Category: Puberty blockers
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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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Boys receiving puberty blockers for gender dysphoria experienced irreversible changes to their testes.
A histological analysis1 of testicular tissue taken from boys receiving puberty blockers for gender dysphoria showed that the tissue showed abnormal development that was likely to be irreversible.
Samples were gathered as part of “fertility preservation surgery,” in which testicular tissue is harvested and preserved in hope that it will be able to produce sperm later. Every boy with gender dysphoria in the study had elected for this surgery due to inability or reluctance to ejaculate. This suggests the possible presence of various psychological and physical conditions that are unexplored in the research.
- Murugesh V, Ritting M, Salem S, Aalam SMM, Garcia J, Chattha AJ, Zhao Y, Knapp DJ, Kalthur G, Granberg CF, Kannan N. Puberty Blocker and Aging Impact on Testicular Cell States and Function. bioRxiv [Preprint]. 2024 Mar 27:2024.03.23.586441. Doi: 10.1101/2024.03.23.586441. PMID: 38585884; PMCID: PMC10996503. ↩︎
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Psychological effects of puberty blockers on young people may be worse than placebo.
An analysis1 comparing psychological effects of puberty blockers on teenagers with gender dysphoria with existing research on placebo effects for various mental health conditions found that placebo effects appeared to be at least as strong as the effect of puberty blockers, if not stronger.
- https://sex-matters.org/wp-content/uploads/2022/12/Teenagers-medication-vs-placebo.pdf ↩︎
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Depression symptoms got worse in children taking puberty blockers.
In a study1 of 94 children with gender dysphoria, aged 8-16 and beginning to take puberty blockers, depression symptoms were more likely to get worse than to improve over two years of treatment. Scores on the Beck Depression Inventory (BDI-Y) went from 72% average, 10% mildly elevated, 10% moderately elevated, and 8% severely elevated at baseline to 75% average, 7% mildly elevated, 14% moderately elevated, and 9% severely elevated after 24 months.
This study was conducted from 2016 to 2021 by Dr. Johanna Olson-Kennedy. In 2024, the New York Times reported2 Dr. Olson-Kennedy saying that publication of this research had been delayed because she feared that research showing that puberty blockers did not improve patients’ mental health would be “weaponized” against the use of puberty blockers by opponents of the practice. The report appeared as a pre-print, not peer-reviewed, in May 2025.
- Johanna Olson-Kennedy, Liyuan Wang, Carolyn F. Wong, Diane Chen, Diane Ehrensaft, Marco A. Hidalgo, Amy C. Tishelman, Yee-Ming Chan, Robert Garofalo, Asa E. Radix, Stephen M. Rosenthal, Emotional Health of Transgender Youth 24 Months After Initiating Gender-Affirming Hormone Therapy, Journal of Adolescent Health, Volume 77, Issue 1, 2025, Pages 41-50, ISSN 1054-139X, https://doi.org/10.1016/j.jadohealth.2024.11.014. ↩︎
- https://www.nytimes.com/2024/10/23/science/puberty-blockers-olson-kennedy.html
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Women taking GnRH agonists for endometriosis experienced memory problems during treatment.
A study1 of women taking GnRH agonists (a/k/a “puberty blockers”) to treat endometriosis found that 31% had “mild” memory problems, 25% had “moderate” problems, and 19% had “marked” problems. Problems were mainly with prospective and short-term memory.
- Christopher Newton, Dianne Slota, Albert A. Yuzpe, Ian S. Tummon, Memory complaints associated with the use of gonadotropin-releasing hormone agonists: a preliminary study, Fertility and Sterility, Volume 65, Issue 6, 1996. ISSN 0015-0282. https://doi.org/10.1016/S0015-0282(16)58351-4. ↩︎
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The IQ of girls given puberty blockers for precocious puberty fell by eight points.
A study1 of 15 girls treated with puberty blockers for central precocious puberty showed that IQ fell by around eight points. The average fell from 102 (55th percentile) to 94 (34th percentile). Two patients were held back a year at school.
