Newer formulations of oral testosterone undecanoate: development and liver side effects.

INTRODUCTION: Testosterone deficiency is a clinical disorder due to either failure of the testes to produce testosterone or failure of the hypothalamus or pituitary to produce sufficient gonadotropins. Previous formulations of oral testosterone therapy, particularly methyltestosterone, have been associated with adverse liver effects. Many different routes of testosterone delivery have been developed, each with their own administrative benefits and challenges. Newer formulations of oral testosterone undecanoate (TU) provide a convenient administration option, although their use has been limited by hepatotoxicity concerns based on older methyltestosterone data, and prescribing physicians may still be concerned about adverse liver effects. OBJECTIVES: In this review, we discuss the history of oral testosterone development, clarify the mechanism of action of oral TU, and describe the relevant liver safety findings. METHODS: Relevant literature was allocated to present a review on the history of oral TU development and the mechanism of action of oral TU. We pooled data from individual studies of oral TU products to present a safety summary. RESULTS: Overall, safety results from studies of the newer formulations of oral TU showed that increased liver function test values are not generally associated with oral TU formulations and that no clinically significant liver toxicities were noted in clinical trials of oral TU. CONCLUSION: Continued research into the safety of oral TU will contribute to a better understanding of the potential risks in patients receiving this therapy, an outcome that highlights the importance of providing patient education and reassurance regarding oral TU safety.

Effect of hormone therapy on personality traits: preliminary evidence in older men and women.

OBJECTIVE: Findings concerning the effects of hormone therapy (HT) on cognition and dementia are mixed, with some trials suggesting increased harm at older ages. Personality, like cognition, changes with dementia, but no clinical trials to date have examined the effects of HT on personality traits. This study aimed to determine the effects of HT on personality traits in older men and women. METHOD: Secondary data analysis was performed from randomized, double-blind, placebo-controlled cross-over studies of menopausal HT in women and testosterone therapy (TT) in men. Participants were community-dwelling cognitively normal adults (mean age = 75.2 years), including 29 men and 22 women. Three months of hormone intervention (for women, 0.625 mg/day conjugated equine estrogen with or without 2.5 mg/day medroxyprogesterone acetate; for men, 200 mg intramuscular testosterone enanthate every 2 weeks) were crossed over with 3 months of identical placebo with a 3-month washout between intervention phases. The main outcome measure was neuroticism and conscientiousness personality domains and facets assessed with the Revised NEO Personality Inventory (NEO-PI-R) after the active and placebo intervention phases. RESULTS: In linear mixed-effect models, HT in women decreased conscientiousness (p < 0.01) and the conscientiousness facet of achievement striving (p < 0.01), and increased vulnerability, a facet of neuroticism (p < 0.05). Testosterone in men decreased conscientiousness (p < 0.05) and the conscientiousness facet of dutifulness (p < 0.05), and increased vulnerability (p < 0.05). CONCLUSION: In a preliminary study of healthy older adults, HT and TT formulations produced adverse changes in vulnerability and conscientiousness facets that parallel personality changes in dementia.

Safety, efficacy, and pharmacokinetics of oral testosterone undecanoate in males with hypogonadism.

BACKGROUND: Testosterone deficiency results from insufficient testosterone production. Testosterone therapy may require dose titration to reach eugonadal serum testosterone concentrations. OBJECTIVE: The primary objective was the efficacy of oral testosterone undecanoate (TLANDO; Antares Pharma Inc.) in male patients with documented hypogonadism. Secondary objectives included a comparison of oral testosterone undecanoate safety and quality-of-life assessments to 1.62% topical testosterone gel (AndroGel 1.62%; AbbVie). MATERIALS AND METHODS: In this phase 3 study, 315 patients were randomized 2:1 to oral testosterone undecanoate or 1.62% topical testosterone gel (NCT02081300). Patients received 225 mg oral testosterone undecanoate twice daily, and doses were adjusted by 75 mg/dose at weeks 4 and 8 based on average serum total testosterone concentration and maximum observed serum concentration. The primary endpoint was the proportion of patients receiving oral testosterone undecanoate with serum total testosterone concentration within the eugonadal reference range (300-1140 ng/dL). Secondary endpoints included the proportion of patients with maximum serum total testosterone concentrations within predetermined limits, safety parameters, and quality-of-life endpoints including the Short Form-36v2 Health Survey, Psychosexual Daily Questionnaire, and International Prostate Symptom Score. RESULTS: Overall mean ± SD baseline testosterone was 205.7 ± 71.6 ng/dL. For patients receiving oral testosterone undecanoate, 87.4% demonstrated a 24-h average serum total testosterone concentration within the reference range following titration. Oral testosterone undecanoate demonstrated a nominal statistically significantly greater mean change from baseline than 1.62% topical testosterone gel for Short Form-36v2 Health Survey measures of mental health (2.91 vs. -0.10; p = 0.035), and mental component summary (3.82 vs. 0.55; p = 0.009); and Psychosexual Daily Questionnaire measure of weekly negative mood (-0.57 vs. -0.20; p = 0.021). Safety endpoints were comparable between therapies. No deaths or treatment-related serious adverse events were reported. DISCUSSION AND CONCLUSION: Male patients with hypogonadism receiving oral testosterone undecanoate 225 mg twice daily demonstrated improvements in libido and sexual frequency. Serum testosterone concentrations were within the reference range in 87% of patients without dose titration.

