The DOI matches its Crossref record; 251 of the 252 references it cites were found in a registry or an index, and 1 are not checked yet; 65 of the 244 sources its claims cite were checked for support.
Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement
Open accessAbstract
The use and misuse of opioids are a growing global problem. Although the effects of these drugs on the human endocrine system have been studied for decades, attention on their related clinical consequences, particularly on the hypothalamic-pituitary system and bone health, has intensified over recent years. This Statement appraises research data related to the impact of opioids on the gonadal and adrenal function. Whereas hypogonadism is well recognized as a side effect of opioids, the significance of their inhibitory actions on the hypothalamic-pituitary-adrenal system and the occurrence of clinically relevant adrenal insufficiency is not fully elucidated. The often-inconsistent results of studies investigating how opioids affect the secretion of GH, prolactin, arginine vasopressin, and oxytocin are assessed. The accumulating evidence of opioid actions on bone metabolism and their negative sequelae on bone mineral density and risk of fracture are also reviewed. In each section, available data on diagnostic and management approaches for opioid endocrine sequelae are described. This Statement highlights a plethora of gaps in research associated with the effects and clinical consequences of opioids on the endocrine system. It is anticipated that addressing these gaps will improve the care of people using or misusing opioids worldwide. The Statement is not intended to serve as a guideline or dictate treatment decisions.
Verified 2026-10-11 · 1 reference not checked yet
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Claims the paper makes
118 No full text of the sources · 43 Own interpretation · 27 Supported · 22 Partly supported · 15 No basis given · 6 Supported so far · 5 Not checked yet · 1 Mixed support · 1 Not supported · 1 Couldn’t confirm · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“An 8-month aerobic gymnastics training program in young opioid-addicted women failed to show any effects on bone quality, as assessed by quantitative ultrasound (253).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Diagnostic approach and management
What the sources say
- Disputedcites [253] Ding, 2021, Effect of eight-month exercise intervention on bone outcomes of young opioid-dependent women, Int J Environ Res Public Health sourceExperimental — accuracy not yet measured
The Abstract reports that bone quality was assessed by quantitative ultrasound and that the exercise group's stiffness index increased significantly after eight months, while the control group's did not. The Conclusions likewise describe a positive effect on bone quality, contrary to the claim of no effect. (LLM, conf=0.95)
Checked by a reasoning model — may be wrong.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“As well as common symptoms of cortisol deficiency, such as fatigue, nausea/vomiting, musculoskeletal pain, weight loss, headache, and light-headedness (119), less common but well recognized manifestations, such as hypercalcemia (123) and hypoglycemia (124) have been described.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Clinical Significance
What the sources say
- Supportedcites [123] Lee, 2015, Opioid-induced secondary adrenal insufficiency presenting as hypercalcaemia, Endocrinol Diabetes Metab Case Rep source
Citation (123) is attached to hypercalcemia, not hypoglycemia. The Background calls adrenal insufficiency a rare but important cause of hypercalcaemia, and the Discussion states that hypercalcaemia can occur in both primary and secondary adrenal insufficiency. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [124] Tabet, 2019, Opioid-induced hypoadrenalism resulting in fasting hypoglycaemia, BMJ Case Rep source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, other studies have reported secondary adrenal insufficiency in people on lower opioid doses, including a cross-sectional one examining the hypothalamic-pituitaryadrenal axis function of 102 patients on various opioids (117).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Supportedcites [117] Li, 2020, Prevalence of opioid-induced adrenal insufficiency in patients taking chronic opioids, J Clin Endocrinol Metab source
The Patients section reports 102 patients taking various opioids, and the Subjects section describes assessment of their hypothalamic–pituitary–adrenal function on admission. The Discussion reports opioid-induced adrenal insufficiency in patients taking 20 and 30 MME per day, supporting the claim that it occurred at lower doses. The cohort was prospectively enrolled, but its admission assessment supports the description of a cross-sectional examination. (LLM, conf=0.90)
plainn = 102- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Interestingly, in a case report of a 61-year-old man with chronic intercostal neuropathic pain managed with methadone, GH treatment with daily doses up to 0.3 mg led to improvement of cognitive capacity (140).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Clinical Significance
What the sources say
- Supportedcites [140] Rhodin, 2014, Recombinant human growth hormone improves cognitive capacity in a pain patient exposed to chronic opioids, Acta Anaesthesiol Scand source
The Case report identifies a 61-year-old man with chronic intercostal neuropathic pain who was receiving methadone. The rhGH treatment section reports daily doses of 0.1–0.2 mg, later increased to 0.3 mg; the Discussion reports improved visuospatial and subjective cognitive functioning after treatment. (LLM, conf=0.94)
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The limited number of included reports and the different protocols used to assess GH deficiency did not allow definite conclusions to be obtained (72).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Supportedcites [72] de Vries, 2020, Opioids and their endocrine effects: a systematic review and meta-analysis, J Clin Endocrinol Metab source
The Results (Somatotropic axis; page not provided) identify only five studies of opioid effects on the GH axis. The Discussion says evidence for an effect on that axis is insufficient, while Strengths and limitations notes that endocrine assessment methods and definitions differed across studies. Together, these support the citing sentence’s conclusion. (LLM, conf=0.88)
plainn = 225- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In a systematic review of 6 studies evaluating the long-term effects of opioids on PRL secretion among 346 patients with either cancer pain or noncancer pain, the results were variable (72).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Partly supportedcites [72] de Vries, 2020, Opioids and their endocrine effects: a systematic review and meta-analysis, J Clin Endocrinol Metab sourceExperimental — accuracy not yet measured
The Results section (page not provided) reviews opioid effects on prolactin secretion and reports differing findings. However, it counts seven studies and 354 patients, not six studies and 346 patients; it does not identify that group as exclusively patients with cancer or noncancer pain. (LLM, conf=0.88)
plainn = 346- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition, high PRL levels were found in 2 of 20 (10%) noncancer pain patients on intrathecal morphine (147).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Supportedcites [147] Duarte, 2013, Hypogonadism and low bone mineral density in patients on long-term intrathecal opioid delivery therapy, BMJ Open source
The Methods (Patients; page not provided) describe 20 patients with chronic non-cancer pain, all receiving intrathecal morphine, either alone or with other drugs. The Discussion (page not provided) reports raised serum prolactin in two patients, matching 2 of 20 (10%). (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In a report of 14 patients on opioids for cancer pain, serum PRL levels were above the reference range in 6 (43%) of them.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Supportedcites [75] Merdin, 2016, Opioid endocrinopathy: a clinical problem in patients with cancer pain, Exp Ther Med source
Table II (shown in the Discussion passage; page not provided) reports prolactin results for 14 patients: 6 (42.9%) were above the reference range. The Results state that all patients received opioids for cancer pain. (LLM, conf=0.95)
plainn = 14- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A data mining study from the US Food and Drug Administration Adverse Event Reporting System demonstrated that in patients with OUD, there was positive association with hyperthyroidism (adjusted odds ratio, 1.46; 95% CI, 1.43-1.49)and hypothyroidism (adjusted odds ratio, 1.45; 95% CI, 1.42-1.48)(162).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Partly supportedcites [162] Pan, 2022, Mining comorbidities of opioid use disorder from FDA adverse event reporting system and patient electronic health records, BMC Med Inform Decis Mak sourceExperimental — accuracy not yet measured
