Cortisol is one of several hormones produced by the adrenal glands, sitting on top of both kidneys. Adrenals produce several families of hormones under regulation of a pituitary hormone called adrenocorticotropic hormone (ACTH). These groups of hormones are derived from three so-called zonae and an area called he hilus of the adrenal gland.
Cortisol, a steroid hormone, is the main product of the zona fasciculate (zF), which produces the so-called glucocorticoid hormones (also called corticosteroids) and is the body’s main stress hormone. In other words, adrenal glands produce the hormone cortisol in response to stress. But, like every producer of a product, adrenals can produce only so much of this stress hormone. If stress is too severe and/or lasts for too long, the adrenals may, simply, run out of cortisol and adrenal glands may become insufficient (i.e., cortisol may become abnormally low or can almost completely disappear). Some physicians use the term “adrenal fatigue” to describe milder cases of adrenal insufficiency, while others strongly dislike the term an consider it misleading and inappropriate.
Cortisol has multiple roles to play: It to a degree controls blood sugar levels, supports breakdown of carbs, proteins, and fats, affects blood pressure (high levels raise blood pressure), suppresses inflammation (i.e., is an excellent suppressor of the immune system), is involved in regulation of the sleep-wake cycle, and raises glucose in response to stress.
The other two zonae are the most outer zona glomerulosa (zG) and most inner zona reticularis (zR), adjacent to the hilus of the adrenals. The zG produces the so-called mineral-corticosteroids, with the principal one being the hormone aldosterone that is essential in control of bodily fluids by causing water retention, increasing sodium in the GI tract, disposing of excess potassium through urine. Finally, the zR produces androgen hormones all androgen hormones in roughly 50/50 partnership with ovaries, except for one androgen hormone, DHEA-S, which is only produced by adrenals.
One additional characteristic of the adrenals of potential importance, though not widely known even among fertility specialists: Ovaries and adrenals share a common embryonic primordium. In other words, ovaries and adrenal glands are derived from the same stem cell lineages. This, of course, can have major relevance to female infertility but has hardly been explored in yet. Another widely unknown fact is that adrenal, after ovaries, have the highest density of AMH-hormone receptors. Presence of hormone receptors in a tissue usually denote a function for this hormone in this tissue. While AMH, of course, has major functions in ovaries, no function on adrenals has been described so-far, however.
The only direct function the adrenals so-far have been demonstrated to exert on ovaries is through their androgen production by the zR. Interestingly, as mostly only the CHR’s investigators have reported, the frequently observed hypo-androgenism in infertile women in association with various infertility diagnoses,1-3 almost universally is due to adrenal rather than ovarian androgen insufficiency and has become the basis for androgen supplementation for many female infertility patients.
But as noted before, all the adrenal zonae are under ACTH control, it, therefore, should not surprise if low adrenal androgen production may also be accompanied by dysfunction in the other two zonae. And the CHR’s investigator, indeed, in 2016 reported that infertile women with low functional ovarian reserve, who almost uniformly are hypo-androgenic,3 also demonstrate a degree of hypo-cortisolims.4,5
Coming back to the immune-suppressive effects of corticosteroids, they, of course, represent a mainstay of medical treatments with all kinds of hyperactive immune systems, from long-term asthma treatments in inhalers to autoimmune diseases and inflammatory diseases as well as allergies. But when we receive treatment with corticosteroid and levels, therefore, rise in our bodies, a message gets back to the pituitary gland (a so-called “feed-back”) that says, enough ACTH already. As ACTH stops stimulating the adrenals, androgen production can stop, as we recently saw in 2 infertile women who came to The CHR after years of failed IVF cycles in multiple centers and having been labeled as suffering from “unexplained infertility.” Both were on long-term corticosteroid treatments and fully recovered, once taken off steroids and supplemented with DHEA to raise their testosterone levels back into normal range. (A paper describing these two cases was just submitted for publication).
One final point on cortisol measurements: they should be obtained early in the morning because levels rise after 10am.
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