Chantal Wiepjes

Dutch Summary (Summary in Dutch)

Transgender people
Transgender people are individuals diagnosed with gender dysphoria. This diagnosis can be made when there is a discrepancy between the sex assigned at birth and the identified gender, and when this causes suffering. Individuals diagnosed with gender dysphoria can undergo medical treatment to adapt their body to their identified gender, which can include hormone treatment and surgery.

Trans women are assigned male at birth but identify as female. Hormone treatment consists of anti-androgens to suppress testosterone and the use of estrogens. This treatment leads to physical changes such as breast growth, female fat distribution, and a decrease in body hair. After at least one year of hormone treatment, surgeries like vaginoplasty can be performed. Trans men are assigned female at birth but identify as male. They are treated with testosterone, resulting in changes like increased body hair, more muscle mass, and a lower voice. Surgical options include mastectomy and hysterectomy.

Bones
Human bones consist of cortical bone (the hard outer layer) and trabecular bone (the spongy inner part). Bone tissue is constantly being formed by osteoblasts and broken down by osteoclasts. The balance between these processes determines whether bone mass increases or decreases. Bone mass typically increases until young adulthood and then gradually decreases with age, more rapidly in postmenopausal women.

Bone health is measured through bone turnover markers in the blood or dual-energy X-ray absorptiometry (DXA) scans, which measure bone mineral density (BMD) to diagnose conditions like osteoporosis.

Hormonal Effects on Bones
Sex hormones play a crucial role in bone development and maintenance. During puberty, boys develop wider bones than girls, partly due to testosterone's direct effects or its indirect effect through muscle mass. In women, estrogens are vital for maintaining bone quality; when estrogen levels drop during menopause, BMD decreases. In men, maintenance of bone health is also significantly regulated by estrogens derived from the aromatization of testosterone.

Thesis Goals and Findings
This thesis investigates the short-term and long-term effects of hormone treatment on bone health in transgender people. Key findings include:

- The population seeking transgender healthcare has grown significantly since 1972, with very low rates of regret after surgery (0.5%).
- In trans women, BMD increased and bone turnover decreased during the first year of treatment, especially in those with higher estrogen levels. Vitamin D supplementation further enhanced these positive effects.
- In trans men, BMD increased, and bone turnover markers shifted towards a more positive balance. Older trans men (over 50) showed the greatest increases, confirming that estrogen (from aromatized testosterone) is a key regulator of bone health in this group.
- Vitamin D deficiency was found to be very common in the study population.
- In trans women, muscle mass and strength decreased, while they increased in trans men. In trans men, the increase in muscle mass was associated with increased BMD.
- Long-term studies (up to 10 years) showed that hormone treatment is safe for bone health. While trans women often had lower initial BMD, it stabilized or improved during treatment. Higher estrogen levels were associated with better bone outcomes.
- Bone geometry analysis showed no significant changes in cortical width during treatment. However, the trabecular bone score (TBS) improved in trans women and slightly decreased in trans men (though remaining within normal ranges), indicating positive effects of estrogen.
- Fracture risk in transgender people using long-term hormone treatment did not exceed that of the general population. While older trans women had a higher risk than cis men, their risk was comparable to that of cis women.

Practical Implications and Conclusion
Regular DXA scans for bone health monitoring during standard hormone treatment are not strictly necessary unless specific risk factors exist. However, baseline scans are recommended for trans women due to a higher prevalence of low initial BMD. Aiming for adequate estrogen levels and addressing vitamin D deficiency are important clinical goals. Overall, the results of this thesis are reassuring regarding the safety of hormonal treatment for bone health in transgender people.