madman
Super Moderator
ABSTRACT
Objective
Individuals with opioid use disorder (OUD) have reduced life expectancy and inferior outcomes when treated for depression, diabetes, and fractures. Their elevated risk of testosterone deficiency may contribute to all of these relationships, however few individuals prescribed opioids are evaluated with testosterone assays. The purpose of this study is to determine whether patients with opioid use disorder are evaluated for testosterone deficiency after development of a symptom that may merit investigation, such as erectile dysfunction (ED).
Method
We conducted a retrospective longitudinal cohort study that utilized data from a national database called TriNetX. Patients were eligible for inclusion if they were 20 to 90yearsof age, male, and diagnosed with erectile dysfunction. We utilized descriptive statistics and logistic regression to address study aims.
Results
Testosterone testing was uncommon for all patients with ED. Among 20,658 patients,it was assessed in 11.2% with OUD and 15.1% without OUD. Among those screened, 40%individuals with OUD and ED had testosterone deficiency. Odds of screening those with OUD were lower than matched controls (RR 0.74).
Conclusions
Individuals with OUD are at increased risk of testosterone deficiency than the general population, but nearly 90% are not evaluated for this condition even after development symptoms. That 40% of individuals assessed were classified as testosterone deficient suggests endocrine disorders may be contributing to increased fracture risk, chronic pain, and severe depression commonly encountered in patients with OUD. Addressing this care gap may reduce morbidity and mortality associated with opioid use disorder.
Introduction
Morphine was first isolated from opium in 1805,and the first opioid receptor (the mu opioid receptor) was identified in binding assays in 1973.1,2 Scientists subsequently discovered that opioid receptors strongly influence fundamental components of human function such as emotion, motivation, respiration, and pain perception.3,4 They also learned in the 1970s that opioids have a tremendous impact on the endocrine system,which has the potential to influence many of these same domains.5 More specifically, opioids inhibit release of GnRH which reduces levels of LH and testosterone.6 Given the prevalence of long term opioid use and potentially devastating symptoms of testosterone deficiency, this may have profound implications to the health of individuals with opioid use disorder (OUD), but also the more general public.7 Untreated, testosterone deficiency can lead to depression refractory to treatment with SSRI, bone demineralization that elevates risk of fracture, hyperglycemia and hyperlipidemia that enhance risk of cardiovascular events, and erectile dysfunction that may impact mood, relationships, and motivation to remain in treatment for opioid use disorder.8–12 However, studies have shown that testosterone replacement among men that have testosterone deficiency can ameliorate these risks; reduce risk of fracture, improve mood in treatment resistant depression, reduce cardiovascular events, improve quality of life, and reduce risk of mortality.13–16 Since an estimated 60-90% of people with long term opioid exposure experience testosterone deficiency, and it is a treatable condition, multiple endocrine societies recommend assessment of testosterone levels in all people that receive long term opioid prescriptions.17–19 However, a recent study demonstrated that evaluation for testosterone deficiency did not occur in more than 80% of people tha treceived long term opioid treatment in the United States.20 The authors concluded this level of screening was suboptimal. Still, many experts suggest that treatment should be reserved for individuals who experience symptoms of testosterone deficiency, and it is not evident from current literature whether people that manifest symptoms of testosterone deficiency who are at elevated risk of opioid induced androgen deficiency might be assessed with testosterone levels more routinely.21 The purpose of this brief report is to determine the prevalence of testing for testosterone deficiency among individuals with a diagnosis of OUD who develop erectile dysfunction (ED), a symptom of testosterone deficiency that should provide impetus for evaluation and treatment.
