Background
Growth hormone (GH) and insulin-like growth factor (IGF-1) are known to play an important role in both health and disease. During puberty, when sex hormone production starts, IGF-1 levels are found to be the highest during life. Later in life, IGF-1 concentrations are thought to be associated with an increased risk for several types of cancer. . This study will investigate the short- and long-term effect of cross-sex hormone treatment on the IGF-1 concentration in healthy adults with gender dysphoria.

Methods
This prospective observational study involves a follow-up of the IGF-1 levels and its binding protein IGF-BP3 in 613 individuals diagnosed with gender dysphoria. 312 transwomen and 301 transmen were administered exogenous cross-sex hormones as part of their treatment, and IGF-1 and IGF-BP3 concentrations were measured up to 36 months after the start of hormone therapy.

Results
In both transmen and transwomen, an average of 12% increase of IGF-1 levels was observed in the first 3 months after the start of sex hormone replacement. After 36 months of treatment, IGF-1 concentrations returned to basal levels. IGF-BP3 does not follow this trend and shows less of an increase. There are no differences observed between the groups that are using cyproterone acetate (CPA) as an androgen suppressor or not, nor between the groups that underwent gonadectomy or not.

Conclusion
A small IGF-1 increase of ~12% after cross-sex hormone administration is observed in the first months after treatment in both transmen and transwomen but is transitory in the longer term. The increase of the IGF-BP3 concentration is slightly less, indicating the biological available IGF-1 concentration increase is higher than that of the total IGF-1 concentration.