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Trans and nonbinary teenagers who receive gender-affirming hormones experience less depression and anxiety and more satisfaction with life than before the treatment, according to a new study published Wednesday in the New England Journal of Medicine.

Researchers followed over 300 adolescents across the U.S. for two years after initiating hormone treatment. The results augment a substantial body of research that shows gender-affirming care improves mental health, but most previous studies had been done with smaller, single-location cohorts and shorter follow-up windows. The new paper also focuses primarily on hormone therapy, while earlier work often included a variety of care options, including drugs to delay onset of puberty.

“It’s nice to have a structured analysis that supports what I and others experience in practice,” said Carl Streed Jr., a physician and research lead at Boston Medical Center’s Center for Transgender Medicine and Surgery, who was not involved with the new study. “This is another big contribution to saying that gender-affirming care is in fact evidence-based and has benefits and should be standard of practice at this point.”

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Despite the mounting evidence, lawmakers in many states continue attempting to restrict or ban gender-affirming care, particularly for teens. Before 2020, no states had attempted these bans. But in 2021, such bills were introduced in almost two dozen state legislatures. Four states — Alabama, Arkansas, Arizona, and Tennessee — have since enacted bans, according to Movement Advancement Project, a nonprofit think tank, though in Alabama and Arkansas, those bans have been blocked temporarily by state judges. Other measures, though, such as Florida’s “Don’t Say Gay” bill, which prohibits teachers from discussing sexuality or gender identity in school, still may leave many queer adolescents feeling unsafe and unable to discuss their medical needs.

Experts say attempts to ban gender-affirming care for teens misunderstand the nature of this care. The NEJM study, led by researchers at Lurie Children’s Hospital’s Stanley Manne Children’s Research Institute in Chicago, found that almost 70% of participants who started the study with severe depression saw it reduced to the minimal or moderate range after two years of hormone therapy. On average, participants started the trial with mild depression and ended with subclinical levels. Almost 40% of participants who started the trial with clinical anxiety saw it reduced to the non-clinical range after two years.

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Hormone therapy fundamentally alters one’s appearance. Among other changes, testosterone may increase body hair growth, deepen a person’s voice, and increase muscle mass; estrogen may slow the growth of body hair, increase breast growth while lowering muscle mass, and more.

The researchers met with participants, who ranged from ages 12-20, every six months to assess their psychosocial functioning. They found that as appearance congruence increased — meaning that as participants felt more comfortable with their changing physical appearance — depression and anxiety decreased, while positive moods and life satisfaction increased.

Unlike previous research, the new study focuses primarily on the effects of gender-affirming hormones — each participant received either testosterone or estradiol hormone treatment, and the vast majority had gone through puberty and never received the separate treatment known as hormone or puberty blockers. Researchers found that those who had not gone through puberty yet (either because of their younger age or because they were part of the small portion of participants who had received puberty blockers) saw even higher levels of appearance congruence, positive affect, and life satisfaction, and lower scores for depression and anxiety. The researchers believe this is likely because, even with hormone therapy, the effects of puberty cannot easily be erased, making appearance congruence harder to achieve.

This reflects previous evidence, the researchers note, that the earlier children can have access to gender-affirming care, the better.

“The adults that I see, every one of them is like, ‘Man, I wish I could have accessed this sooner,’” said Streed, who works mainly with adults in his role at BMC’s clinic. “There is nobody who is like, ‘Boy, I’m glad I waited until this point of my life.’”

Streed sees patients as young as teenagers who are transitioning out of pediatric care into adult care. But, he said, “you have to survive to see me as an adult.” Trans and nonbinary youth die by suicide at higher rates than their cisgender counterparts. In the current study, two participants died by suicide. Streed said that, while every suicide is absolutely tragic, he would have been surprised if there were none in the study, given those higher rates.

“Transgender people disproportionately experience poor mental health symptoms, largely as a result of living in a transphobic society,” Diana Tordoff, a researcher at Stanford who has done similar research on gender-affirming care and mental health, wrote in an email to STAT.

Study participants designated female at birth benefited from hormones more than those designated male at birth in regard to depression, anxiety, and life satisfaction. The authors theorize that this may be related to differences in the ways society accepts transfeminine and transmasculine people.

“We are really happy, and it’s really important,” said Annelou de Vries, a researcher at Amsterdam University Medical Center who co-authored a commentary on the study with colleague Sabine Hannema, also published Wednesday in NEJM. “Then the nuance comes. There remain some questions to be answered, and some of them, this study will not give.”

The amount of research focused on gender-affirming care has increased in recent years, in part due to increased prioritization from the National Institutes of Health. In 2016, the organization formally recognized “sexual and gender minorities” as a “health disparity population” for research. Experts hope that the increased focus will lead to more studies that follow trans and nonbinary people long-term, in order to learn more about potential benefits and effects of treatment long-term.

The study authors, who were not available for interviews, plan to continue following the same cohort to document longer-term results. They are also working on a similar study looking specifically at the effects of puberty blockers.

“Access to gender affirming care is fundamentally a human rights issue,” wrote Tordoff. “Trans people and their families deserve high quality science and research with which to make their own person medical decisions and to inform evidence-based clinical guidelines — not just for access to gender-affirming care, but also for preventive care, screening, and treatment for a wide range of health issues that impact all people.”

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