High levels of estrogen causes an increase in levels of cortisol-binding globulin which – you guessed it – binds cortisol in the blood. The amount of free cortisol available to enter the cell membranes and activate receptors inside the cell is now greatly diminished. In addition, estrogen dominance interferes with the release of cortisol from the adrenal cortex. Another key fact is that cortisol is made from progesterone. When progesterone levels dramatically decline after pregnancy, so does cortisol production. Whether it is an inhibited output of cortisol from the adrenal cortex, an overall decrease in cortisol production or whether cortisol is bound in the bloodstream, all follow with the same result: adrenal fatigue.
In addition, the function of the pituitary and its ability to produce other hormones are tested. Typically, measurements of ACTH — the pituitary hormone most relevant for maintenance of normal adrenal function — along with thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin are made under resting conditions and following provocative simulation, such as following the administration of corticotrophin releasing hormone (CRH), which leads to an increase in ACTH levels under normal conditions.