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."
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five:
- Research on a "smart" bandage for wounds
- A breakthrough in fighting inflammation
- The pros and cons of a new drug for Alzheimer's
- Benefits of the Mediterranean diet - with a twist
- How to recycle a plastic that was un-recyclable
Sexually transmitted infections (STIs) are surging across the U.S. to 2.5 million cases in 2021 according to preliminary data from the CDC. A new prevention and treatment strategy now in clinical trials may provide a way to get a handle on them.
It's easy to overlook the soaring rates of gonorrhea, chlamydia, and syphilis because most of those infections have few or no symptoms and can be identified only through testing. But left untreated, they can lead to serious damage to nerves and tissue, resulting in infertility, blindness, and dementia. Infants developing in utero are particularly vulnerable.
Covid-19 played havoc with regular medical treatment and preventive care for many health problems, including STIs. After formal lockdowns ended, many people gradually became more socially engaged, with increases in sexual activity, and may have prioritized these activities over getting back in touch with their doctors.
A second blow to controlling STIs is that family planning clinics are closing left and right because of the Dobbs decision and legislation in many states that curtailed access to an abortion. Discussion has focused on abortion, but those same clinics also play a vital role in the diagnosis and treatment of STIs.
Routine public health is the neglected stepchild of medicine. It is called upon in times of crisis but as that crisis resolves, funding dries up. Labs have atrophied and personnel have been redirected to Covid, “so access to routine screening for STIs has been decimated,” says Jennifer Mahn, director of sexual and clinical health with the National Coalition of STD Directors.
A preview of what we likely are facing comes from Iowa. In 2017, the state legislature restricted funding to family health clinics in four counties, which closed their doors. A year later the statewide rate of gonorrhea skyrocketed from 83 to 153.7 cases per 100,000 people. “Iowa counties with clinic closures had a significantly larger increase,” according to a study published in JAMA. That scenario likely is playing out in countless other regions where access to sexual health care is shrinking; it will be many months before we have the data to know for sure.
A decades-old antibiotic finds a new purpose
Using drugs to protect against HIV, either as post exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP), has proven to be quite successful. Researchers wondered if the same approach might be applied to other STIs. They focused on doxycycline, or doxy for short. One of the most commonly prescribed antibiotics in the U.S., it’s a member of the tetracycline family that has been on the market since 1967. It is so safe that it’s used to treat acne.
Two small studies using doxy suggested that it could work to prevent STIs. A handful of clinical trials by different researchers and funding sources set out to generate the additional evidence needed to prove their hypothesis and change the standard of care.
Senior researcher Victor Omollo, with the Kenya Medical Research Institute, noted, “These are prevention interventions that women can control on their own without having to seek or get consent from another person,” as is the case with condom use.
The first with results is the DoxyPEP study, conducted at two sexual health clinics in San Francisco and Seattle. It drew from a mix of transgender women and men who have sex with men, who had at least one diagnosed STI over the last year. The researchers divided the participants into two groups: one with people who were already HIV-positive and engaged in care, while the other group consisted of people who were on PrEP to prevent infection with HIV. For the active part of the study, a subset of the participants received doxy, and the rest of the participants did not.
The researchers intentionally chose to do the study in a population at the highest risk of having STIs, who were very health oriented, and “who were getting screened every three months or so as part of their PrEP program or their HIV care program,” says Connie Celum, a senior researcher at the University of Washington on the study.
Each member of the active group was given a supply of doxy and asked to take two pills within 72 hours of having sex where a condom was not used. The study was supposed to run for two years but, in May, it stopped halfway through, when a safety monitoring board looked at the data and recommended that it would be unethical to continue depriving the control group of the drug’s benefits.
Celum presented these preliminary results from the DoxyPEP study in July at the International AIDS Conference in Montreal. “We saw about a 56 percent reduction in gonorrhea, about 80 percent reduction in chlamydia and syphilis, so very significant reductions, and this is on a per quarter basis,” she told a later webinar.
In Kenya, another study is following a group of cisgender women who are taking the same two-pill regimen to prevent HIV, and the data from this research should become available in 2023. Senior researcher Victor Omollo, with the Kenya Medical Research Institute, noted that “these are prevention interventions that women can control on their own without having to seek or get consent from another person,” as is the case with condom use, another effective prevention tool.
Antibiotic resistance is a potentially big concern. About 25 percent of gonorrhea strains circulating in the U.S. are resistant to the tetracycline class of drugs, including doxy; rates are higher elsewhere. But resistance often is a matter of degree and can be overcome with a larger or longer dose of the drug, or perhaps with a switch to another drug or a two-drug combination.
Research has shown that an established bacterial infection is more difficult to treat because it is part of a biofilm, which can leave only a small portion or perhaps none of the cell surface exposed to a drug. But a new infection, even one where the bacteria is resistant to a drug, might still be vulnerable to that drug if it's used before the bacterial biofilm can be established. Preliminary data suggests that may be the case with doxyPEP and drug resistant gonorrhea; some but not all new drug resistant infections might be thwarted if they’re treated early enough.
“There are some tradeoffs” to these interventions, Celum says, and people may disagree on the cost of increased resistance balanced against the benefits of treating the STIs and reducing their spread within the community.
Resistance does not seem to be an issue yet for chlamydia and syphilis even though doxy has been a recommended treatment for decades, but a remaining question is whether broader use of doxy will directly worsen antibiotic resistance in gonorrhea, or promote it in other STIs. And how will it affect the gut microbiome?
In addition, Celum notes that we need to understand whether doxy will generate mutations in other bacteria that might contribute to drug resistance for gonorrhea, chlamydia or syphilis. The studies underway aim to provide data to answer these questions.
“There are some tradeoffs” to these interventions, Celum says, and people may disagree on the cost of increased resistance balanced against the benefits of treating the STIs and reducing their spread within the community. That might affect doctors' willingness to prescribe the drug.
Turning research into action
The CDC makes policy recommendations for prevention services such as taking doxy, requiring some and leaving others optional. Celum says the CDC will be reviewing information from her trial at a meeting in December, but probably will wait until that study is published before making recommendations, likely in 2023. The San Francisco Department of Public Health issued its own guidance on October 20th and anecdotally, some doctors around the country are beginning to issue prescriptions for doxy to select patients.
About half of new STIs occur in young people ages 15 to 24, a group that is least likely to regularly see a doctor. And sexual health remains a great taboo for many people who don't want such information on their health record for prying parents, employers or neighbors to find out.
“People will go out of their way and travel extensive distances just to avoid that,” says Mahn, the National Coalition director. “People identify locations where they feel safe, where they feel welcome, where they don't feel judged,” Mahn explains, such as community and family planning clinics. They understand those issues and have fees that vary depending on a person’s ability to pay.
Given that these clinics already are understaffed and underfunded, they will be hard pressed to expand services covering the labor intensive testing and monitoring of a doxyPEP regimen. Sexual health clinics don't even have a separate line item in the federal budget for health. That is something the National Association of STI Directors is pushing for in D.C.
DoxyPEP isn't a panacea, and it isn't for everyone. “We really want to try to reach that population who is most likely going to have an STI in the next year,” says Celum, “Because that's where you are going to have the biggest impact.”