The Ethics of Navigating Teen Gender Transitions
Transgender teen Theo Zachariah began identifying as trans at age 13, and now at 16, takes testosterone.
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."
Gene Transfer Leads to Longer Life and Healthspan
In August, a study provided the first proof-of-principle that genetic material transferred from one species to another can increase both longevity and healthspan in the recipient animal.
The naked mole rat won’t win any beauty contests, but it could possibly win in the talent category. Its superpower: fighting the aging process to live several times longer than other animals its size, in a state of youthful vigor.
It’s believed that naked mole rats experience all the normal processes of wear and tear over their lifespan, but that they’re exceptionally good at repairing the damage from oxygen free radicals and the DNA errors that accumulate over time. Even though they possess genes that make them vulnerable to cancer, they rarely develop the disease, or any other age-related disease, for that matter. Naked mole rats are known to live for over 40 years without any signs of aging, whereas mice live on average about two years and are highly prone to cancer.
Now, these remarkable animals may be able to share their superpower with other species. In August, a study provided what may be the first proof-of-principle that genetic material transferred from one species can increase both longevity and healthspan in a recipient animal.
There are several theories to explain the naked mole rat’s longevity, but the one explored in the study, published in Nature, is based on the abundance of large-molecule high-molecular mass hyaluronic acid (HMM-HA).
A small molecule version of hyaluronic acid is commonly added to skin moisturizers and cosmetics that are marketed as ways to keep skin youthful, but this version, just applied to the skin, won’t have a dramatic anti-aging effect. The naked mole rat has an abundance of the much-larger molecule, HMM-HA, in the chemical-rich solution between cells throughout its body. But does the HMM-HA actually govern the extraordinary longevity and healthspan of the naked mole rat?
To answer this question, Dr. Vera Gorbunova, a professor of biology and oncology at the University of Rochester, and her team created a mouse model containing the naked mole rat gene hyaluronic acid synthase 2, or nmrHas2. It turned out that the mice receiving this gene during their early developmental stage also expressed HMM-HA.
The researchers found that the effects of the HMM-HA molecule in the mice were marked and diverse, exceeding the expectations of the study’s co-authors. High-molecular mass hyaluronic acid was more abundant in kidneys, muscles and other organs of the Has2 mice compared to control mice.
In addition, the altered mice had a much lower incidence of cancer. Seventy percent of the control mice eventually developed cancer, compared to only 57 percent of the altered mice, even after several techniques were used to induce the disease. The biggest difference occurred in the oldest mice, where the cancer incidence for the Has2 mice and the controls was 47 percent and 83 percent, respectively.
With regard to longevity, Has2 males increased their lifespan by more than 16 percent and the females added 9 percent. “Somehow the effect is much more pronounced in male mice, and we don’t have a perfect answer as to why,” says Dr. Gorbunova. Another improvement was in the healthspan of the altered mice: the number of years they spent in a state of relative youth. There’s a frailty index for mice, which includes body weight, mobility, grip strength, vision and hearing, in addition to overall conditions such as the health of the coat and body temperature. The Has2 mice scored lower in frailty than the controls by all measures. They also performed better in tests of locomotion and coordination, and in bone density.
Gorbunova’s results show that a gene artificially transferred from one species can have a beneficial effect on another species for longevity, something that had never been demonstrated before. This finding is “quite spectacular,” said Steven Austad, a biologist at the University of Alabama at Birmingham, who was not involved in the study.
Just as in lifespan, the effects in various organs and systems varied between the sexes, a common occurrence in longevity research, according to Austad, who authored the book Methuselah’s Zoo and specializes in the biological differences between species. “We have ten drugs that we can give to mice to make them live longer,” he says, “and all of them work better in one sex than in the other.” This suggests that more attention needs to be paid to the different effects of anti-aging strategies between the sexes, as well as gender differences in healthspan.
According to the study authors, the HMM-HA molecule delivered these benefits by reducing inflammation and senescence (cell dysfunction and death). The molecule also caused a variety of other benefits, including an upregulation of genes involved in the function of mitochondria, the powerhouses of the cells. These mechanisms are implicated in the aging process, and in human disease. In humans, virtually all noncommunicable diseases entail an acceleration of the aging process.
