Category: Estrogen
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All-cause mortality is higher for males taking estrogen than for men in general.
A retrospective cohort study1 of patients at an Amsterdam gender clinic found that all-cause mortality increased within a few years of beginning estrogen treatment and continued to increase over time. Men taking estrogen had an overall Standard Mortality Ratio (SMR) of 1.8 compared to men in general. The major causes of death included cardiovascular disease (21%), cancer (32%), infection-related disease (5%), and suicide (7.5%).
- de Blok CJ, Wiepjes CM, van Velzen DM, Staphorsius AS, Nota NM, Gooren LJ, Kreukels BP, den Heijer M. Mortality trends over five decades in adult transgender people receiving hormone treatment: a report from the Amsterdam cohort of gender dysphoria. Lancet Diabetes and Endocrinology. 2021 Oct;9(10):663-670. doi: 10.1016/S2213-8587(21)00185-6. Epub 2021 Sep 2. PMID: 34481559. ↩︎
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Bone mineral density that declines during puberty blockade may not fully recover with cross-sex hormone treatment.
A cohort study1 of trans-identified people who had received puberty blockers and long-term cross sex hormones found that bone mineral density z-scores (which compare the patient with age- and sex-typical values) fell during puberty blockade, and did not fully recover following over a decade of cross-sex hormone treatment. This was especially the case for the lumbar spine of males receiving estrogen.
It is also notable that, of the original 143 eligible participants, only 75 completed this research. Of those who left the cohort, 6 (4%) had discontinued cross-sex hormone treatment and 27 (19%) could not be reached. These figures are consistent with high loss to follow up in other studies of so-called “gender-affirming care.”
- van der Loos MATC, Vlot MC, Klink DT, Hannema SE, den Heijer M, Wiepjes CM. Bone Mineral Density in Transgender Adolescents Treated With Puberty Suppression and Subsequent Gender-Affirming Hormones. JAMA Pediatrics. 2023 Dec 1;177(12):1332-1341. doi: 10.1001/jamapediatrics.2023.4588. PMID: 37902760; PMCID: PMC10616766. ↩︎
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Men taking exogenous estrogen may be at higher risk of branch retinal vein occlusion.
In a case study1 of a man taking “gender-affirming” estrogen, a plausible causal link was suggested between exogenous estrogen and branch retinal vein occlusion (BRVO), based chiefly on existing established links between estrogen and cardiovascular risk. The study also suggests that trans-identified patients may be unwilling to stop using estrogen even when experiencing BRVO.
- Andzembe V, Miere A, Zambrowski O, Glacet-Bernard A, Souied EH. Branch retinal vein occlusion secondary to hormone replacement therapy in a transgender woman. J Fr Ophtalmol. 2023 Feb;46(2):148-151. doi: 10.1016/j.jfo.2022.07.024. Epub 2023 Jan 4. PMID: 36609071. ↩︎
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Males taking estrogen may be at risk of keratoconus.
A case study1 of a 28 year old man taking “gender-affirming” estrogen suggested that such treatment may accelerate the progression of keratoconus.
- Carli M. Deitel, Kevin H. Chen, Ian C. Uber, Possible association of keratoconus progression with gender-affirming hormone therapy: A case report, American Journal of Ophthalmology Case Reports, Volume 30, 2023, 101850, ISSN 2451-9936, https://doi.org/10.1016/j.ajoc.2023.101850. ↩︎
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People taking cross-sex hormones may be at risk of certain ocular problems.
A small study1 of patients at one ophthalmology clinic found that female patients taking testosterone seemed to be at risk of idiopathic intracranial hypertension (IIH), while male patients taking estrogen were more likely to experience chorioretinal conditions (chorioretinitis and central serious chorioretinopathy.) Causality could not be demonstrated and prevalence could not be estimated.
- Nieves-Ríos C, Pulido JS, Thornton S, Dunn JP, Procopio RA, Oliver AL, Lee D, Edwards R, Sergott RC, Moster ML. Instances of ocular findings in transgender patients undergoing hormonal therapy. American Journal of Ophthalmology Case Reports. 2023 Nov 28;32:101965. doi: 10.1016/j.ajoc.2023.101965. PMID: 38077787; PMCID: PMC10701352. ↩︎
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Time until treatment regret emerges may be eight years or more.
