The most common reason for many to consider including it in a steroid stack is for anti-estrogenic activity. An amount of aromatizing steroid marginally over the amount that would be tolerable without Mesterolone became tolerable with the inclusion of it.

The mechanism by which it has some effectiveness in this regard is from binding weakly to the estrogen receptor without activating it, and to the aromatase enzyme. In the first case, this partially reduces the number of receptor sites momentarily available to bind estrogen, thus reducing estrogenic activity. In the second case, some fraction of aromatase molecules at any given moment are unavailable to bind and convert testosterone, their binding sites being occupied with mesterolone. The second most common reason is probably to address a fear that libido might be lost without it. It is true that when added to normal androgen levels, Mesterolone has an androgenic effect that in many cases improves libido.