Hormones

  • Puberty blockers are more than a ‘pause button’: roughly 98% of children who take them go on to take cross-sex hormones. Expand
    Puberty blockers are more than a ‘pause button’: roughly 98% of children who take them go on to take cross-sex hormones.

    A 2021 study from the UK [1] found that only 1 out of 44 children placed on puberty blockers did not continue to take cross-sex hormones.

    Similarly, a Dutch study [2] reported that only 1.9% of adolescents who started puberty suppression treatment abandoned this course and did not take cross-sex hormones.

    In fact, in a different Dutch study [3], “[n]o adolescent withdrew from puberty suppression, and all started cross‐sex hormone treatment, the first step of actual gender reassignment.”

    Puberty blockers are drugs which change young bodies in ways we have yet to understand, and may be permanent. This is an experimental treatment program: puberty blockers have never been licensed to treat children with gender dysphoria, in any country.

    REFERENCES

    [1] Carmichael, P., Butler, G., Masic, U., Cole, T. J., De Stavola, B. L., Davidson, S., Skageberg, E. M., Khadr, S., & Viner, R. M. (2021). Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK. PLOS ONE 16 (2). [Link]

    [2] Wiepjes, C.M., Nota, N.M., de Blok, C.J.M., Klaver, M., de Vries, A.L.C., Wensing-Kruger, S.A., de Jongh, R.T., Bouman, M.B., Steensma, T.D., Cohen-Kettenis, P., Gooren, L.J.G., Kreukels, B.P.C. & den Heijer, M. (2018). The Amsterdam Cohort of Gender Dysphoria Study (1972-2015): Trends in Prevalence, Treatment, and Regrets. Journal of Sexual Medicine 15 (4). [Link]

    [3] de Vries, A.L.C., Steensma, T.D., Doreleijers, T.A. & Cohen-Kettenis, P.T. (2011). Puberty suppression in adolescents with gender identity disorder: a prospective follow-up study. J Sex Med 8 (8): 2276-83. [Link]

  • There is limited evidence that medical transition leads to positive outcomes. Expand
    There is limited evidence that medical transition leads to positive outcomes.

    A number of different studies have noted the paucity of good quality evidence for transition.

    An Australian paper [1] states that most available evidence indicating positive outcomes for gender reassignment is of poor quality.

    A German study [2] “found insufficient evidence to determine the efficacy or safety of hormonal treatment approaches for transgender women in transition”, adding that “[t]his lack of studies shows a gap between current clinical practice and clinical research.”

    A British review [3] conducted by the National Institute for Health and Care Excellence (NICE) graded certainty of evidence for puberty blocker use as “very low” in every category, including impact on gender dysphoria, mental health, body image, global functioning, psychosocial functioning, cognitive functioning, bone density and adverse effects.

    A chapter [4] in an edited volume details the low evidence base for treatment pathways employed at the UK’s Gender Identity Development Service, demonstrating how negative evidence was “ignored or suppressed”.

    Finally, a systematic review [5] commissioned by the World Professional Association for Transgender Health (WPATH) to “systematically review the effect of gender-affirming hormone therapy on psychological outcomes among transgender people” noted that, in some areas, there was low quality or insufficient evidence.

    REFERENCES

    [1] D’Angelo, R. (2018). Psychiatry’s ethical involvement in gender-affirming care. Australasian Psychiatry 26 (5): 460-463. [Link]

    [2] Haupt, C., Henke, M., Kutschmar, A., Hauser, B., Baldinger, S., Saenz, S.R. & Schreiber, G. (2020). Antiandrogen or estradiol treatment or both during hormone therapy in transitioning transgender women. Cochrane Database of Systematic Reviews 11. [Link]

    [3] National Institute for Health and Care Excellence (2021). Evidence review: Gonadotrophin releasing hormone analogues for children and adolescents with gender dysphoria. National Institute for Health and Care Excellence (NICE); NHS England; NHS Improvement. [Link]

    [4] Biggs, M. (2019). The Tavistock’s Experiment with Puberty Blockers. In: Moore, M. & Brunskell-Evans, H. (eds.). Inventing Transgender Children and Young People. Cambridge Scholars Publishing. [Link]

    [5] Baker, K.E., Wilson, L.M., Sharma, R., Dukhanin, V., McArthur, K. & Robinson, K.A. (2021) Hormone Therapy, Mental Health, and Quality of Life Among Transgender People: A Systematic Review. Journal of the Endocrine Society 5 (4). [Link]

  • The chances of developing osteoporosis and cardiovascular problems increase with feminizing hormones. Expand
    The chances of developing osteoporosis and cardiovascular problems increase with feminizing hormones.