The Results section, under “Positive associations between hypothyroidism, hyperthyroidism, type 2-diabetes and OUD,” reports the stated hyperthyroidism association (AOR 1.46; 95% CI 1.43–1.49). However, the Discussion says the study identified potential associations from FAERS and tested them using patient electronic records; the quoted adjusted odds ratio comes from that EHR validation, not directly from FAERS data. (LLM, conf=0.86)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A data mining study from the US Food and Drug Administration Adverse Event Reporting System demonstrated that in patients with OUD, there was positive association with hyperthyroidism (adjusted odds ratio, 1.46; 95% CI, 1.43-1.49)and hypothyroidism (adjusted odds ratio, 1.45; 95% CI, 1.42-1.48)(162).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Partly supportedcites [162] Pan, 2022, Mining comorbidities of opioid use disorder from FDA adverse event reporting system and patient electronic health records, BMC Med Inform Decis Mak sourceExperimental — accuracy not yet measured
The Results section, “Positive associations between hypothyroidism, hyperthyroidism, type 2-diabetes and OUD,” reports the stated positive association and exact adjusted odds ratio for hypothyroidism. However, the Abstract Results and Discussion identify those odds ratios as coming from an independent EHR-based validation, not from the FAERS data mining itself. (LLM, conf=0.88)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
- It may state two separate claims as one. 77
- The quote only partly states this claim. 3
- Probably not a substantial claim. 26
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“In this vein, remifentanil promoted the differentiation of murine pre-osteoclasts and induced their maturation in one experimental setting (220), although the exact opposite effects, namely reduction of the number and size of osteoclasts and the formation of tartrate-resistant acid phosphatase-positive multinuclear osteoclasts by remifentanil, have also been described (221).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioids and bone remodeling/bone healing
What the sources say
- Disputedcites [220] Jeon, 2018, Effect of remifentanil on pre-osteoclast cell differentiation in vitro, J Dent Anesth Pain Med sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 0 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
- Supportedcites [221] Yoon, 2018, Remifentanil negatively regulates RANKL-induced osteoclast differentiation and bone resorption by inhibiting c-Fos/NFATc1 expression, Tissue Eng Regen Med source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Disputed
Every source the paper cites for this claim was checked and supports it.
In the paper
“Nine patients (9%) were diagnosed with secondary adrenal insufficiency (6 based on a combination of clinical assessment, basal morning cortisol, ACTH, and DHEAS levels and 3 after an ACTH1-24 stimulation test), and their minimum MME dose was 20 mg daily.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Supportedcites [117] Li, 2020, Prevalence of opioid-induced adrenal insufficiency in patients taking chronic opioids, J Clin Endocrinol Metab source
The Patients section reports 102 participants using several opioid types. The Adrenal function section reports nine diagnoses (9%), six based on abnormal initial testing and clinical suspicion and three also supported by cosyntropin testing. Table 4 lists 20 mg daily MME as the lowest dose among the diagnosed patients. (LLM, conf=0.94)
plainn = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Despite the millions of people worldwide using oral and transdermal opioids, the number of those diagnosed with opioidinduced secondary adrenal insufficiency is low, and there have been only very few published cases of adrenal crisis (112, 119, 122).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Clinical Significance
What the sources say
- Not checked — no full text of the sourcecites [112] Oltmanns, 2005, Chronic fentanyl application induces adrenocortical insufficiency, J Intern Med source
- Not checked — no full text of the sourcecites [119] Li, 2020, Clinical presentation and outcomes of opioid-induced adrenal insufficiency, Endocr Pract source
- Partly supportedcites [122] Ali, 2019, Secondary adrenal insufficiency induced by long-term use of opioid analgesics, Proc (Bayl Univ Med Cent) sourceExperimental — accuracy not yet measured
The Abstract (p. 417) and Discussion (pp. 417–418) describe opioid-induced adrenal insufficiency as underappreciated and not well recognized, and the paper reports one patient with cardiovascular collapse. They do not establish worldwide oral and transdermal opioid-use figures, a low number of diagnoses, or that very few adrenal-crisis cases have been published. (LLM, conf=0.84)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Among these reports, there was a weighted mean percentage of 15% (95% CI, 6-28) with secondary adrenal insufficiency (72).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Partly supportedcites [72] de Vries, 2020, Opioids and their endocrine effects: a systematic review and meta-analysis, J Clin Endocrinol Metab sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Opioids can cause hyperprolactinemia, most likely by inhibiting the hypothalamic dopamine production (49,141).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Supportedcites [49] Gadelha, 2022, Opioids and pituitary function: expert opinion, Pituitary source
The section ‘Effect of opioids on the hypothalamus-pituitary-gonadal axis’ states that opioids inhibit hypothalamic dopamine secretion, leading to hyperprolactinemia. The ‘Effect of opioids on prolactin’ section likewise says opioids can cause hyperprolactinemia, likely through inhibition of the tuberoinfundibular dopaminergic system. (LLM, conf=0.95)
- Not checked — no full text of the sourcecites [141] Gadelha MR., 2022 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Preclinical studies suggest that ghrelin/GHS-R1a has a significant role in the reinforcing effects of opioids, and in preclinical addiction studies, GHS-R1a antagonism decreased the opioid reward and the symptoms of craving for opioids (139).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Supportedcites [139] Sustkova-Fiserova, 2022, The role of ghrelin/GHS-R1A signaling in nonalcohol drug addictions, Int J Mol Sci source
Section 4.3 (Summary) states that preclinical studies implicate ghrelin/GHS-R1A signaling in the reinforcing effects of opioids. It also reports that GHS-R1A antagonism reduced morphine and fentanyl reward and signs of craving or desire for opioids in addiction models. (LLM, conf=0.94)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In a group of 7 patients, 6 successfully weaned off opioids completely and were able to cease their hydrocortisone (117).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Management
What the sources say
- Supportedcites [117] Li, 2020, Prevalence of opioid-induced adrenal insufficiency in patients taking chronic opioids, J Clin Endocrinol Metab source
The Discussion states that, among seven patients who discontinued opioids and had follow-up, six recovered from adrenal insufficiency and stopped hydrocortisone. The Follow up section reports the same outcome, specifying that the six stopped hydrocortisone after reassessment. (LLM, conf=0.94)
plainn = 7- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Studies evaluating the effects of opioids on the GH axis in humans are limited and data supporting a robust and consistent effect are insufficient (70).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Supportedcites [70] Fountas, 2020, Opioid-induced endocrinopathies, Lancet Diabetes Endocrinol source
The Somatotroph axis section describes limited human evidence and conflicting results for chronic opioid use, concluding that those effects are inconclusive. It also reports an acute, dose-related increase in GH secretion; that finding does not establish a robust and consistent effect across opioid use. (LLM, conf=0.91)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The patient had developed impaired cognitive function as a possible complication of opioid long-term treatment and had been diagnosed with GH deficiency by a GHRH-arginine test.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Clinical Significance
What the sources say
- Supportedcites [140] Rhodin, 2014, Recombinant human growth hormone improves cognitive capacity in a pain patient exposed to chronic opioids, Acta Anaesthesiol Scand source
The Discussion describes the patient's cognitive disabilities as likely caused by long-term opioid treatment. The Results (Hormonal analysis) report that GHRH-arginine testing revealed growth hormone deficiency. Page numbers were not provided in our copy. (LLM, conf=0.94)
hedgedconditionalSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Earlier studies had suggested that morphine induces an antidiuresis in several species, including man, by stimulating the release of arginine vasopressin (AVP) (163, 164).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [163] De Bodo, 1944, THE ANTIDIURETIC ACTION OF MORPHINE, AND ITS MECHANISM, J Pharmacol Exp Ther source
- Supportedcites [164] Schnieden, 1955, The effect of nalorphine on the antidiuretic action of morphine in rats and men, Br J Pharmacol Chemother source
The introduction says morphine inhibits the diuretic response in several mammalian species and reports De Bodo’s suggestion that this reflects release of posterior pituitary antidiuretic hormone. Table V and the human results include antidiuresis in men, while the Discussion describes pituitary action as a suggested mechanism rather than a demonstrated one. (LLM, conf=0.88)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“In contrast, hyperprolactinemia has not been confirmed in other studies involving noncancer pain patients on intrathecal or oral opioids (74, 136, 148), although in one of them, PRL was higher (but still within normal range) in men in the opioidtreated group, as compared with the controls (148).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [74] Abs, 2000, Endocrine consequences of long-term intrathecal administration of opioids, J Clin Endocrinol Metab source