A Precision Oncology Platform to Support Genotype-Tailored Therapy Selection.

There is a critical need for a streamlined process to identify genotype-matched individuals eligible for enrollment into clinical trials and/or targeted therapies, as current methodologies face challenges in integrating diverse molecular data sources. We have developed a precision oncology platform to assist molecular tumor boards and community oncologists in reviewing patients' phenotypes, evaluating related knowledge, and identifying genotype-matched therapies.

Patient perspectives on cancer care during COVID-19: A qualitative study.

PURPOSE: The COVID-19 pandemic posed unique challenges to cancer-related care as health systems balanced competing risks of timely delivery of care and minimizing exposure to infection in a high-risk, immunocompromised patient population. This study aimed to better understand how pandemic-related factors affected the patient experience of cancer care during this time. METHODS: We conducted fifteen semi-structured interviews with adults from rural counties in Maryland who were diagnosed with and/or actively treated for cancer at the TidalHealth healthcare network between January 2020 and October 2022. RESULTS: Interviews from fifteen participants were analyzed. Two major themes emerged including COVID Impact on Care, and COVID Impact on Mental Health. Subthemes under COVID Impact on Care include Staffing Shortages, Hospital Regulations, Visitation, Importance of Advocacy, and Telehealth Utilization, and subthemes under COVID Impact on Mental Health include Loneliness, Support Networks, and Perceptions of COVID and Personal Protection. Overall, participants described positive care experiences despite notable delays, disruptions to continuity of care, difficult transitions to telemedicine, visitation policies that limited patient support, increased mental health struggles related to social distancing measures, and greater desire for patient advocacy. CONCLUSION: Our findings reveal significant impacts of the COVID-19 pandemic on experiences of cancer treatment and survivorship in a more vulnerable, rural patient population with lower healthcare access and income level. Our findings suggest areas for targeted interventions to limit disruptions to quality care in future public health emergencies.

Transgender Women With Suppressed Testosterone Display Lower Burden of Coronary Disease Than Matched Cisgender Men.

Context: Cardiovascular disease (CVD) in transgender women (TW) may be affected by gender-affirming hormone therapy (GAHT) and HIV, but few data compare TW on contemporary GAHT to well-matched controls. Objective: We compared CVD burden and biomarker profiles between TW and matched cisgender men (CM). Methods: Adult TW on GAHT (n = 29) were recruited for a cross-sectional study (2018-2020). CM (n = 48) from the former Multicenter AIDS Cohort Study were matched 2:1 to TW on HIV serostatus, age ±5 years, race/ethnicity, BMI category and antiretroviral therapy (ART) type. Cardiac parameters were measured by CT and coronary atherosclerosis by coronary CT angiography; sex hormone and biomarker concentrations were measured centrally from stored samples. Results: Overall, median age was 53 years and BMI 29 kg/m2; 69% were non-white. All participants with HIV (71%) had viral suppression on ART. Only 31% of TW had testosterone suppression (<50 ng/dL, TW-S). Traditional CVD risk factors were similar between groups, except that TW-S had higher BMI than TW with non-suppressed testosterone (TW-T). TW-S had no evidence of non-calcified coronary plaque or advanced coronary stenosis, whereas TW-T and CM had similar burden. TW had lower prevalence of any coronary plaque, calcified plaque and mixed plaque than CM, regardless of testosterone concentrations and HIV serostatus. Estradiol but not testosterone concentrations moderately and negatively correlated with the presence of coronary plaque and stenosis. Small sample size limited statistical power. Conclusion: Older TW with suppressed total testosterone on GAHT had no CT evidence of non-calcified coronary plaque or advanced coronary stenosis. Longitudinal studies to understand relationships between GAHT and CVD risk in TW are needed.

