Association between comorbidities and longitudinal changes in total testosterone among men from the Baltimore Longitudinal Study of Aging.

BACKGROUND: Previous cross-sectional and longitudinal studies have described decreasing testosterone levels with age in men, without consideration of acquired comorbidities in aging males. AIM: We evaluated the longitudinal association between age and testosterone levels as well as the impact of several comorbidities on this relationship using multivariate panel regression analysis. METHODS: Participants were selected from the Baltimore Longitudinal Study of Aging. Data were obtained on the presence of several comorbidities and total testosterone level during each follow-up visit. A multivariate panel regression analysis was performed to determine the impact of age on testosterone level while controlling for individual comorbidities. OUTCOMES: The primary outcomes were strength of association between age and various comorbidities, and testosterone level. RESULTS: A total of 625 men were included in this study, with a mean age of 65 years and a mean testosterone level of 463 ng/dL. On multivariable-adjusted panel regression analysis, age was not significantly associated with testosterone decline, while anemia, diabetes mellitus, heart failure, obesity, peripheral artery disease, and stroke were inversely associated with total testosterone level. We report no association between cancer and total testosterone. CLINICAL IMPLICATIONS: This study indicates that a decline in testosterone levels over time may be due to the presence of various comorbidities, which affects the medical management of hypogonadism in aging men. STRENGTHS AND LIMITATIONS: The strengths of this study include the standardized acquisition of testosterone tests and uniform collection of variables, while limitations include the lack of follow-up data from 205 patients and the limited racial/ethnic diversity in the cohort. CONCLUSIONS: In this large longitudinal study, we found that when adjusted for the presence of concomitant comorbidities, age does not predict a significant decline in testosterone level. With the overall increase in life expectancy and the simultaneous rise in the incidence of comorbidities such as diabetes and dyslipidemia, our findings may help optimize screening and treatment for late-onset hypogonadism in patients with multiple comorbidities.

Testosterone Therapy is Associated With Depression, Suicidality, and Intentional Self-Harm: Analysis of a National Federated Database.

BACKGROUND: Long-term use of testosterone can be associated with mood destabilizing effects. Most studies investigating psychiatric complications of anabolic steroids have used small samples, but a comprehensive assessment of the risk of developing mental health disorders after testosterone use has not been performed at the population level. AIM: To determine whether testosterone therapy is associated with major depressive disorder or suicide attempts in men. METHODS: We conducted a retrospective cohort study of 70.3 million electronic health records collected from 46 healthcare organizations encompassing flagship hospitals, satellite hospitals, and outpatient clinics since 2008 to determine whether testosterone use is associated with major depressive disorder and suicide attempts in a large population. We included men 18 or older who either used testosterone or did not, defined by reported use, insurance claim, or prescription use of testosterone documented in the electronic health record. We propensity-score matched by age, race, ethnicity, obesity, and alcohol-related disorder. Additionally, a sub-group analysis was performed in testosterone deficient (<300 ng/dL) men comparing those with TD on testosterone therapy to a control group of men with TD who are not using testosterone. OUTCOMES: We determined measures of association with a new diagnosis of major depressive disorder and suicide attempt or intentional self-harm following testosterone use within 5 years. RESULTS: A total of 263,579 men who used testosterone and 17,838,316 men who did not were included in the analysis. Testosterone use was independently associated with both Major Depressive Disorder (OR 1.99, 95% CI 1.94-2.04, P < .0001) and Suicide Attempt/Intentional Self-Harm (OR 1.52, 95% CI 1.40-1.65, P < .0001). Results remained significant in testosterone deficient sub-group analysis. CLINICAL IMPLICATIONS: Men who use testosterone should be screened for and counseled about risks of depression and suicidality. STRENGTHS AND LIMITATIONS: Strengths of this study include a large sample size, the ability to account for chronology of diagnoses, the use of propensity score matching to control for potentially confounding variables, and the consistency of results with sub-group analyses. Limitations include the potential for incorrect coding within the electronic health record, a lack of granular information regarding testosterone therapy adherence, the possibility that unrecorded testosterone or anabolic steroid use were prevalent but not captured within the control group, and a lack of data regarding testosterone withdrawal. CONCLUSION: Testosterone use is independently associated with new-onset mental health disorders. Future studies are necessary to elucidate the role that androgen withdrawal plays and whether a causal relationship exists. Nackeeran S, Patel MS, Nallakumar DT, et al. Testosterone Therapy is Associated With Depression, Suicidality, and Intentional Self-Harm: Analysis of a National Federated Database. J Sex Med 2022;19:933-939.

