In the JournalsPerspective

Hypogonadism, hypocortisolism common in chronic opioid use

Hypogonadism occurs in more than half of men using opioids, and hypocortisolism occurs in approximately one-fifth of all patients, according to findings from a meta-analysis of more than 50 studies.

Amir Zamanpoor Najafabadi

“Use of opioids does impact the hormone system and mainly results in lower testosterone and cortisol concentrations,” Amir Zamanpoor Najafabadi, BSc, an MD/PhD candidate and fellow in clinical epidemiology at Leiden University Medical Center, the Netherlands, told Endocrine Today. “The results of this meta-analysis indicate that hypogonadism is present among approximately 63% of male patients on chronic opioids, while hypocortisolism is present in 15% to 24% of patients of both sexes. These hormone deficiencies can cause a wide variety of symptoms, such as infertility, extreme fatigue and malaise.”

In a systematic review and meta-analysis, Najafabadi and colleagues analyzed data from 52 studies assessing the endocrine effects of opioid use in 18,428 adults, conducted through May 2018 (62% published after 2010; 21 studies included patients with chronic pain). Primary outcome was the percentage of patients with dysfunction of one or more pituitary axes. Researchers also assessed the effects of opioids on hypothalamic-pituitary-end organ axes (gonadal, adrenal, thyroid, somatotroph and prolactin secretion), as well as the effects of hormone replacement on opioid-related endocrine deficiencies.

Across studies, 34 analyzed the effect of opioids on the gonadotropic axis, 24 studies assessed the effect of opioids on the hypothalamic-pituitary-adrenal axis, eight analyzed effects on the hypothalamo-pituitary-thyroid axis, nine assessed prolactin secretion and five analyzed the effect of opioids on the somatotropic axis.

Opioids 
Hypogonadism occurs in more than half of men using opioids, and hypocortisolism occurs in approximately one-fifth of all patients.
Source: Adobe Stock

The most frequently used opioid was methadone (n = 13 studies), followed by morphine (n = 12 studies).

Among 15 studies assessing hypogonadism, researchers found the prevalence was 63% (n = 3,250).

“Sensitivity studies, among seven studies with a low risk of bias, showed hypogonadism among 69% of male patients,” the researchers wrote.

The prevalence of hypocortisolism relying on dynamic and nondynamic testing, assessed in five studies, was 15% (n = 205 patients; 57.5% men), and it was 24% for two studies that used the insulin tolerance test (n = 97). In four of seven studies assessing prolactin levels, participants using opioids showed an increase in serum prolactin levels, whereas one study showed that 40% of opioid users had hyperprolactinemia and all others had normal levels, according to researchers.

“Based on the results of this meta-analysis, periodic evaluation of the gonadal axis in males and adrenal axis is advisable when patients are exposed to long-term exogenous opioids, in particular in case of complaints compatible with endocrine deficits,” Najafabadi said. “This should be included in international guidelines on opioid use.”

Najafabadi said future studies should focus on the added value of screening for endocrine deficiencies and their possible treatment.

“We furthermore currently lack data on the impact of opioids on the gonadal system in female patients,” Najafabadi said. – by Regina Schaffer

For more information:

Amir Zamanpoor Najafabadi, BSc, can be reached at the Center for Endocrine Tumor Leiden, Department of Neurosurgery, Clinical Epidemiology, Langegracht 70, 2312 NV, Leiden, the Netherlands; email: amir@lumc.nl.

Disclosures: The authors report no relevant financial disclosures.

Hypogonadism occurs in more than half of men using opioids, and hypocortisolism occurs in approximately one-fifth of all patients, according to findings from a meta-analysis of more than 50 studies.

Amir Zamanpoor Najafabadi

“Use of opioids does impact the hormone system and mainly results in lower testosterone and cortisol concentrations,” Amir Zamanpoor Najafabadi, BSc, an MD/PhD candidate and fellow in clinical epidemiology at Leiden University Medical Center, the Netherlands, told Endocrine Today. “The results of this meta-analysis indicate that hypogonadism is present among approximately 63% of male patients on chronic opioids, while hypocortisolism is present in 15% to 24% of patients of both sexes. These hormone deficiencies can cause a wide variety of symptoms, such as infertility, extreme fatigue and malaise.”