- Not checked — no full text of the sourcecites [136] Valverde-Filho, 2015, Chronic spinal and oral morphine-induced neuroendocrine and metabolic changes in noncancer pain patients, Pain Med source
- Supportedcites [148] Wong, 2011, Opioid analgesics suppress male gonadal function but opioid use in males and females does not correlate with symptoms of sexual dysfunction, Pain Res Manag source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Furthermore, basal TSH values have been reported to be lower (149, 153), unaffected (74, 116, 136, 155-160), or increased (118, 161).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [149] Moshtaghi-Kashanian, 2005, Enhanced prolactin levels in opium smokers, Addict Biol source
- Not checked — no full text of the sourcecites [153] Devilla, 1985, Morphine-induced TSH release in normal and hypothyroid subjects, Neuroendocrinology source
- Not checked — no full text of the sourcecites [74] Abs, 2000, Endocrine consequences of long-term intrathecal administration of opioids, J Clin Endocrinol Metab source
- Not checked — no full text of the sourcecites [116] Lamprecht, 2018, Secondary adrenal insufficiency and pituitary dysfunction in oral/transdermal opioid users with non-cancer pain, Eur J Endocrinol source
- Not checked — no full text of the sourcecites [136] Valverde-Filho, 2015, Chronic spinal and oral morphine-induced neuroendocrine and metabolic changes in noncancer pain patients, Pain Med source
- Not checked — no full text of the sourcecites [155] Brambilla, 1980, Effects of chronic heroin addiction on pituitary-thyroid function in man, J Endocrinol Invest source
- Not checked — no full text of the sourcecites [156] Vescovi, 1984, Effect of methadone on TSH and thyroid hormone secretion, Horm Metab Res source
- Not checked — no full text of the sourcecites [157] Spagnolli, 1987, Prolactin and thyrotropin pituitary response to thyrotropin releasing hormone in young female heroin addicts, Drug Alcohol Depend source
- Not checked — no full text of the sourcecites [158] Fraser, 2009, Oral opioids for chronic non-cancer pain: higher prevalence of hypogonadism in men than in women, Exp Clin Endocrinol Diabetes source
- Partly supportedcites [159] Gozashti, 2014, The effect of opium addiction on thyroid function tests, J Diabetes Metab Disord sourceExperimental — accuracy not yet measured
The Introduction reports decreased TSH during morphine consumption, while the Discussion reports unchanged TSH in heroin-dependent men and increased TSH following buprenorphine or heroin consumption. The source does not establish that the reported decrease and increase were specifically in chronic users; one decrease it describes followed short-term morphine consumption. Our copy provides section labels but no page numbers for these passages. (LLM, conf=0.82)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“T3 resin uptake, reflecting thyroid hormone binding globulin, has been reported to be lower (159).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Supportedcites [159] Gozashti, 2014, The effect of opium addiction on thyroid function tests, J Diabetes Metab Disord source
The Discussion reports lower T3 resin uptake (T3RU) in opium addicts than in non-addicts and explains that T3RU is used to assess thyroid-binding globulin, with an inverse relationship between them. The Results also report a significant association between opium consumption and decreased T3RU after adjustment for age and smoking. (LLM, conf=0.93)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“PRL values seemed to increase with higher opioid doses, but this finding did not reach statistical significance, possibly because of the small sample size (75).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Partly supportedcites [75] Merdin, 2016, Opioid endocrinopathy: a clinical problem in patients with cancer pain, Exp Ther Med sourceExperimental — accuracy not yet measured
The Results report that prolactin increased as morphine-equivalent daily dose increased, but the association was not statistically significant (P=0.083); the Statistical analysis section sets significance at P<0.05. The study included 20 patients, but our copy does not attribute the nonsignificant result to its sample size. (LLM, conf=0.85)
hedgedcorrelationaln = 14- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Variable results have also been described for the peripheral thyroid hormones; T4 levels were unaffected (74, 118, 136, 159, 160) or decreased (116, 160-162) and T3 levels were increased (74, 159) or unaffected (160) or decreased (161).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [74] Abs, 2000, Endocrine consequences of long-term intrathecal administration of opioids, J Clin Endocrinol Metab source
- Not checked — no full text of the sourcecites [118] Rhodin, 2010, Opioid endocrinopathy: a clinical problem in patients with chronic pain and long-term oral opioid treatment, Clin J Pain source
- Not checked — no full text of the sourcecites [136] Valverde-Filho, 2015, Chronic spinal and oral morphine-induced neuroendocrine and metabolic changes in noncancer pain patients, Pain Med source
- Supportedcites [159] Gozashti, 2014, The effect of opium addiction on thyroid function tests, J Diabetes Metab Disord source
The Results report no significant association for total T4 or free T3, but lower free T4 and higher total T3 in the adjusted analysis. These findings support the variable outcomes attributed to this source; the citing sentence assigns decreased T3 to a different reference. The distinction between total and free hormone levels matters here. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [160] Shenkman, 1972, Effects of chronic methadone administration on the hypothalamic-pituitary-thyroid axis, J Clin Endocrinol Metab source
- Not checked — no full text of the sourcecites [116] Lamprecht, 2018, Secondary adrenal insufficiency and pituitary dysfunction in oral/transdermal opioid users with non-cancer pain, Eur J Endocrinol source
- Supportedcites [161] Pezeshki, 2023, Thyroid function and opium use disorder: a cross-sectional study on the Fasa adults cohort study (FACS), 2017, BMC Endocr Disord source
The Discussion reports earlier studies finding increased T3 with unchanged T4, and another finding no effect on either hormone. The Results report lower T4 in opium users and no statistically significant overall difference in T3, while the Discussion describes lower T3 in the study population. Together, these passages support the range of findings described. (LLM, conf=0.91)
- Could not verifycites [162] Pan, 2022, Mining comorbidities of opioid use disorder from FDA adverse event reporting system and patient electronic health records, BMC Med Inform Decis Mak sourceExperimental — accuracy not yet measured
The Results section reports associations between opioid use disorder and diagnoses of hypothyroidism and hyperthyroidism, not measurements of peripheral thyroid hormones. A search for T3, T4, thyroxine, and triiodothyronine found no passage describing the claimed increases, decreases, or unchanged levels. (LLM, conf=0.76)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The only opioid, however, that has been associated with hyponatremia in case reports is tramadol, a weak opioid analgesic with the hyponatremia usually occurring within the first 30 days after initiation of this drug (170-173).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Partly supportedcites [170] Hunter, 2004, Tramadol and hyponatraemia, Aust Prescr sourceExperimental — accuracy not yet measured
The Comment section reports four elderly patients who developed hyponatraemia while taking tramadol, and the Medicinal mishap section describes one case detected nine days after initiation. The paper does not establish that tramadol is the only opioid reported in such cases or that hyponatraemia usually occurs within 30 days; it also does not describe tramadol as a weak opioid. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [171] Abadie, 2013, [“serious”? adverse drug reactions with tramadol: a 2010–2011 pharmacovigilance survey in France], Therapie source
- Not checked — no full text of the sourcecites [172] Le Berre, 2007, [Hyponatremia due to tramadol], Rev Med Interne source
- Not checked — no full text of the sourcecites [173] Lota, 2012, Profound hyponatraemia following a tramadol overdose, QJM source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Moreover, maternal consumption of morphine in rats led to impairment of longitudinal bone growth, as well inhibition of protein expression of chondrogenic and osteogenic markers in their offspring (209).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioids and bone remodeling/bone healing
What the sources say
- Supportedcites [209] Saeidinezhad, 2021, Effects of maternal consumption of morphine on rat skeletal system development, BMC Musculoskelet Disord source
