Dehydroepiandrosterone Sulfate (DHEAS): Overview and Clinical Significance
Dehydroepiandrosterone sulfate (DHEAS) is the most abundant circulating steroid hormone in humans, primarily produced by the adrenal gland's zona reticularis, serving as a precursor to testosterone and estradiol in peripheral tissues. 1
Biochemistry and Production
- DHEAS is the sulfated form of dehydroepiandrosterone (DHEA), which is produced mainly in the adrenal cortex
- DHEA/DHEAS levels reach maximum circulating concentrations between ages 20-30, followed by a steady gradual decline with age 2
- Unlike other adrenal hormones, DHEA/DHEAS are not essential for life but play important physiological roles 3
- DHEA can cross the blood-brain barrier and is also produced locally in brain tissue, functioning as a neuroactive steroid 4
Diagnostic Applications
Role in PCOS Diagnosis
- DHEAS serves as a second-line diagnostic marker for polycystic ovary syndrome (PCOS) with:
- Moderate sensitivity (0.75)
- Lower specificity (0.67) compared to other androgen markers 1
- DHEAS levels >3800 ng/ml are considered abnormal for individuals aged 20-29 1
- DHEAS is the most reliable measure of adrenal androgen production 2
Measurement Considerations
- Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is preferred over direct immunoassays for accurate measurement 2, 1
- Age-specific reference ranges are crucial when interpreting DHEAS levels 1
- Morning measurements are recommended for most accurate results 1
Therapeutic Applications
Adrenal Insufficiency
- DHEA replacement may benefit patients with primary adrenal insufficiency who are deficient in adrenal androgens 1, 3
- Typical dosing: oral DHEA tablets (10-50 mg), often 25 mg as a single daily dose 1
- Benefits may include:
- Improved quality of life and psychological well-being
- Enhanced body composition
- Better bone health
- Improved metabolic markers 3
Sexual Function
- DHEA may improve sexual satisfaction and vaginal atrophy in postmenopausal women 1, 5
- May benefit female patients with persistent lack of libido and/or low energy levels despite optimized glucocorticoid and mineralocorticoid replacement 1
Cancer Survivors
- Vaginal DHEA (prasterone) can be considered for vaginal dryness or pain with sexual activity 2
- Several studies show DHEA to be effective at reducing dyspareunia in postmenopausal individuals 2
- A randomized controlled trial of 464 survivors of breast or gynecologic cancer showed vaginal DHEA led to significant improvements in sexual desire, arousal, pain, and overall sexual function 2
Safety Considerations
- DHEA should be used with caution in cancer survivors receiving aromatase inhibitor therapy, as vaginal DHEA increases levels of circulating androgens that could potentially impact aromatase inhibitor activity 2, 1
- Safety data for androgen-based therapy in survivors of hormonally mediated cancers are limited 2
- The safety of vaginal hormones has not been firmly established in survivors of estrogen-dependent cancers 2
- Regular monitoring of androgen levels is recommended during DHEA therapy 1
Common Pitfalls in Clinical Practice
- Relying solely on one androgen marker without considering the full clinical picture
- Not accounting for age-related changes in DHEAS levels
- Using inappropriate assay methods (direct immunoassays vs. LC-MS/MS)
- Overinterpreting DHEAS levels without considering other clinical factors 1
- Failing to recognize that DHEAS has lower specificity compared to other androgen markers like total testosterone or free testosterone in diagnosing hyperandrogenism 2
While DHEA/DHEAS has shown promise in various clinical applications, large-scale randomized controlled trials are still needed to establish optimal dosing protocols and indications for routine clinical practice.