So, would the gene that creates HMM-HA have similar benefits for longevity in humans? “We think about these questions a lot,” Gorbunova says. “It’s been done by injections in certain patients, but it has a local effect in the treatment of organs affected by disease,” which could offer some benefits, she added.
“Mice are very short-lived and cancer-prone, and the effects are small,” says Steven Austad, a biologist at the University of Alabama at Birmingham. “But they did live longer and stay healthy longer, which is remarkable.”
As for a gene therapy to introduce the nmrHas2 gene into humans to obtain a global result, she’s skeptical because of the complexity involved. Gorbunova notes that there are potential dangers in introducing an animal gene into humans, such as immune responses or allergic reactions.
Austad is equally cautious about a gene therapy. “What this study says is that you can take something a species does well and transfer at least some of that into a new species. It opens up the way, but you may need to transfer six or eight or ten genes into a human” to get the large effect desired. Humans are much more complex and contain many more genes than mice, and all systems in a biological organism are intricately connected. One naked mole rat gene may not make a big difference when it interacts with human genes, metabolism and physiology.
Still, Austad thinks the possibilities are tantalizing. “Mice are very short-lived and cancer-prone, and the effects are small,” he says. “But they did live longer and stay healthy longer, which is remarkable.”
As for further research, says Austad, “The first place to look is the skin” to see if the nmrHas2 gene and the HMM-HA it produces can reduce the chance of cancer. Austad added that it would be straightforward to use the gene to try to prevent cancer in skin cells in a dish to see if it prevents cancer. It would not be hard to do. “We don’t know of any downsides to hyaluronic acid in skin, because it’s already used in skin products, and you could look at this fairly quickly.”
“Aging mechanisms evolved over a long time,” says Gorbunova, “so in aging there are multiple mechanisms working together that affect each other.” All of these processes could play a part and almost certainly differ from one species to the next.
“HMM-HA molecules are large, but we’re now looking for a small-molecule drug that would slow it’s breakdown,” she says. “And we’re looking for inhibitors, now being tested in mice, that would hinder the breakdown of hyaluronic acid.” Gorbunova has found a natural, plant-based product that acts as an inhibitor and could potentially be taken as a supplement. Ultimately, though, she thinks that drug development will be the safest and most effective approach to delivering HMM-HA for anti-aging.
A new study provides key insights in what causes Alzheimer's: a breakdown in the brain’s system for clearing waste.
In recent years, researchers of Alzheimer’s have made progress in figuring out the complex factors that lead to the disease. Yet, the root cause, or causes, of Alzheimer’s are still pretty much a mystery.
In fact, many people get Alzheimer’s even though they lack the gene variant we know can play a role in the disease. This is a critical knowledge gap for research to address because the vast majority of Alzheimer’s patients don’t have this variant.
A new study provides key insights into what’s causing the disease. The research, published in Nature Communications, points to a breakdown over time in the brain’s system for clearing waste, an issue that seems to happen in some people as they get older.
Michael Glickman, a biologist at Technion – Israel Institute of Technology, helped lead this research. I asked him to tell me about his approach to studying how this breakdown occurs in the brain, and how he tested a treatment that has potential to fix the problem at its earliest stages.
Dr. Michael Glickman is internationally renowned for his research on the ubiquitin-proteasome system (UPS), the brain's system for clearing the waste that is involved in diseases such as Huntington's, Alzheimer's, and Parkinson's. He is the head of the Lab for Protein Characterization in the Faculty of Biology at the Technion – Israel Institute of Technology. In the lab, Michael and his team focus on protein recycling and the ubiquitin-proteasome system, which protects against serious diseases like Alzheimer’s, Parkinson’s, cystic fibrosis, and diabetes. After earning his PhD at the University of California at Berkeley in 1994, Michael joined the Technion as a Senior Lecturer in 1998 and has served as a full professor since 2009.
Dr. Michael Glickman