The Ethics of Navigating Teen Gender Transitions
At first, Miriam Zachariah's teenage nephew Theo, who was born female, came out as gay. But he "presented as very gender fluid," she says, which suggested that he hadn't made "a clear choice one way or another."
Families, physicians, and psychologists have pondered whether it's better, neutral, or worse to postpone gender transitions until adulthood.
Zachariah decided to ask her nephew, "Do you think you might be trans?" While he answered "no," the question "broke something open for him," she recalls.
A month later, at age 13, he began identifying as trans. And at 14 1/2, he started undergoing gender transition with an endocrine-blocking injection. More recently, at age 16, he added testosterone injections, and soon he won't need the endocrine blocker any longer.
"His voice is deepening, and his muscle mass is growing," says Zachariah, a principal of two elementary schools in Toronto who became her nephew's legal guardian while he was starting to transition.
There are many medical and bioethical aspects associated with the transition to one's self-identified gender, especially when the process involves children and adolescents. Families, physicians, and psychologists have pondered whether it's better, neutral, or worse to postpone the transition until adulthood, while remaining cognizant of the potential consequences to puberty suppression with cross-sex hormones and the irreversibility of transgender surgeries.
Studies have found a higher prevalence of mental health issues among transgender and gender nonconforming youth, particularly if they are unable to express themselves in the self-identified gender. Research also has shown that transgender adults in the process of transitioning initially experienced worse mental health problems than their adolescent counterparts.
The Endocrine Society, a professional medical organization that provides recommendations for clinical practice, stipulates in its guidelines that the diagnosis of gender identity be limited to qualified mental health professionals for those under age 18. This is important because children are still evolving in their thought processes and capacity to articulate themselves, says endocrinologist Joshua Safer, inaugural executive director of the Center for Transgender Medicine and Surgery at the Icahn School of Medicine at Mount Sinai in New York.
A transition can begin safely in gradations, by allowing young children to experiment with haircuts and clothes of either gender before puberty. "If it just ends up being a stage of life, we haven't done anything permanent," says Safer, who is president of the United States Professional Association for Transgender Health as well as steering committee co-chair of TransNet, the international transgender research consortium.
After changes in appearance, the next step would be to try puberty blockers. Also used to halt precocious puberty, the injections are "a reasonably established intervention" for transgender youth, although there are some concerns that the drugs could interfere with bone health in the future, he says.
From a mental health standpoint, "hormones for youth who qualify for them have offered a tremendous boost in well-being and also a reduction in anxiety, depression, and suicidality that often plague transgender youth when they experience their bodies as totally discordant with their self-knowledge of their authentic gender," says psychologist Diane Ehrensaft, director of mental health in the Child and Adolescent Gender Center at Benioff Children's Hospital of the University of California at San Francisco.
Many of these youth have either known about or have been living in their authentic gender since early childhood; others discovered their true identities in adolescence, often with the onset of puberty, says Ehrensaft, associate professor of pediatrics. The effects of gender-affirming hormone treatments are at least partially reversible, she adds, whereas surgical procedures are irreversible. Regardless of reversibility, best practices include careful consideration of all interventions to ensure they are in a youth's best interests in promoting gender health and general well-being.
When a child exhibits signs of gender dysphoria, parents and guardians should at a minimum take these feelings seriously.
In determining readiness for a transgender operation, an assessment of maturity is as important as chronological age, says Loren Schechter, plastic surgeon and director of the Center for Gender Confirmation Surgery at Weiss Memorial Hospital in Chicago. With the consent of a parent or guardian, he commonly performs mastectomies on adolescents at age 17 and sometimes earlier, based on the clinical circumstances and along with a multidisciplinary team that includes a primary care provider and a mental health professional.
"Typically, before surgery, people have had the opportunity and time to consider their options," Schechter says, observing that "the incidence of regret or changing one's mind is extremely low." Others may opt to transition socially but not surgically. "We recognize that gender is not binary," he explains. Some individuals may not "discreetly fit into male or female" in how they perceive themselves.
When a child exhibits signs of gender dysphoria, parents and guardians should at a minimum take these feelings seriously, not dismiss them. They may want to enlist the assistance of a gender identity clinic to address the social environment and guide the child in exploring activities with the self-identified gender, says Kelly McBride Folkers, research associate in the Division of Medical Ethics at New York University School of Medicine.