Limitations
There are a number of limitations that should be considered in this study. First, our study relies on electronic health record data, which are incomplete and susceptible to misclassification bias.Furthermore, since the data are de-identified wedo not have the capacity to audit, so the level of misclassification bias cannot be determined. Moreover, the data lack specificity regarding dose ,duration, and timing of opioid exposure. As such,we are not able to determine the level of opioid exposure that results in increased risk of testosterone deficiency. Finally, this study only assessed evaluation after a single symptom of hypogonadism. It is not evident whether individuals with other symptoms are screened at a higher rate than those who are assessed after a diagnosis of erectile dysfunction.
Although this brief report has clear limitations,we feel it is important to disseminate for a number of reasons. First, the data were sourced from a large national database that has been utilized for hundreds of published studies. The large and geographically heterogenous nature of the data reduces likelihood they are biased by local or regional practice patterns, and the volume of previously published studies speak to acceptability of the data source. Second, these data align with previously published research from separate data sources that also demonstrate very limited assessment of testosterone levels among people prescribed opioids. The alignment between these data and findings from separate data sources enhances confidence in the reliability of our study. Finally, we believe it is critical to highlight and address this care gap to advance the clinical care of patients with opioid use disorder, and the science of addiction medicine.
Conclusions
Long term opioid exposure leads to testosterone deficiency which can result in a number of adverse outcomes that may be preventable, however our data suggest that evaluation for testosterone deficiency is not routine, even after development of a recognizable symptom of this condition. We agree with the multiple professional societies that recommend screening for testosterone deficiency for all people with long term opioid prescriptions and OUD (particularly after development of symptoms consistent with androgen deficiency) to reduce risk of adverse outcomes associated with long term opioid exposure. Future studies should focus on the level of opioid exposure (dose and duration) that may lead to testosterone deficiency to inform screening guidelines for this population. However, in the interim, providers may consider symptom triggered evaluations of testosterone levels among individuals with chronic opioid exposure to assess the extent that testosterone maybe influencing symptoms such as ED, depression,fatigue, and to prevent pathologic fractures that may result in chronic pain. In addition, further research that clarifies risks and benefits regarding testosterone replacement among people with OUD, chronic opioid exposure, and subpopulations of these groups are warranted.
Objective
Individuals with opioid use disorder (OUD) have reduced life expectancy and inferior outcomes when treated for depression, diabetes, and fractures. Their elevated risk of testosterone deficiency may contribute to all of these relationships, however few individuals prescribed opioids are evaluated with testosterone assays. The purpose of this study is to determine whether patients with opioid use disorder are evaluated for testosterone deficiency after development of a symptom that may merit investigation, such as erectile dysfunction (ED).
Method
We conducted a retrospective longitudinal cohort study that utilized data from a national database called TriNetX. Patients were eligible for inclusion if they were 20 to 90yearsof age, male, and diagnosed with erectile dysfunction. We utilized descriptive statistics and logistic regression to address study aims.
Results
Testosterone testing was uncommon for all patients with ED. Among 20,658 patients,it was assessed in 11.2% with OUD and 15.1% without OUD. Among those screened, 40%individuals with OUD and ED had testosterone deficiency. Odds of screening those with OUD were lower than matched controls (RR 0.74).
Conclusions
Individuals with OUD are at increased risk of testosterone deficiency than the general population, but nearly 90% are not evaluated for this condition even after development symptoms. That 40% of individuals assessed were classified as testosterone deficient suggests endocrine disorders may be contributing to increased fracture risk, chronic pain, and severe depression commonly encountered in patients with OUD. Addressing this care gap may reduce morbidity and mortality associated with opioid use disorder.
