News Release

Cross-sex hormone therapy raises risk for vascular events in transgender women

Peer-Reviewed Publication

American College of Physicians

Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information.

1. Cross-sex hormone therapy raises risk for vascular events in transgender women


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Cross-sex hormone therapy may increase the risk for certain vascular events among transgender women. According to the study authors, these risks need to be weighed against the important benefits of gender-affirming treatment. The findings are published in Annals of Internal Medicine.

A person whose gender identity differs from their sex assigned at birth is transgender. A specific area of concern in transgender health is the risk for acute cardiovascular events, including venous thromboembolism, ischemic stroke, and myocardial infarction, which might plausibly be related to hormone therapy, but evidence has been sparse and inconsistent.

Researchers from Emory University and Kaiser Permanente studied electronic medical records for patients enrolled at Kaiser Permanente sites in Georgia and northern and southern California to compare acute cardiovascular event incidence rates in a large cohort of transgender persons with rates observed in age-, race-, site-, and membership-matched cisgender men and women. They found that transgender women (n = 2,842) had a higher incidence of venous thromboembolism compared to cisgender men (n = 48,686) and cisgender women (n = 48,755). Incidences of ischemic stroke and myocardial infarction were similar to those found in cisgender men, but higher than rates observed in cisgender women. Among transgender women who initiated hormone therapy at Kaiser Permanente, pronounced increases in risk for venous thromboembolism and ischemic stroke were observed after approximately 2 to 6 years of follow-up. Evidence was insufficient to draw conclusions about risk for transgender men.

According to the authors, the data on hormone replacement therapy in postmenopausal cisgender women are probably not generalizable to transgender women. Their study represents an early phase of this research and more research is needed to better understand the roles of specific formulations, doses, drug combinations and routes of administration.

Media contact: For an embargoed PDF, please contact Lauren Evans at To interview the lead author, Michael Goodman, MD, MPH, please contact, Myra Oviatt at or Kelly Jordan at

2. Using HCV-infected kidneys is cost-effective, greatly reduces wait time for transplantation, and improves survival for patients already infected with HCV



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Transplanting hepatitis C (HCV)-infected kidneys to patients already infected with HCV was found to be cost-effective when patients were treated with interferon-free direct-acting antivirals following transplantation. This strategy would greatly reduce the wait time for a donated kidney and improve survival by decreasing time spent receiving dialysis. Findings of a cost-effectiveness analysis are published in Annals of Internal Medicine.

Only 3.8 percent of patients on dialysis for end stage renal disease get kidney transplants, in part due to limited organ availability. The scarcity of kidneys for transplantation and the high mortality on dialysis while awaiting transplant has led many physicians and patients to consider the transplantation of organs that may not have been considered previously, such as those from donors with HCV.

Researchers from the University of Cincinnati sought to determine if transplanting more readily available kidneys from HCV-infected donors and then treating HCV after transplantation would be more effective and more cost-effective than treating HCV while receiving dialysis but waiting longer to get an HCV-uninfected kidney. The researchers used a computer model to compare outcomes, since large-scale trials do not yet exist. They found that transplanting HCV-infected patients with HCV-infected kidneys increased quality-adjusted life expectancy and reduced costs compared with a strategy of transplanting HCV-infected patients with HCV-uninfected kidneys.

According to the authors of an accompanying editorial, these findings should inform discussions about transplantation and improve care for HCV-infected patients waiting for a kidney. The availability and effectiveness of direct-acting antiviral therapies make the authors' strategy superior to waiting, but patient-preferences and organ availability may affect treatment decisions.

Media contact: For an embargoed PDF, please contact Lauren Evans at To interview the lead author, Mark H. Eckman, MD, MS, please contact Cedric Ricks at

3. Newer and older insulin formulations offer similar glucose-lowering effect

Some regimens may be associated with lower risk for nocturnal hypoglycemia or less weight gain


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A comparison of 10 basal insulin analogues for type 2 diabetes found that newer and older regimens do not substantially differ in their glucose-lowering effects or safety profiles. Certain insulins were associated with lower risk for nocturnal hypoglycemia (Deg-100, Deg-200, and Glar-300) or less weight gain (detemir and Glar-300), which may be a consideration when choosing a therapy. Findings from a systematic evidence review and meta-analysis are published in Annals of Internal Medicine.

Guidelines suggest that patients with inadequate glucose control be treated with basal insulin therapy with oral medications. This was accomplished with intermediate-acting neutral protamine Hagedorn (NPH) insulin prior to the use of longer-acting basal insulin analogues, insulin glargine (100 U/mL) and insulin detemir. Recently, a new generation of long-acting insulin analogues were developed that aimed for a more stable and prolonged action along with minimal risk for hypoglycemia and weight gain. The comparative effectiveness and safety of these older and newer regimens has not been evaluated for patients with type 2 diabetes.

Researchers from Aristotle University of Thessaloniki, Thessalonki, Greece reviewed 39 published randomized trials to compare the efficacy and safety of 10 basal insulin analogues for adults with type 2 diabetes. They found low-quality evidence that the differences in glycemic control among the different regimens were minimal and probably lacked clinical significance. Detemir caused less weight gain than any other regimen, whereas Glar-300 had a favorable weight profile compared with Deg-100, Deg-200, Deg-3TW, Glar-100, and LY2963016. Fewer patients treated with Deg-100, Deg-200, and Glar-300 experienced nocturnal hypoglycemia compared with those treated with other basal insulin analogues.

According to the authors, these findings may help inform decisions about insulin therapy for patients with type 2 diabetes. In addition to short-term efficacy and safety, effects of individual drugs on long-term cardiovascular outcomes and cost-effectiveness data should also be considered.

Media contact: For an embargoed PDF, please contact Lauren Evans at To interview the lead author, Apostolos Tsapas, MD, PhD, MSc, please contact him directly at

Also new in this issue:

From Colorectal Cancer Screening Guidelines to Headlines: Beware!

Michael Bretthauer, MD, PhD ; Mette Kalager, MD, PhD; David S. Weinberg, MD, MSc

Ideas and Opinions


Opioid Use Disorder, Stigma, and Transplantation: A Call to Action

Sarah E. Wakeman, MD; Keren Ladin, PhD, MSc; Tim Brennan, MD; Raymond T. Chung, MD

Ideas and Opinions



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