Evaluation of the delay in the initiation and intensity of estrogen replacement therapy on peak bone mass in women with Turner syndrome

• Grant number: 24/19211-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2024
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Patrícia Teófilo Monteagudo
• Grantee: Ana Julia de Oliveira Spada Bonfim
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Turner Syndrome (TS) is a rare genetic condition affecting females, characterized by the complete or partial absence of the second sex chromosome, resulting in short stature, delayed puberty, primary ovarian insufficiency, and increased risk of autoimmune diseases, type 2 diabetes, and osteoporosis. This study investigates the impact of Hormone Replacement Therapy (HRT) and growth hormone (GH) on bone mineral density (BMD) in patients with TS. The research analyzes the correlation between the late onset of HRT and bone mass gain, proposing that the peak bone mass may be delayed in these patients due to the late increase in the concentration of steroid hormones.Patients with Turner Syndrome (TS) frequently present with estrogen and progesterone deficiencies due to primary ovarian insufficiency, which causes an imbalance in bone remodeling, leading to bone mass loss and an increased risk of fractures. Early intervention with Hormone Replacement Therapy (HRT) and Growth Hormone (GH) is crucial to maximize Bone Mineral Density (BMD) and reduce the risk of osteoporosis. The retrospective study analyzed 42 patients followed by the Department of Endocrinology at Escola Paulista de Medicina, considering factors such as age at diagnosis, final height, age at the start of HRT, GH use, and vitamin D and calcium supplementation. Additionally, physical activity was assessed to promote bone health.The central hypothesis of the study is that patients who start HRT later, after the usual age of BMD stabilization, may continue to gain bone mass beyond 20 years of age. This investigation aims to provide evidence that, even with a late initiation of therapy, the continued use of estrogen and GH can promote additional bone mass gains, reducing the risk of osteoporosis and fractures in TS patients. This analysis may reveal that peak bone mass is delayed in these patients due to delayed hormonal maturation, making early intervention even more vital for long-term bone health preservation.The expected outcomes include not only bone mass gain in patients who started HRT late but also a detailed analysis of how the Cumulative Estrogen Exposure Dose (CEED) influences this gain, providing an important quantitative metric to estimate the impact of hormonal nutrition over time. It is expected that patients who used higher doses for longer periods will show significant increases in BMD, surpassing the usual age for peak bone mass, which in women without TS occurs around 20 to 30 years. The study also aims to establish the prevalence of this deficiency in the population and how supplementation can impact BMD levels. Another expected outcome is the adjustment of BMD levels for the short stature of TS patients through the Bone Apparent Mineral Density (BAMD) adjustment, which may provide a more accurate view of bone health in these patients compared to the general population.Finally, this study is expected to identify specific risk factors for low bone mass in TS patients, allowing for the development of personalized strategies for osteoporosis prevention, such as an optimized combination of hormonal regulation, nutritional supplementation, and early intervention with GH. These findings have the potential to significantly improve the clinical management of these patients, enabling better control of bone health throughout life.