A peer-reviewed review article published in Discover Mental Health in 2025 examines emerging and accumulating safety signals associated with the use of exogenous estrogen, often combined with anti-androgens, in trans-identified men.
The authors review a wide range of existing studies, including systematic reviews, cohort studies, case series, and pharmacovigilance reports. while estrogen has been used in clinical practice with the stated aim of alleviating distress associated with gender dysphoria, the overall risk–benefit profile remains uncertain due to limited long-term and high-quality outcome data.
The paper highlights that recent systematic reviews have found evidence of benefit to be of low or very low certainty for many psychological and quality-of-life outcomes. In contrast, a number of physiological risks have been previously recognised, including infertility and venous thromboembolism, with additional emerging safety signals reported in the medical literature.
These emerging signals include associations between estrogen use and increased cardiovascular events, metabolic changes such as insulin resistance, possible autoimmune conditions, certain cancers, and changes observed in brain structure and neurochemical markers. The authors emphasise that many of the available studies are observational and cannot establish causality, but argue that such signals remain clinically important, particularly when interventions may be long-term or lifelong.
The review also discusses the ethical implications for informed consent, noting that reliable, up-to-date information about potential risks is necessary for patients, families, and clinicians to make balanced decisions. The authors call for improved research, including long-term follow-up studies and systematic investigation of adverse outcomes, to better inform clinical practice and safeguarding standards.
The article concludes that, given the current limitations of the evidence base and the seriousness of some reported adverse outcomes, further rigorous research is urgently needed to clarify both benefits and risks associated with estrogen use in this population.