In recent years, administering estrogen to males who identify as transgender women has become increasingly common, including among adolescents. Often paired with testosterone blockers, this treatment is marketed as part of “gender-affirming care”—a term used to describe medical interventions intended to “align” a person’s body with his or her “gender identity.” But as more young people pursue medical transition in the absence of long-term studies, concerns about safety, efficacy, and informed consent have grown more urgent.
A recent review article in Discover Mental Health, entitled “Emerging and accumulating safety signals for the use of estrogen among transgender women,” and authored by Lauren Schwartz and colleagues, tries to fill that gap. It compiles studies, case reports, and group data to spotlight a range of serious health risks—some well-known, others emerging—associated with long-term estrogen use in males.
One of the best-known risks associated with estrogen use in males is infertility. In their new review, Schwartz et al. note that while some patients retain limited sperm production, many do not—and they exhibit “testicular atrophy, hyalinization, and fibrosis,” meaning shrinkage, scarring, and tissue changes that may signal elevated cancer risk.
Cardiovascular complications are another well-documented concern. Multiple studies cited in the review report higher rates of dangerous blood clots—known as venous thromboembolism (VTE)—and strokes among trans-identifying males taking estrogen.
The paper also highlights potential cognitive risks, including memory loss and early-onset impairment.
Perhaps the most alarming finding cited in the paper is the increased risk of early death. Schwartz and colleagues reference a Dutch cohort study of patients treated at a major gender identity clinic, which found that “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.
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.
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.”
That this kind of research is only now being done—after thousands of teens have already started irreversible treatments—is troubling. That many of the safety signals are only now becoming detectable—because so many people have recently been exposed to these interventions—should be a sobering wake-up call.