Online communication skill training of patients with cancer: A test of the behavioral intention predictive framework for communication skills.

Objective: To assess the Behavioral Intention Predictive Framework's utility in explaining variation in cancer patients' strong behavioral intention (SBI) to use LEAPS (Listen, Educate, Assess, Partner, Support) communication skills after viewing training videos. Methods: Ninety-eight patients were enrolled through anonymized online platforms to view LEAPS training videos, complete background and communication questionnaires and report their SBI to use LEAPS skills. Results: On average, patients indicated SBI to use 6 of 13 skills and 46% of patients expressed SBI across individual skills. The framework explained 27.7% of the adjusted variance in SBI with significant predictors of frequent past use of LEAPS-related shared decision-making behaviors, poor emotional health, being rarely accompanied to visits and positive ratings of narrative videos. Finally, 21.7% of the adjusted variance in problem communication was explained by infrequent use of LEAPS-related information behaviors, patient accompaniment of another adult and positive narrative scores. Conclusion: Patients SBI to use multiple LEAPS skills and past problem communication were explained by framework predictors. Innovation: Despite theoretical and empirical evidence that behavioral intention significantly predicts behavior, it has not been studied in patient communication research. Application of the novel framework to LEAPS training videos contributes an innovative address of this research gap.

Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men : Individual Participant Data Meta-analyses.

BACKGROUND: Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial. PURPOSE: To clarify associations of sex hormones with these outcomes. DATA SOURCES: Systematic literature review to July 2019, with bridge searches to March 2024. STUDY SELECTION: Prospective cohort studies of community-dwelling men with sex steroids measured using mass spectrometry and at least 5 years of follow-up. DATA EXTRACTION: Independent variables were testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol concentrations. Primary outcomes were all-cause mortality, CVD death, and incident CVD events. Covariates included age, body mass index, marital status, alcohol consumption, smoking, physical activity, hypertension, diabetes, creatinine concentration, ratio of total to high-density lipoprotein cholesterol, and lipid medication use. DATA SYNTHESIS: Nine studies provided individual participant data (IPD) (255 830 participant-years). Eleven studies provided summary estimates (n = 24 109). Two-stage random-effects IPD meta-analyses found that men with baseline testosterone concentrations below 7.4 nmol/L (<213 ng/dL), LH concentrations above 10 IU/L, or estradiol concentrations below 5.1 pmol/L had higher all-cause mortality, and those with testosterone concentrations below 5.3 nmol/L (<153 ng/dL) had higher CVD mortality risk. Lower SHBG concentration was associated with lower all-cause mortality (median for quintile 1 [Q1] vs. Q5, 20.6 vs. 68.3 nmol/L; adjusted hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.95]) and lower CVD mortality (adjusted HR, 0.81 [CI, 0.65 to 1.00]). Men with lower baseline DHT concentrations had higher risk for all-cause mortality (median for Q1 vs. Q5, 0.69 vs. 2.45 nmol/L; adjusted HR, 1.19 [CI, 1.08 to 1.30]) and CVD mortality (adjusted HR, 1.29 [CI, 1.03 to 1.61]), and risk also increased with DHT concentrations above 2.45 nmol/L. Men with DHT concentrations below 0.59 nmol/L had increased risk for incident CVD events. LIMITATIONS: Observational study design, heterogeneity among studies, and imputation of missing data. CONCLUSION: Men with low testosterone, high LH, or very low estradiol concentrations had increased all-cause mortality. SHBG concentration was positively associated and DHT concentration was nonlinearly associated with all-cause and CVD mortality. PRIMARY FUNDING SOURCE: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

Effectiveness of artificial intelligence vs. human coaching in diabetes prevention: a study protocol for a randomized controlled trial.

