Long-term opioid treatment and endocrine measures in chronic non-cancer pain patients.

BACKGROUND: The prevalence of chronic non-cancer pain (CNCP) has increased dramatically the past decades, which combined with indiscriminate use of prescribed opioids has become a public health problem. Endocrine dysfunction may be a complication of long-term opioid treatment (L-TOT), but the evidence is limited. This study aimed at investigating the associations between L-TOT and endocrine measures in CNCP patients. METHODS: Cortisol (spot and after stimulation), thyrotropin (TSH), thyroxin (T4), insulin-like growth factor 1 (IGF-1), prolactin (PRL), 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone (DHEAS), sex hormone-binding globulin (SHBG), total testosterone (TT) and free testosterone (fT) were measured. Group comparisons were done between CNCP patients in L-TOT and controls as well as between patients on high- or low-dose morphine equivalents. RESULTS: Eighty-two CNCP patients (38 in L-TOT and 44 controls not receiving opioids) were included. Low TT (p = 0.004) and fT concentrations (p < 0.001), high SHBG (p = 0.042), low DEAS (p = 0.017) and low IGF-1 (p = 0.003) in men were found when comparing those in L-TOT to controls and high PRL (p = 0.018), low IGF-1 standard deviation score (SDS) (p = 0.006) along with a lesser, but normal cortisol response to stimulation (p = 0.016; p = 0.012) were found when comparing L-TOT to controls. Finally, a correlation between low IGF-1 levels and high opioid dose was observed (p < 0.001). CONCLUSIONS: Our study not only supports previous findings but even more interestingly disclosed new associations. We recommend future studies to investigate endocrine effects of opioids in larger, longitudinal studies. In the meanwhile, we recommend monitoring endocrine function in CNCP patients when prescribing L-TOT. SIGNIFICANCE: This clinical study found associations between L-TOT, androgens, growth hormone and prolactin in patients with CNCP compared to controls. The results support previous studies as well as add new knowledge to the field, including an association between high opioid dose and low growth hormone levels. Compared to existing research this study has strict inclusion/exclusion criteria, a fixed time period for blood sample collection, and adjustments for potential confounders, which has not been done before.

Long-term opioid treatment and endocrine measures in patients with cancer-related pain: a systematic review.

OBJECTIVES: Opioid analgesics are the main stay for cancer pain management; however, long-term opioid treatment (L-TOT) may suppress the endocrine system. This systemic review aimed at investigating effects of L-TOT on the endocrine system in patients with cancer-related pain. METHODS: A search on MEDLINE, EMBASE and Web of Science databases was performed. Inclusion criteria were clinical studies investigating endocrine measures in adult patients with cancer-related pain in L-TOT (≥4 weeks). Outcomes and quality of evidence were assessed. RESULTS: A total of 252 abstracts were identified; out of which 247 were excluded and five cross-sectional studies were included and analyzed. L-TOT was associated with lower serum concentration levels of total- and free testosterone in males, follicular stimulating hormone in females, and luteinizing hormone in both sexes. Moreover, higher morphine equivalent daily doses (MEDDs) were correlated with higher levels of cortisol and lower levels of LH in both sexes, and lower levels of total- and free testosterone in males. Sexual dysfunction was associated with low sex hormone levels. Level of evidence was low/very low. CONCLUSIONS: The studies identified demonstrated that patients with cancer-related pain in L-TOT may have gonadal hypofunction causing sexual dysfunction, which may be correlated with opioid dose level. In addition, high serum concentrations of cortisol were positively correlated with high opioid dose levels. However, the evidence was weak and further research is necessary. PROSPERO, ID-number: CRD42020213059.

Computed tomography quantification of emphysema in people living with HIV and uninfected controls.

People living with HIV (PLWH) may be more susceptible to the development of emphysema than uninfected individuals. We assessed prevalence and risk factors for emphysema in PLWH and uninfected controls. Spirometry and chest computed tomography scans were obtained in PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study and in uninfected controls from the Copenhagen General Population Study (CGPS) who were >40 years. Emphysema was quantified using a low attenuation area < -950 Hounsfield units (%LAA-950) and the 15th percentile density index (PD15) and assessed by semi-quantitative visual scales. Of 742 PLWH, 21.2% and 4.7% had emphysema according to the %LAA-950 threshold with cut-offs at 5% and 10%, respectively. Of 470 uninfected controls, these numbers were 24.3% (p=0.23) and 4.0% (p=0.68). HIV was not associated with emphysema (adjusted OR 1.25, 95% CI 0.68-2.36 for %LAA-950 >10%) by PD15 or by visually assessed emphysema. We found no interaction between HIV and cumulative smoking. Breathlessness and sputum production were more common in PLWH with emphysema, and emphysema seemed to be more prevalent in PLWH with airflow limitation. HIV was therefore not independently associated with emphysema, but the clinical impact of emphysema was greater in PLWH than in uninfected controls.