The Conclusion (page not provided) reports harmful effects of prenatal morphine exposure on offspring bone length and identifies downregulation of chondrogenic and osteogenic proteins. The Discussion (page not provided) also reports decreased staining of osteocalcin and alkaline phosphatase and reduced detection of cartilage markers, supporting the paraphrase. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These results were replicated in a murine model, in which treatment with morphine inhibited mineral nodule formation (207), and in human bone marrow-derived mesenchymal stem cells, where morphine altered the ability of mesenchymal stem cells to differentiate into adipocytes or osteoblasts (206).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioids and bone remodeling/bone healing
What the sources say
- Partly supportedcites [207] Marczak, 2009, Orally administered H-Dmt-Tic-Lys-NH-CH2-Ph (MZ-2), a potent mu/delta-opioid receptor antagonist, regulates obese-related factors in mice, Eur J Pharmacol sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [206] Holan, 2018, The impact of morphine on the characteristics and function properties of human mesenchymal stem cells, Stem Cell Rev Rep source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A randomized, double-blind clinical trial in heroin-dependent subjects showed that acute oxytocin treatment reduced craving and withdrawal scores, without, however, a significant effect on anxiety (201).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Supportedcites [201] Moeini, 2019, The effects of oxytocin on withdrawal, craving and stress response in heroin-dependent patients: a randomized, double-blind clinical trial, Eur Addict Res source
The Abstract describes a randomized, double-blind, placebo-controlled trial in heroin-dependent male patients receiving a single intranasal oxytocin dose. The Effects of OT on Withdrawal, Craving and Anxiety Scores section reports significantly reduced craving and withdrawal scores, but no significant difference in anxiety scores compared with placebo. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“As the population ages, next to the burden to the individual, pain is bound to have considerable economical and societal impact (230).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioid prescription in the elderly population and bone health
What the sources say
- Could not verifycites [230] Chau, 2008, Opiates and elderly: use and side effects, Clin Interv Aging sourceExperimental — accuracy not yet measured
The Introduction reports that pain is common among older adults, but it does not address the economic or societal impact of pain as the population ages. Searches for economic costs and societal burden found no passage addressing that point. (LLM, conf=0.72)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“with only 3.2% of the study population using an opioid for cancerrelated pain (232).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioid prescription in the elderly population and bone health
What the sources say
- Supportedcites [232] Mörttinen-Vallius, 2021, The prevalence of and exact indications for daily opioid use among aged home care clients with and without dementia, Aging Clin Exp Res source
The Results state that only 3.2% of the study population used an opioid for cancer-related pain. Table 3 also lists cancer as the indication for 3.2% of all opioid users. (LLM, conf=0.95)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“For example, tramadol was shown to enhance osteoprotegerin synthesis in osteoblasts, thus indirectly suppressing the formation and function of osteoclasts (218, 219).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioids and bone remodeling/bone healing
What the sources say
- Not checked — no full text of the sourcecites [218] Hioki, 2021, Amplification by tramadol of PGD(2)-induced osteoprotegerin synthesis in osteoblasts: involvement of μ-opioid receptor and 5-HT transporter, Prostaglandins Leukot Essent Fatty Acids source
- Partly supportedcites [219] Kim, 2020, Tramadol enhances PGF(2α)-stimulated osteoprotegerin synthesis in osteoblasts, Heliyon sourceExperimental — accuracy not yet measured
The Results (page not supplied) show that tramadol enhanced PGF2α-stimulated osteoprotegerin release in osteoblast-like cells, but had little effect on its own. The Introduction and Discussion explain how osteoprotegerin can inhibit osteoclast differentiation and activation; the study did not demonstrate that tramadol itself suppressed osteoclast formation or function. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“In this vein, a second smaller study in a tertiary academic center confirmed decrease in pain scores, daily morphine consumption and improvement in functional status after kyphoplasty (236).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioid prescription in the elderly population and bone health
What the sources say
- Supportedcites [236] Tolba, 2014, Kyphoplasty increases vertebral height, decreases both pain score and opiate requirements while improving functional status, Pain Pract source
The Methods describe a retrospective study of 67 patients at a tertiary academic referral center. The Results report lower pain scores and daily morphine-equivalent doses after kyphoplasty, while most patients reported improved activity; the Discussion also describes improved function. The claim accurately summarizes these observed changes without asserting that kyphoplasty caused them. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Under hypoxiareoxygenation conditions, remifentanil preconditioning enhanced the cell viability and maturation of human fetal osteoblasts (216), whereas in the pre-osteoblast C2C12 murine cell line, it increased osteoblast differentiation by upregulation of the expression of two key osteogenic transcription factors Runt-related transcription factor 2 and osterix (217).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioids and bone remodeling/bone healing
What the sources say
- Partly supportedcites [216] Baik, 2015, Effects of remifentanil preconditioning on osteoblasts under hypoxia-reoxygenation condition, Int J Med Sci sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [217] Yoon, 2019, Remifentanil promotes osteoblastogenesis by upregulating Runx2/osterix expression in preosteoblastic C2C12 cells, J Dent Anesth Pain Med sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“reported prevalence of 9.3% in opioid use for long periods”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioid prescription in the elderly population and bone health
What the sources say
- Partly supportedcites [232] Mörttinen-Vallius, 2021, The prevalence of and exact indications for daily opioid use among aged home care clients with and without dementia, Aging Clin Exp Res sourceExperimental — accuracy not yet measured
The Abstract Results report that 9.3% of older home care clients used opioids daily, not that 9.3% met a specified threshold for long-term use. The Results report a median prior use of 357 days, and the Discussion says prolonged use was common, but neither establishes 9.3% as the prevalence of long-term use. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“opioids were mostly continued during the follow-up year”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioid prescription in the elderly population and bone health
What the sources say
- Supportedcites [232] Mörttinen-Vallius, 2021, The prevalence of and exact indications for daily opioid use among aged home care clients with and without dementia, Aging Clin Exp Res source
The Results report that 232 of 282 opioid users (82.3%) still used opioids at the end of their follow-up period, defined as 12 months or until death. They also report that 201 (71.3%) used an opioid daily throughout that period, supporting the claim that opioids were mostly continued. (LLM, conf=0.95)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“median duration of use was 357 days before study entry”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioid prescription in the elderly population and bone health
What the sources say
- Supportedcites [232] Mörttinen-Vallius, 2021, The prevalence of and exact indications for daily opioid use among aged home care clients with and without dementia, Aging Clin Exp Res source
The Results section states that the median duration of opioid use before study entry was 357 days, exactly matching the attributed claim. (LLM, conf=0.95)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“risk factors significantly associated with low BMD were male gender, low BMI, low testosterone levels, methadone or heroin use, and longer duration of heavy alcohol use (244).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Bone mass in patients on opioids
What the sources say
- Supportedcites [244] Ramli, 2021, Factors associated with low bone density in opioid substitution therapy patients: a systematic review, Int J Med Sci source
The Results section (“Risk Factors for Low Bone Mineral Density”) explicitly lists all five factors as significantly associated with low BMD in the opioid substitution therapy population. The citing sentence closely paraphrases that list. (LLM, conf=0.95)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“There are no universally agreed-on criteria for the diagnosis of opioid-induced adrenal insufficiency.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Diagnostic approach
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whereas hypogonadism is well recognized as a side effect of opioids”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“For example, in a study that included people both on and not on opioids, a cortisol of below 10 mcg/dL (276 nmol/L) was 100% sensitive to diagnose adrenal insufficiency in outpatients, but the specificity was only 54% (131).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Diagnostic approach
What the sources say