In another study2 of 30 children experiencing early puberty and treated with puberty blockers, IQ fell by around seven points.
- Wojniusz S, Callens N, Sütterlin S, Andersson S, De Schepper J, Gies I, Vanbesien J, De Waele K, Van Aken S, Craen M, Vögele C, Cools M, Haraldsen IR. Cognitive, Emotional, and Psychosocial Functioning of Girls Treated with Pharmacological Puberty Blockage for Idiopathic Central Precocious Puberty. Frontiers in Psychology. 2016 Jul 12;7:1053. doi: 10.3389/fpsyg.2016.01053. PMID: 27462292; PMCID: PMC4940404. ↩︎
- Mul D, Versluis-den Bieman HJ, Slijper FM, Oostdijk W, Waelkens JJ, Drop SL. Psychological assessments before and after treatment of early puberty in adopted children. Acta Paediatrica. 2001 Sep;90(9):965-71. doi: 10.1080/080352501316978011. PMID: 11683207. ↩︎
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IQ fell in a male patient whose puberty was blocked due to gender distress.
A case study1 of a male patient whose puberty was blocked at age 11 showed a decline in several measurements of intelligence over the following three years, including decline of 10 points in global IQ and 15 points in verbal comprehension.
Verbal comprehension showed a continuous decline. Other measurements showed some improvement after an initial decline, but never recovered to baseline levels. Processing speed index scores initially improved, but then fell below baseline.
- Schneider MA, Spritzer PM, Soll BMB, Fontanari AMV, Carneiro M, Tovar-Moll F, Costa AB, da Silva DC, Schwarz K, Anes M, Tramontina S, Lobato MIR. Brain Maturation, Cognition and Voice Pattern in a Gender Dysphoria Case under Pubertal Suppression. Frontiers in Human Neuroscience. 2017 Nov 14;11:528. doi: 10.3389/fnhum.2017.00528. PMID: 29184488; PMCID: PMC5694455. ↩︎
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Animal studies suggest puberty blockers may impair brain development, sometimes irrevocably.
A review1 of studies of the effect of puberty blockers on animals (sheep, mice, macaque monkeys) suggests that brain development and neurological functioning may be compromised by the treatment. In some cases, hormone replacement (i.e. testosterone replacement in male sheep given GnRH agonists) did not mitigate or undo the observed changes. A variety of sex-specific effects were also observed.
- Baxendale S. The impact of suppressing puberty on neuropsychological function: a review. Acta Paediatrica. 2024; 113(6): 1156-1167. doi:10.1111/apa.17150 ↩︎
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More patients on puberty blockers saw their distress deteriorate than improve.
A study1 of children from 12-15 receiving puberty blockers via the Gender Identity and Development Service showed that 37-70% of patients showed no improvement in levels of distress. 15-34% showed deterioration, while only 9-29% showed improvement.
The highest rate of deterioration (34%) was recorded at the 12 month evaluation, when the sample size was at its largest. Evaluations at 24 and 36 months were affected by significant loss to follow-up, which compromises the data.
- McPherson, S., & Freedman, D. E. P. (2023). Psychological Outcomes of 12–15-Year-Olds with Gender Dysphoria Receiving Pubertal Suppression in the UK: Assessing Reliable and Clinically Significant Change. Journal of Sex & Marital Therapy, 50(3), 315–325. https://doi.org/10.1080/0092623X.2023.2281986 ↩︎
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Rates of suicidality and self-harm did not improve in teenagers taking puberty blockers.
In a prospective study1 of patients aged 12-15 referred to University College Hospital, London by the Gender Identity Development Service, patients on puberty blockers showed no change in rates of suicidality or self-harm.
This study is compromised by the lack of follow-up once patients reached the age of 16, meaning there were significant effective drop-out rates at 24 and 36 months.
- Carmichael P, Butler G, Masic U, Cole TJ, De Stavola BL, Davidson S, Skageberg EM, Khadr S, Viner RM. 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. 2021 Feb 2;16(2):e0243894. doi: 10.1371/journal.pone.0243894. PMID: 33529227; PMCID: PMC7853497. ↩︎
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The height of teenagers taking puberty blockers did not increase at an age-appropriate rate.
