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Ensuring Bone Health for Adolescents Identifying as Transgender

September 26, 2022

About 1.4% of American adolescents report identifying as transgender.

That figure comes from a report released in June by the University of California, Los Angeles School of Law’s Williams Institute, after analyzing data from the U.S. Centers of Disease Control and Prevention. This estimate almost doubles the organization’s previous figure for that age group from 2017 and contributes to an estimated total of 1.6 million persons in the country who identify as transgender.

“For many people, to have one’s physical characteristics not align with their own internal sense of their gender is highly distressing,” said Dr. Stuart Weinzimer, a professor of pediatrics at Yale School of Medicine and the research director of the Yale Gender Program. “We call it dysphoria — feelings of extreme discomfort with one’s own self, that your body and identity are not in sync.”

This discomfort can grow at puberty, a time when physical changes can trigger initial concerns about a gender assigned at birth or amplify longstanding distress.

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

Gender dysphoria can present serious, even life-threatening risks, including anxiety, depression, and suicidality. The Yale Pediatric Gender Program provides thorough psychosocial evaluations for those who are experiencing this “disconnect” in their gender identity and seeking help. Individuals considering or already pursuing a social transition are seen with their parents or caregivers and provided the opportunity to discuss and better understand these experiences. After comprehensive consultation, next steps based on individual goals are discussed. In this context, gender-affirming hormone therapy (GAHT) may be offered as a possible option.

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

Hormones and Bone Strength

Bones are a live organ. On an ongoing basis, bones respond to weight stressors by strengthening themselves, like a computerized bridge programmed with the sense and capacity to somehow reinforce itself and support the load of traffic above. Bones also work a little like an individual retirement plan, in that people make contributions (via minerals deposited in their bones) throughout their lives so when they are older, they can make withdrawals to support themselves. The most rapid period of such investments for increasing bone strength occurs in late adolescence before typically plateauing through an individual’s 20s and 30s and generally starting to diminish in the 40s.

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

Under the influence of the male hormone testosterone, the strong cylinder around the outside of bones, known as the periosteum, grows in thickness. This is why cisgender adult men (assigned 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 remodeling as some cells deposit calcium and other minerals and other cells chew up bone cells and dissolve them. In this way, estrogen slows the degradation of bones. This is why cisgender women experiencing lower levels of estrogen through menopause are at greater risk for 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 regimens 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 a lot of links,” Carpenter said. “But if you have one link that is thin, that is where your chain is likely to break. You have to determine if there are those weak spots.”

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

In addition, the study, based on work begun by former post-doctoral 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 interfere with normal skeletal health in this population as they age.

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

Possible strategies could include changes to diet and exercise or adjusting hormonal regimens.

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

“We know that GAHT saves lives,” Weinzimer said. “Even though it is effective, we know there are risks. The way to address the risks is not to say, ‘It’s dangerous — don’t do it.’ It is to identify what those risks are, understand the physiology, and learn how to counteract the negative effects.”

Submitted by Jessica Quistorff on September 13, 2022