Trends in outpatient versus inpatient urologic surgery at a university academic medical center.

PURPOSE OF REVIEW: To analyze trends in outpatient and inpatient urologic surgeries at a large university academic medical center and test the hypothesis that the proportion of outpatient surgeries has been increasing as compared to inpatient surgeries in urology. RECENT FINDINGS: We analyzed a total of 33,054 claims for urologic surgeries at a large university academic medical center from 2010 to 2020, of which 23.2% met inpatient criteria (n = 7695), whereas 76.7% were outpatient (n = 25,359). Although outpatient claims increased yearly by an average of 24%, inpatient claims increased yearly by an average of only 1%. Over the same period, Medicare-specific outpatient claims mirrored these trends, and Medicare-specific inpatient claims decreased. SUMMARY: Outcomes of inpatient surgeries are used as a metric for quality by the Centers for Medicare and Medicaid Services (CMS) as well as US News and World Report (USNWR) rankings. However, with increasing numbers of minimally invasive operations, a large proportion of urologic surgeries are performed on an outpatient basis. As this trend continues, it will be important for organizations like CMS and USNWR to incorporate methods of measuring quality that better reflect outpatient surgical outcomes for the urologic subspecialty.

COVID-19 vaccination is associated with a decreased risk of orchitis and/or epididymitis in men.

Vaccine hesitancy is a major public health obstacle to fighting the ongoing COVID-19 epidemic. Due to studies that show COVID-19 infection can affect sperm parameters and lead to orchitis, the public are concerned about the effect of the COVID vaccines on male reproduction. In this study, we investigated the association between COVID-19 vaccination and risk of developing orchitis and/or epididymitis outcomes in a cohort of men using a large, US-based, electronic health record database. After balancing for confounding variables, we found that receiving at least 1 COVID-19 vaccine is associated with a decreased risk of developing orchitis and/or epididymitis.

Varicocele is underdiagnosed in men evaluated for infertility: Examination of multi-center large-scale electronic health record data.

Varicocele is the most common reversible cause of male infertility, affecting up to 20% of healthy men and 40% of men with primary infertility. The objective of this study was to investigate the prevalence of varicocele in men evaluated for infertility, and to determine rates of subsequent varicocele repair. Since reproductive endocrinologists are the first specialists seen for male infertility care in North America, we hypothesized that varicocele would be underdiagnosed when compared to its reported prevalence among men with infertility. TriNetX, a large, multicenter electronic health record (EHR) database was queried to establish a cohort of all men (above 18 years of age) with a diagnosis of male infertility. This cohort was used to identify those with ensuing varicocele diagnosis. Men who received varicocelectomy or venous embolization after a diagnosis of varicocele were then identified. Out of 101,309 men with a diagnosis of male infertility in the network, only 9768 (9.6%) had a diagnosis of varicocele. Mean age of men with varicocele was 34. Varicocelectomy or venous embolization was performed in 1699 (20.2%) and 69 (0.76%) of men with varicocele, respectively. In this cross-sectional EHR study, varicocele was underdiagnosed in men evaluated for infertility when compared with prior epidemiological studies.

Majority of men with premature ejaculation do not receive pharmacotherapy.

Premature ejaculation is the most common male sexual dysfunction, with therapies including selective serotonin reuptake inhibitors, clomipramine, topical anesthetics, dapoxetine and tramadol. However, it is currently unknown how many men are receiving pharmacotherapy for premature ejaculation. Using the TriNetX Research network, a large multicenter database containing over 75 million patient records from hospitals across the United States, we evaluated prescribing patterns for treatment of premature ejaculation and assessed variations in prescription patterns among patients from 2015-2021. In addition, we examined if the prescription patterns for tramadol changed with the establishment of Prescription Drug Monitoring Programs. We found that most men (51.7%) were not receiving any pharmacotherapy for premature ejaculation. However, men with mental health disorders, were more likely (56.0%), to have been treated than those without (44.4%). On further analysis, men with mental health diagnoses were significantly more likely to be treated with Selective Serotonin Reuptake Inhibitors (45.0 vs 32.2%) and Tramadol (5.1% vs 3.5%). While the pharmacotherapy for premature ejaculation has been well researched, our findings revealed that most patients diagnosed with premature ejaculation do not receive pharmacotherapy and that patients are more likely to be prescribed premature ejaculation medications if they have a pre-existing mental health diagnosis.

