers to optimal use. Even the Trump administration has made solving the opioid epidemic part of its platform.

“Apart from the gonadal axis, robust data on the impact of opioids on other parts of the endocrine system and its clinical significance are lacking. One of the main reasons for this is the under-recognition of the problem and its consequences, thereby attracting limited attention at a research level. The first steps for improving the landscape of opioid-induced endocrinopathy is provision of adequate funding for research and engaging the endocrine academic community on this hot topic.” – Niki Karavitaki, MSc, PhD, FRCP, University of Birmingham, United Kingdom

And while the government and patients’ and physicians’ groups are still struggling with the best ways to tackle this problem, an audience member in that ENDO session stood up and commented on a seemingly elegant and possibly easy solution, especially as it relates to how opioids affect the endocrine system. “If you tell men up front that opioids decrease sex drive and make them feel weaker, they will often opt for alternative treatment,” she said.

“An important element of effective patient consultation involves providing accurate information on the pros and cons of any medical treatment and balancing the risks and benefits of it,” Karavitaki says. “These will lead to an informed decision by the patient. I anticipate that if the potential endocrine adverse effects were discussed with all patients prescribed opioids, a number of them would possibly opt for alternative pain management treatments.”

But for Karavitaki, endocrinologists and others who are researching how opioids affect the endocrine system still have work to do. Acute administration of opioids and chronic administration of these drugs affect parts of the endocrine system in different ways. And while hypogonadism is the most well recognized of these opioid-induced endocrinopathies, more research is needed to clarify the prevalence and clinical significance of the other effects these drugs have on the endocrine system. “Increasing awareness of the endocrine sequelae amongst clinicians and patients is vital,” Karavitaki says, “particularly given the substantial growth in the use of these agents over the past two decades.”

— Bagley is the senior editor of Endocrine News. He wrote about a Von Hippel-Lindau patient’s story in the August issue.

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