BACKGROUND: Prediabetes is a highly prevalent condition that heralds an increased risk of progression to type 2 diabetes, along with associated microvascular and macrovascular complications. The Diabetes Prevention Program (DPP) is an established effective intervention for diabetes prevention. However, participation in this 12-month lifestyle change program has historically been low. Digital DPPs have emerged as a scalable alternative, accessible asynchronously and recognized by the Centers for Disease Control and Prevention (CDC). Yet, most digital programs still incorporate human coaching, potentially limiting scalability. Furthermore, existing effectiveness results of digital DPPs are primarily derived from per protocol, longitudinal non-randomized studies, or comparisons to control groups that do not represent the standard of care DPP. The potential of an AI-powered DPP as an alternative to the DPP is yet to be investigated. We propose a randomized controlled trial (RCT) to directly compare these two approaches. METHODS: This open-label, multicenter, non-inferiority RCT will compare the effectiveness of a fully automated AI-powered digital DPP (ai-DPP) with a standard of care human coach-based DPP (h-DPP). A total of 368 participants with elevated body mass index (BMI) and prediabetes will be randomized equally to the ai-DPP (smartphone app and Bluetooth-enabled body weight scale) or h-DPP (referral to a CDC recognized DPP). The primary endpoint, assessed at 12 months, is the achievement of the CDC's benchmark for type 2 diabetes risk reduction, defined as any of the following: at least 5% weight loss, at least 4% weight loss and at least 150 min per week on average of physical activity, or at least a 0.2-point reduction in hemoglobin A1C. Physical activity will be objectively measured using serial actigraphy at baseline and at 1-month intervals throughout the trial. Secondary endpoints, evaluated at 6 and 12 months, will include changes in A1C, weight, physical activity measures, program engagement, and cost-effectiveness. Participants include adults aged 18-75 years with laboratory confirmed prediabetes, a BMI of ≥ 25 kg/m2 (≥ 23 kg/m2 for Asians), English proficiency, and smartphone users. This U.S. study is conducted at Johns Hopkins Medicine in Baltimore, MD, and Reading Hospital (Tower Health) in Reading, PA. DISCUSSION: Prediabetes is a significant public health issue, necessitating scalable interventions for the millions affected. Our pragmatic clinical trial is unique in directly comparing a fully automated AI-powered approach without direct human coach interaction. If proven effective, it could be a scalable, cost-effective strategy. This trial will offer vital insights into both AI and human coach-based behavioral change strategies in real-world clinical settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05056376. Registered on September 24, 2021, https://clinicaltrials.gov/study/NCT05056376.

Cancer care partners' behavioral intention to use autonomy enhancing communication skills during accompanied visits after online skill training.

OBJECTIVE: The study objective is to evaluate an adaptation of the LEAPS skill framework for cancer care partners (CPs) focusing on autonomy enhancing skills and assessed by strong behavioral intention (SBI) to use these skills METHOD: Cancer CPs were recruited through public platforms to view and rate 4 LEAPS cancer-specific narratives and 52 skill demonstration videos, indicate SBI to use demonstrated skills and provide information on skill-related measures. RESULTS: Half of CPs expressed SBI to use an average of 6.5 of 13 LEAPS skills which did not vary by LEAPS communication domains or examples used to demonstrate skills. Significant predictors of SBI include positive ratings of program narratives and past use of LEAPS-related behaviors in the communication domain of shared decision making (SDM). CONCLUSION: CPs indicated SBIs to use multiple autonomy enhancing skills and positively rated program videos after exposure to the brief LEAPS training program. PRACTICE IMPLICATIONS: The brevity of the LEAPS training videos make it possible for users to view an individual cancer-specific narrative and 13 skill demonstrations in roughly 6 min. This ultra-brief training can benefit care partners and the patients they accompany by increasing the likelihood that autonomy enhancing skills are used during accompanied visits.

Factors Associated With Circulating Sex Hormones in Men : Individual Participant Data Meta-analyses.

