No. In theory, at steady state it should not change. This applies to TRT with constant dosing. Otherwise you have to consider possible HPTA suppression.
Here's an analogy: Think of SHBG as a pond with water flowing in and out. Free testosterone is analogous to the water running out. Now consider mesterolone as a bunch of boulders you throw into the pond. When this happens there is a transient surge of out-flow—free testosterone—but over time the flow of water leaving the pond again matches what's flowing in.
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