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May 10 9 tweets 4 min read Read on X
New peer-reviewed study finds that the evidence base for pediatric gender medicine is weak: individual studies are inconsistent, and systematic reviews show no clear benefits. Guidelines that state or imply that medical transition is the standard of care aren't evidence-based. /1 Image
The study is not a systematic review (a limitation that the authors note), but it provides a comprehensive overview about what's known about the evidence base underpinning youth gender medicine. /2
link.springer.com/article/10.100…
Studies originating from gender clinics tend to focus on measuring the magnitude of the hypothesized psychological benefits. There is less focus on studying the risks and harms. This new publication provides a succinct summary of expected harms, along with the rationale. /3 Image
The authors illustrate how selective outcome reporting compromises even the best-known studies in the field, such as the study by Chen et al. This NIH-funded study tracked 19+ measures, but reported on only 4. The study also spun mixed/disappointing outcomes as highly positive./4 Image
The authors bring in an important bioethical angle, discussing the implications of recommending treatments to minors when the harms are expected to be significant but the benefits are at best uncertain. They observe:

"When medications that cause irreversible physical and physiologic effects—including infertility and sexual dysfunction—are being recommended to minors, and, moreover, vulnerable members of a minority group, clinicians would do well to make sure they know (1) what the exact rationale for intervention is, (2) what the expected benefits are supposed to be, and (3) what the evidence says (and what it does not)." /5Image
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The new publication also discuses the Cass Review, which is a comprehensive review of pediatric gender medicine in the UK, with significant worldwide implications. Those uncertain about what the Cass Review is will find a succinct summary helpfully provided by the authors. /6 Image
The authors also provide a helpful explanation of "umbrella reviews," which are similar to systematic reviews (SR) but the unit of analysis is an SR rather than an individual study. This methodology was utilized in the HHS evidence review of the practice published May 1st. /7 Image
The authors conclude that there are serious risks to hormonal interventions for gender-distressed youth yet evidence of mental health benefit is weak. They emphasize the need to update guidelines in pediatric gender medicine to reflect the reality of the limited evidence. /8 Image
The full study, "Pediatric Gender Affirming Care is Not Evidence-based," is available at the link below:
link.springer.com/article/10.100…

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More from @segm_ebm

Jun 18
The new study from the early Dutch cohort of puberty suppressed youth will require substantial analysis, but several important preliminary points can be made. /1
👉To cut to the chase, the study cannot answer the key question of whether early pubertal blockade (at Tanner stage 2) leads to worse adult sexual outcomes, because there were only 5 cases of early puberty blockade.

To increase the sample, the authors lumped early puberty (Tanner 2) with mid puberty (Tanner 3). The resulting sample (n=17) was still too small, and it was not possible to perform statistical analysis comparing sexual function outcomes of early/mid puberty suppression with later pubertal suppression (Tanner 4/5).

Therefore, no conclusions can be made about the effects of earlier vs. later pubertal suppression on future sexual function, and it is unclear how the authors concluded that early PB has no adverse effects on sexual function. /2
👉The only conclusion that can be made with some degree of confidence is that puberty-suppressed individuals have high rates of sexual dysfunction in adulthood (at average age 29). About 30% have not been sexually active in a year. In addition, 50% of males (MtF) and 58% of females (FtM) reported having one or more sexual dysfunction.

Not all typical domains of sexual dysfunction are accounted for in the study. There is no reporting on pain during sexual activity - previous studies have shown this is a frequent problem identified in transgender people after gender affirming medical treatment. Thus, this study may seriously underestimate sexual dysfunction.

Still, assuming the respondents' answers focused on recent sexual experiences as adults, the reported rate of sexual dysfunction (50-58%) compares unfavorably to the general Dutch population, where only 7%–17% report sexual dysfunction in the last 12 months (see table below).

However, even that cannot be assumed, since the respondents were asked if they had *ever had sexual difficulties, which means such difficulties may have occurred at any stage in their life: during puberty blockade; while on cross-sex hormones pre-surgery, immediately post-surgery, or well after the surgery.

