New Study Sounds Alarm on Estrogen Risks for Natal Males

A ground-breaking new peer-reviewed study reveals extensive health risks for natal males using feminizing hormones (estrogen and/or anti-androgens). Compiling over 50 studies, this open-access review fundamentally shifts the conversation from a lack of proven benefits to clear indications of potential direct harm, demanding urgent attention.

The review documents risks across multiple systems, leading to potentially significantly shortened lifespans among men on cross-sex hormones. Some of the more prominent risks include:

• Cardiovascular Risks: A 5.1-fold increase in blood clots (VTE) after two years and a nearly 10-fold rise in stroke risk after six years, with risks escalating over time.
• Fertility Loss: Likely permanent testicular atrophy and cessation of sperm production.
• Cancer Risks: Elevated rates of testicular (potentially 26.5x higher), breast (potentially >40x higher than non-TGNB men), and thyroid cancer.
• Autoimmune Diseases: Increased incidence of lupus, rheumatoid arthritis, and systemic sclerosis.
• Cognitive & Mental Health: Brain changes, links to cognitive decline, and depression.
• Mortality: A large Dutch study found an 80% higher overall mortality risk (Standardized Mortality Ratio 1.8) compared to general population men.

These are not minor concerns; the review suggests these risks could contribute to significantly reduced lifespans. Compare the situation to historical drug withdrawals like Vioxx (when Merck paid a fine of nearly $5 billion), which was removed from the market for elevated cardiovascular risks, despite offering some proven benefits.

In stark contrast, robust evidence for benefits remains weak. Even affirming studies show no psychosocial improvement in male adolescents; indeed, a re-analysis of Turban et al. indicated that natal males on estrogen were more likely to plan or attempt suicide. This echoes writer Andrea Long Chu, who wrote in the New York Times, “I feel demonstrably worse since I started on hormones… Like many of my trans friends, I’ve watched my dysphoria balloon since I began transition… I was not suicidal before hormones. Now I often am.”

While some proponents now emphasize patient autonomy (an argument Chu also explored), an autonomy-based defense is deeply challenged by the extensive safety signals of severe, lifelong systemic harms detailed in this review. While patient autonomy is a key ethical principle, it does not supersede a clinician’s primary duty of non-maleficence (“first, do no harm”). Given the severe, lifelong risks and unproven benefits—a starkly different profile from proven and safe procedures like abortion or birth control—medical professionals cannot abdicate their responsibility by simply prescribing whatever a patient desires, just as they would not affirm a patient’s desire to eat less in severe anorexia nervosa..

This call for caution is gaining traction internationally. Recent reports, such as Hannah Barnes’ article (May 2025) detailing UK Shadow Health Secretary Wes Streeting expressing greater concern over cross-sex hormones for minors after coming across the evidence of documented harms.

Given the limited evidence for benefits versus an array of potentially life-threatening risk signals, this new review compels a critical re-evaluation of current practices.

Examine the evidence directly: read the full study here.

The research includes contributions from M. Lal of The Killarney Group Think Tank at Genspect.