Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate versus Subcutaneous Testosterone Enanthate.

PURPOSE: Intramuscular testosterone cypionate (IM-TC) is known to cause significant rises in estradiol (E2), hematocrit (HCT), and prostate specific antigen (PSA) due to its supraphysiological testosterone peaks, whereas a novel subcutaneous testosterone enanthate autoinjector (SCTE-AI) was designed with a lower testosterone peak-to-trough ratio to mitigate these reactions. We compare the total testosterone (TT), E2, HCT and PSA response to treatment with IM-TC versus SCTE-AI. MATERIALS AND METHODS: A total of 234 hypogonadal men were treated with testosterone replacement therapy (TRT) via IM-TC 100 mg weekly or SCTE-AI 100 mg weekly. TT, E2, HCT and PSA levels were obtained at baseline and 12 weeks post-treatment. Significant differences in baseline and post-treatment levels were identified by univariate analysis. Linear regression models determined whether treatment modality was independently associated with post-TRT levels of TT, E2, HCT and PSA. RESULTS: Post-TRT, both cohorts had significant increases in trough TT compared to their baseline levels (IM-TC: 313.6 ng/dL to 536.4 ng/dL, p <0.001; SCTE-AI: 246.6 ng/dL to 552.8 ng/dL, p <0.001). After linear regression, type of TRT modality was not found to be associated with TT levels (p=0.057). SCTE-AI was independently associated with lower post-therapy E2 (p <0.001) and HCT (p <0.001). Neither TRT modality was associated with significant post-therapy elevation of PSA (p=0.965). CONCLUSIONS: While IM-TC and SCTE-AI provide a significant increase in TT levels, SCTE-AI is associated with lower levels of post-therapy HCT and E2 compared to IM-TC after adjusting for significant covariates. SCTE-AI is an effective testosterone delivery system with a potentially preferable safety profile over IM-TC.

Post-market safety and efficacy profile of subcutaneous testosterone enanthate-autoinjector: a cohort analysis.

A subcutaneous testosterone enanthate-autoinjector (SCTE-AI) was recently approved by the Food and Drug Administration for patient-administered weekly testosterone replacement therapy (TRT). From January 2019 to October 2019, 110 hypogonadal men were treated with SCTE-AI at two institutions. Patients were assessed in a pretherapy visit prior to receiving SCTE-AI and re-assessed 6 weeks after treatment initiation. Patients with a history of prostate cancer were excluded. Trough serum total testosterone (TT), estradiol (E2), prostate-specific antigen (PSA), and hematocrit (HCT) levels were collected at clinic visits. Therapeutic phlebotomy was recommended for HCT > 54%, and treatment was discontinued for significant increases in PSA as well as for significant treatment-related adverse events. Values from each visit were compared with univariate analysis. 110 patients completed the 6 weeks of observation with a mean age of 40.3 (SD: 10.5). TT significantly rose from 246.6 ng/dL (SD:113.3) pretherapy to 538.4 ng/dL (SD: 209.3) at 6 weeks (p < 0.001). Post-therapy, 101/110 (91.8%) of patients had TT > 300 ng/dL. No patients had HCT > 54%. 74 patients (70.5%) had PSA increase with only 3 (2.9%) experiencing an increase >1.0 ng/dL. There was a significant increase in mean PSA from 1.07 ng/dL (SD: 0.8) pretherapy to 1.18 ng/dL (SD: 0.9) at 6 weeks (p = 0.01). One patient had immediate treatment cessation following diagnosis of prostate cancer. This is the largest non-industry sponsored safety and efficacy profile of SCTE-AI application in urology clinics. After 6 weeks of observation, TT levels increased significantly without any reports of adverse events. SCTE-AI is a safe and effective alternative delivery system of TRT.

Intralesional Injection Therapy and Atypical Peyronie's Disease: A Systematic Review.

INTRODUCTION: Peyronie's disease (PD) is an inflammatory disorder of the tunica albuginea causing fibrotic changes including abnormal penile curvature, pain, and erectile dysfunction. Approximately 10% of PD patients will have atypical features including ventral plaques, hourglass deformities, unilateral indentations, severely shortened penile length, and multiplanar curvatures. Currently, the only intralesional treatment approved by the United States Food and Drug Administration is considered off-label for atypical PD. Furthermore, treatment of atypical PD, especially ventral plaques, is met with hesitation, in part due to potential urethral injury. OBJECTIVES: To systematically review the available literature for the safety and efficacy of intralesional injections for atypical PD. METHODS: A thorough literature search of the PubMed database was performed on manuscripts published between 1982 and 2020. Keywords included atypical Peyronie's disease, ventral plaque, hourglass deformity, and injection. RESULTS: 15 articles met the criteria for evaluation. Overall, 1,357 patients with PD were treated with intralesional therapy, of which 250 patients were considered to have an atypical presentation. 162 (648%) of the patients were treated with intralesional collagenase Clostridium histolyticum, 49 (19.6%) with verapamil, 29 (11.6%) with interferon alfa-2b, 5 (2.0%) with hyaluronic acid, and another 5 (2.0%) with onabotulinumtoxinA. There was only 1 reported severe adverse event (penile fracture), which was surgically repaired. There were no reports of urethral injury. CONCLUSION: Intralesional injection treatment may be a safe alternative option for atypical PD. There is a great need for future research to closely monitor the role of intralesional therapy in this cohort. Choi EJ, Xu P, El-Khatib FM, et al. Intralesional Injection Therapy and Atypical Peyronie's Disease: A Systematic Review. Sex Med Rev 2021;9:434-444.