At one end of the spectrum, some parents and guardians are overzealous in supporting their child's gender-identity pursuits while the youngster is still in an early phase of decision-making. On the flipside, other parents and guardians are not at all supportive, leaving the child at risk for long-term psychological effects, says Folkers, who is also associate director of the High School Bioethics Project at NYU, an educational program that aids teachers and students in examining ethical and conceptual concepts across various areas, one of which is gender.
"It's important to help children navigate through this process early, so that they have all of the social and familial support they need if and when they choose to seek medical options for gender affirmation later," she says.
There are various reasons why children and adolescents want to explore the opposite gender when they reach puberty. "It's a small percentage who will persist and insist and be consistent with that opposite gender identity," says Nicole Mihalopoulos, adolescent medicine physician and associate professor of pediatrics at the University of Utah School of Medicine in Salt Lake City.
Turning to a social work support system can help bring clarity for teens, parents, and guardians.
For those youth, it's appropriate to start the conversation about a medication to block puberty, but without actually promoting a hormonal transition to the opposite gender, in order for the child to further explore living as the opposite gender. "Children need to start at puberty because we need to know that their bodies are physiologically normal," Mihalopoulos says.
A lack of breast development in girls or a lack of testicular development in boys could point to an abnormality in the hypothalamus, pituitary gland, or ovaries/testicles. "That needs to be identified and corrected first," she explains, "before I would say, 'Let's start on the medical transition path of the alternate gender.' "
For parents and guardians, says Theo Zachariah's aunt Miriam, it's very tempting to misinterpret a child's struggling attempts to articulate being trans as an adolescent identity crisis. That's when turning to a social work support system can bring clarity. A youth mental health agency with experience in trans issues made a positive impact on Theo's family through one-on-one counseling and in groups for teens and parents.
"The dialogue they were able to engage in with my nephew, his mom and us," she says, was very instrumental "in helping us all figure out what to do and how to navigate the change."
A new type of cancer therapy is shrinking deadly brain tumors with just one treatment
Few cancers are deadlier than glioblastomas—aggressive and lethal tumors that originate in the brain or spinal cord. Five years after diagnosis, less than five percent of glioblastoma patients are still alive—and more often, glioblastoma patients live just 14 months on average after receiving a diagnosis.
But an ongoing clinical trial at Mass General Cancer Center is giving new hope to glioblastoma patients and their families. The trial, called INCIPIENT, is meant to evaluate the effects of a special type of immune cell, called CAR-T cells, on patients with recurrent glioblastoma.
How CAR-T cell therapy works
CAR-T cell therapy is a type of cancer treatment called immunotherapy, where doctors modify a patient’s own immune system specifically to find and destroy cancer cells. In CAR-T cell therapy, doctors extract the patient’s T-cells, which are immune system cells that help fight off disease—particularly cancer. These T-cells are harvested from the patient and then genetically modified in a lab to produce proteins on their surface called chimeric antigen receptors (thus becoming CAR-T cells), which makes them able to bind to a specific protein on the patient’s cancer cells. Once modified, these CAR-T cells are grown in the lab for several weeks so that they can multiply into an army of millions. When enough cells have been grown, these super-charged T-cells are infused back into the patient where they can then seek out cancer cells, bind to them, and destroy them. CAR-T cell therapies have been approved by the US Food and Drug Administration (FDA) to treat certain types of lymphomas and leukemias, as well as multiple myeloma, but haven’t been approved to treat glioblastomas—yet.
CAR-T cell therapies don’t always work against solid tumors, such as glioblastomas. Because solid tumors contain different kinds of cancer cells, some cells can evade the immune system’s detection even after CAR-T cell therapy, according to a press release from Massachusetts General Hospital. For the INCIPIENT trial, researchers modified the CAR-T cells even further in hopes of making them more effective against solid tumors. These second-generation CAR-T cells (called CARv3-TEAM-E T cells) contain special antibodies that attack EFGR, a protein expressed in the majority of glioblastoma tumors. Unlike other CAR-T cell therapies, these particular CAR-T cells were designed to be directly injected into the patient’s brain.
The INCIPIENT trial results
The INCIPIENT trial involved three patients who were enrolled in the study between March and July 2023. All three patients—a 72-year-old man, a 74-year-old man, and a 57-year-old woman—were treated with chemo and radiation and enrolled in the trial with CAR-T cells after their glioblastoma tumors came back.
