Evaluating the Risk of Venous Thromboembolism in Transfeminine and Gender Diverse People: A Retrospective Analysis.

OBJECTIVE: The risk of venous thromboembolism (VTE) with feminizing gender-affirming hormone therapy is an area of concern. This analysis aimed to assess whether gender-affirming hormone therapy and other potential risk factors are associated with VTE in transfeminine and gender diverse individuals. METHODS: We conducted a chart review of 2126 transfeminine and gender diverse adults receiving care within a large urban health system. The primary outcomes were the prevalence of VTE and odds ratios for the association of VTE with insurer, use of estrogen, and select comorbidities. RESULTS: A history of VTE was documented in 0.8% of the cohort. Those with a history of VTE were older (P < .001), more often self-identified as Hispanic or Black compared to White or Asian (P < .05) and were more likely to have Medicaid or Medicare (P < .01) when compared to those without a history of VTE. The prevalence of hyperlipidemia (P < .001), diabetes mellitus (P < .05), and hypercoagulable conditions (P < .001) were all greater in the positive VTE group. Hyperlipidemia (P < .001), diabetes mellitus (P < .05), and insurer (P < .05) were associated with increased odds of VTE in univariate analyses. None of the exposure variables analyzed were associated with VTE when controlling for age, race, and the number of comorbidities. CONCLUSIONS: The prevalence of VTE in our cohort was lower than previously observed. VTE was not associated with any one risk factor, including estrogen use, when controlling for age, race, and the number of comorbidities. Those of advanced age and those with multiple cardiometabolic comorbidities may benefit from increased surveillance and mitigation of modifiable risk factors.

Erythrocytosis Is Rare With Exogenous Testosterone in Gender-Affirming Hormone Therapy.

CONTEXT: Studies have found a variable incidence of erythrocytosis among people using testosterone as part of gender-affirming hormone therapy (GAHT). OBJECTIVE: To examine the effect of using exogenous testosterone as GAHT on hematocrit in a large North American cohort. METHODS: We conducted a cross-sectional analysis of testosterone and hematocrit laboratory values in 6670 patients who were prescribed testosterone through Plume, a national provider of GAHT. The prevalence of erythrocytosis, the mean hematocrit at predetermined testosterone thresholds and with varying routes of testosterone administration were assessed. RESULTS: Among 6670 individuals, 560 (8.4%) had a hematocrit ≥50%, 182 ≥ 52% (2.7%), and 60 ≥ 54% (0.9%). There was significant variation (P < .001) in hematocrit between different clinically relevant testosterone thresholds (T < 50 vs T 50-299 vs T 300-999 vs T ≥ 1000 ng/dL) and when comparing serum testosterone in increments of 50 ng/dL within the target range for males (300-1000 ng/dL) (P < .001). Mean hematocrit ranged from 41.84% (T < 50 ng/dL) to 45.68% (T 900-949 ng/dL). Patients on intramuscular testosterone had a higher mean hematocrit than those on transdermal testosterone (44.96% vs 43.41%, P < .001). Both route of administration (P < .001) and testosterone level (P < .001) had statistically significant associations with hematocrit when controlling for each other. CONCLUSION: While the magnitude of change in hematocrit with serum level and route of administration of testosterone was statistically significant, the absolute levels were within the normal range, unlikely to be clinically meaningful. These findings, along with the low prevalence of erythrocytosis, should help allay concerns about the use of testosterone as GAHT.

CARDIOVASCULAR HEALTH MAINTENANCE IN AGING INDIVIDUALS: THE IMPLICATIONS FOR TRANSGENDER MEN AND WOMEN ON HORMONE THERAPY.

OBJECTIVE: To review screening guidelines for cardiometabolic disease in aging patients and review literature describing the effect of hormone therapy (HT) on several key cardiometabolic processes to inform providers caring for older transgender individuals. METHODS: A traditional literature review was performed using PubMed and Google Scholar databases. RESULTS: The risk of cardiovascular disease increases with age. Exogenous sex hormones may interact with hormone-dependent metabolic pathways and affect some biochemical assays, but they do not necessarily impact clinical outcomes. While long-term HT is associated with an increased risk of some adverse cardiovascular outcomes, modern treatment regimens minimize this risk. CONCLUSION: Screening for cardiometabolic derangements and risk reduction are important for all aging individuals. Currently, there is insufficient evidence to propose separate screening recommendations for transgender individuals on long-term HT. Aging transgender men and women should be monitored for cardiovascular disease in much the same way as their cisgender counterparts.

Participants with schizophrenia retain the information necessary for informed consent during clinical trials.

OBJECTIVE: Cognitive impairment is a characteristic of schizophrenia. This impairment may affect the retention of information required for ongoing knowledgeable participation in clinical trials. This study monitored retention of study-related knowledge-including assessment of therapeutic misconception-in people with stable, DSM-IV schizophrenia during participation in placebo-controlled clinical trials of adjunctive agents. Stability was defined as being on an antipsychotic with no change in medication or dose over the previous 4 weeks. METHOD: This longitudinal study assessed retention of clinical trial-related consent information. Individuals enrolling in 1 of 8 clinical trials were approached for participation. Participants came from research clinics and community mental health centers. At baseline, clinical trial consent forms were reviewed and study knowledge assessed. Participants were randomized to follow-up assessments at weeks 1, 4, and 8; weeks 4 and 8; or at week 8 only. Clinical trial consent forms were not rereviewed at any follow-up visit. RESULTS: Fifty-nine participants were enrolled; analysis included 52 participants with at least 1 follow-up visit. Study knowledge did not decrease meaningfully in any group. Therapeutic misconception was not observed in participants during the study. The group assessed most frequently demonstrated significant improvement over baseline (t44 = 3.43, P = .001). Retention of study knowledge was not related to symptoms but had a weak correlation with cognitive capacity (R = 0.28, P = .07). Performance did not differ between participants from research clinics and those from community mental health centers. CONCLUSIONS: Clinically stable people with schizophrenia enrolling in a placebo-controlled adjunctive medication study, once determined to have capacity to consent to a clinical trial, retained appropriate study knowledge for at least 8 weeks. In the absence of a specific reason to suspect a loss of decisional capacity, there appears to be no need to routinely reevaluate participants during this type of clinical trial.

Characteristics of rare disease marketing applications associated with FDA product approvals 2006-2010.

New drug and biologic product marketing applications submitted to FDA's Center for Drug Evaluation and Research (CDER) between 2006 and 2010 were analyzed to identify rare disease application characteristics associated with higher approval rates. The results show that approval rates were similar for rare and common disease applications. Larger company size, prior regulatory experience and priority review designation were associated with higher approval rates. The study findings show that rare disease product development is feasible, and increased interactions between product developers and FDA in early investigational phases can facilitate product development.