Category: Testosterone
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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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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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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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Females taking testosterone may be at increased risk of intracranial hypertension.
A case study1 of idiopathic intracranial hypertension (IIH) in a woman taking “gender-affirming” testosterone suggests that there may be a causal link between elevated testosterone and the onset and progression of IIH.
- Hornby C, Mollan SP, Mitchell J, Markey KA, Yangou A, Wright BLC, O’Reilly MW, Sinclair AJ. What Do Transgender Patients Teach Us About Idiopathic Intracranial Hypertension? Neuroophthalmology. 2017 May 10;41(6):326-329. doi: 10.1080/01658107.2017.1316744. PMID: 29238388; PMCID: PMC5706971. ↩︎
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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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“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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Testosterone therapy is associated with nearly doubled depression risk and 52% higher suicide attempt rates in men within five years.
In a 2022 study1 published in the Journal of Sexual Medicine, researchers analyzed 70.3 million electronic health records from 46 healthcare organizations to examine mental health outcomes in men using testosterone therapy. The study compared 263,579 men who used testosterone to over 17.8 million men who did not. Results showed testosterone use was independently associated with a 99% increased risk of major depressive disorder (OR 1.99, 95% CI 1.94-2.04) and a 52% increased risk of suicide attempts or intentional self-harm (OR 1.52, 95% CI 1.40-1.65) within 5 years of use. These associations remained significant even when analyzing only men with clinically diagnosed testosterone deficiency, suggesting the mental health risks persist regardless of baseline testosterone levels.
- Nackeeran, S., Patel, M. S., Nallakumar, D. T., Ory, J., Kohn, T., Deibert, C. M., Carto, C., & Ramasamy, R. (2022). Testosterone Therapy is Associated With Depression, Suicidality, and Intentional Self-Harm: Analysis of a National Federated Database. Journal of Sexual Medicine, 19(6), 933-939. PMID: 35437187. [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]
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Polycystic ovary syndrome (PCOS) is more prevalent in females seeking medical transition.
A 2025 study1 from Argentina found that 26.6% of female adults presenting for “gender-affirming hormone therapy” had polycystic ovary syndrome (PCOS) prior to starting any hormonal treatment. PCOS is a hormonal disorder characterized by irregular periods, excess male hormone levels, and cysts on the ovaries. This rate is 2-3 times higher than the 8-13% prevalence in the general female population.2
A 2024 study3 from the Cleveland Clinic similarly found 23.8% of adolescent females presenting for “gender-affirming hormone therapy” had PCOS, with higher male hormone levels, higher BMIs, and increased rates of dyslipidemia than those without PCOS.
- Calvar, C. E., Di Noto, M., Lema Villacis, M., Blanco Hirota, N., & Anticona Sayán, M. I. (2025). Prevalencia, distribución fenotípica y riesgo cardiometabólico del síndrome de ovario poliquístico en población transgénero [Prevalence, phenotype distribution and cardiometabolic risk of polycystic ovarian syndrome in transgender population]. Medicina, 85(1), 31–38. [Link] ↩︎
- March, W. A., Moore, V. M., Willson, K. J., Phillips, D. I., Norman, R. J., & Davies, M. J. (2010). The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Human reproduction, 25(2), 544-551. [Link]
↩︎ - Rangi, S. K., Rehmer, J., & Ferrando, C. A. (2024). Prevalence of polycystic ovarian syndrome in young and adolescent transmasculine patients presenting for gender-affirming care. Journal of Pediatric and Adolescent Gynecology, 37(1), 51-55. [Link] ↩︎
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Long-term testosterone use in females may induce early menopause, leading to pelvic dysfunction, increased mortality risk and many other challenges
A 2024 study by da Silva et al1. found that 94.1% of 68 trans-identified females using testosterone experienced pelvic dysfunctions typically seen in postmenopausal women, including urinary (86.7%), sexual (52.9%), and bowel (45.6%) problems. These symptoms appeared as early as age 18, with an average onset age of 28.
This early onset of menopausal-like symptoms is particularly concerning given findings from another 2024 study by Haapakoski et al.2, which demonstrated increased mortality risks associated with early menopause. The study found that women experiencing early menopause (n=5,800) were twice as likely to die from heart disease and four times more likely to die from cancer compared to those with typical menopause onset (n=23,000).
Testosterone use may induce early menopause by inhibiting ovarian function3 and decreasing estrogen production in the body4.