In a prospective study1 of patients aged 12-15 referred to University College Hospital, London by the Gender Identity Development Service, patients on puberty blockers did grow taller, but not by as much as others in their age group.
- Carmichael P, Butler G, Masic U, Cole TJ, De Stavola BL, Davidson S, Skageberg EM, Khadr S, Viner RM. 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. 2021 Feb 2;16(2):e0243894. doi: 10.1371/journal.pone.0243894. PMID: 33529227; PMCID: PMC7853497. ↩︎
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Teenagers taking puberty blockers report more negative mood changes over time.
In a prospective study1 of patients aged 12-15 referred to University College Hospital, London by the Gender Identity Development Service, patients reported increases in negative mood and decreases in positive mood over time since beginning puberty blockage.
This study is compromised by the lack of follow-up once patients reached the age of 16, meaning there were significant effective drop-out rates at 24 and 36 months.
- Carmichael P, Butler G, Masic U, Cole TJ, De Stavola BL, Davidson S, Skageberg EM, Khadr S, Viner RM. 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. 2021 Feb 2;16(2):e0243894. doi: 10.1371/journal.pone.0243894. PMID: 33529227; PMCID: PMC7853497. ↩︎
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The bone mineral density of teenagers taking puberty blockers did not increase to age-appropriate levels
In a prospective study1 of patients aged 12-15 referred to University College Hospital, London by the Gender Identity Development Service, bone mineral density (BMD) in the hip showed no change from baseline over 36 months. Spinal BMD showed some increase at 24 months, but at no point did BMD show an age-appropriate increase.
This study is compromised by the lack of follow-up once patients reached the age of 16, meaning there were significant effective drop-out rates at 24 and 36 months.
- Carmichael P, Butler G, Masic U, Cole TJ, De Stavola BL, Davidson S, Skageberg EM, Khadr S, Viner RM. 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. 2021 Feb 2;16(2):e0243894. doi: 10.1371/journal.pone.0243894. PMID: 33529227; PMCID: PMC7853497. ↩︎
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Puberty blockers did not improve psychological functioning of GIDS patients.
In a prospective study1 of patients aged 12-15 referred to University College Hospital, London by the Gender Identity Development Service, psychological functioning (measured using the Child Behaviour Checklist) was not shown to improve 12, 24 or 36 months after beginning puberty blockage.
This study is compromised by the lack of follow-up once patients reached the age of 16, meaning there were significant effective drop-out rates at 24 and 36 months.
- Carmichael P, Butler G, Masic U, Cole TJ, De Stavola BL, Davidson S, Skageberg EM, Khadr S, Viner RM. 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. 2021 Feb 2;16(2):e0243894. doi: 10.1371/journal.pone.0243894. PMID: 33529227; PMCID: PMC7853497. ↩︎
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Boys show a clear athletic advantage over girls even before puberty.
Performance data from Little Athletics Australia1 reveals that boys outperform girls in every track and field event from under-9 to under-15 age groups, even prior to puberty. This challenges the common claim that pre-pubertal boys or those on puberty blockers have no competitive edge over girls. The male performance advantage appears early in childhood and is evident across sprinting, jumping, and throwing events.
- Little Athletics Australia. (2018). Australian best performances as at August 2018 [PDF]. https://www.littleathletics.com.au/wp-content/uploads/2019/03/ABP-as-at-August-2018-V1.pdf
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- Little Athletics Australia. (2018). Australian best performances as at August 2018 [PDF]. https://www.littleathletics.com.au/wp-content/uploads/2019/03/ABP-as-at-August-2018-V1.pdf
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Puberty blockers potentially have a negative impact on neuropsychological functioning
A 2024 review by Sallie Baxendale1 extensively examined the neuropsychological impacts of puberty blockers. The review indicated that animal studies showed a non-reversible negative impact on cognitive and behavioral functions. In human studies, the evidence suggested detrimental effects on IQ among those treated with puberty blockers for precocious puberty. Specifically, one study documented an average decrease in full-scale IQ of 7 points, including a case where an individual’s IQ fell by 15 points from 138 to 123 after treatment. Another case study involving a gender dysphoric young person reported a drop of 9 points in global (overall) IQ and 15 points in working memory during the course of treatment with puberty blockers.