- Not checked — no full text of the sourcecites [131] Colling, 2022, The biochemical diagnosis of adrenal insufficiency with modern cortisol assays: reappraisal in the setting of opioid exposure and hospitalization, Clin Endocrinol (Oxf) source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In this study, 54% of patients were extensive metabolizers, 41% intermediate, and 5% poor metabolizers.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [121] Jannetto, 2009, Utilization of pharmacogenomics and therapeutic drug monitoring for opioid pain management, Pharmacogenomics source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, treating hypogonadism with testosterone in men leads to improvement in androgen deficiency symptoms including sexual function, to reduction in fat mass and increase in lean body mass.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Management
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“As previously mentioned, ITT is considered the gold standard for diagnosing secondary adrenal insufficiency, although it has some limitations (128).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Diagnostic approach
What the sources say
- Not checked — no full text of the sourcecites [128] Sarlos, 2013, Selective use of the insulin tolerance test to diagnose hypopituitarism, Intern Med J source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The frequency of the hypothalamic-pituitary-adrenal axis assessment in patients on opioids is not known but occurrence of manifestations of cortisol deficiency should prompt investigations for the integrity of the cortisol reserve.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Diagnostic approach
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“They also can inhibit the secretion of dopamine from the hypothalamus leading to hyperprolactinemia, which further contributes to the suppressive action on the hypothalamic-pituitary-gonadal axis (65).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [65] Fountas, 2018, MECHANISMS OF ENDOCRINOLOGY: endocrinology of opioids, Eur J Endocrinol source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Manifestations of secondary adrenal insufficiency include fatigue, nausea, vomiting, postural hypotension/light-headedness, cognitive decline, muscle weakness, and arthralgia/myalgia, but these may also be observed in patients on opioids with normal adrenal function.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Diagnostic approach
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Opioids inhibit pulsatile GnRH secretion from the hypothalamus and the secretion of gonadotropins (mainly LH and to a lesser extent FSH) from the pituitary gland and of sex steroids from the gonads (61)(62)(63)(64).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [61] Böttcher, 2017, Impact of the opioid system on the reproductive axis, Fertil Steril source
- Not checked — no full text of the sourcecites [62] Petraglia, 1986, Opioid control of LH secretion in humans: menstrual cycle, menopause and aging reduce effect of naloxone but not of morphine, Life Sci source
- Not checked — no full text of the sourcecites [63] Vuong, 2010, The effects of opioids and opioid analogs on animal and human endocrine systems, Endocr Rev source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In routine clinical practice, the most frequently used tests of hypothalamic-pituitary-adrenal axis function are the basal morning cortisol and the ACTH1-24 stimulation test (126).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Diagnostic approach
What the sources say
- Not checked — no full text of the sourcecites [126] Husebye, 2021, Adrenal insufficiency, Lancet source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Another remarkable aspect of the possible interplay between opioids and GH that deserves attention involves ghrelin, which stimulates GH release via the GH secretagogue receptor type 1a (GHS-R1a).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“However, 26% of the methadonetreated group and 31% of the heroin-addicted people exhibited abnormal GH peak on the ITT (138).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [138] Cushman, 1972, Growth hormone in narcotic addiction, J Clin Endocrinol Metab source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“There is only a single randomized double-blind crossover trial of glucocorticoid replacement in opioid-induced secondary adrenal insufficiency that utilized a reduced cortisol response to a cold pain stimulus as the inclusion criterion (this test is not validated for the diagnosis of adrenal insufficiency) (132).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Management
What the sources say
- Not checked — no full text of the sourcecites [132] Nenke, 2015, Low-dose hydrocortisone replacement improves wellbeing and pain tolerance in chronic pain patients with opioid-induced hypocortisolemic responses. A pilot randomized, placebo-controlled trial, Psychoneuroendocrinology source
plainn = 17- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The closest was fatigue, where 14 of 29 patients reported subjective improvement.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Management
What the sources say
- Not checked — no full text of the sourcecites [119] Li, 2020, Clinical presentation and outcomes of opioid-induced adrenal insufficiency, Endocr Pract source
plainn = 29- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Nine opioid-treated patients (15%) had a peak GH value consistent with severe GH deficiency (below 3 mcg/L), a finding not demonstrated in any control patient.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [74] Abs, 2000, Endocrine consequences of long-term intrathecal administration of opioids, J Clin Endocrinol Metab source
plaincorrelationaln = 9- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Finally, in a report of 22 patients with chronic pain on oral opioids, serum IGF-I levels and glucagon-stimulated peak GH were not different from a control group of 15 subjects on nonopioid analgesia (137).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [137] Merza, 2003, Patients with chronic pain and abnormal pituitary function require investigation, Lancet source
plainn = 22- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Mean peak GH during ITT did not differ between the groups and, although also not statistically significant, peak GH below 3.2 mcg/L was detected in 11% of the intrathecal opioid users (136).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [136] Valverde-Filho, 2015, Chronic spinal and oral morphine-induced neuroendocrine and metabolic changes in noncancer pain patients, Pain Med source
plainn = 18- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Early studies have shown that acute administration of opioids increases prolactin (PRL) secretion, an effect that is reversed by dopamine agonists (142).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [142] Tolis, 1978, Opiates, prolactin, and the dopamine receptor, J Clin Endocrinol Metab source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There is a paradox in that opioid use, often at high dose, is prevalent, yet there are relatively low percentages of people with biochemically diagnosed secondary adrenal insufficiency and only very rare instances of adrenal crisis.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Management
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Nevertheless, the study found that physiological glucocorticoid substitution had benefits in improving vitality and perceived pain compared to placebo (132).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Management
What the sources say
- Not checked — no full text of the sourcecites [132] Nenke, 2015, Low-dose hydrocortisone replacement improves wellbeing and pain tolerance in chronic pain patients with opioid-induced hypocortisolemic responses. A pilot randomized, placebo-controlled trial, Psychoneuroendocrinology source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
In the paper
“In a study of 40 patients on oral or transdermal opioids for chronic pain (for more than 6 months at an MME dose ≥25 mg) and 25 controls not taking opioids, the opioid users had lower IGF-I (138 mcg/L [99-161] vs 168 mcg/L [138-214]; P = .004),although none of them had levels below the lower limit of the reference ranges (116).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [116] Lamprecht, 2018, Secondary adrenal insufficiency and pituitary dysfunction in oral/transdermal opioid users with non-cancer pain, Eur J Endocrinol source
plaincorrelationaln = 40- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Finally, similar PRL levels were found between 21 noncancer pain patients on oral opioids and a control group of 15 noncancer pain patients on nonopioid analgesia; hyperprolactinemia was detected only in 1 case of the control group (137).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [137] Merza, 2003, Patients with chronic pain and abnormal pituitary function require investigation, Lancet source
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Accordingly, opioids are mentioned in review articles as inducing the syndrome of inappropriate antidiuresis (168), an effect initially considered to be due to a direct enhancement of AVP release (169).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [168] Liamis, 2008, A review of drug-induced hyponatremia, Am J Kidney Dis source
