A Thread on the Endocrine Society’s Response to the Cass Review

Original Twitter thread by Will Malone, MD

A thread on the Endocrine Society response to the Cass Review: The 2017 Endocrine Society (ES) @TheEndoSociety gender dysphoria guidelines justified the use of puberty blockers for children just entering puberty by stating that appearance changes were more important than avoiding harm: “These recommendations place a high value on avoiding an unsatisfactory physical outcome…. and a lower value on avoiding potential harm from early pubertal suppression”.

Earlier this month, the ES dug in its heels saying the Cass Review “does not contain any new research that would contradict the recommendations made in our Clinical Practice Guideline on gender-affirming care.”

In her NYT interview, Dr. Cass countered, cautioning that the Endocrine Society (and AAP) are misleading the public by overstating the quality of evidence.

My analysis of the Endocrine Society response is below.

“Hilary Cass Says U.S. Doctors Are ‘Out of Date’ on Youth Gender Medicine”

In 2017, the Endocrine Society published guidelines that were based on several key assumptions about puberty blockers for gender dysphoria: 1) Blocking puberty (vs. allowing it to proceed) would result in physical/appearance changes in an adolescent 2) These changes would yield credible, sustained mental health benefits 3) The harms would be minimal. The 2017 Endocrine Society official justification for the use of puberty blockers stated: “These recommendations place a high value on avoiding an unsatisfactory physical outcome when secondary sex characteristics have become manifest and irreversible, a higher value on psychological well-being, and a lower value on avoiding potential harm from early pubertal suppression” (Hembree et al., 2017, p. 13)” The decision to prioritize appearance changes over potential harms reflected a clear stance, setting the tone for clinical practice in managing gender dysphoria.

In 2024, the landscape has shifted significantly. According to the Cass Review, which utilized 8 systematic evidence appraisals: 1) PBs do indeed alter physical appearance; 2) Contrary to previous beliefs, these alterations have not been shown to translate to credible mental health benefits; 3) There is a significant harm-signal related to bone and brain development, as well as a risk of locking in gender-related distress. This new evidence prompted the UK to halt PB use for GD and to also issue a strong caution about the use of cross-sex hormones which extends not just to <18s but also to young adults.

The Endocrine Society’s statement of “no new research” is highly misleading. What is new is the appraisal of the totality of the evidence, which fundamentally shifts the risk-benefit ratio. The biggest change is the finding that despite 30 years’ worth of studies, there is no credible evidence of sustained psychological benefits—and the evidence of harms, while still uncertain, is starting to mount. The balance of benefits and harms has shifted to signal harms will likely outweigh benefits for most.

The Endocrine Society’s assertion that ‘nothing has changed’ is disconnected from current evidence. Prioritizing the cosmetic “benefits” of PBs over the avoidance of harms might have been justified in 2017 when there was a significant expectation that the psychological downstream effects would be significant. Now that the Cass Review (and Sweden, Finland, and Germany) have systematically and critically appraised the studies and found no credible evidence of benefits, the goal for treatment with puberty blockers has been effectively reduced to accommodating a child’s fear of puberty and desire to maintain a pre-pubertal appearance. The ES disinterest in engaging with the mounting harms (physical, developmental, and psychological) raises serious ethical and professional concerns about the current leadership’s commitment to evidence-based care.

I am also troubled by the society’s continued promotion of puberty blockers as ‘life-saving care.” The Cass Report clearly states that the risk of suicide among GD youth, while a serious concern, is low and not demonstrably mitigated by hormonal interventions. This misuse of the suicide risk argument to support medical interventions is not only irresponsible but potentially harmful. Families and patients deserve accurate information about the risks and benefits of medical treatments. True support for these youths involves comprehensive, evidence-based mental health strategies that address the roots of distress without undue risks.

As an American endocrinologist and a member of the Endocrine Society, I continue to hold out hope that the leadership of the @TheEndoSociety will acknowledge the need to reconsider its current politicized stance and will return to the time-honored principles of evidence-based medicine. Otherwise, it risks losing the trust of the international community not only in regards to its approach to gender-dysphoric minors, but potentially in other important areas of medicine as well.