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How Prescription Drugs Are Creating Cortisol Chaos in Your Body

Updated: May 6, 2019

The human stress response system is extremely complex and is influenced by a plethora of internal and external factors. Age, gender, ethnicity, childhood experiences, personality type, and occupation are only some of the factors capable of affecting how we individually respond to various stressors. Studies have shown that chronic stress can adversely affect health in many ways. Not only can it indirectly lead to nuisance physical and emotional symptoms, it also can contribute to the formation of diseases such as heart disease, diabetes, and cancer.

Although medical practices around the world are gradually embracing a more ‘integrative’ approach to patient care, many health care professionals remain quick to reach for their prescription pads when faced with a patient who suffers from symptoms such as chronic fatigue or depression. This approach may offer patients temporary or partial relief from their ailments, however many of these drugs can have untoward effects on the body, including its ability to function normally under stressful conditions. In fact, many of the over 4000 prescription drugs as well as over the counter medications and illicit drugs can inhibit the body’s ability to properly make stress hormones, cortisol in particular.

Medications that Affect Perceptions

Imagine yourself in a very stressful situation. Perhaps you are getting ready to give a seminar to a large audience or you are having a very heated discussion with your spouse. One area of your brain processes cues in your environment and then sends messages to another part of your brain which interprets these messages as harmless or ‘stressful’. If your brain perceives you to be in imminent danger, cortisol and other ‘fight or flight’ hormones are released. Now, imagine you are in the same situations but are now under the influence of a medication that affects your perception of stress in your environment. What happens to cortisol production now? Studies have shown that individuals who take medications such as anti-depressants, anti-anxiety medications, and chronic pain medications have a reduction in stress induced cortisol release. Certainly, in some situations, is potentially beneficial. For example, extensive medical literature verifies elevations in cortisol to be a cause of major depression. As such, giving anti-depressant medications to lower their cortisol may be beneficial. However, in patients who suffer from ‘atypical’ depression, a condition associated with low cortisol, prescribing the same medication may actually be ineffective or even detrimental.

Medication that Affect Cortisol Production

Cortisol , as well as all of the other steroid hormones (testosterone, progesterone, DHEA, etc), is manufactured from cholesterol. The four step process of conversion of cholesterol to cortisol requires four different chemicals or ‘enzymes’. Various medications can affect every aspect of this conversion process. For example, medications used to lower cholesterol levels could clearly be problematic. How are we going to make a loaf of bread (cortisol) without enough flour (cholesterol)? The enzymes responsible for converting cholesterol into cortisol can also be turned up, down, or even off by certain drugs. Progestin (not progesterone) containing oral contraceptives have also been implicated in lowering cortisol production, presumably from their negative effects on the production of progesterone, another important ingredient in our cortisol production recipe.

Medications that Influence Circulating Cortisol Levels

Cortisol is a ‘lipophilic’ (drawn to fatty tissue) hormone and is therefore unable to circulate in the blood stream in its ‘free’ or ‘bio-available’ form. In order to circulate, cortisol must bind to a protein called cortisol binding globulin (CBG). I often use the analogy of passengers (cortisol molecules) who require vehicles (CBG molecules) to transport them away from their jobs. If more vehicles (CBG) are available, then more passengers (cortisol) will get into them and fewer will be available to work. So essentially, the more CBG driving around your blood stream, the less free cortisol will be available to do its job.

Not only can pharmaceutical agents indirectly influence cortisol by affecting the absolute amount of CBG (i.e. oral contraceptives, oral estrogens) they can also affect how ‘tightly’ CBG will bind to cortisol. For instance, body temperature is one important factor influencing how well CBG will hold on to cortisol. In the case of elevations in body temperature, such as fever, CBG will release more cortisol so it can modulate the immune response to attack the cause of the fever. If a patient takes acetaminophen or an anti-inflammatory medication, drugs known to decrease fever, then CBG will hold onto cortisol more tightly leaving less of it available in the blood stream to do its immune enhancing job.

Medications that Inhibit Adrenal Cortisol Production

The production of hormones in the body is under tight regulation. Structures in the brain (the hypothalamus and the pituitary) control when and how much a particular gland will produce its respective hormone(s). If these brain structures detect too much of a hormone in the body, they will ‘turn down’ the messages sent to various glands to reduce production of said hormone(s). Under normal circumstances, properly functioning adrenal glands produce cortisol in response to these central commands.

Picture what can happen to this tightly controlled system if an oral, topical, or inhaled steroid medication is suddenly introduced. If central command receives word that hormones are coming in from another source, they will tell the adrenal glands to halt cortisol production in order to protect the body from the harmful effects of excess cortisol. In the short term, this may not be particularly problematic. However, if these steroid medications are given for weeks, months, or even years, endogenous cortisol production plummets. To add insult to injury, even if steroid medications are weaned gradually, it may take an extensive period of time for the adrenal glands to resume normal cortisol production.

Be Educated

Although prescription medications are useful and necessary in certain medical situations, both health care professionals and patients need to be aware of the potential negative effects drugs can have on the integrity of the stress response system. Prior to testing for stress hormone abnormalities, consideration may be given to slowly discontinuing any unnecessary medications in order to obtain accurate test results.


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2. Hibel LC, Granger DA, Kivlighan KT, Blair C, et al. “Individual differences in salivary cortisol: Associations with common over-the-counter and prescription medication status in infants and their mothers”. Hormones and Behavior. 2006; 50:293-300.

3. Kirschbaum C, Kudielka M, Gaag J, Schommer NC, Helhammer DH. “Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis”. Psychosom Med. 1999; 61:154-162.

4. Kudielka BM, Helhammer DH, Wust S. “Why do we respond so differently? Reviewing determinants of human salivary cortisol responses to challenge”. Psychoneuroendocrinology. 2009; 34:2-18.


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