BACKGROUND: Various factors modulate circulating testosterone in men, affecting interpretation of testosterone measurements. PURPOSE: To clarify factors associated with variations in sex hormone concentrations. DATA SOURCES: Systematic literature searches (to July 2019). STUDY SELECTION: Prospective cohort studies of community-dwelling men with total testosterone measured using mass spectrometry. DATA EXTRACTION: Individual participant data (IPD) (9 studies; n = 21 074) and aggregate data (2 studies; n = 4075). Sociodemographic, lifestyle, and health factors and concentrations of total testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone, and estradiol were extracted. DATA SYNTHESIS: Two-stage random-effects IPD meta-analyses found a nonlinear association of testosterone with age, with negligible change among men aged 17 to 70 years (change per SD increase about the midpoint, -0.27 nmol/L [-7.8 ng/dL] [CI, -0.71 to 0.18 nmol/L {-20.5 to 5.2 ng/dL}]) and decreasing testosterone levels with age for men older than 70 years (-1.55 nmol/L [-44.7 ng/dL] [CI, -2.05 to -1.06 nmol/L {-59.1 to -30.6 ng/dL}]). Testosterone was inversely associated with body mass index (BMI) (change per SD increase, -2.42 nmol/L [-69.7 ng/dL] [CI, -2.70 to -2.13 nmol/L {-77.8 to -61.4 ng/dL}]). Testosterone concentrations were lower for men who were married (mean difference, -0.57 nmol/L [-16.4 ng/dL] [CI, -0.89 to -0.26 nmol/L {-25.6 to -7.5 ng/dL}]); undertook at most 75 minutes of vigorous physical activity per week (-0.51 nmol/L [-14.7 ng/dL] [CI, -0.90 to -0.13 nmol/L {-25.9 to -3.7 ng/dL}]); were former smokers (-0.34 nmol/L [-9.8 ng/dL] [CI, -0.55 to -0.12 nmol/L {-15.9 to -3.5 ng/dL}]); or had hypertension (-0.53 nmol/L [-15.3 ng/dL] [CI, -0.82 to -0.24 nmol/L {-23.6 to -6.9 ng/dL}]), cardiovascular disease (-0.35 nmol/L [-10.1 ng/dL] [CI, -0.55 to -0.15 nmol/L {-15.9 to -4.3 ng/dL}]), cancer (-1.39 nmol/L [-40.1 ng/dL] [CI, -1.79 to -0.99 nmol/L {-51.6 to -28.5 ng/dL}]), or diabetes (-1.43 nmol/L [-41.2 ng/dL] [CI, -1.65 to -1.22 nmol/L {-47.6 to -35.2 ng/dL}]). Sex hormone-binding globulin was directly associated with age and inversely associated with BMI. Luteinizing hormone was directly associated with age in men older than 70 years. LIMITATION: Cross-sectional analysis, heterogeneity between studies and in timing of blood sampling, and imputation for missing data. CONCLUSION: Multiple factors are associated with variation in male testosterone, SHBG, and LH concentrations. Reduced testosterone and increased LH concentrations may indicate impaired testicular function after age 70 years. Interpretation of individual testosterone measurements should account particularly for age older than 70 years, obesity, diabetes, and cancer. PRIMARY FUNDING SOURCE: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

Leflutrozole in male obesity-associated hypogonadotropic hypogonadism: Ph 2b double-blind randomised controlled trial.

OBJECTIVE: Assessment of the efficacy and safety/tolerability of the aromatase inhibitor leflutrozole to normalise testosterone in Obesity-associated Hypogonadotropic Hypogonadism (OHH). DESIGN: Placebo-controlled, double-blind, RCT, in 70 sites in Europe/USA. METHODS: Patient inclusion criteria: men with BMI of 30-50 kg/m2, morning total testosterone (TT) < 10.41 nmol/L, and two androgen deficiency symptoms (at least one of sexual dysfunction). Patients randomised to weekly leflutrozole (0.1/0.3/1.0 mg) or placebo for 24 weeks. Primary endpoint: normalisation of TT levels in ≥75% of patients after 24 weeks. Secondary endpoints (included): time to TT normalisation and change in LH/FSH. Safety was assessed through adverse events and laboratory monitoring. RESULTS AND CONCLUSIONS: Of 2103 screened, 271 were randomised, 81 discontinued. Demographic characteristics were similar across groups. Mean BMI was 38.1 kg/m2 and TT 7.97 nmol/L. The primary endpoint was achieved in all leflutrozole-treated groups by 24 weeks with a dose-tiered response; mean TT 15.89; 17.78; 20.35 nmol/L, for leflutrozole 0.1 mg, 0.3 mg, and 1.0 mg groups respectively, vs 8.04 nmol/L for placebo. LH/FSH significantly increased in leflutrozole vs placebo groups. No improvements in body composition or sexual dysfunction were observed. Semen volume/total motile sperm count improved with leflutrozole vs placebo. Treatment-emergent adverse events, more common in leflutrozole-treated groups included, raised haematocrit, hypertension, increased PSA, and headache. Some reduction in lumbar bone density was observed with leflutrozole (mean -1.24%, -1.30%, -2.09%) and 0.66% for 0.1 mg, 0.3 mg, 1.0 mg, and placebo, respectively, without change at the hip. This RCT of leflutrozole in OHH demonstrated normalisation of TT in obese men. FSH/LH and semen parameter changes support that leflutrozole may preserve/improve testicular function. CLINICAL TRIAL REGISTRATION NUMBER: NCT02730169.