In a systematic review and meta-analysis, Najafabadi and colleagues analyzed data from 52 studies assessing the endocrine effects of opioid use in 18,428 adults, conducted through May 2018 (62% published after 2010; 21 studies included patients with chronic pain). Primary outcome was the percentage of patients with dysfunction of one or more pituitary axes. Researchers also assessed the effects of opioids on hypothalamic-pituitary-end organ axes (gonadal, adrenal, thyroid, somatotroph and prolactin secretion), as well as the effects of hormone replacement on opioid-related endocrine deficiencies.

Across studies, 34 analyzed the effect of opioids on the gonadotropic axis, 24 studies assessed the effect of opioids on the hypothalamic-pituitary-adrenal axis, eight analyzed effects on the hypothalamo-pituitary-thyroid axis, nine assessed prolactin secretion and five analyzed the effect of opioids on the somatotropic axis.

Opioids 
Hypogonadism occurs in more than half of men using opioids, and hypocortisolism occurs in approximately one-fifth of all patients.
Source: Adobe Stock

The most frequently used opioid was methadone (n = 13 studies), followed by morphine (n = 12 studies).

Among 15 studies assessing hypogonadism, researchers found the prevalence was 63% (n = 3,250).

“Sensitivity studies, among seven studies with a low risk of bias, showed hypogonadism among 69% of male patients,” the researchers wrote.

The prevalence of hypocortisolism relying on dynamic and nondynamic testing, assessed in five studies, was 15% (n = 205 patients; 57.5% men), and it was 24% for two studies that used the insulin tolerance test (n = 97). In four of seven studies assessing prolactin levels, participants using opioids showed an increase in serum prolactin levels, whereas one study showed that 40% of opioid users had hyperprolactinemia and all others had normal levels, according to researchers.

“Based on the results of this meta-analysis, periodic evaluation of the gonadal axis in males and adrenal axis is advisable when patients are exposed to long-term exogenous opioids, in particular in case of complaints compatible with endocrine deficits,” Najafabadi said. “This should be included in international guidelines on opioid use.”

Najafabadi said future studies should focus on the added value of screening for endocrine deficiencies and their possible treatment.

“We furthermore currently lack data on the impact of opioids on the gonadal system in female patients,” Najafabadi said. – by Regina Schaffer

For more information:

Amir Zamanpoor Najafabadi, BSc, can be reached at the Center for Endocrine Tumor Leiden, Department of Neurosurgery, Clinical Epidemiology, Langegracht 70, 2312 NV, Leiden, the Netherlands; email: amir@lumc.nl.

Disclosures: The authors report no relevant financial disclosures.

    Perspective

    The authors’ overall conclusions are unsurprising, given that the suppressive effects of opioids on the gonadal axis and prolactin are well known. However, precise percentages cannot be drawn from this meta-analysis, which included studies that used a range of methods and thresholds to diagnose deficiencies, some of which do not meet current guidelines. When assessing adrenal insufficiency, it is important to understand which studies found definitive adrenal deficiency vs. lower absolute levels still within normal range and via which tests. The lack of ability to mount an appropriate stress response can be fatal, and additional studies on adrenal insufficiency may be warranted.

    Clinicians should be aware that patient quality of life may be affected by alterations to hormone levels while taking opioids. Symptoms suggestive of endocrine abnormalities bear testing and, on a case be case basis, consideration for replacement. It is also important to consider the condition of patients taking opioids. The reason for opioid use — a person with opioid use disorder vs. a person with cancer pain or other chronic pain — may itself impact hormone levels.

    • Tamara Wexler, MD, PhD
    • Clinical Assistant Professor
      Department of Rehabilitation Medicine
      NYU Langone Medical Center in New York

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