The results, which were published earlier this year in the New England Journal of Medicine (NEJM), were called “rapid” and “dramatic” by doctors involved in the trial. After just a single infusion of the CAR-T cells, each patient experienced a significant reduction in their tumor sizes. Just two days after receiving the infusion, the glioblastoma tumor of the 72-year-old man decreased by nearly twenty percent. Just two months later the tumor had shrunk by an astonishing 60 percent, and the change was maintained for more than six months. The most dramatic result was in the 57-year-old female patient, whose tumor shrank nearly completely after just one infusion of the CAR-T cells.
The results of the INCIPIENT trial were unexpected and astonishing—but unfortunately, they were also temporary. For all three patients, the tumors eventually began to grow back regardless of the CAR-T cell infusions. According to the press release from MGH, the medical team is now considering treating each patient with multiple infusions or prefacing each treatment with chemotherapy to prolong the response.
While there is still “more to do,” says co-author of the study neuro-oncologist Dr. Elizabeth Gerstner, the results are still promising. If nothing else, these second-generation CAR-T cell infusions may someday be able to give patients more time than traditional treatments would allow.
“These results are exciting but they are also just the beginning,” says Dr. Marcela Maus, a doctor and professor of medicine at Mass General who was involved in the clinical trial. “They tell us that we are on the right track in pursuing a therapy that has the potential to change the outlook for this intractable disease.”
Since the early 2000s, AI systems have eliminated more than 1.7 million jobs, and that number will only increase as AI improves. Some research estimates that by 2025, AI will eliminate more than 85 million jobs.
But for all the talk about job security, AI is also proving to be a powerful tool in healthcare—specifically, cancer detection. One recently published study has shown that, remarkably, artificial intelligence was able to detect 20 percent more cancers in imaging scans than radiologists alone.
Published in The Lancet Oncology, the study analyzed the scans of 80,000 Swedish women with a moderate hereditary risk of breast cancer who had undergone a mammogram between April 2021 and July 2022. Half of these scans were read by AI and then a radiologist to double-check the findings. The second group of scans was read by two researchers without the help of AI. (Currently, the standard of care across Europe is to have two radiologists analyze a scan before diagnosing a patient with breast cancer.)
The study showed that the AI group detected cancer in 6 out of every 1,000 scans, while the radiologists detected cancer in 5 per 1,000 scans. In other words, AI found 20 percent more cancers than the highly-trained radiologists.
Scientists have been using MRI images (like the ones pictured here) to train artificial intelligence to detect cancers earlier and with more accuracy. Here, MIT's AI system, MIRAI, looks for patterns in a patient's mammograms to detect breast cancer earlier than ever before. news.mit.edu
But even though the AI was better able to pinpoint cancer on an image, it doesn’t mean radiologists will soon be out of a job. Dr. Laura Heacock, a breast radiologist at NYU, said in an interview with CNN that radiologists do much more than simply screening mammograms, and that even well-trained technology can make errors. “These tools work best when paired with highly-trained radiologists who make the final call on your mammogram. Think of it as a tool like a stethoscope for a cardiologist.”
AI is still an emerging technology, but more and more doctors are using them to detect different cancers. For example, researchers at MIT have developed a program called MIRAI, which looks at patterns in patient mammograms across a series of scans and uses an algorithm to model a patient's risk of developing breast cancer over time. The program was "trained" with more than 200,000 breast imaging scans from Massachusetts General Hospital and has been tested on over 100,000 women in different hospitals across the world. According to MIT, MIRAI "has been shown to be more accurate in predicting the risk for developing breast cancer in the short term (over a 3-year period) compared to traditional tools." It has also been able to detect breast cancer up to five years before a patient receives a diagnosis.
The challenges for cancer-detecting AI tools now is not just accuracy. AI tools are also being challenged to perform consistently well across different ages, races, and breast density profiles, particularly given the increased risks that different women face. For example, Black women are 42 percent more likely than white women to die from breast cancer, despite having nearly the same rates of breast cancer as white women. Recently, an FDA-approved AI device for screening breast cancer has come under fire for wrongly detecting cancer in Black patients significantly more often than white patients.
As AI technology improves, radiologists will be able to accurately scan a more diverse set of patients at a larger volume than ever before, potentially saving more lives than ever.