Androgens and Selective Androgen Receptor Modulators to Treat Functional Limitations Associated With Aging and Chronic Disease.

Testosterone, many steroidal androgens, and nonsteroidal ligands that bind to androgen receptor and exert tissue-specific transcriptional activity (selective androgen receptor modulators [SARMs]) are being developed as function-promoting therapies to treat functional limitations associated with aging and chronic diseases. This narrative review describes preclinical studies, mechanisms, and randomized trials of testosterone, other androgens, and nonsteroidal SARMs. Sex differences in muscle mass and strength and empiric use of anabolic steroids by athletes to increase muscularity and athletic performance provide supportive evidence of testosterone's anabolic effects. In randomized trials, testosterone treatment increases lean body mass, muscle strength, leg power, aerobic capacity, and self-reported mobility. These anabolic effects have been reported in healthy men, hypogonadal men, older men with mobility limitation and chronic diseases, menopausal women, and HIV-infected women with weight loss. Testosterone has not consistently improved walking speed. Testosterone treatment increases volumetric and areal bone mineral density, and estimated bone strength; improves sexual desire, erectile function, and sexual activity; modestly improves depressive symptoms; and corrects unexplained anemia in older men with low testosterone levels. Prior studies have not been of sufficient size or duration to determine testosterone's cardiovascular and prostate safety. The efficacy of testosterone in reducing physical limitations, fractures, falls, progression to diabetes, and correcting late-onset persistent depressive disorder remains to be established. Strategies to translate androgen-induced muscle mass and strength gains into functional improvements are needed. Future studies should evaluate the efficacy of combined administration of testosterone (or a SARM) plus multidimensional functional exercise to induce neuromuscular adaptations required for meaningful functional improvements.

Reaching Populations to Address Disparities in Cancer Care Delivery: Results From a Six-Site Initiative.

BACKGROUND: Large segments of the US population do not receive quality cancer care due to pervasive and systemic inequities, which can increase morbidity and mortality. Multicomponent, multilevel interventions can address inequities and improve care, but only if they reach communities with suboptimal access. Intervention studies often underenroll individuals from historically excluded groups. METHODS: The Alliance to Advance Patient-Centered Cancer Care includes 6 grantees across the United States who implemented unique multicomponent, multilevel intervention programs with common goals of reducing disparities, increasing engagement, and improving the quality of care for targeted populations. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework informed the evaluation efforts across sites. Each Alliance site identified their intended populations, which included underrepresented minorities (eg, Black and Latinx persons), individuals who prefer a language other than English, and rural residents. We evaluated the demographic characteristics of participants to determine program reach. RESULTS: Between 2018 and 2020, a total of 2,390 of 5,309 potentially eligible participants were enrolled across the 6 sites. The proportion of enrolled individuals with selected characteristics included 38% (n=908) Black adults, 24% (n=574) Latinx adults, 19% (n=454) preferring a language other than English, and 30% (n=717) rural residents. The proportion of those enrolled who were the intended population was commensurate to the proportion with desired characteristics in those identified as potentially eligible. CONCLUSIONS: The grantees met or exceeded enrollments from their intended populations who have been underserved by quality cancer care into patient-centered intervention programs. Intentional application of recruitment/engagement strategies is needed to reach individuals from historically underserved communities.

Treatment patterns and unmet needs in adults with classic congenital adrenal hyperplasia: A modified Delphi consensus study.