Hypogonadism and its treatment among prostate cancer survivors.

Adult-onset hypogonadism (AOH) is associated with sexual dysfunction, poor bone mineralization, decreased muscle mass, metabolic syndrome disorder, and cognitive suppression. Historically, testosterone has been contraindicated in men with a history of prostate cancer. However, there has been a modern resurgence in re-evaluating this belief. Not only can testosterone be safely utilized to alleviate AOH symptoms in prostate cancer survivors, it has been also touted as a treatment option for aggressive prostatic cancer. While much work remains in understanding the relationship between testosterone and prostate cancer, those who survive this disease should not be automatically turned away from an opportunity to be treated and restored.

Determinants of the regulation of Helicobacter pylori adhesins include repeat sequences in both promoter and coding regions as well as the two-component system ArsRS.

PURPOSE: We investigated the transcription of adhesin-encoding genes sabA, hopZ and labA in Helicobacter pylori strain J99. Each possesses a repeating homopolymeric nucleotide tract within their promoter regions, and sabA and hopZ possess repeats within their 5' coding regions. METHODOLOGY: We altered the repeat lengths associated with the adhesin genes and quantified mRNA levels by real-time quantitative PCR. Using adherence to AGS cells and IL-8 assays, we examined the effects of altered transcript levels. We assessed the role of ArsRS in transcription using an arsS null mutant and by examining ArsR binding to promoter regions via electrophoretic mobility shift assays. RESULTS: Extensions or truncations of promoter region repeats in hopZ and labA increased transcript levels, mirroring results shown by our lab and others for mutations in the sabA promoter. Altered lengths of the poly-cytosine thymine tract within the 5' coding region of sabA demonstrated that switching from phase-off to phase-on significantly increased mRNA levels. However, mutations in the poly-thymine tract of sabA, which increased mRNA levels, do not behave synergistically with phase-on mutations. Phase-on mutations of sabA resulted in increased H. pylori adherence to AGS cells, but only a modest effect on IL-8. hopZ and labA, and sabA paralogue sabB, transcript levels were increased in an arsS mutant and ArsR bound the promoter regions for each of these genes in vitro. CONCLUSION: This work highlights the complex nature of adhesin regulation, its impact on H. pylori attachment and the pervasive role of ArsRS in adhesin expression. Such regulation may help facilitate the decades-long persistence of infection.

Impact of coronary collaterals on outcome following percutaneous coronary intervention (from the National Heart, Lung, and Blood Institute Dynamic Registry).

Coronary collateral circulation is beneficial in patients with coronary artery disease, but controversy still exists regarding the association between angiographic collaterals and outcome after percutaneous coronary intervention (PCI). We compared the baseline characteristics and cumulative 1-year event rates of consecutive patients undergoing PCI by target vessel collateral status-no angiographic evidence of collateral circulation (NC; n = 5051), treated artery supplied collaterals (SC; n = 239), and treated artery received collaterals (RC; n = 893)-using the National Heart, Lung, and Blood Institute Dynamic Registry. Patients in the SC group were older and had more previous coronary bypass surgery, myocardial infarction, co-morbid illness, and heart failure than the NC and RC groups and had less often undergone revascularization for acute myocardial infarction (p <0.01 for all). The total angiographic PCI success was comparable for the SC and NC groups but higher than for the RC group (94.1% vs 94.4% vs 83.9%, respectively; p <0.001). Overall stent use was 77.5% and was highest in the SC group (82.4%, p <0.001). At 1 year, significant differences in outcome were observed by collateral status. Compared with the NC group, patients with PCI of a SC artery had higher adjusted mortality (relative risk [RR] 1.95, 95% confidence interval [CI] 1.27 to 3.01, p = 0.002) and death/myocardial infarction (RR 1.75, 95% CI 1.26 to 2.45, p <0.001) rates. Patients with PCI of a RC vessel, conversely, had lower adjusted death/myocardial infarction (RR 0.72, 95% CI 0.54 to 0.96, p = 0.02) and repeat revascularization (RR 0.73, 95% CI 0.59 to 0.91, p = 0.005) rates. In conclusion, our results suggest that PCI on collateralized vessels is warranted, but that patients with PCI in arteries that supply collaterals are a high-risk group that may benefit from closer follow-up and complete revascularization.