    A 2012 paper [1] found that a quarter of the male-to-female transsexuals it studied had osteoporosis at the lumbar spine and radius.

    In the same study, 6% of male-to-female transsexuals experienced a thromboembolic event (a blood clot causing obstruction), and another 6% experienced other cardiovascular problems. These effects were observed after only 11.3 years of hormone treatment on average.

    A further study [2] found that long-term bone mineral density decreases in transwomen who take cross-sex hormones in the long term.

    REFERENCES

    [1] Wierckx, K., Mueller, S., Weyers, S., Van Caenegem, E., Roef, G., Heylens, G. & T’Sjoen, G. (2012). Long-Term Evaluation of Cross-Sex Hormone Treatment in Transsexual Persons. The Journal of Sexual Medicine 9 (10): 2641-2651. [Link]

    [2] Delgado-Ruiz, R., Swanson, P., & Romanos, G. (2019). Systematic Review of the Long-Term Effects of Transgender Hormone Therapy on Bone Markers and Bone Mineral Density and Their Potential Effects in Implant Therapy. Journal of clinical medicine 8 (6): 784. [Link]

  • Medical transition puts both males and females at risk of infertility. Expand
    Medical transition puts both males and females at risk of infertility.

    A wide-ranging study [1] found that gender-related drug regimens place patients at risk of infertility:

    Suppression of puberty with gonadotropin-releasing hormone agonist analogs (GnRHa) in the pediatric transgender patient can pause the maturation of germ cells, and thus, affect fertility potential. Testosterone therapy in transgender men can suppress ovulation and alter ovarian histology, while estrogen therapy in transgender women can lead to impaired spermatogenesis and testicular atrophy. The effect of hormone therapy on fertility is potentially reversible, but the extent is unclear.

    On surgeries, the study noted that cross-sex surgery that includes hysterectomy and oophorectomy in transmen or orchiectomy in transwomen results in permanent sterility.

    REFERENCES

    [1] Cheng, P.J., Pastuszak, A.W., Myers, J.B., Goodwin, I.A. & Hotaling, J.M. (2019). Fertility concerns of the transgender patient. Transl Androl Urol. 8 (3): 209-218. [Link]

  • Long-term testosterone use in natal females can cause vaginal atrophy, which makes sex painful. Expand
    Long-term testosterone use in natal females can cause vaginal atrophy, which makes sex painful.

    A study [1] of 16 female-to-male transgender individuals concluded that long-term testosterone administration leads to vaginal atrophy (Baldassarre et al., 2013). The study noted that:

    Vaginal samples from FtM showed a loss of normal architecture of the epithelium, intermediate and superficial layers were completely lost, and glycogen content was depleted.

    Vaginal atrophy, characterized by thinning of vaginal walls and poor lubrication of vaginal tissues, leads to tearing, micro abrasions, bleeding, and painful intercourse.

    REFERENCES

    [1] Baldassarre, M., Giannone, F., Foschini, M., Battaglia, C., Busacchi, P., Venturoli, S., & Meriggiola, M. (2013). Effects of long-term high dose testosterone administration on vaginal epithelium structure and estrogen receptor-α and -β expression of young women. International Journal Of Impotence Research, 25 (5): 172-177. [Link]

  • In one study, 11% of transmen who took testosterone developed a condition called erythrocytosis, which impacts red blood cells and slows the blood flow. Expand
    In one study, 11% of transmen who took testosterone developed a condition called erythrocytosis, which impacts red blood cells and slows the blood flow.

    A study [1] of 776 transmen who took testosterone demonstrated that 11% of them developed erythrocytosis, a condition which slows the blood flow, and can lead to headaches, confusion, high blood pressure, nosebleeds, blurred vision, itching and fatigue.

    REFERENCES

    [1] Madsen, M.C., van Dijk, D. Wiepjes, C.M., Conemans, E.B., Thijs, A. & den Heijer, M. (2021). Erythrocytosis in a Large Cohort of Trans Men Using Testosterone: A Long-Term Follow-Up Study on Prevalence, Determinants, and Exposure Years. The Journal of Clinical Endocrinology & Metabolism 106 (6): 1710–1717. [Link]

  • Feminizing hormones reduce sexual function in males. Expand
    Feminizing hormones reduce sexual function in males.