Background: Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a rare autosomal recessive condition characterized by cortisol deficiency and excess androgen production. The current standard of care is glucocorticoid (GC) therapy, and sometimes mineralocorticoids, to replace endogenous cortisol deficiency; however, supraphysiologic GC doses are usually needed to reduce excess androgen production. Monitoring/titrating GC treatment remains a major challenge, and there is no agreement on assessment of treatment adequacy. This study surveyed expert opinions on current treatment practices and unmet needs in adults with classic CAH. Methods: A modified two-round Delphi process with adult endocrinologists was conducted via online questionnaire. Survey questions were organized into three categories: practice characteristics/CAH experience, GC management, and unmet needs/complications. Anonymized aggregate data from Round 1 were provided as feedback for Round 2. Responses from both rounds were analyzed using descriptive statistics. Consensus was defined a priori as: full consensus (100%, n=9/9); near consensus (78% to <100%, n=7/9 or 8/9); no consensus (<78%, n<7/9). Results: The same nine panelists participated in both survey rounds; five (56%) were based in North America and four (44%) in Europe. Most panelists (78%) used hydrocortisone in the majority of patients, but two (22%) preferred prednisone/prednisolone. Panelists agreed (89%) that adequate control is best evaluated using a balance of clinical presentation and androgen/precursor laboratory values; no consensus was reached on optimal timing of collecting samples for androgen testing or laboratory values indicating good control. Despite lack of consensus on many aspects of CAH management, panelists agreed on the importance of many disease- and GC-related complications, and that there is a large unmet need for new treatments. With currently available treatments, panelists reported that 46% of classic CAH patients did not have optimized androgen levels, regardless of GC dose. Conclusions: The limited areas of consensus obtained in this study reflect the variability in treatment practices for adults with classic CAH, even among clinicians with expertise in treating this population. However, all panelists agreed on the need for new treatments for classic CAH and the importance of many disease- and GC-related complications, which are difficult to manage with currently available treatments.

Improving cancer care for underserved populations in an academic and community practice setting: protocol for a community health worker pilot navigation programme.

INTRODUCTION: Delaying cancer treatment following diagnosis impacts health outcomes, including increasing patient distress and odds of mortality. Interventions to promote timely healthcare engagement may decrease patient-reported stress and improve quality of life. Community health workers (CHWs) represent an enabling resource for reducing delays in attending initial oncology treatment visits. As part of an ongoing programme evaluation coordinated by the Merck Foundation, we will implement a pilot navigation programme comprising CHW-conducted needs assessments for supporting patients and their caregivers. We aim to investigate (1) the programme's influence on patients' healthcare utilisation within the period between their first diagnosis and initial treatment visit and (2) the logistic feasibility and acceptability of programme implementation. METHODS AND ANALYSIS: We will employ a hybrid implementation design to introduce the CHW navigation programme at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. CHW team members will use a consecutive sampling approach. Participants will complete the Problem-Checklist, Chronic Illness Distress Scale and the Satisfaction with Life Domains instruments. CHWs will provide tailored guidance by sharing information available on the Johns Hopkins Electronic Resource databases. The investigators will evaluate patients' time to initial oncology treatment and healthcare utilisation by reviewing electronic medical records at 3 and 6 months postintervention. Bivariate analyses will be completed to evaluate the relationships between receiving the programme and all outcome measures. ETHICS AND DISSEMINATION: This study's protocol was approved by the Johns Hopkins School of Medicine's institutional review board (IRB00160610). Informed consent will be obtained by phone by the CHW navigator. Dissemination planning is ongoing through regular meetings between members of the investigator team and public members of two community advisory groups. Study plans include collaborating with other experts from the Johns Hopkins Institute for Clinical and Translational Research and the Johns Hopkins Center for Health Equity for ideating dissemination strategies.

Effects of Erectile Dysfunction Drugs Use on T-cells and Immune Markers on Men Who Have Sex with Men.

Objective: Examine prospective relationships between erectile dysfunction (ED) drugs EDand CD4 and CD8 T-cells, and immune markers among men who have sex with men (MSM). Methods: Data from Multicenter AIDS Cohort Study, an observational prospective cohort study, with semi-annual follow-ups conducted in four U.S. centers from 1998 onwards was used. Marginal structural models using g-computation was fitted to estimate the mean differences for the effects of self-reported ED drug use on CD4 and CD8 T-cell outcomes and immune biomarkers. Results: Total of 1,391 men with HIV (MWH) and 307 men without HIV (MWOH) was included. Baseline mean CD4 cell count among MWH and MWOH was 499.9 cells/µL and 966.7 cells/µL, respectively. At baseline, 41.8% of MWH were virally suppressed. ED drug users reported a mean of 44.4 months of exposure to ED drugs. ED drug use was associated with increased CD4 cell outcomes among MWH but not MWOH. Mean differences in CD4 cell counts after 1 year of ED drug use was 57.6 cells/µL and increased to 117.7 after 10 years among MWH. CD8 counts were higher in ED drug users among MWH over 10 years than non-users; no consistent differences were found among MWOH. ED drug use appeared to reduce immune marker levels, such as IL-6 and increase markers, such as IL-10. We observed similar effects of ED drug use on biomarker levels among MWOH. Conclusion: Long-term use of ED drugs do not adversely affect immune function among MWH or MWOH. Future studies on the relationships between different types of ED drugs and effects on T-cell subtypes are warranted.

