Ensuring Bone Health for Transgender-Identifying Adolescents

About 1.4% of American adolescents report identifying as transgender.

That figure comes from a report published in June by the Williams Institute at the University of California, Los Angeles, after analyzing data from the US Centers for Disease Control and Prevention. This estimate nearly doubles the organization’s previous figure for this age group from 2017 and adds to the estimated 1.6 million people in the country who identify as transgender.

“For many people, having someone’s physical characteristics not match their own internal sense of their gender is deeply distressing,” said Dr. Stuart Weinzimmer, professor of pediatrics at Yale School of Medicine and research director of the Yale Gender Program. “We call it dysphoria—a feeling of extreme discomfort with yourself, that your body and identity are out of sync.”

This discomfort can increase in puberty, a time when physical changes can trigger initial concerns about gender assigned at birth or increase long-term distress.

“One of the main tasks of adolescence is to develop one’s identity, including gender identity,” Weinzimmer said. “Most people really don’t think twice about their gender identity because they don’t have to, just like you don’t have to think about breathing. Just do it. However, for people who are not physically in sync with how they feel inside, this disconnect can become a barrier to mental health. A barrier to one’s own personality formation.”

Gender dysphoria can pose serious, even life-threatening risks, including anxiety, depression, and suicidality. The Yale Pediatric Gender Program provides in-depth psychosocial assessments for those who experience this “disconnection” in their gender identity and seek help. People who are considering or already seeking a social transition are seen with their parents or carers and given the opportunity to discuss and better understand these experiences. After a comprehensive consultation, next steps are discussed according to individual goals. In this context, gender-affirming hormone therapy (GAHT) can be suggested as a possible option.

As is true with many medications, GAHT may present risks as well as benefits to the individual. For example, patients undergoing GAHT with testosterone may develop adverse cholesterol profiles that may increase long-term heart health risk. Patients undergoing GAHT with estrogen may have an increased risk of blood clots. GAHT may also pose other health risks that have not yet been fully studied. Yet, despite knowing the potential risks, the experience of gender dysphoria may be so clear and overwhelming that GAHT may be chosen.

Hormones and bone strength

Bones are a living organ. Constantly, bones respond to weight-related stressors by strengthening themselves, like a computerized bridge programmed with the sense and capacity to somehow strengthen and support the load from the traffic above. Bones also works a bit like an individual pension plan, as people make contributions (via minerals deposited in their bones) throughout their lives, so when they’re older they can make withdrawals to support themselves. The most rapid period of such investment to increase bone strength occurs in late adolescence, before typically plateauing in an individual’s 20s and 30s and generally beginning to decline in the 40s.

“You build bone strength in your early years, so you have that reserve,” said Dr. Thomas Carpenter, professor of pediatrics and orthopedics and rehabilitation at Yale School of Medicine. “The presence of sex hormones at puberty plays an important role in building this strength.”

Under the influence of the male hormone testosterone, the tough cylinder around the outside of the bones, known as the periosteum, grows in thickness. This is why cisgender male adults (defined as male at birth and identifying as male) tend to have larger, thicker, and stronger bones.

The female hormone estrogen tends to inhibit or suppress the breakdown of bones, which are regularly remodeled as some cells deposit calcium and other minerals and other cells chew on bone cells and dissolve them. In this way, estrogen slows down the breakdown of bones. This is why cisgender women who experience lower estrogen levels during menopause are at greater risk of osteoporosis and fractures.

The typical patterns and timing of pubertal development are altered in those who undergo GAHT during adolescence, and the effects of these hormonal patterns on the process of bone development are not fully understood.

A better picture of bone health

Standard bone density measurements use an X-ray machine (commonly called DXA), which cannot detect variability in the microstructures that affect bone quality.

“Bone structure is like having a strong chain with many links,” Carpenter said. “But if you have one link that’s thin, that’s where your chain is likely to break. You need to determine if there are these weak spots.

With a grant from WHRY, Dr. Weinzimer, in collaboration with Dr. Carpenter and Yale Pediatric Program Director and Founder Dr. Christy Olezeski, used more sophisticated methods to obtain a picture of the dynamic process of bone development. including bone density, quality, and architecture, and they assessed bone changes during the first year of GAHT in adolescents who identify as transgender.

In addition, the study, building on work started by former postdoctoral fellow Apoorva Ravindranath Waikar, will catalog metabolic markers of bone health and identify demographic, clinical and behavioral variables such as diet and exercise that may facilitate or impede normal skeletal health in this population as they age.

“This study represents an important step in being able to see for the first time how these indicators change in people undergoing gender-affirming hormone therapy,” Weinzimer said. “We don’t yet know what that looks like, and we may find that these measures of variability are very different in this population.” If we find that, then we need to look for ways to reduce the risk in that population.

Possible strategies may include changes in diet and exercise or adjusting hormone regimens.

The study will ultimately help inform central clinical questions in GAHT during adolescence, including: Are current treatments effective in optimizing skeletal health when these hormonal therapies are initiated? What role do nonpharmacological influences, such as physical activity and diet, play in the trajectories of these indicators over time? And how can we use this data to counsel individuals and their families so that the healthiest decisions are made about when to start these treatments?

“We know GAHT saves lives,” Weinzimer said. “Although it is effective, we know there are risks. The way to deal with risks is not to say, “It’s dangerous – don’t do it.” It’s about identifying what those risks are, understanding the physiology and learning how to counteract the negative effects.

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