What are the implications of elevated Dehydroepiandrosterone sulfate (DHEAS) and Sex Hormone-Binding Globulin (SHBG) levels?

From the Guidelines

Elevated DHEAS and SHBG levels can indicate several underlying conditions, including polycystic ovary syndrome (PCOS), congenital adrenal hyperplasia, adrenal tumors, or Cushing's syndrome, and require comprehensive medical evaluation and treatment. The most common causes of elevated DHEAS, an adrenal androgen, include PCOS, congenital adrenal hyperplasia, adrenal tumors, or Cushing's syndrome, as noted in a study published in the Journal of Neurology, Neurosurgery and Psychiatry 1. Treatment depends on the underlying cause but may include lifestyle modifications, oral contraceptives, anti-androgens like spironolactone (50-200 mg daily), or metformin (500-2000 mg daily) if insulin resistance is present, as suggested by a systematic review and diagnostic meta-analysis published in Human Reproduction Update 1. Elevated SHBG, which binds sex hormones in the blood, is commonly associated with hyperthyroidism, liver disease, estrogen excess, or certain medications like oral contraceptives, as discussed in a study published in the Journal of Neurology, Neurosurgery and Psychiatry 1. Management focuses on treating the underlying condition, such as anti-thyroid medications for hyperthyroidism or addressing liver dysfunction. Both abnormalities require comprehensive evaluation including physical examination, additional hormone testing (cortisol, thyroid function, other sex hormones), and possibly imaging studies of the adrenal glands or pelvic organs. Some key points to consider in the evaluation and management of elevated DHEAS and SHBG include:

• The diagnostic accuracy of androgen measurement in PCOS, with a systematic review and diagnostic meta-analysis suggesting that total testosterone (TT) and calculated free testosterone (cFT) are the most accurate measures 1
• The importance of considering multiple hormonal disturbances in the evaluation and management of elevated DHEAS and SHBG, as noted in a study published in the Journal of Neurology, Neurosurgery and Psychiatry 1
• The potential impact of antiepileptic drugs on sex hormone levels and the development of PCOS, as discussed in a study published in the Journal of Neurology, Neurosurgery and Psychiatry 1 Overall, the combination of elevated DHEAS and SHBG is somewhat unusual and suggests multiple hormonal disturbances that need careful investigation to determine the appropriate treatment approach.

From the Research

Implications of Elevated DHEAS and SHBG Levels

• Elevated DHEAS levels are associated with higher values of testosterone and androstenedione in women with polycystic ovary syndrome (PCOS) 2, 3.
• A high prevalence of increased DHEAS levels has been reported in women with PCOS, particularly in those with non-classic (B or C) phenotypes 3.
• DHEAS levels are negatively correlated with age, and their values decrease by 40% in patients moving from their twenties to thirties 3.
• Elevated SHBG levels can be associated with a marked elevation of testosterone, possibly as a result of medication having an estrogenic effect, hyperthyroidism, or liver disease 4.
• Normal testosterone levels in patients with clear clinical symptoms of hyperandrogenism must be interpreted with care, as SHBG is normally reduced in the event of overweight, metabolic syndrome, or familial history of diabetes 4.

Clinical Significance

• Elevated DHEAS levels can indicate a diagnosis of androgen-secreting adrenal cortical adenoma if the level is over 600 mg/dl 4.
• Metformin therapy can result in a significant decrease in total testosterone levels and fasting blood sugar, leading to a significant improvement in the clinical manifestation of hyperandrogenism in women with PCOS 5.
• The effect of metformin on subjects with elevated DHEAS levels is different from that on individuals with normal DHEAS levels, with significant improvements in the length of the menstrual cycle, BMI, and testosterone and DHEAS levels in the latter group 5.

Pathophysiology

• The exact cause of adrenal precursor androgen (APA) excess in PCOS remains unclear, although it may reflect a generalized and inherited exaggeration in androgen biosynthesis of an inherited nature 6.
• Women with PCOS and APA excess appear to have a generalized exaggeration in adrenal steroidogenesis in response to ACTH stimulation, although they do not have an overt hypothalamic-pituitary-adrenal axis dysfunction 6.
• Extra-adrenal factors, including obesity, insulin, and glucose levels, and ovarian secretions, play a limited role in the increased APA production observed in PCOS 6.