Does Sertraline affect cortisol regulation? (3+ effects)

In this article, we will explore the relationship between Sertraline and cortisol levels in the body. Additionally, we will discuss whether this interaction has potential clinical significance.

Does Sertraline affect Cortisol regulation?

Sertraline may affect cortisol regulation in some individuals. Cortisol, a hormone produced by the adrenal glands, plays a crucial role in the body’s stress response (1). While Sertraline primarily targets the serotonin neurotransmitter, it can indirectly influence other neurotransmitters and hormones, including Cortisol (1,2).

Nevertheless, it is important to recognize that individual responses to this medication can differ, and not everyone may experience changes in cortisol levels while on this medication.

Research has indicated that individuals suffering from mental health disorders, such as depression and anxiety, often experience elevated cortisol levels associated with these conditions (3).

Sertraline, prescribed to manage these disorders, can impact the hypothalamus pituitary adrenal axis (HPA-axis), which, in turn, influences the production and release of cortisol hormone levels, affecting cortisol levels and effects in the body (1,3,4).

What does research suggest?

The available research on how Sertraline impacts cortisol regulation in the body is limited. However, ongoing research is exploring the interaction between cortisol and Sertraline.

One study found that Sertraline enhances glucocorticoid receptor (GR) mediated gene transcription and cortisol action in both the brain and periphery. This effect is achieved by inhibiting steroid transporters that regulate intracellular cortisol concentration (4,6).

Furthermore, this mechanism may reverse glucocorticoid resistance associated with GR downregulation in depressive disorders.

Additionally, the study hypothesized that antidepressants may also induce GR downregulation through the activation of GR translocation (4,6).

A separate study on Sertraline’s impact on the cortisol response to corticotropin-releasing hormone (CRH) indicated that acute and chronic administration of Sertraline increases cortisol secretion in the body (6).

Factors influencing Sertraline’s effect on cortisol regulation:

Several factors can influence how Sertraline affects corrisol regulation in individuals. These factors include:

  • Dosage: The dose of Sertraline can influence its effects on cortisol. Higher doses may have more pronounced effects on cortisol levels.
  • Duration of treatment: Sertraline’s effects on cortisol regulation become more pronounced with long-term use.
  • Underlying conditions: Underlying medical conditions such as cushing’s syndrome can influence Sertraline’s effects on cortisol levels.
  • Drug interactions: Other medications taken alongside Sertraline may interact and influence its impact on cortisol levels.

What are the Sertraline-induced effects on Cortisol regulation?

Sertraline’s impact on cortisol regulation can result in both therapeutic and adverse outcomes as elaborated below (4,5,6):

Therapeutic effects:

Sertraline modulates the hypothalamus-pituitary-adrenal (HPA) axis by influencing the release of corticotropin-releasing (CRH) from the hypothalamus and adrenocorticotropin hormone (ACTH) from the pituitary gland.

By influencing the HPA axis, Sertraline helps regulate the body’s response to stress. It reduces the hyperactivity of the HPA axis potentially lowering stress levels in individuals. This is particularly beneficial in Sertraline’s action in managing anxiety, depression and post-traumatic stress disorder (PTSD).

Adverse effects:

Sertraline administration has been associated with increased cortisol secretion in the body. This may result in abnormally high cortisol levels in the bloodstream (hypercortisolemia). Hypercortisolemia may lead to conditions like Cushing’s syndrome, and disruptions in the circadian rhythm. 

Disruptions in the circadian rhythm may potentiate some of Sertraline’s side effects such as changes in appetite, weight, insomnia, sweating and bowel changes.

How to minimise the effects of Sertraline on cortisol regulation?

If you experience undesirable effects while taking Sertraline you should:

  • Maintain frequent consultations with your doctor – While using this medication, it is essential to have regular consultations with your primary healthcare provider. Your doctor needs to monitor you closely for potential side effects to maintain safe and efficacious treatment.
  • Dose adjustments – Your doctor may modify the dosage of the medication to reduce the likelihood of encountering these side effects.
  • Consideration of alternative medications – Your doctor may consider transitioning you to an alternative medication with fewer side effects.


Sertraline may affect cortisol levels in the body inducing both therapeutic and adverse effects on the body. Therefore it is important to maintain frequent consultations with your doctor.

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Jones C, Gwenin C. Cortisol level dysregulation and its prevalence—Is it nature’s alarm clock? Physiological Reports [Internet]. 2020 Dec 19 [cited 2023 Oct 6];8(24). Available from:




Singh HK, Saadabadi A. Sertraline [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2021 [cited 2023 Oct 5]. Available from:




Dziurkowska E, Wesolowski M. Cortisol as a Biomarker of Mental Disorder Severity. Journal of Clinical Medicine [Internet]. 2021 Jan 1 [cited 2023 Oct 6];10(21):5204. Available from:




Yehuda R, Yang RK, Golier JA, Grossman RA, Bierer LM, Tischler L. Effect of Sertraline on Glucocorticoid Sensitivity of Mononuclear Leukocytes in Post-Traumatic Stress Disorder. Neuropsychopharmacology [Internet]. 2005 Aug 10 [cited 2023 Oct 6];31(1):189–96. Available from:




Yehuda R. Dose-Response Changes in Plasma Cortisol and Lymphocyte Glucocorticoid Receptors Following Dexamethasone Administration in Combat Veterans With and Without Posttraumatic Stress Disorder. Archives of General Psychiatry [Internet]. 1995 Jul 1 [cited 2023 Oct 6];52(7):583. Available from:




Carpenter LL, Tyrka AR, Lee JK, Tracy AP, Wilkinson CW, Price LH. A placebo-controlled study of sertraline’s effect on cortisol response to the dexamethasone/corticotropin-releasing hormone test in healthy adults. Psychopharmacology [Internet]. 2011 May 27 [cited 2023 Oct 6];218(2):371–9. Available from:


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