Category: Cross-Sex Hormones
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All-cause mortality is higher for women taking testosterone than for women in general.
A retrospective cohort study1 of patients at an Amsterdam gender clinic found that all-cause mortality increased for females receiving testosterone and continued to increase over time. Women taking testosterone had an overall Standard Mortality Ratio (SMR) of 1.8 compared to women in general. Deaths from non-natural causes were especially high.
- 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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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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Around one in six young people treated with cross sex hormones ceased treatment.
An exploratory study1 of adolescents and young adults in Canada and the US found that 16.8% of those receiving “gender affirming medical treatment” (puberty blockers and cross sex hormones) stopped “treatment” within around five years of declaring a “trans” or “non binary” identity.
Of those who discontinued treatment, 37.3% did so for health reasons. 32% ended treatment due to a change in gender identity. 12% were persuaded by health professionals or a partner to explore different ways of approaching their gender dysphoria.
Stopping treatment was associated with having a “non binary” identity. Both continuing and non-continuing cohorts had a mean age of 16.1 when “coming out”, but those discontinuing treatment were slightly older (22.1 vs. 20.9.)
- MacKinnon KR, Jeyabalan T, Strang JF, Delgado-Ron JA, Lam JSH, Gould WA, Cooper A, Salway T. Discontinuation of Gender-Affirming Medical Treatments: Prevalence and Associated Features in a Nonprobabilistic Sample of Transgender and Gender-Diverse Adolescents and Young Adults in Canada and the United States. Journal of Adolescent Health. 2024 Oct;75(4):569-577. doi: 10.1016/j.jadohealth.2024.05.015. Epub 2024 Jun 28. PMID: 38944803. ↩︎
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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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94% of females taking testosterone experience pelvic floor dysfunction.
In a study1 of 68 women taking testosterone, 94.1% had some form of pelvic floor dysfunction. 86.7% had urinary symptoms. Other problems included storage symptoms (69.1%), sexual dysfunction (52.9%), anorectal symptoms (45.6%), and flatal incontinence (39.7%.)
- da Silva LMB, Freire SND, Moretti E, Barbosa L. Pelvic Floor Dysfunction in Transgender Men on Gender-affirming Hormone Therapy: A Descriptive Cross-sectional Study. International Urogynecology Journal. 2024 May;35(5):1077-1084. doi: 10.1007/s00192-024-05779-3. Epub 2024 Apr 25. PMID: 38662108. ↩︎
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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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Exogenous testosterone in females is correlated with symptoms of glaucoma.
A prospective study1 comparing twenty females taking “gender-affirming” testosterone with twenty other women and twenty men found that exogenous testosterone was associated with higher intra-ocular pressure, reduced ocular blood flow, and increased thickness of the retinal nerve fiber layer, ganglion cell complex, and macula.
- Alpogan O, Donmez EE, Balık AÖ, Vural F, Kaplan G. Effects of testosterone on intraocular pressure, thicknesses of retinal nerve fiber layer, ganglion cell complex, macula and on ocular blood flow in female-to-male transgender persons. International Ophthalmology. 2021 Nov;41(11):3651-3661. doi: 10.1007/s10792-021-01921-y. Epub 2021 Jul 8. PMID: 34240322. ↩︎
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There may be a causal link between exogenous testosterone and idiopathic intracranial hypertension (IIH.)
In a study1 of a series of cases of females taking “gender-affirming” testosterone, a plausible causal relationship was suggested between the exogenous testosterone and the precipitation of symptoms of idiopathic intracranial hypertension (IIH). Onset of IIH was between ten weeks and ten years after beginning testosterone treatment.
- Gutkind NE, Tse DT, Johnson TE, Tse BC. Idiopathic Intracranial Hypertension in Female-to-Male Transgender Patients on Exogenous Testosterone Therapy. Ophthalmic Plastic and Reconstructive Surgery. 2023 Sep-Oct 01;39(5):449-453. doi: 10.1097/IOP.0000000000002344. Epub 2023 Feb 21. PMID: 36804335; PMCID: PMC10440365. ↩︎
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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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Testosterone induces distinct cellular changes in female reproductive organs—including prostate-like tissue in the vagina, uterine atrophy, cyst-filled ovaries, and male-pattern cells in the cervix.
A 2025 study1 retrospectively reviewed histopathology slides from 20 trans-identifying females (ages 16–35) who underwent “gender-affirming” gynecologic surgery following 4–63 months of testosterone therapy (mean duration 21.7 ± 17.8 months).
Key findings included:
- 100% showed NKX3.1-positive basal keratinocytes in the cervix (a marker normally found in male prostate tissue)
- 55% and 60% of cervical samples showed transitional and prostatic-type metaplasia (cell changes resembling male urethral and prostate tissue)
- 100% and 50% of vaginal samples showed the same respective patterns
- 75% had an inactive uterine lining (endometrium)
- 55% showed ciliated cell metaplasia (development of hair-like cells typically not present)
- 65% had stromal expansion and decidua-like change (tissue patterns resembling early pregnancy)
- 70% had numerous cystic follicles in the ovaries, and 60% showed signs of follicular maturation
- One patient had ovarian endometriosis; one had a mucinous cyst adenofibroma
- Fallopian tubes had paratubal mesonephric remnants, but no hypertrophy (enlargement)
A comparison group of 25 benign hysterectomy samples from females of reproductive age showed no transitional or prostatic-type metaplasia, and only 2 cases (8%) had focal NKX3.1 positivity.
- Bakshi, N., Nanda, B., Rao, S., Badwal, S., & Dhawan, S. (2025). Spectrum of Histopathologic Findings in Transgender Men Undergoing Gender-Affirming Gynecologic Surgery Following Preoperative Androgen Therapy: A Tertiary Care Center Study. International journal of surgical pathology, 10668969251363990. Advance online publication. https://doi.org/10.1177/10668969251363990 ↩︎
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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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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] ↩︎
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Testosterone use in females triggers biological signs of kidney stress and injury within just three months.
In a 2025 study in the Journal of Clinical Investigation1, females taking testosterone for gender transition showed biological changes consistent with subclinical kidney stress and tubular injury after three months—including a 134% increase in a urinary marker linked to kidney inflammation (YKL-40) and an 8% rise in an inflammatory blood protein (TNF receptor-1). Although overall kidney filtration remained unchanged, testosterone negatively affected kidney-protective proteins and activated pathways tied to inflammation, tissue remodeling, and fibrosis. The researchers called for long-term studies in larger populations to assess potential lasting effects.
- van Eeghen, S. A., Pyle, L., Narongkiatikhun, P., Choi, Y. J., Obeid, W., Parikh, C. R., … & Nokoff, N. J. (2025). Unveiling mechanisms underlying kidney function changes during sex hormone therapy. The Journal of Clinical Investigation. [Link]
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- van Eeghen, S. A., Pyle, L., Narongkiatikhun, P., Choi, Y. J., Obeid, W., Parikh, C. R., … & Nokoff, N. J. (2025). Unveiling mechanisms underlying kidney function changes during sex hormone therapy. The Journal of Clinical Investigation. [Link]