    Feminizing hormonal treatments lead to a lessening drive, erectile dysfunction, and shrinking of testes and penis [1], significantly compromising sexual function.

    A Belgian doctoral thesis study [2] found that 69.7% of transwomen reported a decrease in sexual desire — while the opposite effect is found in transmen.

    REFERENCES

    [1] Levine, S. (2018). Informed Consent for Transgendered Patients. Journal Of Sex & Marital Therapy, 45(3), 218-229. [Link]

    [2] Elaut, E. (2014). Biopsychosocial factors in the sexual desire of contraception‐using couples and trans persons. Doctoral thesis, University of Ghent. [Link]

  • Transmen are four or five times more likely than females in general to suffer a heart attack. Expand
    Transmen are four or five times more likely than females in general to suffer a heart attack.

    A 2019 study [1] found that post-operative female-to-male transgender people were 4.9 times as likely to suffer a myocardial infarction (heart attack) than women in general.

    Another study [2] also found a somewhat smaller yet still large discrepancy, concluding that transmen were 3.69 more likely to suffer a heart attack than women in general.

    REFERENCES

    [1] Alzahrani, T. Nguyen, T., Ryan, A., Dwairy, A. McCaffrey, J., Yunus, R., Forgione, J., Krepp, J., Nagy, C., Mazhari, R. & Reiner, J. (2019). Cardiovascular Disease Risk Factors and Myocardial Infarction in the Transgender Population. Circulation: Cardiovascular Quality and Outcomes 12 (4). [Link]

    [2] Nota, N.M., Wiepjes, C.M., de Blok, C.J.M., Gooren, L.J.G., Kreukels, B.P.D. & den Heijer, M. (2019). Occurrence of Acute Cardiovascular Events in Transgender Individuals Receiving Hormone Therapy: Results From a Large Cohort Study. Circulation 139: 1461-1462. [Link]

  • One year of cross sex hormone therapy causes robust increases in muscle mass and strength in transmen (females) but modest changes in transwomen (males). Expand
    One year of cross sex hormone therapy causes robust increases in muscle mass and strength in transmen (females) but modest changes in transwomen (males).

    Thigh muscle volume increased 15% in transmen, which was paralleled by increased quadriceps cross-sectional area (CSA) (15%) and radiological density 6%. In transwomen, the corresponding parameters decreased by –5% (muscle volume) and –4% (CSA), while density remained unaltered. The transmen increased strength over the assessment period, while the transwomen generally maintained their strength levels [1]:

    REFERENCES

    [1] Wiik, A., Lundberg, T. R., Rullman, E., Andersson, D. P., Holmberg, et al. (2019). Muscle strength, size, and composition following 12 months of gender-affirming treatment in transgender individuals. The Journal of Clinical Endocrinology & Metabolism, 105(3). [Link]

  • Long term use of anabolic-androgenic steroids (synthetic testosterone) is associated with brain ageing and a decline in cognitive processing.
    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 al. [1] 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.

    REFERENCES

    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]

  • Long term testosterone use potentially compromises fertility and negatively affects ovarian follicle health
    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 al. [1] 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.

    REFERENCES

    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]

  • Long term use of male sex hormones in females is deleterious to their health.
    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 interventions. [1]

    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.

    REFERENCES

    [1] 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]

  • Evidence suggests that treatments used to feminize transgender women result in altered brain structures.
    Evidence suggests that treatments used to feminize transgender women result in altered brain structures.

    One study showed that estradiol valerate and cyproterone acetate, treatments used to feminize adult male rats mirroring those in transgender women, resulted in altered brain structure, including reduced volume and elevated specific metabolites. 

    In a 2020 study [1], Goémez et al. used a rat model to investigate the effects of feminizing hormonal treatments, specifically estradiol valerate and cyproterone acetate, akin to those given to transgender women. They monitored changes over 30 days using structural MRI and Diffusion Tensor Imaging. The researchers found that these treatments led to a generalized bilateral decrease in cortical volume. Additionally, they noted increases in the relative concentration of brain metabolites, including glutamate and glutamine. The study concludes that these hormonal treatments induce significant changes in brain structure and metabolite concentration. 

    REFERENCES

    [1] Gómez, Á., Cerdán, S., Pérez-Laso, C., Ortega, E., Pásaro, E., Fernández, R., … & Guillamon, A. (2020). Effects of adult male rat feminization treatments on brain morphology and metabolomic profile. Hormones and behavior, 125, 104839. [Link]