- da Silva, L. M. B., Freire, S. N. D., Moretti, E., & Barbosa, L. (2024). Pelvic Floor Dysfunction in Transgender Men on Gender-affirming Hormone Therapy: A Descriptive Cross-sectional Study. International Urogynecology Journal, 1-8. [Link] ↩︎
- Haapakoski, H., Silven, H., Pesonen, P., Savukoski, S., & Niinimaki, M. (2024, May). Mortality among women with POI, nationwide register based case-control study. In Endocrine Abstracts (Vol. 99). Bioscientifica. [Link] ↩︎
- Bailie, E., Maidarti, M., Hawthorn, R., Jack, S., Watson, N., Telfer, E. E., & Anderson, R. A. (2023). The ovaries of transgender men indicate effects of high dose testosterone on the primordial and early growing follicle pool. Reproduction and Fertility, 4(2). [Link] ↩︎
- Chan, K. J., Jolly, D., Liang, J. J., Weinand, J. D., & Safer, J. D. (2018). Estrogen levels do not rise with testosterone treatment for transgender men. Endocrine Practice, 24(4), 329-333. [Link] ↩︎
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Female world-class athletes largely view the inclusion of trans-identified males in female sport categories as unfair, particularly in sports that emphasize physical capacity
Among female world-class athletes, 77% opposed the inclusion of trans-identified males in female categories, citing significant fairness concerns. This opposition was especially pronounced in sports relying heavily on physical capacity, such as track and field and weightlifting. Precision sports like archery saw much lower levels of concern, with only 35.7% of athletes viewing the inclusion as unfair
Shaw et. al (2024)1 surveyed female 175 athletes, stratified into three competitive levels based on proximity to world records and level of competition: 26 world-class (Tier 5) athletes, including Olympic or World Championship finalists or those within 2% of world records; 49 elite (Tier 4) athletes, who have competed internationally or are within 7% of world records; and 100 national level (Tier 3) athletes, who have competed nationally or are within 20% of world records. Overall, 58% of these athletes supported categorizing sports based on biological sex.
- Shaw, A. L., Williams, A. G., Stebbings, G. K., Chollier, M., Harvey, A., & Heffernan, S. M. (2024). The perspective of current and retired world class, elite and national athletes on the inclusion and eligibility of transgender athletes in elite sport. Journal of Sports Sciences, 42(5), 381-391. [Link] ↩︎
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There is a significant burden of chronic pain in trans-identified individuals, with an increased risk among those receiving cross-sex hormones
A 2024 large US clinical database study1 of 98,352 trans-identified individuals (56,470 females and 41,882 males) found significantly higher rates of chronic pain compared to the general population. Of particular concern, those receiving cross-sex hormones showed even higher risks – females on testosterone had a 20% increased hazard of chronic pain diagnosis compared to those not taking testosterone, while males on estrogen showed a 19.4% increased risk.
- Tabernacki, T., Gilbert, D., Rhodes, S., Scarberry, K., Pope, R., McNamara, M., … & Mishra, K. (2024). The burden of chronic pain in transgender and gender diverse populations: Evidence from a large US clinical database. European Journal of Pain. [Link] ↩︎
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Long term use of male sex hormones in females is deleterious to their health
The state-sponsored doping program of the German Democratic Republic (GDR) systematically administered androgens and other drugs to several thousand athletes, including minors, from 1966 onwards, leading to harmful side effects such as virilization in adolescent girls and female athletes, and other damaging effects that required medical and surgical interventions1.
Initiated in 1966, the German Democratic Republic (GDR) embarked on an extensive state-sponsored doping program. This program involved the systematic delivery of androgens and other substances to thousands of athletes, some of whom were minors. Women and adolescent girls were at the core of this program as the introduction of androgens was discovered to dramatically enhance their athletic performance. The ensuing side effects, including virilization in females, were deleterious and often so severe that they required medical and surgical responses. The program’s existence was only unveiled with the fall of the GDR in 1990, through the recovery of preserved classified documents.
- Franke, W. W., & Berendonk, B. (1997). Hormonal doping and androgenization of athletes: a secret program of the German Democratic Republic government. Clinical chemistry, 43(7), 1262-1279. [Link] ↩︎
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Long term testosterone use potentially compromises fertility and negatively affects ovarian follicle health
One study in 2023 found that long-term testosterone exposure, as seen in transgender men undergoing gender-affirming therapy, could potentially compromise fertility by negatively affecting ovarian follicle growth, health, and DNA integrity.
In 2023, a study by Bailie et al1. explored the effects of long-term testosterone exposure on ovarian follicles in transgender men receiving gender-affirming endocrine therapy. The research indicated that testosterone was linked with decreased follicle growth activation, poor follicle health, and increased DNA damage, suggesting possible impacts on fertility. Further, these negative effects were intensified following six days of in vitro culture. These findings may have crucial implications for reproductive health and fertility considerations among transgender men receiving testosterone as part of their gender-affirming therapy.
- Bailie, E., Maidarti, M., Hawthorn, R., Jack, S., Watson, N., Telfer, E. E., & Anderson, R. A. (2023). The ovaries of transgender men indicate effects of high dose testosterone on the primordial and early growing follicle pool. Reproduction and Fertility, 4(2). [Link] ↩︎
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Long term use of anabolic-androgenic steroids (synthetic testosterone) is associated with brain ageing and a decline in cognitive processing
One study suggests that long-term use of anabolic-androgenic steroids (AAS) may cause accelerated brain ageing in certain regions, which could lead to cognitive abnormalities.
A 2021 study by Bjørnebekk et al1. aimed to investigate the effects of long-term anabolic-androgenic steroid (AAS) use on brain ageing. The study included 229 male participants, 130 of whom were long-term AAS users and 99 were non-users. The participants underwent T1-weighted magnetic resonance imaging (MRI) scans to assess brain ageing. The results showed that long-term AAS use is associated with accentuated brain ageing in certain regions, particularly the frontal and cingulate regions. The study highlights the need for further research on the long-term effects of AAS use on brain health and cognition.
- Bjørnebekk, A., Kaufmann, T., Hauger, L. E., Klonteig, S., Hullstein, I. R., & Westlye, L. T. (2021). Long-term anabolic–androgenic steroid use is associated with deviant brain ageing. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 6(5), 579-589. [Link] ↩︎