In 16 studies of hormonal interventions with 1,132 participants, only 2 had control subjects. "Controls were not matched for important confounders, which means caution should be applied to any conclusions. We found no randomized controlled trials or controlled trials."
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Puberty blockers: "Little is known about its safety profile in the context of gender dysphoria: use is based largely on effects of treatment of central precocious puberty."
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"Evidence suggests that children will change their minds as they age: approximately ¾ of pre-pubescent children attending gender identity clinics will not want to change their gender once puberty starts."
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Out of ten studies that analysed the effects of puberty blockers, six studies were funded by industry: 4 received funding from Ferring. "The denominators in all of these ten studies are tiny and mostly from retrospective case reports or small case series."
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"Many are done in single clinics and lack long term longitudinal outcomes on the effects (both benefits and harms) of puberty blockers." "We found four studies reporting on the use of GnHRa alone."
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"Problems within these studies, however, make it difficult to assess whether early pubertal changes regress under GnRHa treatment and whether prolonged puberty suppression is safe." For example, lack of controls and lack of blinding means results are unclear.
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Without controls we can't say for certain that improvement in psychosocial well-being is an effect of hormonal treatment: getting older is also positively associated with maturity and well-being.
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Oestrogens and testosterone "SHOULD ONLY BE taken in the context of medical supervision to monitor risks." "Neuroimaging studies suggest CSHs affect brain structure and circuitries, ventricular volume and thickness, hypothalamic neuroplasticity, and functional connectivity."
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The DeVries studies (2011, 2014) are used by activists to prove benefits of hormonal treatments. Conclusion here: "High levels of bias with study participation mean the results should be treated with caution." This was a very carefully selected cohort to start with.
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Conclusions: "There are significant problems with how the evidence for Gender-affirming cross-sex hormone has been collected and analysed that prevents definitive conclusions to be drawn."
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Problems include: small sample sizes; retrospective methods, loss of considerable numbers of patients in follow-up, lack of control groups and blinding, subjective outcomes prone to bias which can be explained by regression to the mean.
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Treatments "remain largely experimental. There are a large number of unanswered questions that include the age at start, reversibility; adverse events, long term effects on mental health, quality of life, bone mineral density, osteoporosis in later life and cognition."
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