“the overall mortality risk of [trans-identifying men] . . . was higher compared to men in the general population . . . and even higher compared to women.” Leading causes of death included heart disease, cancer, and suicide. An earlier study found a 51 percent higher mortality rate in trans-identifying males than the general population. Notably, current estrogen use, rather than past use, was linked to these increased risks, suggesting long-term exposure to feminizing hormones may amplify health risks over time.
And that's not all.
Beyond these headline findings, the paper outlines several additional risks. Autoimmune diseases such as lupus and systemic sclerosis have occasionally appeared or worsened following the initiation of estrogen therapy. One patient with a skin-limited autoimmune condition developed life-threatening kidney complications after starting hormones. At the population level, males with gender identity disorders have been found to have a more than sixfold increased risk of developing multiple sclerosis—raising the possibility that estrogen may act as a trigger for autoimmune responses in some individuals.
Estrogen also appears to affect metabolism. Hormone therapy has been associated with increased fat mass, muscle loss, and reduced insulin sensitivity—an early warning sign for diabetes. In one study, insulin resistance rose by more than 80 percent over two years of use. Elevated triglycerides—a type of fat in the blood—have been linked to serious complications in trans-identifying males, including pancreatitis and gallstones.
The authors also review cancer risks. Trans-identifying males on estrogen are significantly more likely to develop breast cancer than non-trans-identifying men. One cited analysis estimated the risk to be 22 to 40 times higher. While breast cancer remains rare in men overall, such increases are noteworthy.
The paper also highlights elevated rates of thyroid and testicular cancers among trans-identifying males on estrogen. Some studies suggest a potential link between testicular cancer and long-term use of estrogen or testosterone blockers. Public drug safety databases in the U.S. and France reflect similar concerns, listing tumors, cardiovascular complications, and brain tumors—such as meningiomas—among the most frequently reported adverse events.
One especially unsettling section explores how estrogen may affect the male brain. A few small brain-imaging studies found that several months of estrogen use led to “an increase in ventricular volume and a decrease in brain volume.” Studies in male rats showed similar effects: estrogen and testosterone blockers reduced brain volume and altered brain chemistry. The authors suggest these changes may result from disruptions in how water is regulated in brain cells—potentially mimicking patterns seen in degenerative diseases.
The paper also notes that levels of BDNF—a brain chemical critical for mood and memory—tend to decline in patients on cross-sex hormones. Low BDNF is associated with depression and shrinkage of the hippocampus, a brain region essential for memory. Taken together, these findings raise the possibility that estrogen may produce lasting changes in male brain structure and function.
Not to worry. It's all part of "gender-affirming care".
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