now released. NC. The full link is below, this is the summary. It's not looking good.
Discussion
A key limitation to identifying the effectiveness and safety of GnRH analogues for children and adolescents with gender dysphoria is the lack of reliable comparative studies. The lack of clear, expected outcomes from treatment with a GnRH analogue (the purpose of which is to suppress secondary sexual characteristics which may cause distress from unwanted pubertal changes) also makes interpreting the evidence difficult.
The studies included in this evidence review are all small, uncontrolled observational studies, which are subject to bias and confounding, and all the results are of very low certainty using modified GRADE. They all reported physical and mental health comorbidities and concomitant treatments very poorly. All the studies are from a limited number of, mainly European, care facilities. They are described as either tertiary referral or expert services but the low number of services providing such care and publishing evidence may bias the results towards the outcomes in these services only and limit extrapolation.
Many of the studies did not report statistical significance or confidence intervals. Changes in outcome scores for clinical effectiveness and bone density were assessed with regards to statistical significance. However, there is relatively little interpretation of whether the changes in outcomes are clinically meaningful.
In the observational, retrospective studies providing evidence on bone density, participants acted as their own controls and change in bone density was determined between starting GnRH analogues and follow up. Observational studies such as these can only show an association with GnRH analogues and bone density; they cannot show that GnRH analogues caused any differences in bone density seen. Because there was no comparator group and participants acted as their own controls, it is not known whether the findings are associated with GnRH analogues or due to changes over time.
Conclusion
The results of the studies that reported impact on the critical outcomes of gender dysphoria and mental health (depression, anger and anxiety), and the important outcomes of body image and psychosocial impact (global and psychosocial functioning), in children and adolescents with gender dysphoria are of very low certainty using modified GRADE. They suggest little change with GnRH analogues from baseline to follow-up.
Studies that found differences in outcomes could represent changes that are either of questionable clinical value, or the studies themselves are not reliable and changes could be due to confounding, bias or chance. It is plausible, however, that a lack of difference in scores from baseline to follow-up is the effect of GnRH analogues in children and adolescents with gender dysphoria, in whom the development of secondary sexual characteristics might be expected to be associated with an increased impact on gender dysphoria, depression, anxiety, anger and distress over time without treatment. The study by de Vries et al. 2011 reported statistically significant reductions in the Child Behaviour Checklist (CBCL) and Youth Self-Report (YSR) scores from baseline to follow up, which include measures of distress. As the aim of GnRH analogues is to reduce distress caused by the development of secondary sexual characteristics, this may be an important finding.
However, as the studies all lack appropriate controls who were not receiving GnRH analogues, any positive changes could be a regression to mean.
The results of the studies that reported bone density outcomes suggest that GnRH analogues may reduce the expected increase in bone density (which is expected during puberty). However, as the studies themselves are not reliable, the results could be due to confounding, bias or chance. While controlled trials may not be possible, comparative studies are needed to understand this association and whether the effects of GnRH analogues on bone density are seen after they are stopped. All the studies that reported safety outcomes provided very low certainty evidence.
No cost-effectiveness evidence was found to determine whether or not GnRH analogues are cost-effective for children and adolescents with gender dysphoria.
The results of the studies that reported outcomes for subgroups of children and adolescents with gender dysphoria, suggest there may be differences between sex assigned at birth males (transfemales) and sex assigned at birth females (transmales).
arms.nice.org.uk/resources/hub/1070905/attachment