Introduction
Morphine was first isolated from opium in 1805,and the first opioid receptor (the mu opioid receptor) was identified in binding assays in 1973.1,2 Scientists subsequently discovered that opioid receptors strongly influence fundamental components of human function such as emotion, motivation, respiration, and pain perception.3,4 They also learned in the 1970s that opioids have a tremendous impact on the endocrine system,which has the potential to influence many of these same domains.5 More specifically, opioids inhibit release of GnRH which reduces levels of LH and testosterone.6 Given the prevalence of long term opioid use and potentially devastating symptoms of testosterone deficiency, this may have profound implications to the health of individuals with opioid use disorder (OUD), but also the more general public.7 Untreated, testosterone deficiency can lead to depression refractory to treatment with SSRI, bone demineralization that elevates risk of fracture, hyperglycemia and hyperlipidemia that enhance risk of cardiovascular events, and erectile dysfunction that may impact mood, relationships, and motivation to remain in treatment for opioid use disorder.8–12 However, studies have shown that testosterone replacement among men that have testosterone deficiency can ameliorate these risks; reduce risk of fracture, improve mood in treatment resistant depression, reduce cardiovascular events, improve quality of life, and reduce risk of mortality.13–16 Since an estimated 60-90% of people with long term opioid exposure experience testosterone deficiency, and it is a treatable condition, multiple endocrine societies recommend assessment of testosterone levels in all people that receive long term opioid prescriptions.17–19 However, a recent study demonstrated that evaluation for testosterone deficiency did not occur in more than 80% of people tha treceived long term opioid treatment in the United States.20 The authors concluded this level of screening was suboptimal. Still, many experts suggest that treatment should be reserved for individuals who experience symptoms of testosterone deficiency, and it is not evident from current literature whether people that manifest symptoms of testosterone deficiency who are at elevated risk of opioid induced androgen deficiency might be assessed with testosterone levels more routinely.21 The purpose of this brief report is to determine the prevalence of testing for testosterone deficiency among individuals with a diagnosis of OUD who develop erectile dysfunction (ED), a symptom of testosterone deficiency that should provide impetus for evaluation and treatment.
Limitations
There are a number of limitations that should be considered in this study. First, our study relies on electronic health record data, which are incomplete and susceptible to misclassification bias.Furthermore, since the data are de-identified wedo not have the capacity to audit, so the level of misclassification bias cannot be determined. Moreover, the data lack specificity regarding dose ,duration, and timing of opioid exposure. As such,we are not able to determine the level of opioid exposure that results in increased risk of testosterone deficiency. Finally, this study only assessed evaluation after a single symptom of hypogonadism. It is not evident whether individuals with other symptoms are screened at a higher rate than those who are assessed after a diagnosis of erectile dysfunction.
Although this brief report has clear limitations,we feel it is important to disseminate for a number of reasons. First, the data were sourced from a large national database that has been utilized for hundreds of published studies. The large and geographically heterogenous nature of the data reduces likelihood they are biased by local or regional practice patterns, and the volume of previously published studies speak to acceptability of the data source. Second, these data align with previously published research from separate data sources that also demonstrate very limited assessment of testosterone levels among people prescribed opioids. The alignment between these data and findings from separate data sources enhances confidence in the reliability of our study. Finally, we believe it is critical to highlight and address this care gap to advance the clinical care of patients with opioid use disorder, and the science of addiction medicine.
Conclusions
Long term opioid exposure leads to testosterone deficiency which can result in a number of adverse outcomes that may be preventable, however our data suggest that evaluation for testosterone deficiency is not routine, even after development of a recognizable symptom of this condition. We agree with the multiple professional societies that recommend screening for testosterone deficiency for all people with long term opioid prescriptions and OUD (particularly after development of symptoms consistent with androgen deficiency) to reduce risk of adverse outcomes associated with long term opioid exposure. Future studies should focus on the level of opioid exposure (dose and duration) that may lead to testosterone deficiency to inform screening guidelines for this population. However, in the interim, providers may consider symptom triggered evaluations of testosterone levels among individuals with chronic opioid exposure to assess the extent that testosterone maybe influencing symptoms such as ED, depression,fatigue, and to prevent pathologic fractures that may result in chronic pain. In addition, further research that clarifies risks and benefits regarding testosterone replacement among people with OUD, chronic opioid exposure, and subpopulations of these groups are warranted.