- Not checked — no full text of the sourcecites [169] Langfeldt, 2003, Syndrome of inappropriate antidiuretic hormone secretion in malignancy: review and implications for nursing management, Clin J Oncol Nurs source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, based on the published literature, acute administration of opioids increases serum PRL, whereas in patients on long-term opioids, PRL has been found normal or elevated.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Higher PRL concentrations (as compared with healthy people) and hyperprolactinemia have been reported in people addicted to heroin and opium smokers (149).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [149] Moshtaghi-Kashanian, 2005, Enhanced prolactin levels in opium smokers, Addict Biol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the findings of these preclinical studies suggest a pro-osteogenic role of opioid receptors antagonists, although this will need to be validated in humans.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioids and bone remodeling/bone healing
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Furthermore, after delivery, morphine inhibited the rise in oxytocin secretion in breast-feeding women but the amount of breast milk was not measured in this study (196).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [196] Lindow, 1999, Morphine suppresses the oxytocin response in breast-feeding women, Gynecol Obstet Invest source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The conflicting results might be due to discrepancies in fluid/hydration status, as well as from side effects of opioids leading to nonosmotically stimulated AVP.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Clinical Significance
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In this case, an increase of AVP levels could not explain the hyponatremia because she was not able to produce AVP due to her AVP deficiency.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [182] Bhat, 2017, Opioid-induced hyponatremia in a patient with central diabetes insipidus: independence from ADH, J Pediatr Endocrinol Metab source
hedgedSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Systemic opioids have a long tradition in analgesia during labor; in line with the inhibiting effect of opioids on oxytocin, in a nonrandomized study, women offered opioid analgesia had longer labor and more need for oxytocin augmentation compared to controls not on labor analgesia (199).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [199] Miyakoshi, 2013, Perinatal outcomes: intravenous patient-controlled fentanyl versus no analgesia in labor, J Obstet Gynaecol Res source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Besides the release from axonal terminals, there is dendritic release of oxytocin into the central extracellular space with local action and direct projection to other brain regions, including the amygdala, hippocampus, and brainstem, where it acts as a neurotransmitter (191).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [191] Ludwig, 2006, Dendritic peptide release and peptide-dependent behaviours, Nat Rev Neurosci source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Exogenous opioids exert detrimental effects on bone homeostasis and metabolism and are associated with low bone mineral density (BMD) and an increased fracture risk.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Data on the impact of opioids on oxytocin in humans outside pregnancy or labor are lacking.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Clinical Significance
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Oxytocin has a key role in the regulation of socioemotional functioning, including attachment and pair bonding, fear extinction, emotion recognition, and empathy (186-189).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [186] Domes, 2007, Oxytocin attenuates amygdala responses to emotional faces regardless of valence, Biol Psychiatry source
- Not checked — no full text of the sourcecites [187] Heinrichs, 2009, Oxytocin, vasopressin, and human social behavior, Front Neuroendocrinol source
- Not checked — no full text of the sourcecites [188] Meyer-Lindenberg, 2011, Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine, Nat Rev Neurosci source
- Not checked — no full text of the sourcecites [189] Neumann, 2016, Oxytocin in general anxiety and social fear: a translational approach, Biol Psychiatry source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“However, during the first stage of labor, morphine inhibited plasma oxytocin levels, whereas naloxone had no effect (195).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [195] Lindow, 1992, The effect of morphine and naloxone administration on plasma oxytocin concentrations in the first stage of labour, Clin Endocrinol (Oxf) source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Similarly, other opioid analgesics, such as fentanyl, did not suppress oxytocin levels during pregnancy, but inhibited them during the onset of labor (197,198).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [197] Shibli, 2001, Effect of intrathecal fentanyl on oxytocin secretion in pregnant women not in labour, Clin Sci (Lond) source
- Not checked — no full text of the sourcecites [198] Stocche, 2001, Effects of intrathecal sufentanil on plasma oxytocin and cortisol concentrations in women during the first stage of labor, Reg Anesth Pain Med source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on the published literature, the effects of exogenous opioids on AVP secretion in humans are inconclusive and their clinical significance is unclear.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Clinical Significance
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A strong correlation between plasma AVP (when measured with a well-established radio-immunoassay) and copeptin levels has been demonstrated in healthy volunteers (184), and, therefore, copeptin measurement could be an alternative marker to elucidate the effects of opioids on AVP.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [184] Balanescu, 2011, Correlation of plasma copeptin and vasopressin concentrations in hypo-, iso-, and hyperosmolar states, J Clin Endocrinol Metab source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Treatment with high concentrations of the MOR agonist morphine significantly inhibited the expression of osteocalcin, a marker of osteoblast activity, without influencing the secretion of alkaline phosphatase (208).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioids and bone remodeling/bone healing
What the sources say
- Not checked — no full text of the sourcecites [208] Pérez-Castrillón, 2000, Expression of opioid receptors in osteoblast-like MG-63 cells, and effects of different opioid agonists on alkaline phosphatase and osteocalcin secretion by these cells, Neuroendocrinology source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In line with this, it may act as a stress-buffering hormone and influence the hypothalamic-pituitary-adrenal axis because there was a trend toward attenuated cortisol levels by oxytocin (190).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [190] Heinrichs, 2003, Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress, Biol Psychiatry source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A recent murine study using continuous morphine delivery via subcutaneous osmotic minipumps for 25 days indicated a sex difference in the bone outcome, where male mice treated with morphine had reduced trabecular bone volume and trabecular BMD in the distal femur compared with vehicle, whereas bone microarchitecture had not changed in females after morphine treatment (205).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioids and bone remodeling/bone healing
What the sources say
- Not checked — no full text of the sourcecites [205] Carvalho, 2022, Sustained morphine delivery suppresses bone formation and alters metabolic and circulating miRNA profiles in male C57BL/6J mice, J Bone Miner Res source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“in this study, the effect of opioids on AVP seemed to be dependent on the hydration status, as DAMME infused into water-deprived healthy volunteers produced diuresis that was attenuated by naloxone, whereas when subjects were hydrated, there was no change in water excretion (177).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
What the sources say
- Not checked — no full text of the sourcecites [177] Grossman, 1980, Inhibition of vasopressin release in man by an opiate peptide, Lancet source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Oxytocin receptors are present in the uterus, consistent with their known role in parturition, and in diverse other tissues.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“In a large cohort of elderly patients admitted in a tertiary care hospital in Australia, analgesics were prescribed in 69% of them (more commonly in women)”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioid prescription in the elderly population and bone health
What the sources say
- Not checked — no full text of the sourcecites [231] Al-Qurain, 2020, Prevalence and factors associated with analgesic prescribing in poly-medicated elderly patients, Drugs Aging source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In humans, higher serum concentrations of the bone resorption marker β C-terminal telopeptide were reported in male heroin users compared to healthy volunteers (222), a finding replicated in men receiving opioid substitution therapy (223).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioids and bone remodeling/bone healing
