Do Transgender Youth Benefit from Hormone-Replacement Therapy? Part I
The New England Journal of Medicine tries—and fails—to answer
The latest issue of the New England Journal of Medicine (NEJM) attempts to answer a question that has been repeatedly posed by anti-transgenderism activists: does “gender-affirming care” help young people struggling with gender dysphoria?
Opponents of medical transition for minors—in which young people are prescribed “puberty blockers,” synthetic hormones, and even surgery in order to present as the opposite sex or as androgynous—have pointed to the obvious dangers of all these treatments. Jazz Jennings, the child reality star who underwent the full scope of gender-affirming care, serves as an instructive example.
Jennings began a course of puberty blockers at the age of 11 and eventually moved on to synthetic hormones and surgical procedures, all in an attempt to medically transition from male to female. At the age of 17, Jennings’s male sexual development was severely stunted. From a medical standpoint, this posed serious problems. Among other things, it severely complicated attempts to surgically alter Jennings’s genitalia to resemble those of a female; Jennings also had virtually no sex drive. Attempts at workarounds led to ongoing complications, which have been covered in detail elsewhere. In addition to the host of medical challenges Jennings now faces, the chances for this young person to have a healthy sex life have been curtailed and possibly eradicated.
The case of Jazz Jennings offers just a few examples of the costs of this kind of gender transition for minors. Across the board, major side effects include fertility loss, bone-density loss, and stunted overall growth; less severe side effects include weight gain, hot flashes, and headaches, among other issues. Anti-transgenderism activists such as attorney and author Abigail Shrier and podcast host Matt Walsh have challenged the idea that the purported benefits of these treatments justify the harms. In doing so, they point to the lack of long-term evidence that gender-affirming medical interventions are meaningfully helpful for young people navigating mental-health crises.
This brings us to the NEJM’s January 19, 2023, issue, which includes an article titled “Psychosocial Functioning in Transgender Youth after 2 Years of Hormones,” by Diane Chen, Ph.D., and others. The article concludes that gender-affirming hormones “improved appearance congruence and psychosocial functioning” for the young people being studied. The results, however, do not justify that conclusion.
Chen and her team recruited 315 youths, aged 12 to 20, who had received treatment from gender clinics in Chicago, Boston, Los Angeles, and San Francisco. This is important to note: the participants in the study were personally recruited by researchers after they had already begun to pursue affirming care at gender clinics. In other words, it was not a randomized sample of people who were seeking treatment for a medical condition, and who were then presented with the option of joining a medical trial for synthetic hormones. These patients had already been presented with this particular treatment option by the physicians at their respective clinics—and had likely been seeking it out in the first place. The physicians and patients involved were already persuaded of the correctness of this mode of care. This is one way in which the standard safeguards against bias in research that are baked into randomized, double-blind clinical trials were not present here.
In a randomized, double-blind trial, at least one control group is present. Neither participants nor researchers know which patients are receiving the experimental treatment and which are receiving a placebo or an alternate, more conventional treatment. In the case of young people with gender dysphoria, a placebo might be a course of sugar pills rather than synthetic hormones; alternate treatments might include social transition or talk therapy. The progress of each group is measured in an objective fashion and then compared. Only once the trial has concluded do researchers and participants learn if and how any particular treatment succeeded or failed, and to what extent, relative to A) doing nothing, or B) other treatments. And, again, participants are randomly selected, rather than personally recruited, which reduces the likelihood that patients will have “bought in” to the idea of the particular treatment under review.
Considering the demonstrable risks of medical transition for young people, the question the Chen study should have asked is a simple one: Is medical transition for young people better than doing nothing? As structured, the study does not ask or answer that question. Nor does it rigorously evaluate the therapy it claims to be examining. We cannot know if such treatments are better than nothing—we are offered nothing to measure them against.
To be clear, these are safeguards against bias on the part of both participants and researchers, who may be understandably keen to demonstrate the efficacy of the experimental treatment they are studying. And since the endpoints in a study of treatment for gender dysphoria are inherently subjective and self-reported—boiling down to whether participants state they are happier or more comfortable with themselves rather than, e.g., patients with high blood pressure responding well in a measurable way to blood-pressure medication—it is extremely important that these measures to prevent bias are in place.
This is not to say that the study offers no information. It provides a longitudinal observation of a group of young people suffering from a similar condition and pursuing a similar course of treatment. It concludes that these people, with some notable exceptions, enjoyed improved mental states after two years of such treatment. This kind of longitudinal study has its place in medical literature; such studies are often published in specialty journals and can serve as the basis for more robust clinical trials down the line. But the study is not, properly understood, a medical trial. It does not meet the standards typically required for NEJM research; every other original article in this issue alone, for example, includes a randomized trial.
This is a problem. The NEJM is considered the world’s premier medical journal— more prestigious than even the Journal of the American Medical Association (JAMA), the Lancet, or the British Medical Journal. An NEJM citation is considered the gold standard, and this study will undoubtedly be widely shared as such. Its shortfalls as a piece of research notwithstanding, it will be used as political “citation fodder” to bolster the idea that hormone therapy for minors is demonstrably beneficial. This is in spite of the following:
The Swedish government recently ended the practice of prescribing puberty blockers, cross-sex hormones, and gender-affirming mastectomies for anyone under the age of 18, admitting that such “care has been characterized by both deficiencies in accessibility and a lack of knowledge about the results of the care.”
The “Dutch model” of administering puberty blockers to gender-dysphoric youth (so called because it was originally developed by a team of Dutch researchers) rose to international prominence since its introduction in the 1990s, but has since come under intense scrutiny and has been abandoned by medical boards across Europe. Several studies attempting to test the Dutch model on young people have shown negative results.
Two participants in the NEJM study committed suicide, while 11 continued to experience suicidal ideation at the conclusion of the study.
Most troubling is the baldly stated conclusion of the researchers that “[gender-affirming hormones] improved appearance congruence and psychosocial functioning” for the young people in the study. Without a control group with which to compare the results, we cannot know that this is true.