An Individualized Approach to Managing Testosterone Therapy in the Primary Care Setting.

The incidence of testosterone deficiency and the use of testosterone therapy have increased in recent years, and currently the majority of testosterone prescriptions in the United States and Canada are written by primary care physicians. Meanwhile, the range of available testosterone therapy formulations has widened to include buccal tablets, intramuscular injections, transdermal gels, intranasal gel, subcutaneous injections, oral capsules, and subdermal pellets, each with unique pharmacokinetic and clinical characteristics. Despite the growing use of testosterone therapy and its overall efficacy and safety as demonstrated in clinical trials, concerns exist about the potential impact of testosterone therapy on spermatogenesis and fertility, development of prostate cancer, and risk of polycythemia and cardiovascular events. In addition, ongoing research aims to better characterize the effects of testosterone therapy in specific populations, such as patients aged 65 years and older, patients with obesity and type 2 diabetes, and transgender patients. The range of treatment options and the diversity of patients' goals, preferences, comorbidities, and risk factors necessitate an individualized approach to testosterone therapy that considers each patient's clinical needs alongside the distinct features of different testosterone formulations.

Prostate Cancer in Male-to-Female Transgender Individuals: Histopathologic Findings and Association With Gender-affirming Hormonal Therapy.

Male-to-female (MtF) transgender individuals are at risk for prostate cancer, although guidelines for screening and management in this population are not well established. We describe a series of 9 MtF transgender patients who underwent prostate tissue sampling and highlight histopathologic features and challenges related to pathologic interpretation of prostate tissue in this patient population. Seven of 9 total patients were diagnosed with prostate cancer and all had elevated prostate-specific antigen at the time of diagnosis. Three of the 7 patients diagnosed with prostate cancer had received different types of hormone therapy for gender affirmation before the diagnosis of prostate cancer, and in all 3 of these patients, there was histologic evidence of hormone therapy effect in both benign prostate tissue and/or the adenocarcinoma. The 2 patients with benign prostate tissue underwent transurethral resection for lower urinary tract symptoms and were previously on hormone therapy for gender affirmation. Both of these specimens showed diffuse glandular atrophy and basal cell hyperplasia, indicative of hormone therapy effect on benign prostatic tissue. In the patients diagnosed with prostate cancer, a spectrum of grades was observed, ranging from Grade Group 1 to Grade Group 5. Four patients underwent radical prostatectomy, with 2 cases showing extraprostatic extension and Grade Group 5 prostatic adenocarcinoma, and 2 showing Grade Group 2 prostatic adenocarcinoma. Three of the 4 patients who underwent radical prostatectomy had received gender-affirming hormone therapy before surgery, and all 3 of these specimens showed hormone therapy effect in non-neoplastic prostate tissue and focal hormone therapy effect in prostatic adenocarcinoma. The presence of areas of viable carcinoma without hormone therapy effect enabled the assignment of a Gleason score and Grade Group in these 3 cases. Hormone therapy administered for gender identity affirmation induces histopathologic changes to both benign prostate tissue (nonkeratinizing squamous metaplasia, diffuse atrophy, basal cell hyperplasia, and stromal dominance with decreased numbers of glands) and prostatic adenocarcinoma (nuclear pyknosis, atrophy, cytoplasmic vacuolization, and architectural patterns that would qualify for Gleason 4 and 5 in the absence of hormone therapy effect) that have been traditionally seen in cis-male prostate cancer patients receiving hormone therapy. In the absence of hormone therapy, the morphology of prostatic adenocarcinoma in transgender patients shows classic morphologic features similar to those seen in cis-male patients not on hormone therapy. Prostate cancer with hormone therapy effect may not only be histologically quite subtle and may be overlooked if not suspected, but also should not be assigned a Gleason score because the Gleason score would substantially overstate its biologic potential. Therefore, similar to cis-male patients who have received androgen deprivation therapy for prostate cancer, transgender patients on hormone therapy for gender affirmation may be at risk for both underrecognition and over-grading of prostate cancer, particularly if the pathologist is not aware of the clinical history.