The Changing Landscape in the Assessment of Steroid Hormone concentrations: is it time to let them free? (CLASH-free)

Steroid hormones such as testosterone or vitamin D are vital for
human physiology. In circulation, steroid hormones bind to specific
binding proteins and albumin, with only a small fraction circulating
freely. The ‘free hormone hypothesis’ suggests that this free fraction
is responsible for biological activity. Though experimental and clinical
data support this, routinely available methods measure total hormone
levels. Relying on total hormone levels could lead to incorrect
diagnosis and treatment, especially in conditions where binding
protein production is altered (e.g. obesity, pregnancy). Direct free
hormone measurements are not available in clinical routine.
Formulas to estimate free steroid hormone concentrations are used
instead, but their applicability in many clinical conditions is
questionable, so is the correctness of therapeutic actions based on
these results.
With CLASH-free, we will improve the clinical applicability of free
steroid hormone concentrations in patients with specific conditions by
using state-of-the-art methods. We will first survey current clinical
practices in steroid measurements. Next, we will develop methods for
direct free steroid hormone measurements and investigate the
reliability of free hormones in conditions with alterations in binding
protein production. Based on these findings, we will improve current
formulas to better estimate free hormone levels. Finally, we will
investigate the clinical relevance of free steroid hormones.