Testosterone therapy in females is not associated with increased cardiovascular or breast cancer risk: a claims database analysis.

BACKGROUND: Testosterone therapy (TTh) has been shown to improve libido in women with sexual dysfunction, but its utilization has been limited due to concern for cardiovascular events and past studies reporting highly variable results. AIM: To assess the association of TTh in women with major adverse cardiac events (MACEs), including heart attack, stroke, or death, using a large database. METHODS: The TriNetX Diamond Network was queried from 2009 to 2022. Our study cohort included adult females with ≥3 systemic testosterone prescriptions within a year. Our control cohort excluded females with any testosterone prescriptions, polycystic ovary syndrome, or androgen excess. Both cohorts excluded females with prior heart failure, unstable angina, intersex surgery (female to male), personal history of sex reassignment, or gender identity disorders. Propensity matching between the cohorts was performed. A subanalysis by age was conducted (18-55 and >55 years). OUTCOMES: We evaluated the association of TTh to the following: MACE, upper or lower emboli or deep vein thrombosis (DVT), pulmonary embolism (PE), breast neoplasm, and hirsutism within 3 years of TTh. RESULTS: When compared with propensity-matched controls, adult females with TTh had a lower risk of MACE (risk ratio [RR], 0.64; 95% CI, 0.51-0.81), DVT (RR, 0.61; 95% CI, 0.42-0.90), PE (RR, 0.48; 95% CI, 0.28-0.82), and malignant breast neoplasm (RR, 0.48; 95% CI, 0.37-0.62). Similarly, females aged 18 to 55 years with TTh had a lower risk of MACE (RR, 0.49; 95% CI, 0.28-0.85) and DVT (RR, 0.48; 95% CI, 0.25-0.93) and a similar risk of malignant breast neoplasm (RR, 0.62; 95% CI, 0.34-1.12). Females aged ≥56 years with TTh had a similar risk of MACE (RR, 0.84; 95% CI, 0.64-1.10), DVT (RR, 0.82; 95% CI, 0.50-1.36), and PE (RR, 0.52; 95% CI, 0.26-1.05) and a significantly lower risk of malignant breast neoplasm (RR, 0.51; 95% CI, 0.38-0.68). Risk of hirsutism was consistently higher in those with TTh as compared with propensity-matched controls. CLINICAL IMPLICATIONS: Our results contribute to safety data on TTh, a therapy for sexual dysfunction in women. STRENGTHS AND LIMITATIONS: The TriNetX Diamond Network allows for significant generalizability but has insufficient information for some factors. CONCLUSIONS: We found a decreased risk of MACE among women with TTh as compared with matched controls and a similar risk of MACE in postmenopausal women while demonstrating a similar or significantly lower risk of breast cancer on age-based subanalysis.

Pain control is comparable between opioid versus non-opioid management after otolaryngology procedures.

Objective: The current study aims to measure patient-reported satisfaction with pain control using opioid and non-opioid medications after undergoing the following otolaryngology procedures: parathyroidectomy, thyroid lobectomy, total thyroidectomy, and bilateral tonsillectomy. Materials and Methods: A prospective cohort study was performed at an academic medical center that included a telephone questionnaire and chart review. Opioid prescriptions, usage, and patient-reported pain outcomes were recorded. Bivariate analyses were used to compare opioid and non-opioid users. Results: Of the 107 total patients undergoing otolaryngology procedures included in the study, 49 (45.8%) used an opioid for pain management postoperatively and 58 (54.2%) did not. Among the 81 patients who underwent endocrine procedures (parathyroidectomy, total thyroidectomy/lobectomy), most patients reported being "very satisfied" or "satisfied" with pain control whether they used opioids (n = 27/30, 90%) or not (n = 50/51, 98%). Of the 26 patients who underwent bilateral tonsillectomy, 19 (73%) were prescribed opioids and among these, most (n = 17/19, 89%) reported they were "very satisfied" or "satisfied" with pain control. In the non-opioid usage group, all patients (n = 7/7, 100%) reported they were "satisfied" with pain control. There was no statistically significant difference in patient-reported satisfaction with pain control between opioid and non-opioid users for any of the procedures listed. Conclusion: The results of our study suggest that patients who did not use opioids have a similar level of satisfaction with pain control compared to those using opioids after thyroid, parathyroid and tonsillectomy surgeries. Considering the magnitude of the opioid crisis, providers should reassess the need for opioid prescriptions following certain ENT procedures. Level of Evidence: IV.

A population analysis of delayed ejaculation using a claims database: characteristics and national trends in prevalence, incidence, and pharmacotherapy.

We investigated the prevalence, incidence, and rates of pharmacological treatment of delayed ejaculation using the TriNetX Diamond Network. We included all men evaluated in the inpatient, outpatient, and emergency settings. Prevalence was determined by comparing the number of men diagnosed with delayed ejaculation to the entire population. Incidence was determined by comparing the number of men diagnosed with delayed ejaculation without a prior diagnosis to the overall population without a prior diagnosis. Rates of pharmacologic treatment were calculated by comparing the number of men who received a prescription to the total number of men with delayed ejaculation. Trends in prevalence and incidence were compared using six-month intervals, while trends in pharmacologic treatment were compared using one-year intervals. A total of 23,164 adult males were diagnosed with delayed ejaculation from 2013 to 2019. During the final six-month interval (July to December 2019), 2,747 of 16,496,744 men received a delayed ejaculation diagnosis, and 1,375 of 16,488,270 men without a prior diagnosis were diagnosed with delayed ejaculation. In 2019, only 916 of 4,733 (19.4%) men diagnosed with delayed ejaculation received any prescription, with the most common being testosterone (9.5%), bupropion (6.6%), and buspirone (2.3%). Prevalence, incidence and pharmacologic treatment all had increasing trends.