Efficacy and safety outcomes of a compounded testosterone pellet versus a branded testosterone pellet in men with testosterone deficiency: a single-center, open-label, randomized trial.

Background: Testosterone deficiency (TD) is a prevalent condition, especially in men ≥45 years old, and testosterone therapy (TTh) can improve the quality of life in these patients. Aim: To evaluate the safety profile of compounded subcutaneous testosterone pellets and to compare the efficacy between compounded and market brand testosterone pellets for TTh: E100 (Empower Pharmacy) and Testopel (Food and Drug Administration approved), respectively. Methods: This was a prospective, phase 3, randomized, noninferiority clinical trial. We enrolled 75 men diagnosed with TD and randomized them 1:1 to a market brand group and a compounded pellet group. The patients were implanted with their respective testosterone pellets: Testopel (10 pellets of 75 mg) and E100 (8 pellets of 100 mg). Outcomes: We evaluated adverse events after implantation and followed men at 2, 4, and 6 months for morning laboratory levels (prior to 10 am): serum testosterone, estradiol, hematocrit, and prostate-specific antigen. Results: After randomization, 33 participants were enrolled in the Testopel arm and 42 in the E100 arm. Serum testosterone levels were similar between the groups at 2, 4, and 6 months, with most men (82%) dropping to <300 ng/dL by the end of the trial. Adverse events were also similar, such as elevations in prostate-specific antigen, estradiol, and hematocrit. Most dropouts were related to persistent TD symptoms and serum testosterone <300 ng/dL, with similar rates between the groups in the study. Clinical Implications: Men treated with Testopel and E100 pellets had comparable serum testosterone levels and similar adverse event rates, providing an effective choice of long-term TTh among men with TD. Strengths and Limitations: Strengths include the prospective, randomized, single-blinded study design and adequate follow-up. Limitations include the lack of external validity and the single-institution cohort. Conclusion: E100 compounded testosterone pellets are a noninferior option of TTh as compared with Testopel for men presenting with TD.

Testosterone Therapy in Men with Klinefelter Syndrome: Analysis of a Global Federated Research Network.

Introduction: The objective of this study was to determine the rates of hypogonadism and prescription of testosterone replacement therapy (TRT) in men with Klinefelter syndrome (KS). We hypothesized that men with KS are under-treated for testosterone deficiency with TRT due to a combination of factors, including a poor understanding of hypogonadism in this population and neurocognitive issues leading to delay in seeking of treatment for hypogonadism. Materials & Methods: We queried TriNetX, a large multicenter electronic health record database, to identify all men with a diagnosis of KS (ICD-10-CM Q98.4). Prevalence of testosterone deficiency was determined as defined by testosterone level < 300 ng/dL. The primary outcome of the study was prescription of any of the following forms of TRT on the day of diagnosis or later. Results: There were in total 5437 men with diagnosis of KS. A total of 1581 men with KS received laboratory measurement of testosterone level, 1113 (70.4%) of whom were hypogonadal. Mean testosterone level in this group was 354 ng/dL [50-658]. Of the 1113 men found to be hypogonadal, only 657 (59.0%) men were given prescription for TRT. Discussion & Conclusion: This is the first study to evaluate TRT prescribing habits in men with KS. In this large retrospective study, TRT was underprescribed in men with KS. Further studies are needed to corroborate these findings and to evaluate barriers to receiving care in this population.

Consumption of a Healthy Plant-based Diet is Associated With a Decreased Risk of Erectile Dysfunction: A Cross-sectional Study of the National Health and Nutrition Examination Survey.

