Venous thromboses are well‐established complications of hormonal therapy. Thrombosis risk is seen with both hormonal contraceptive agents and with hormone replacement therapy for menopause and gender transition. Over the past several decades, large epidemiological studies have helped better define these risks.

http://www.rpthjournal.org/article/S2475037922023433/pdf

Hormonal therapies and venous thrombosis: Considerations for prevention and management

Men seem to have a higher intrinsic risk of venous thromboembolism (VTE) than women, regardless of age. To date, this difference has not been explained. By integrating state‐of‐the‐art research presented at the International Society on Thrombosis and Haemostasis Congress of 2021 with the available literature, we address potential explanations for this intriguing risk difference between men and women. We discuss the role of exogenous and endogenous sex hormones as the most important known sex‐specific determinants of VTE risk. In addition, we highlight clues on the role of sex hormones and VTE risk from clinical scenarios such as pregnancy and the polycystic ovary syndrome. Furthermore, we address new potential sex‐specific risk factors and unanswered research questions, which could provide more insight in the intrinsic risk difference between men and women, such as body height and differences in body fat distribution, leading to dysregulation of metabolism and inflammation.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/rth2.12722

Sex‐specific aspects of venous thromboembolism: What is new and what is next?

Abstract Background In studies of cellular function in cancer, researchers are increasingly able to choose from many -omics assays as functional readouts. Choosing the correct readout for a given study can be difficult, and which layer of cellular function is most suitable to capture the relevant signal remains unclear. Results We consider prediction of cancer mutation status (presence or absence) from functional -omics data as a representative problem that presents an opportunity to quantify and compare the ability of different -omics readouts to capture signals of dysregulation in cancer. From the TCGA Pan-Cancer Atlas that contains genetic alteration data, we focus on RNA sequencing, DNA methylation arrays, reverse phase protein arrays (RPPA), microRNA, and somatic mutational signatures as -omics readouts. Across a collection of genes recurrently mutated in cancer, RNA sequencing tends to be the most effective predictor of mutation state. We find that one or more other data types for many of the genes are approximately equally effective predictors. Performance is more variable between mutations than that between data types for the same mutation, and there is little difference between the top data types. We also find that combining data types into a single multi-omics model provides little or no improvement in predictive ability over the best individual data type. Conclusions Based on our results, for the design of studies focused on the functional outcomes of cancer mutations, there are often multiple -omics types that can serve as effective readouts, although gene expression seems to be a reasonable default option. 

/pdf/widespread-redundancy-in-omics-profiles-of-cancer-mutation-2u0s25nb.pdf

Widespread redundancy in -omics profiles of cancer mutation states

JAK2 unmutated or non‐polycythemia vera (PV) erythrocytosis encompasses a heterogenous spectrum of hereditary and acquired entities.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ajh.26920

JAK2 unmutated erythrocytosis: 2023 Update on diagnosis and management

Purpose: The goal of this study was to evaluate contributing factors and management strategies for polycythemia in transmasculine patients on testosterone therapy. Methods: A retrospective analysis of medical records was performed for transmasculine patients on testosterone for at least 12 months. Data collected from each patient included age, body mass index (BMI), nicotine dependence, pulmonary disease status, obstructive sleep apnea (OSA) status, oophorectomy status, and testosterone route of administration. For patients who developed polycythemia, polycythemia management strategy data were collected. Results: Five-hundred-eleven patients were evaluated and 113 (22%) experienced an episode of polycythemia. Within the polycythemia group, 77% of patients were younger than age 40, 56% had a BMI >30.0, 44% had current or former nicotine dependence, 12% had a pulmonary disease, 12% had OSA, and 47% had received an oophorectomy. The polycythemia group had a significantly higher average age, BMI, and dose of testosterone, and also had a higher proportion of patients with OSA and an oophorectomy. Conclusion: These results revealed that polycythemia is a common side effect for transmasculine patients on testosterone. Importantly, previous oophorectomy may be associated with polycythemia which appears to be a novel finding. This finding requires further research but provides the potential to be an important screening consideration for transmasculine patients after oophorectomy. Polycythemia will continue to be a major concern for patients on testosterone therapy, and this study provided important information for clinical practice and future research that will lead to improved outcomes.

Incidence, Contributing Factors, and Implications for Clinical Management of Polycythemia in Transmasculine Patients on Testosterone.

Erythrocytosis and thromboembolic events in transgender individuals receiving gender-affirming testosterone.

Genes implicated in tumorigenesis often exhibit diverse sets of genomic variants in the tumor cohorts within which they are frequently mutated. For many genes, neither the transcriptomic effects of these variants nor their relationship to one another in cancer processes have been well-characterized. We sought to identify the downstream expression effects of these mutations and to determine whether this heterogeneity at the genomic level is reflected in a corresponding heterogeneity at the transcriptomic level. By applying a novel hierarchical framework for organizing the mutations present in a cohort along with machine learning pipelines trained on samples’ expression profiles we systematically interrogated the signatures associated with combinations of mutations recurrent in cancer. This allowed us to catalogue the mutations with discernible downstream expression effects across a number of tumor cohorts as well as to uncover and characterize over a hundred cases where subsets of a gene’s mutations are clearly divergent in their function from the remaining mutations of the gene. These findings successfully replicated across a number of disease contexts and were found to have clear implications for the delineation of cancer processes and for clinical decisions. The results of cataloguing the downstream effects of mutation subgroupings across cancer cohorts underline the importance of incorporating the diversity present within oncogenes in models designed to capture the downstream effects of their mutations.

/pdf/systematic-interrogation-of-mutation-groupings-reveals-49d3fhey1k.pdf

Hannah D. Holly

Papers

Erythrocytosis and thromboembolic events in transgender individuals receiving gender-affirming testosterone.

Systematic interrogation of mutation groupings reveals divergent downstream expression programs within key cancer genes