A Case Report of Refractory Postherpetic Neuralgia After Ramsay Hunt Syndrome Treated With Tympanic Nerve Neurectomy.

Ramsay Hunt syndrome is a facial nerve palsy that arises from herpes zoster infection. In rare cases, postherpetic neuralgia is a complication following Ramsay Hunt syndrome. Pain management to address postherpetic neuralgia includes facial nerve blocks, medications such as gabapentin, carbamazepine and botulinum toxin injections, and pulsed radiofrequency. Despite the reported benefits for patients with glossopharyngeal nerve pain, neurectomy as a treatment has rarely been described. A 45-year-old patient visited our ENT clinic for chronic right-sided facial, ear, and jaw pain that persisted for 9 years following the development of Ramsay Hunt syndrome. She trialed multiple medications including gabapentin, carbamazepine, and botulinum toxin injections with minimal relief to her symptoms. The patient underwent a diagnostic myringotomy with topical application of lidocaine to the tympanic nerve. This resulted in temporary relief of her pain until the effects of the lidocaine subsided. The patient was subsequently offered lysis of the right tympanic nerve for more definitive management. The patient experienced significant pain reduction after the right tympanic neurectomy procedure. Chronic postherpetic neuralgia following Ramsay Hunt syndrome can cause significant impairment in a patient's quality of life. For patients with ear pain refractory to conservative management, a tympanic neurectomy can be considered.

Opioid Use and Associated Patient Satisfaction With Pain Control After Endoscopic Surgery and Robotic-Assisted Radical Prostatectomy.

OBJECTIVE: To evaluate patient reported measures in patients undergoing endourologic procedures and robotic assisted radical prostatectomy (RARP) to demonstrate the efficacy of non-opioid postoperative pain management strategies. MATERIALS AND METHODS: A prospective cohort study performed at an academic medical center included a patient telephone questionnaire and chart review. Opioid prescriptions, opioid use, and patient reported outcomes were recorded. Bivariate analyses were used to compare patients who did and did not use opioids in the RARP cohort while overall trends were reported for the endourologic procedures. RESULTS: Of the 68 patients undergoing endoscopic intervention, 14 (21%) were prescribed an opioid and 6 (9%) reported any opioid use. 58 (85%) reported their pain was very well or well controlled while 9 reported their pain was poorly controlled. 59 (87%) were satisfied or very satisfied with their pain control. Fifty-three (93%) of the 57 patients undergoing RARP received an opioid prescription and only 23 reported any opioid use. All but 1 patient reported that their pain was well or very well controlled and almost all (54) of the patients were satisfied with their level of pain control. 36 (63%) reported their pain was less than expected while only 7 (12%) reported it was more than expected. CONCLUSION: Most patients undergoing endourologic procedures do not use postoperative opioids and report favorable outcomes regarding their pain control. Similarly, after RARP, most patients do not use opioids even when they are prescribed and are satisfied with their pain control.

The molecular link between obesity and genomic instability in cancer development.

Obesity has been known to be a major risk factor for various types of cancers for several decades. More recently, the relationship between dysregulated adipokines and cancer development has been the focus of much research. Adipose tissue is an important endocrine organ that secretes adipokines that affect both autocrine and paracrine signaling. These adipokines modulate inflammation, induce insulin resistance, and regulate their own behavior and production. Adipokine-production dysregulation is due to physiological changes in adipose tissue that prompt molecular modifications, including low-grade inflammation and the stimulatory production of reactive oxygen species. Additionally, studies have linked DNA damage response, genomic instability, and the innate immune response to tumorigenesis. Further investigation of adipokines and their role in the promotion of genomic instability may clarify the link between obesity and cancer, as well as elucidate potential pharmaceutical targets. In this review, we discuss the progress of recent literature, focusing on the impact of adipokines, genomic instability, and the innate immune response on increasing the risk of cancer.

Inhibition of the ATM/Chk2 axis promotes cGAS/STING signaling in ARID1A-deficient tumors.

ARID1A, a component of the chromatin-remodeling complex SWI/SNF, is one of the most frequently mutated genes in human cancer. We sought to develop rational combination therapy to potentiate the efficacy of immune checkpoint blockade in ARID1A-deficient tumors. In a proteomic analysis of a data set from The Cancer Genomic Atlas, we found enhanced expression of Chk2, a DNA damage checkpoint kinase, in ARID1A-mutated/deficient tumors. Surprisingly, we found that ARID1A targets the nonchromatin substrate Chk2 for ubiquitination. Loss of ARID1A increased the Chk2 level through modulating autoubiquitination of the E3-ligase RNF8 and thereby reducing RNF8-mediated Chk2 degradation. Inhibition of the ATM/Chk2 DNA damage checkpoint axis led to replication stress and accumulation of cytosolic DNA, which subsequently activated the DNA sensor STING-mediated innate immune response in ARID1A-deficient tumors. As expected, tumors with mutation or low expression of both ARID1A and ATM/Chk2 exhibited increased tumor-infiltrating lymphocytes and were associated with longer patient survival. Notably, an ATM inhibitor selectively potentiated the efficacy of immune checkpoint blockade in ARID1A-depleted tumors but not in WT tumors. Together, these results suggest that ARID1A's targeting of the nonchromatin substrate Chk2 for ubiquitination makes it possible to selectively modulate cancer cell-intrinsic innate immunity to enhance the antitumor activity of immune checkpoint blockade.