From the Guidelines
Hyperandrogenism and hypercortisolism are interconnected through shared metabolic pathways, and addressing the underlying cause of cortisol dysregulation is crucial in managing hyperandrogenism. The relationship between hyperandrogenism and hypercortisolism is complex, with cortisol excess potentially shifting production toward androgens in the adrenal glands, particularly in conditions like congenital adrenal hyperplasia or Cushing's syndrome 1. For patients with suspected hyperandrogenism related to cortisol abnormalities, a comprehensive evaluation including morning cortisol levels, ACTH stimulation testing, and 24-hour urinary free cortisol is recommended. Treatment typically involves addressing the underlying cause, and medications like ketoconazole, osilodrostat, metyrapone, mitotane, etomidate, or somatostatin receptor agonists like pasireotide may be prescribed to control cortisol levels, with careful monitoring for hyperandrogenism in women 1. Additionally, lifestyle modifications including stress management techniques, regular exercise, and adequate sleep are also important as chronic stress can elevate cortisol levels, potentially exacerbating hyperandrogenism. Key considerations in the management of hyperandrogenism related to hypercortisolism include:
- Monitoring for signs of Cushing's syndrome, such as buffalo hump, moon facies, hypertension, abdominal striae, centripetal distribution of fat, easy bruising, or proximal myopathies 1
- Screening for other causes of androgen excess, such as androgen-secreting tumors, exogenous androgens, nonclassic congenital adrenal hyperplasia, acromegaly, genetic defects in insulin action, primary hypothalamic amenorrhea, primary ovarian failure, thyroid disease, and prolactin disorders 1
- Careful selection of medications to control cortisol levels, with consideration of potential effects on androgen production and monitoring for hyperandrogenism in women 1.
From the Research
Relationship Between Hyperandrogenism and Hypercortisolism
- Hyperandrogenism, or elevated androgen levels, is a key feature of Polycystic Ovarian Syndrome (PCOS) and can be assessed clinically or determined by biochemical assays 2.
- Hypercortisolism, or elevated cortisol levels, is associated with Cushing's Syndrome, which can also present with hyperandrogenism 3.
- The diagnosis of Cushing's Syndrome should be considered in women with PCOS phenotype, particularly if they are also affected by other disturbances that increase their pretest probability, such as osteoporosis or bone fractures 3.
- Approximately 70-80% of women with Cushing's Syndrome present menstrual abnormalities, and PCOS findings are found in 46% of these patients 3.
Diagnostic Challenges
- The diagnosis of Cushing's Syndrome can be challenging, and its differentiation from PCOS is not straightforward, as isolated PCOS may be associated with hypothalamic-pituitary-adrenal axis disruption, leading to false-positive results in screening tests 3.
- The diagnostic utility of serum androgen assessment is controversial, but the use of high-performance liquid chromatography and gas chromatography-mass spectrometry for urinary steroid profiling is showing promising results 3.
- The presence of features atypical of PCOS, such as the onset of symptoms outside the decade of 15-25 years, rapid progression of symptoms, or the development of virilization, should prompt more extensive evaluation than that usually undertaken 4.
Biochemical Markers
- Androgen-secreting adrenal tumors can be associated with severe hyperandrogenism, and regression of hypercortisolism after treatment causes disappearance of hyperandrogenism 3.
- The levels of dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and androstenedione are generally elevated or in the upper normal range in patients with ACTH-dependent Cushing's Syndrome 3.
- Adrenal androgens are generally low in patients with cortisol-secreting adrenocortical adenoma 3.