Opioids and pituitary function: expert opinion

Monica Gadelha, Niki Karavitaki, Jeffrey Fudin, Jeffrey Bettinger, Hershel Raff, Anat Ben-Shlomo

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Purpose: Opioids are highly addictive potent analgesics and anti-allodynics whose use has dramatically increased in recent decades. The precipitous rise in opioid dependency and opioid use disorder is an important public health challenge given the risks for severely adverse health outcomes. The long-term opioid impact on hypothalamic–pituitary axes is particularly underappreciated among both endocrinologists and primary care physicians. We review the effects of opioids on hypothalamic–pituitary-target gland function and their implications for clinical practice.

Methods: Experts in hypothalamic–pituitary disorders and opioid pharmacology reviewed recently published literature and considered strategies for diagnosing and managing these opioid-induced endocrine effects.

Results: Opioid suppression of hypothalamic–pituitary axes can lead to hypogonadotropic hypogonadism, central adrenal insufficiency, and hyperprolactinemia. These important clinical manifestations are often under-estimated, poorly evaluated, and typically either untreated or not optimally managed. Data on biochemical testing for diagnosis and on the effect of hormone replacement in these patients is limited and prospective randomized controlled studies for guiding clinical practice are lacking.

Conclusions: Patients should be informed about risks for hypogonadism, adrenal insufficiency, and hyperprolactinemia, and encouraged to report associated symptoms. Based on currently available evidence, we recommend clinical and biochemical evaluation for potential central adrenal insufficiency, central hypogonadism, and/or hyperprolactinemia in patients chronically treated with opioids as well as the use of current expert guidelines for the diagnosis and treatment of these conditions.
Original languageEnglish
Pages (from-to)52-63
Issue number1
Early online date23 Jan 2022
Publication statusE-pub ahead of print - 23 Jan 2022


  • Adrenal insufficiency
  • Hyperprolactinemia
  • Hypogonadism
  • Hypopituitarism
  • Opioids


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