What the sources say
- Not checked — no full text of the sourcecites [222] Balodimos, 2015, The effect of opioid dependence on conventional and novel biochemical parameters of bone metabolism, Am J Drug Alcohol Abuse source
- Not checked — no full text of the sourcecites [223] Gotthardt, 2017, Bone mineral density and its determinants in men with opioid dependence, J Bone Miner Metab source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“with oxycodone being the most prescribed opioid (56%) (231).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioid prescription in the elderly population and bone health
What the sources say
- Not checked — no full text of the sourcecites [231] Al-Qurain, 2020, Prevalence and factors associated with analgesic prescribing in poly-medicated elderly patients, Drugs Aging source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“whereas opioids were prescribed in 34% of analgesic users (231).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioid prescription in the elderly population and bone health
What the sources say
- Not checked — no full text of the sourcecites [231] Al-Qurain, 2020, Prevalence and factors associated with analgesic prescribing in poly-medicated elderly patients, Drugs Aging source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The effects of opioids on osteoclasts are less well described.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioids and bone remodeling/bone healing
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Pain is common in elderly patients, being reported in up to 50% of the elderly population and up to 80% of care facility inhabitants (229).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioid prescription in the elderly population and bone health
What the sources say
- Not checked — no full text of the sourcecites [229] Kaye, 2010, Pain management in the elderly population: a review, Ochsner J
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Pregnant women addicted to heroin and cocaine displayed low serum levels of osteocalcin, a finding also corroborated in the umbilical arteries of their newborns, which also suggests toxic effects of these drugs on osteoblasts (213).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioids and bone remodeling/bone healing
What the sources say
- Not checked — no full text of the sourcecites [213] Rico, 1990, Lower serum osteocalcin levels in pregnant drug users and their newborns at the time of delivery, Obstet Gynecol
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Chronic pain is a limiting factor in daily activities and is linked to deconditioning, frailty, increased risk of accidents, and polypharmacy (229).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Opioid prescription in the elderly population and bone health
What the sources say
- Not checked — no full text of the sourcecites [229] Kaye, 2010, Pain management in the elderly population: a review, Ochsner J
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As previously stated, the increased fracture risk among individuals with chronic opioid use is attributed to three main reasons: reduced BMD caused by direct opioid effects on bone metabolism, chronic opioid-induced hypogonadism, and increased risk of falls caused by CNS side effects, including sedation, gait disorders, and lack of concentration.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Fracture risk in patients on opioids
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A small observational study of male hypogonadal patients on intrathecal opioids for noncancer pain who received testosterone substitution corrected the decreased testosterone levels and improved BMD (239).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Diagnostic approach and management
What the sources say
- Not checked — no full text of the sourcecites [239] Finch, 2015, Effects of testosterone treatment on bone mineral density in hypogonadal men receiving intrathecal opioids, Pain Pract source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Regular exercise has effects on bone density, size, and shape, resulting in substantial improvements in mechanical strength (252)”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Diagnostic approach and management
What the sources say
- Not checked — no full text of the sourcecites [252] Tveit, 2015, Exercise in youth: high bone mass, large bone size, and low fracture risk in old age, Scand J Med Sci Sports source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Regarding CNS side effects, it has been shown that the rates of hospital visits for falls and fractures is disproportionally high at the initiation phase of opioid treatment, a trend not seen with other analgesics, such as nonsteroidal anti-inflammatory drugs (249).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Fracture risk in patients on opioids
What the sources say
- Not checked — no full text of the sourcecites [249] Guan, 2022, Opioid initiation and the hazard of falls or fractures among older adults with varying levels of central nervous system depressant burden, Drugs Aging source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Furthermore, a small case-control study including young women on MMT compared with age-and BMI-matched controls found only marginally lower BMD at the hip of these subjects with no differences in other skeletal sites, despite a largely unhealthy lifestyle in patients (high alcohol and nicotine intake) (241).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Bone mass in patients on opioids
What the sources say
- Not checked — no full text of the sourcecites [241] Milos, 2011, Bone mineral density in young women on methadone substitution, Calcif Tissue Int source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“reported mean BMD values at each skeletal site approximately 10% below the population mean in men, albeit not in women (224).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Bone mass in patients on opioids
What the sources say
- Not checked — no full text of the sourcecites [224] Grey, 2011, Decreased bone density in men on methadone maintenance therapy, Addiction source
plainn = 48- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion, low BMD is a long-term side effect of opioids, and especially in male patients, it appears to be pathophysiologically connected to hypogonadism.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Bone mass in patients on opioids
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“cases with compromised response of GH on dynamic testing have been reported.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Summary of Key Points on Actions of Exogenous Opioids on Endocrine System in Humans
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“low basal morning cortisol levels and inadequate response of cortisol on dynamic testing have been reported”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Summary of Key Points on Actions of Exogenous Opioids on Endocrine System in Humans
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“proposed implicated mechanisms for these negative sequelae include direct effects on bone remodeling, increased risk of falls, and hypogonadism.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Summary of Key Points on Actions of Exogenous Opioids on Endocrine System in Humans
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nonetheless, the existing evidence is not sufficient to elucidate this area and clinical recommendations are not possible.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Bone health
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the significance of these effects and the occurrence of clinically relevant adrenal insufficiency is not fully elucidated.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Summary of Key Points on Actions of Exogenous Opioids on Endocrine System in Humans
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“• Data on the effects of opioids on AVP secretion are inconclusive.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Summary of Key Points on Actions of Exogenous Opioids on Endocrine System in Humans
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“• Evidence of opioid actions on oxytocin derived from studies of women in labor suggests an inhibitory effect (opioids can inhibit plasma oxytocin levels during labor).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Summary of Key Points on Actions of Exogenous Opioids on Endocrine System in Humans
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“reduced BMD and increased risk of fracture have been reported”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Summary of Key Points on Actions of Exogenous Opioids on Endocrine System in Humans
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Long-term use of opioids has been associated with hyperprolactinemia, the true prevalence of which is not clear”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Bone health
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“• Opioids inhibit the hypothalamic-pituitary-gonadal axis and can cause hypogonadism.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Summary of Key Points on Actions of Exogenous Opioids on Endocrine System in Humans
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The effects of opioids on AVP in humans are inconclusive and their clinical significance is not well defined.”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Bone health
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
The paper relies on this without support.