OBJECTIVE: To investigate the association between the plant-based content of diet and erectile dysfunction in men from the National Health and Nutrition Examination Survey (NHANES). METHODS: We collected de-identified information from the NHANES database on demographics, comorbidities, diet, and erectile dysfunction (ED). Exclusion criteria were age <20 or >70 years, incomplete plant-based diet index information, history of prostate cancer, or other missing information. Using the food frequency questionnaire, an overall plant-based diet index (PDI) and healthful plant-based diet index (hPDI) were developed. A higher score on the PDI and hPDI is indicative of greater consumption of plant-based foods. RESULTS: A total of 2549 men were analyzed, of those 1085 (42.6%) have good erectile function and 1464 (57.4%) have some degree of ED [usually have erections 521 (20.4%), sometimes have erection 690 (27.1%), or never have erections 253 (9.9%)]. The median age and BMI were 54 [41-64] years and 28.8 [25.5-32.6] kg/m2, respectively. The median PDI and hPDI were 50 [46-54] and 50 [45-56], respectively. In multivariable adjusted logistic regression analysis, hPDI was negatively associated with ED (OR = 0.98, 95% CI: 0.96-0.99; P = .001). There was no association between PDI and ED. CONCLUSION: In a well characterized national database, we showed that a healthful plant-based diet is associated with less chance of having erectile dysfunction. Whether interventions with a plant-based diet will improve erectile function remains to be studied.

The Presence of Nucleated Red Blood Cells as an Indicator for Increased Mortality and Morbidity in Burn Patients.

Nucleated red blood cells (NRBCs) have been studied in critically ill and injured patients as a predictor of increased in-hospital mortality and poor clinical outcomes. While prior studies have demonstrated the prognostic power of NRBCs in the critical patient, there has been a paucity of literature available describing their value as a prognostic indicator in the severely burned patient. This retrospective observational study was conducted from 2012 to 2017. Inclusion criteria for this study included all burn patients with total body surface area > 10% who were aged ≥ 15 years. Demographic and clinical data were collected from the electronic medical record system. Data analysis consisted of descriptive and comparative analysis using SPSS. Two hundred and nineteen patients (17.5%) met inclusion criteria with 51 (23.3%) patients positive for NRBCs. The presence of NRBCs had an increased mortality rate with an odds ratio of 6.0 (P = .001; 2.5, 14.5); was more likely to appear in older patients (P < .001); and was associated with increased hospital length of stay (P < .001), injury severity scores (P < .001), and complications. The presence of NRBCs even at the low concentrations reported in our study showed a 6-fold increase in the rate of mortality. With the current improvements in burn care leading to higher survival rates, the need to improve upon the numerous models that have been developed to predict mortality in severe burn patients is clear given the significantly increased risk of death that the presence of NRBCs portends.

Absence of cognitive symptoms in a 6-year-old male with post-traumatic increased intracranial pressure - A case report.

INTRODUCTION: Traumatic Brain Injuries (TBIs) can range from mild to severe, and may result in increased intracranial pressure (ICP). Increased ICP causes hallmark physical signs, such as diaphoresis, emesis, fixed pupils, and altered mental status. Monitoring the patient's score on the Glasgow Coma Scale (GCS) and cranial CT scans are routine measures used in clinical practice to monitor the development of a TBI. PRESENTATION OF THE CASE: A 6-year-old male fell off his father's shoulders and subsequently presented to ED for suspected head trauma. He was transferred to our Level 1 Trauma Center after a head CT scan demonstrated a subdural hematoma. His GCS score remained 15. The next day he began to have episodes of apnea and desaturation. Further imaging indicated expansion of the hematoma with a 5mm midline shift. He remained consistently alert and a neurological exam revealed cranial nerves to be grossly intact. Increased ICP was reduced with several days of hypertonic saline treatment without surgical intervention. DISCUSSION: TBIs can have long-lasting effects in pediatric patients and are typically assessed using both diagnostic imaging and clinical judgment. CT scans are used to assess for hematoma development, while loss of consciousness (LOC) and altered mental status are standard clinical diagnostic indicators of increased ICP. This patient remained alert with a GCS score of 15, although he had clinical signs of increased ICP including apnea and bradycardia with a midline shift confirmed on imaging. CONCLUSION: While GCS is an important prognostic indicator in TBI, patients should still be monitored to assure resolution of all symptoms.