Clinical endocrinology · 2026
Endocrinopathies and Their Recovery in a 20-Year Cohort Study of People With Heroin Dependence.
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Tremonti Chris, Twigg Stephen M, Mills Katherine L, Marel Christina, Teesson Maree, Haber Paul S
Аннотация
OBJECTIVE: Chronic opioid use suppresses hypothalamic-pituitary signalling, leading to hypogonadism and adrenal insufficiency. Whether these abnormalities persist following long-term opioid cessation remains unclear. In particular, data on the female gonadal axis are limited, while other endocrine outcomes are predominantly reported in male cohorts. This study examined endocrine function in a long-term prospective cohort of people with opioid use disorder, comparing those in sustained remission with those continuing opioid use, exploring associations with opioid exposure, sex and depression.
DESIGN: Prospective cohort study using data from the Australian Treatment Outcome Study 18-20 year follow-up.
PATIENTS AND MEASUREMENTS: Participants underwent a structured interview and fasting endocrine assessment, including gonadal, adrenal, thyroid, and prolactin measurements. Endocrinopathies were defined using prespecified biochemical and clinical criteria. Prevalence was compared between opioid-free and opioid-using participants. Associations with opioid exposure, sex and depression were examined using Firth logistic regression.
RESULTS: Among 123 participants with complete endocrine data, 71 (57.7%) had at least one endocrinopathy. Thirty-five participants (28.4%) were opioid-free. Hypogonadism was markedly less common in opioid-free participants (3.3% vs. 26.7%), and no opioid-free participant had hypocortisolism, compared with 14.8% of those with continuing opioid use. Methadone dose, male sex, and depression were independently associated with hypogonadism. Men prescribed methadone had significantly lower testosterone and luteinising hormone levels. No participant with hypogonadism or hypocortisolism had been previously diagnosed or treated.
CONCLUSIONS: Opioid-induced endocrine suppression appears reversible with sustained opioid abstinence. Higher methadone dose, male sex, and depression were associated with hypogonadism. Despite frequent healthcare contact, patients remained undiagnosed, highlighting a gap in clinical awareness of opioid-associated endocrinopathies and the need for routine screening in opioid agonist treatment settings.
DESIGN: Prospective cohort study using data from the Australian Treatment Outcome Study 18-20 year follow-up.
PATIENTS AND MEASUREMENTS: Participants underwent a structured interview and fasting endocrine assessment, including gonadal, adrenal, thyroid, and prolactin measurements. Endocrinopathies were defined using prespecified biochemical and clinical criteria. Prevalence was compared between opioid-free and opioid-using participants. Associations with opioid exposure, sex and depression were examined using Firth logistic regression.
RESULTS: Among 123 participants with complete endocrine data, 71 (57.7%) had at least one endocrinopathy. Thirty-five participants (28.4%) were opioid-free. Hypogonadism was markedly less common in opioid-free participants (3.3% vs. 26.7%), and no opioid-free participant had hypocortisolism, compared with 14.8% of those with continuing opioid use. Methadone dose, male sex, and depression were independently associated with hypogonadism. Men prescribed methadone had significantly lower testosterone and luteinising hormone levels. No participant with hypogonadism or hypocortisolism had been previously diagnosed or treated.
CONCLUSIONS: Opioid-induced endocrine suppression appears reversible with sustained opioid abstinence. Higher methadone dose, male sex, and depression were associated with hypogonadism. Despite frequent healthcare contact, patients remained undiagnosed, highlighting a gap in clinical awareness of opioid-associated endocrinopathies and the need for routine screening in opioid agonist treatment settings.