From the Guidelines
Elevated DHEA-S in females is a significant indicator of potential hyperandrogenism and should be addressed with a comprehensive diagnostic workup to identify underlying causes such as polycystic ovary syndrome (PCOS), congenital adrenal hyperplasia, adrenal tumors, or Cushing's syndrome, with treatment aimed at managing symptoms and improving quality of life. The diagnostic approach should include confirming the elevation with repeat testing, followed by additional hormone tests (testosterone, androstenedione, 17-hydroxyprogesterone, cortisol), pelvic ultrasound, and possibly adrenal imaging with CT or MRI if adrenal pathology is suspected 1.
Key Considerations
- Elevated DHEA-S levels can lead to symptoms of hyperandrogenism including hirsutism, acne, male-pattern hair loss, menstrual irregularities, and in some cases, infertility.
- The 2023 International PCOS Guidelines recommend using total testosterone (TT), free testosterone (FT), and free androgen index (FAI) as first-line laboratory tests to assess biochemical hyperandrogenism in the diagnosis of PCOS, with liquid chromatography with tandem mass spectrometry (LC-MS/MS) being the preferred method for androgen measurement due to its high accuracy 1.
- If TT or FT are not elevated but clinical suspicion is high, measuring androstenedione (A4) and DHEA-S could be considered, noting their poorer specificity 1.
- Treatment depends on the underlying cause and may include lifestyle modifications, combined oral contraceptives, anti-androgens such as spironolactone, or metformin, particularly if insulin resistance is present, with surgical intervention being necessary for adrenal tumors 1.
Diagnostic and Treatment Approach
- Confirm elevation of DHEA-S with repeat testing.
- Pursue a comprehensive workup including additional hormone tests and imaging studies as necessary.
- Treat underlying causes with a focus on managing symptoms and improving quality of life, considering the use of LC-MS/MS for accurate androgen measurement.
- Regular monitoring of hormone levels and symptom improvement is essential during treatment, with adjustments to the treatment plan as needed to optimize outcomes.
From the Research
Implications of Elevated DHEA-S in Females
- Elevated DHEA-S levels in females can indicate an androgen-secreting adrenal cortical adenoma if the level is over 600 mg/dl 2
- In cases where DHEA-S is normal, the diagnosis could be either ovarian hyperthecosis or androgen-secreting ovarian tumour 2
- Very high DHEA-S levels can also be observed in premature adrenarche and congenital adrenal hyperplasia, and can be associated with a heterozygous nonsense mutation in the STS gene and a known heterozygous missense variant in the BCRP gene 3
- A high prevalence of increased DHEA-S levels has been reported in women with polycystic ovary syndrome (PCOS), although the exact cause of this excess remains unclear 4, 5
- DHEA-S levels have been found to correlate with other androgens, such as total testosterone and androstenedione, but not with other ovarian, pituitary or metabolic markers 4
- The use of spironolactone as an antiandrogen can affect DHEA-S levels, although the response can vary greatly among individuals 6
- Elevated levels of DHEA-S may be protective against cardiovascular risk in women, although the role of DHEA-S in modulating this risk in women with PCOS remains unknown 5
DHEA-S and PCOS
- Approximately 20-30% of PCOS women demonstrate excess adrenal precursor androgen production, primarily using DHEA-S as a marker 5
- The prevalence of increased DHEA-S levels is significantly higher in the PCOS group than in the control group, especially in phenotypes A and C 4
- DHEA-S assay appears to be of no interest for positive diagnosis or understanding of the pathophysiology of PCOS, except in case of very high testosterone levels 4