An analysis1 showed that the median time to surgical regret may be as high as eight years. For cross-sex hormone treatment, the time to regret may be almost eleven years (130 months). However, the analysis points out that the lack of thorough follow up in much of the research in this field, and the lack of detailed research into the detransitioner/desister population, mean that accurate figures are very hard to discern.
- Cohn, J. The Detransition Rate Is Unknown. Archives of Sexual Behaviour 52, 1937–1952 (2023). https://doi.org/10.1007/s10508-023-02623-5 ↩︎
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Cross-sex hormone treatment is stopped within four years by up to a third of patients.
In a study1 of the medical and pharmaceutical records of spouses and children of American military personnel, only 70.2% of those who started cross-sex hormone treatment continued the treatment after four years. Rates were lower for females taking male hormones (64.4%) than for males taking female hormones (81.0%).
- Christina M Roberts, David A Klein, Terry A Adirim, Natasha A Schvey, Elizabeth Hisle-Gorman, Continuation of Gender-affirming Hormones Among Transgender Adolescents and Adults, The Journal of Clinical Endocrinology & Metabolism, Volume 107, Issue 9, September 2022, Pages e3937–e3943, https://doi.org/10.1210/clinem/dgac251 ↩︎
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Males on feminizing hormones face over double the risk of kidney stones.
A 2025 analysis1 of NIH medical records found that 10.3% of males on feminizing hormone therapy developed kidney stones, compared to 4.8% of those not on hormones. The risk was especially elevated for those on both estrogen and antiandrogens, with odds more than 2.5 times higher.
- Frangopoulos, E., Savin, Z., Gupta, K., Durbhakula, V., Gallante, B., Atallah, W. M., & Gupta, M. (2025). Increased Risk of Kidney Stones in Transgender Women and Gender-Diverse Adults on Gender-Affirming Hormone Therapy: Insights from a Large Database Study. Journal of Endourology. ↩︎
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“Gender-affirming” hormone therapy increases BMI.
A 2025 systematic review and meta-analysis1 of 29 studies (28 included in meta-analysis) involving 2,674 individuals found that “gender-affirming” hormone therapy led to statistically significant body mass index (BMI) increases. The mean age across studies ranged from 16 to 56 years, and no prior puberty suppression was reported before the initiation of GAHT. The researchers excluded studies with adolescent samples or with pubertal suppression prior to hormone therapy. Natal males receiving feminizing hormones experienced an average BMI increase of 0.55 kg/m², while natal females receiving masculinizing testosterone showed a larger average increase of 0.92 kg/m². The study authors noted these represent modest weight gains with moderate certainty of evidence, though they concluded the changes reflect expected hormonal effects rather than pathological outcomes.
- Gois, Í., Rodrigues, F. B., Pereira, M., Dias-da-Silva, M. R., & Gomes, S. M. (2025). Body mass index and body composition changes in transgender people undergoing gender-affirming hormone therapy: a systematic review and meta-analysis. Reviews in Endocrine and Metabolic Disorders, 1-17. [Link] ↩︎
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Estrogen use in trans-identified males is associated with a wide range of serious health risks—including blood clots, stroke, cancer, infertility, and cognitive decline.
A 2025 review1 summarizes wide-ranging risks tied to estrogen use in trans-identified males:
- 2.2× higher risk of blood clots (VTE)
- Up to 10× higher risk of stroke after 6 years on estrogen
- 1.8× higher all-cause mortality compared to other males
- 22.5–40.7× higher risk of breast cancer vs. male baseline
- 3× higher risk of cardiovascular death with estradiol use
- 72% increase in insulin resistance after 1 year; additional 9% in year 2
- Reduced brain volume and slower processing speed with long-term use
- Cognitive decline and elevated depression markers over time
- Only 0–24% retain sperm production after starting estrogen
- 6.6× higher incidence of multiple sclerosis
- Case reports of pancreatitis, autoimmune flare-ups, and brain tumors (meningioma)
The review emphasizes that many of these risks are under-recognized in clinical practice, raising urgent concerns about safety and informed consent.
- Schwartz, L., Lal, M., Cohn, J., Mendoza, C. D., & MacMillan, L. (2025). Emerging and accumulating safety signals for the use of estrogen among transgender women. Discover Mental Health, 5(1), 1-17. [Link] ↩︎