Failure to differentiate between the stages when the sexual difficulties occurred is a major methodological limitation which makes the data shared by the authors extremely challenging to interpret. /3
rutgers.nl/wp-content/upl…Image
Read 8 tweets
Jun 13
Given the skewed sex ratios among gender-dysphoric youth, most attention has focused on females. But the number of males has sharply risen as well—and the effects of androgen blockers & estrogen on males remain under-discussed. A new peer-reviewed paper addresses this gap. /1 ⬇️ Image
While systematic reviews provide only low-certainty evidence of harms of estrogen and testosterone blockers in males, in reality the harms are likely, as explained by the authors of the paper. Lack of evidence of harm ≠ evidence of lack of harm. /2
link.springer.com/article/10.100…
The authors highlight a broad range of risks from estrogen use in males: sterility, stroke, brain volume loss, cognitive impairment, dementia risk, autoimmune disease, metabolic dysfunction, pancreatitis, and elevated rates of breast, thyroid, and testicular cancer and brain tumors, and early mortality. Many of these risks remain under-discussed in clinical settings. /3
Read 10 tweets
Jun 7
📢 The volume of research in youth gender medicine has exploded in recent years. To meet the growing need for rigorous analysis, we’re launching SEGM Digest: concise, scientifically grounded reviews of influential publications. Issue 1 covers 7 major papers from Apr–May 2025. /1Image
📄 HHS Review (2025):
Issue 1 of SEGM Digest opens with an overview of the landmark 2025 HHS Review of pediatric gender dysphoria treatments. The Review's evidence and ethics analysis do not support the provision of hormones and surgery as the standard of care for GD youth. /2
segm.org/SEGM-Digest-Is…Image
📄 Utah Report (2024):
Utah’s Department of Health commissioned an assessment of safety and efficacy of hormones in GD minors. Puzzlingly, the report omits an evidence synthesis—the primary aspect of any credible evidence review, limiting its utility. /3
segm.org/SEGM-Digest-Is…Image
Read 9 tweets
Mar 28
🧵Germany’s new GD guidelines represent a shift toward caution, by acknowledging that most youth with gender distress have temporary "gender non-contentedness" and should not be medically transitioned. Still, significant problems remain, as we explain in our Spotlight. Link⬇️ /1Image
The final Guidelines are the result of a year-long debate and revisions following the release of the earlier draft. The final recommendations are now more cautious, but core issues remain.

Chief among them: the guidelines are not evidence-based. /2

segm.org/German-guideli…
Originally, the Guidelines were intended to be “evidence-based.” However, the team abandoned its systematic reviews in 2020, and chose to rely on WPATH's. When WPATH suppressed its own systematic reviews, the guidelines lost the ability to claim the evidence-based "S3" status. /3 Image
Read 13 tweets
Feb 4
A new peer-reviewed article examining the criticisms of the Cass Review, just published. The authors found that the primary source of the criticism, a non-peer-reviewed paper published on the Yale Law School website, contains numerous inaccurate and misleading claims.
Link👇/1Image
The link to the article is below:

/2tandfonline.com/doi/full/10.10…
The authors of the new publication conclude:
"The Cass Review’s careful, balanced investigations and judgments were a comprehensive, evidence-based response to the controversies in this pediatric clinical arena. Recently-published critiques of the Review have contained incorrect or inadequately contextualized claims. Because accurate information about medical interventions is essential to informed consent, it is important to correct errors in potentially influential publications." /3Image
Read 7 tweets
Dec 16, 2024
🚨 Italy's National Bioethics Committee (CNB) just updated its stance on puberty blockers (PB) for gender dysphoria. The November 2024 guidance states that PBs should only be provided after mental health internvetions failed, and only in the context of proper research trials./1 Image
The Italian National Bioethics Committee's (CNB) key recommendations are:

* Puberty blocker prescriptions for gender dysphoria should occur only after the documented failure of psychotherapy or psychiatric interventions.

*All clinical assessments must be multidisciplinary, and decisions thoroughly documented.

*Clinical trials should follow the double-blind, randomized, controlled model, ensuring robust data.

*Use of puberty blockers outside clinical trials for this indication must adhere to the same rigorous criteria, with all data transmitted to a national registry. /2
The translated text, abstract (machine-translation):

The answer to the question posed by the Ministry of Health concerns strictly and solely the use of the drug in the context indicated by the question.

As a result of expert hearings and the evaluation of available literature, the CNB highlighted, in general, the insufficiency of scientific data on the use of puberty blockers and the need to strengthen them. Consequently, the CNB stresses the need for the Ministry of Health to take charge of funding independent clinical studies aimed at obtaining decisive data on the efficacy and risks of drug administration, of higher quality than those already carried out, which do not appear adequate to the objective.

From an ethical perspective, regarding trial design, the CNB recalls that the gold standard for clinical trials for drug approval is a double-blind, randomized controlled clinical trial. The CNB recommends that clinical evaluations should be multidisciplinary, and the prescription of tryptorelin should only occur following a finding of ineffectiveness of a psychotherapeutic/psychological, and possibly psychiatric, course. The decision-making process should always be thoroughly documented in all its steps.

Given the uncertainty about the risk-benefit ratio of triptorelin puberty blockade, the CNB would like to see prescriptions only within the scope of trials sponsored by the Ministry of Health.

Even where administrations occur outside of trials, that is, in the case of denial of consent or as a result of specific clinical evaluations by the physician that should always be documented, the CNB recommends that the same criteria indicated for trials be followed, and that in any case all data always be submitted to a dedicated registry. This is also in light of the fact that, at the moment, data on the use of tryptorelin reported by the regions (i.e., on its use during the period 2019-2023) are lacking and fragmentary.

The opinion was approved by a large majority of those present, with 4 of the non-voting members joining, and was accompanied by one dissenting note, one abstention note, and two explanations of vote, one of which was signed by 15 members, and the other by 7.
/3
Read 4 tweets

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