Can elevated Adrenocorticotropic Hormone (ACTH) and cortisol levels be associated with Polycystic Ovary Syndrome (PCOS)?

From the Guidelines

Elevated Adrenocorticotropic Hormone (ACTH) and cortisol levels can be associated with Polycystic Ovary Syndrome (PCOS) due to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased production of cortisol and adrenal androgens, which contribute to the classic symptoms of PCOS. The relationship between PCOS and hormonal imbalances, including those involving ACTH and cortisol, is complex and not fully understood, but research suggests that some women with PCOS may experience dysregulation of the HPA axis, which controls stress hormones including cortisol 1. This dysregulation can lead to increased ACTH production from the pituitary gland, which stimulates the adrenal glands to produce more cortisol and adrenal androgens, exacerbating symptoms such as irregular periods, acne, excess hair growth, and infertility. Additionally, elevated cortisol can worsen insulin resistance, a common issue in PCOS patients, creating a cycle that further exacerbates hormonal imbalances 1. Key points to consider in the diagnosis and management of PCOS-related hormonal imbalances include:

• Testing for hormonal abnormalities, such as morning cortisol levels, ACTH stimulation tests, or 24-hour urinary cortisol measurements, to distinguish PCOS-related changes from other conditions like Cushing's syndrome.
• Addressing stress management as part of a comprehensive treatment plan, potentially including medications that target adrenal hormone production.
• Recognizing the complexity of PCOS and the need for individualized treatment approaches, taking into account the presence of hormonal imbalances and their impact on overall health and well-being.

From the Research

Association between Elevated ACTH and Cortisol Levels and PCOS

• Elevated Adrenocorticotropic Hormone (ACTH) and cortisol levels have been observed in women with Polycystic Ovary Syndrome (PCOS) 2, 3, 4, 5
• Studies have shown that women with PCOS exhibit an exaggerated response of ACTH and cortisol to corticotropin-releasing hormone (CRH) stimulus 5
• The increased production rate of cortisol and androgens in PCOS may be related to altered cortisol metabolism, including enhanced 5alpha-reduction and impaired reactivation of cortisol from cortisone 2
• Insulin resistance and hyperinsulinemia may also contribute to the elevated cortisol production rate in PCOS 2, 3

Adrenal Androgen Production in PCOS

• Adrenal androgen excess is present in 20-30% of patients with PCOS, detectable primarily by elevated dehydroepiandrosterone sulfate (DHEAS) levels 3
• The production of adrenal androgens in response to ACTH appears to be closely related to altered factors regulating glucose-mediated glucose disposal and increased peripheral metabolism of cortisol 3
• Adrenal hyperresponsiveness to stimulation is characteristic of PCOS, and may be due to excess stimulation of the adrenal by ACTH or increased cortisol clearance with compensatory hypersecretion of ACTH 6

Evaluation of the Pituitary-Adrenal Axis in PCOS

• Impaired adrenal function is common in patients with PCOS, with abnormal regulation of cytochrome P450 17 alpha believed to cause the exaggerated 17-hydroxyprogesterone (17OHP) response to ACTH stimulation 4
• The exaggerated 17OHP response to ACTH stimulation in PCOS is revealed by stimulation at a pharmacological dose (250 microg) but not by a physiological dose (1 microg) 4
• Women with PCOS may demonstrate hyperfunction of the hypothalamic-pituitary-adrenal axis, which may be involved in the physiopathologic events leading to the complexity of the syndrome 5