Study Finds Almost No Good Evidence on Gender Dysphoria Drugs for Young People

Two new meta-analyses make a case for individualistic approaches to puberty blockers and hormone treatments, driven by patients, parents, and doctors rather than the state.

Based on current evidence, it's impossible to say whether puberty blockers and hormone therapy are helpful or harmful for young people with gender-related distress, according to two new papers published in the Archives of Disease in Childhood journal.

In these two meta-analyses, Canadian researchers looked at prior studies on puberty blockers and "gender-affirming hormone therapy" (GAHT) in minors and young adults up to age 26.

Puberty blockers are hormonal medications meant to suppress sex hormones in adolescents, with the aim of delaying puberty and its associated physical changes. Hormone therapy for gender dysphoria uses masculinizing or feminizing hormones to induce secondary sex characteristics that align with one's gender identity.

Both interventions have become popular for treating young people who express discomfort with the sex or gender to which they were born—aka gender dysphoria. Proponents say such treatments are vital for the psychological health and social acceptance of transgender youth. Detractors worry about potential long-term effects and suggest that doctors are too quick to prescribe these medications, handing them out to people for whom psychological interventions (or simply the passage of time) may be a more appropriate remedy.

In the first of the two new analyses, a team of researchers led by McMaster University's Anna Miroshnychenko looked at evidence from 10 studies on the effects of puberty blockers. Three of these studies compared patients given puberty blockers to those who were not, while the others assessed patients before and after being treated with puberty blockers. In both sets of studies, there was "very low certainty evidence" on tested outcomes, including their effect on gender dysphoria, depression, and bone mineral density.

"Most studies provided very low certainty evidence about the outcomes of interest, thus, we cannot exclude the possibility of benefit or harm," write the study authors.

"All other published systematic reviews had similar conclusions to our review: the current best available evidence about the effects of puberty blockers in the population of interest is very low certainty, and high-quality studies evaluating short and long-term outcomes of puberty blockers are needed," they add.

The second analysis—also led by Miroshnychenko—looked at evidence related to hormone therapy, using data from 24 studies. Evidence about the effects of hormone therapy was mostly low certainty or very low certainty, they found. Many of the study designs were "limited in assessing intervention effects" and the studies were at risk of "bias and imprecision" resulting "from an insufficient sample size."

"The best available evidence reporting on the effects of [hormone therapy] in individuals experiencing [gender dysphoria] ranged from moderate to high certainty for cardiovascular events, and low to very low certainty for the outcomes of [gender dysphoria], global function, depression, sexual dysfunction, [bone mineral density], and death by suicide," they write.

On one level, these analyses don't tell us much about the best course of action when it comes to young people with gender dysphoria and hormone treatments. They leave open the possibility that puberty blockers and hormone therapy may be beneficial, but also the possibility that they may be harmful or have little effect at all.

On another level, however, that uncertainty is a sort of guide. It suggests, first, a cautious approach to prescribing and advocating for these therapies. If they were as unambiguously helpful as some supporters say, we should see much more robust evidence to this effect and the fact that we don't would seem to preclude them from being some sort of panacea.

It suggests, also, a highly individualistic approach—neither the hyper-liberal prescribing patterns that some supporters advocate, nor the extremely restrictive schemes that detractors want. Ultimately, these analyses seem to caution against more universal solutions, for now.

"Since the current best evidence…is predominantly very low certainty," these decisions come down to "the individualistic nature of values and preferences," suggest the authors. The best clinicians can do is "clearly communicate this evidence to patients and caregivers," and consider the uncertainty of the evidence along with "patient's values and preferences" when making treatment decisions. Meanwhile, "guideline developers and policy makers should be transparent about which and whose values they are prioritizing when making recommendations and policy decisions," they write in the puberty blocker paper.

"Beyond evidence certainty, decision-making should consider other factors, including the magnitude and consequences of potential benefits and harms, patients' and caregivers' values and preferences, resource use, feasibility, acceptability, and equity," they write in the hormone therapy analysis paper, again urging policymakers to "transparently state which and whose values they prioritize when developing treatment recommendations and policies."

"There is considerable uncertainty…and we cannot exclude the possibility of benefit or harm," Miroshnychenko and her team conclude. "Methodologically rigorous prospective studies are needed to produce higher certainty evidence."

This implies that better evidence is capable of being obtained with the right studies, and surely some sorts of evidence can be. But perhaps the difficulty in determining whether puberty blockers and hormone interventions are harmful or helpful comes down to the fact that there is no one-size-fits-all or even one-size-fits-most answer when it comes to certain outcomes, like those in the mental health realm.

Puberty blockers and hormone therapies may be helpful in many cases and neutral or harmful in many others. The fact that there's no consensus is all the more reason to leave this decision to patients, parents, and doctors rather than the state.