Opioid plasma concentration depends on drug dose, absorption, and metabolism.
“In turn, the concentration depends on several factors, such as drug dose, absorption, and metabolism.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
“The only opioid, however, that has been associated with hyponatremia in case reports is tramadol, a weak opioid analgesic with the hyponatremia usually occurring within the first 30 days after initiation of this drug (170-173).”
§ Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement > Effects of Opioids
“Indeed, in a case report of a 19-year-old female with complete AVP deficiency since the age of 6 years, the patient developed hyponatremia on treatment with hydrocodone offered after the extraction of her wisdom teeth (182).”
Citations
Cites
Centers for Disease Control and Prevention
Branum, A. (2007) · Sage eBooks · doi:10.4135/9781412952644.n74 · Cited by 6,434
CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016
Dowell, D., Haegerich, T. M., & Chou, R. (2016) · JAMA · doi:10.1001/jama.2016.1464 · Cited by 5,161
By the 2019 American Geriatrics Society Beers Criteria® Update Expert Panel (2019) · Journal of the American Geriatrics Society · doi:10.1111/jgs.15767 · Cited by 3,163
CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016
Dowell, D., Haegerich, T. M., & Chou, R. (2016) · MMWR. Recommendations and Reports · doi:10.15585/mmwr.rr6501e1 · Cited by 2,697
Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain
Chou, R., Fanciullo, G. J., Fine, P. G., Adler, J. A., Ballantyne, J. C., Davies, P., Donovan, M. I., Fishbain, D. A., Foley, K. M., Fudin, J., et al. (2009) · The Journal of Pain · doi:10.1016/j.jpain.2008.10.008 · Cited by 2,192
Heinrichs, M., Baumgartner, T., Kirschbaum, C., & Ehlert, U. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00465-7 · Cited by 2,091
Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline.
Bhasin, S., Brito, J. P., Cunningham, G. R., Hayes, F. J., Hodis, H. N., Matsumoto, A. M., Snyder, P. J., Swerdloff, R. S., Wu, F. C., & Yialamas, M. A. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-00229 · Cited by 1,736
Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine
Meyer-Lindenberg, A., Domes, G., Kirsch, P., & Heinrichs, M. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3044 · Cited by 1,688
Oxytocin Modulates Neural Circuitry for Social Cognition and Fear in Humans
Kirsch, P., Esslinger, C., Chen, Q., Mier, D., Lis, S., Siddhanti, S., Gruppe, H., Mattay, V. S., Gallhofer, B., & Meyer-Lindenberg, A. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3984-05.2005 · Cited by 1,639
Molecular mechanisms of opioid receptor-dependent signaling and behavior
Al-Hasani, R., & Bruchas, M. R. (2011) · Anesthesiology · doi:10.1097/aln.0b013e318238bba6 · Cited by 1,067
Research works printed but not linked: 3
- Weiss, 2006, Healthcare Cost and Utilization Project (HCUP) Statistical Briefs
- Schumacher, 2021, Opioid Agonists & Antagonists. Basic & Clinical Pharmacology
- Bettinger, 2018, Fentanyl: separating fact from fiction, Pract Pain Manag, 18
Cited by
Sorted by citations
Adrenal Insufficiency in Adults: A Review
Vaidya, A., Findling, J., & Bancos, I. (2025) · JAMA · doi:10.1001/jama.2025.5485 · Cited by 75
Lee, K. I.-R., Chen, J.-H., & Chen, K.-H. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27020641 · Cited by 26
“To this end, Table 4 summarizes the clinical risk factors, typical dosages, and treatment durations associated with clinically significant bone loss for the pharmacologic agents discussed [31,109,145–148].”
Drug-induced hyponatremia in clinical care
Mannheimer, B., Lindh, J. D., Bergh, C. F., Issa, I., Falhammar, H., & Skov, J. (2025) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2025.04.034 · Cited by 20
Nissan, E. C., Berkovich, Y., Maman, D., et al. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14113832 · Cited by 6
“Opioid endocrinopathy and wound healing processes are influenced by the intensity and chronicity of opioid use [11,21,22,24].”
InfluentialDan, Y., Pei, X., Xu, D., Liu, Z., Wang, Y., Yin, M., Li, L., & Yu, G. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1533565 · Cited by 3
Metadata
- Authors
- Karavitaki, N., Bettinger, J. J., Biermasz, N., Christ-Crain, M., Gadelha, M. R., Inder, W. J., Tsourdi, E., Wakeman, S. E., & Zatelli, M.
- Affiliations
- University Hospitals Birmingham NHS Foundation Trust (GB)
- Saratoga Hospital (US)
- Leiden University Medical Center (NL)
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel , 4031 Basel ,
- Endocrine Unit and Neuroendocrinology Research Center, Medical School and Hospital Universitário Clementino Fraga Filho—Universidade Federal do Rio de Janeiro (UFRJ) , Rio de Janeiro, 21941-913 ,
- The University of Queensland (AU)
- Technische Universität Dresden (DE)
- Harvard University (US)
- University of Ferrara (IT)
- ORCID
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2024-10-23
- Volume
- 45
- Issue
- 6
- Pages
- 773-794
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W4403713388
- Semantic Scholar
- 5b0e7af69f3f1d154c344be93560eb12f5266091
- Cited by
- 14
- References
- 252
- Citations by year
- 2026: 6 · 2025: 8
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (publishedVersion, other-oa)
- Funders
- Amgen
- Eli Lilly and Company
- Sanofi
- Alexion Pharmaceuticals
- Recordati Rare Diseases
- Novo Nordisk
- Ipsen
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- exogenous opioids, opioid misuse, hypothalamic-pituitary-adrenal axis, adrenal insufficiency, hypogonadism, gonadal function, growth hormone secretion, prolactin, vasopressin, oxytocin, bone metabolism, bone mineral density, fracture risk
- MeSH terms
- Analgesics, Opioid, Endocrine System, Endocrinology, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Societies, Scientific, Bone Density
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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