- Baxendale, S. (2024). The impact of suppressing puberty on neuropsychological function: A review. Acta Paediatrica, 113(7), 1156-1167. [Link] ↩︎
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There is no high-quality evidence supporting the use of puberty blockers for gender distress
A 2024 systematic review by Taylor et al. at the University of York1 was commissioned by the Cass Review to rigorously assess the safety and effectiveness of puberty suppression in adolescents with gender dysphoria. Analyzing studies up to April 2022, the review included 11 cohort, 8 cross-sectional, and 31 pre-post studies, but only one cross-sectional study met high-quality standards. The meta-analysis of moderate to high-quality studies showed limited and inconsistent evidence of benefits in areas like gender dysphoria, mental health, and body satisfaction.
This finding aligns with the previous 2020 review by the British National Institute for Clinical Excellence (NICE) on puberty blockers2, which described the supporting evidence as “very low” quality. The review noted minimal changes in key outcomes like gender dysphoria, mental health, and quality of life due to small, uncontrolled observational studies. Furthermore, a 2024 review from Germany by Zepf et al.3, adhering to NICE criteria, confirmed the absence of new studies on puberty blockers for gender dysphoria since the NICE review.
- Taylor, J., Mitchell, A., Hall, R., Heathcote, C., Langton, T., Fraser, L., & Hewitt, C. E. (2024). Interventions to suppress puberty in adolescents experiencing gender dysphoria or incongruence: a systematic review. Archives of disease in childhood, archdischild-2023-326669. [Link] ↩︎
- 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] ↩︎
- Zepf, F. D., König, L., Kaiser, A., Ligges, C., Ligges, M., Roessner, V., … & Holtmann, M. (2024). Beyond NICE: Aktualisierte systematische Übersicht zur Evidenzlage der Pubertätsblockade und Hormongabe bei Minderjährigen mit Geschlechtsdysphorie. Zeitschrift für Kinder-und Jugendpsychiatrie und Psychotherapie. [Link] ↩︎
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Suppressing sex hormones in males, using treatments like those prescribed as puberty blockers, is linked to an increased risk of dementia
A 2025 systematic review and meta-analysis1 found that men receiving androgen deprivation therapy (ADT) for prostate cancer had an increased risk of dementia, with a 26% higher likelihood for all types of dementia and a 9% higher risk specifically for Alzheimer’s disease, compared to men not receiving this treatment. ADT reduces the effects of male sex hormones (androgens) such as testosterone and dihydrotestosterone (DHT). This is achieved using medications, including GnRH agonists (which initially stimulate and then suppress hormone production via the pituitary gland), GnRH antagonists (which directly block hormone receptor activity), or through other pharmaceutical and surgical approaches. Notably, some of the same medications used for ADT—GnRH agonists, GnRH antagonists, and certain antiandrogens—are also employed as “puberty blockers” to delay puberty in children and adolescents.
- Ma, L., Tan, E. C., Goudey, B., Jin, L., & Pan, Y. (2025). Unraveling the bidirectional link between cancer and dementia and the impact of cancer therapies on dementia risk: A systematic review and meta‐analysis. Alzheimer’s & Dementia, e14540. [Link] ↩︎
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Medical transition puts both males and females at risk of infertility
A wide-ranging study1 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.
- 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] ↩︎
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One study found that puberty blockers did not alleviate negative thoughts in children with gender dysphoria
A British study1 found that puberty blockers used to treat children aged 12 to 15 who have severe and persistent gender dysphoria had no significant effect on their psychological function, thoughts of self-harm, or body image.
However, as expected, the children experienced reduced growth in height and bone strength by the time they finished their treatment at age 16.
- 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] ↩︎