Endocrine News speaks with Niki Karavitaki, MSc, PhD, FRCP, of the University of Birmingham, Birmingham Health Partners, and the University Hospitals Birmingham National Health Service Foundation Trust in Birmingham, U.K., chair of the Endocrine Society’s recent Scientific Statement on opioids’ impact on the endocrine system. She discusses gaps in research, as well as why healthcare professionals should be aware of opioid-induce endocrinopathies.
Last October, the Endocrine Society published a Scientific Statement highlighting research gaps associated with the effects of opioid use on the endocrine system. The paper, “Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement,” published in Endocrine Reviews, examines data related to the use and misuse of opioids and the effects of these drugs on the endocrine system. It also discusses recent research on the clinical consequences of opioids, especially on the hypothalamic-pituitary system and bone health.
Opioids still seem to command as many headlines as new blockbuster drugs like GLP-1 agonists, but for different reasons – these drugs can and do lead to addiction and even death. The authors of the Statement point out that United States opioid prescribing “catapulted” in the late 1990s and early 2000s, followed by a significant increase of opioid-related overdose deaths.
“Three distinct waves of opioid mortality have been described in the current overdose crisis; the first began with increased prescribing of opioid pain relievers (natural and semisynthetic opioids and methadone) in the 1990s, the second started in 2010 and was dominated by heroin, whereas the third started in 2013 and was driven predominantly by illicitly manufactured fentanyl and related analogs,” the authors write. “In recent years, co-use of stimulants with opioids has risen, leading to what some experts are now calling the fourth, polysubstance wave of the overdose crisis.”
Since then, guidelines have been revised, legislation has been passed, and healthcare system policies have seen dramatic shifts, often limiting overall doses of opioids that could be used for chronic noncancer pain and emphasizing the need to utilize other modalities to treat pain. Still, opioid prescribing rates remain high, especially in North America, the region with the highest consumption of opioids for pain management in the world. Vicodin remains one of the most prescribed drugs in the United States.
The above is not really a secret to anyone in a healthcare profession or even just a casual consumer of health news. And endocrinologists don’t typically prescribe opioids, at least not as much as providers in other specialties. But more research is implicating opioid use in endocrine health consequences.
“Prescription opioids are used to manage chronic or acute pain by millions of people,” says lead Statement author Niki Karavitaki, MSc, PhD, FRCP, of the University of Birmingham, Birmingham Health Partners, and the University Hospitals Birmingham National Health Service Foundation Trust in Birmingham, U.K. “Furthermore, the risks of prescription misuse, opioid use disorder, and overdose have been a growing concern globally. The endocrine effects of opioids can have negative health sequelae, and this Scientific Statement is needed not only to enhance the awareness of various healthcare professionals on these sequelae but also to highlight current gaps in knowledge on this field that will open perspectives for exciting and impactful future research.”
Walk the Line
Opioids do have their place in successfully treating pain. No one is denying their potential benefit for patients who need them. The Statement authors recognize this, writing that the United States and the world are still trying to find the best way to maintain the balance of “dealing with the worst overdose crisis in the history of humankind and still considering that opioids may be necessary, and therapeutically appropriate, to treat different types of pain.”
“One of the most important ways to help ‘walk the pain management line’ is to enhance one’s understanding of opioid pharmacology and physiochemical characteristics, and how they relate to analgesic and potential adverse effects,” the authors continue.
“The endocrine effects of opioids can have negative health sequelae, and this Scientific Statement is needed not only to enhance the awareness of various healthcare professionals on these sequelae but also to highlight current gaps in knowledge on this field that will open perspectives for exciting and impactful future research.” — Niki Karavitaki, MSc, PhD, FRCP, University of Birmingham, Birmingham Health Partners; University Hospitals Birmingham National Health Service Foundation Trust; Birmingham, U.K.
And again, this Statement is designed to do just that: enhance endocrinologists’ understanding of these drugs because more patients may present with opioid-induced endocrine disorders. “Endocrinologists should be aware how these drugs can impact the endocrine system,” Karavitaki says. “This will facilitate their involvement in the optimal holistic care of patients on opioids along with the specialists prescribing opioids or the specialists looking after people who misuse opioids or have been diagnosed with opioid use disorder.”
Mind the Gap
The Statement reviews research related to the impact of opioids on gonadal and adrenal function, and bone health. The authors report hypogonadism as a well-recognized side effect of opioids and provide more clarity around the drug’s lesser-known effects on the hypothalamic-pituitary system and bone health. They discuss the link between opioids and the development of hyperprolactinemia and how more research is needed to understand their effect on secondary adrenal insufficiency.
“We address the many research gaps associated with the effects and clinical consequences of opioids on the endocrine system within this Scientific Statement,” Karavitaki says. “We hope bringing attention to recent research in the space, including opioid use’s impact on gonadal, bone, and adrenal conditions, will improve the endocrine health of people using or misusing opioids worldwide.”
The Statement authors also reviewed research into opioid’s actions on bone metabolism and their negative impact on bone mineral density and risk of fracture. 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.
“In my opinion, gaps that relate with the effects of opioids of the hypothalamic-pituitary-gonadal axis, the hypothalamic-pituitary-adrenal axis and the bone need to be prioritized,” Karavitaki continues.
Moving Forward
In 2018, Karavitaki gave a Meet-the-Professor talk at ENDO in Chicago on opioid-induced endocrinopathies, mentioning that she sees patients in her clinic on various types of opioids presenting with hypogonadism. In 2025, she says she still sees cases like these, and pain specialists now often contact endocrinologists in her clinic for advice, which seems like a step in the correct multidisciplinary direction. “I think the awareness of the endocrinologists on this topic has increased and I hope that this has had an impact in clinical practice,” Karavitaki says. “Research though on this topic has not progressed as much as we would have liked to see.”
And while physicians and legislators are still trying to stay on the tightrope with things like drug monitoring programs, endocrinologists may be uniquely positioned to offer solutions. For example, patients who find out opioids reduce libido and cause hypogonadism may opt for alternative pain management treatments. “If patients are well informed of side effects of opioids may be more open for other management options that would be considered appropriate by the relevant specialists,” Karavitaki says. “Having said that, patients with complicated issues require treatment with opioids.”
“We address the many research gaps associated with the effects and clinical consequences of opioids on the endocrine system within this Scientific Statement. We hope bringing attention to recent research in the space, including opioid use’s impact on gonadal, bone, and adrenal conditions, will improve the endocrine health of people using or misusing opioids worldwide.” — Niki Karavitaki, MSc, PhD, FRCP, University of Birmingham, Birmingham Health Partners; University Hospitals Birmingham National Health Service Foundation Trust; Birmingham, U.K.
The Scientific Statement is a call to action, identifying areas of further research that, as the authors write, will enhance endocrinologists’ understanding on the consequences of the available opioids and will provide evidence guiding the optimal diagnostic approach and management of their endocrine adverse sequelae. “These are additionally mandated by the opioid pandemic we are witnessing and will open perspectives for exciting and impactful future research,” they write.
“Exogenous opioids have various effects on the human endocrine system and some of these are associated with negative sequelae,” Karavitaki says. “Nonetheless, we still need to fill in gaps in our knowledge on this topic with methodologically robust studies that will enhance our understanding on the actions of opioids, their potential consequences and the optimal endocrine care of people using these agents.”
Bagley is the senior editor of Endocrine News. He wrote about the impact of thyroid-disrupting chemicals on pregnant women in a lower socioeconomic class in the January issue.
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