Management of Low DHEA Sulfate Levels in Patients on Testosterone Therapy
For patients on testosterone therapy with low DHEA sulfate levels, supplementation with oral DHEA at 25-50 mg daily is recommended to restore physiological levels and potentially improve clinical outcomes. 1, 2
Diagnostic Evaluation
- Confirm low DHEA sulfate levels with a morning blood test, as a single low reading is insufficient for diagnosis 3
- Measure serum luteinizing hormone (LH) levels to help establish the etiology of testosterone deficiency and determine if additional tests are needed 4
- Measure serum prolactin levels in patients with low testosterone and low/normal LH levels to screen for hyperprolactinemia 4, 3
- Consider pituitary MRI if total testosterone is <150 ng/dL with low/normal LH levels, as non-secreting adenomas may be present 4, 3
- Evaluate for conditions that may cause secondary hypogonadism and low DHEA levels: obesity, diabetes, pituitary dysfunction, HIV/AIDS, chronic narcotic use, chronic corticosteroid use 3
Clinical Significance of Low DHEA Sulfate
- DHEA and DHEAS are the most abundant circulating steroid hormones in humans, with DHEAS having a much slower clearance rate (MCR ~13L/day) than DHEA (MCR ~2000L/day) 5
- Low DHEA/DHEAS levels have been associated with age-related changes and may impact overall health outcomes 1
- DHEA and DHEAS can be converted in peripheral tissues to androstenedione, testosterone, and dihydrotestosterone, and can be aromatized to estrogens 5
- Exogenous testosterone therapy may suppress endogenous DHEA production through feedback mechanisms on the hypothalamic-pituitary-adrenal axis 3
Treatment Approach
- For patients with confirmed low DHEA sulfate levels on testosterone therapy:
- Start with oral DHEA supplementation at 25-50 mg daily 2, 6
- A 25 mg daily dose has been shown to effectively increase DHEA, DHEAS, and downstream hormones in postmenopausal women 2
- A 50 mg daily dose has demonstrated benefits in patients with hypoadrenalism 6
- Higher doses (100 mg daily) may be considered for more significant deficiencies but should be monitored closely 7
Monitoring and Follow-up
- Monitor serum DHEA and DHEAS levels after 3 months of supplementation to ensure restoration to physiological ranges 2
- Evaluate downstream hormones including androstenedione, testosterone, and estradiol, particularly in women 2, 6
- Monitor for potential side effects including:
Expected Benefits
- Potential improvements in physical and psychological well-being 1, 7
- Possible increases in muscle strength and reduction in body fat, particularly in men 7
- Improved bone mineral density 1
- Enhanced immune function with increased numbers of monocytes, T cells, and natural killer cells 1
- Possible improvement in insulin sensitivity 1, 6
Important Considerations
- Adjust testosterone therapy dosing to achieve total testosterone levels in the middle tertile of the normal reference range (450-600 ng/dL) 4
- DHEA supplementation may have different effects in men versus women, with women showing more pronounced increases in downstream androgens 7, 2
- In patients with adrenal insufficiency, DHEA supplementation has been shown to restore DHEA/DHEAS and androstenedione levels, reduce total cholesterol, improve well-being, sexual satisfaction, and insulin sensitivity 1
- Counsel patients about lifestyle modifications such as weight loss and increased physical activity, which may help improve both testosterone and DHEA levels 4
Contraindications and Cautions
- Use caution in patients with hormone-sensitive conditions such as breast cancer, prostate cancer, or endometriosis 1
- Monitor PSA in men over 40 years of age who are receiving both testosterone and DHEA supplementation 4
- Monitor hemoglobin/hematocrit, as testosterone therapy can increase these values, and the addition of DHEA might potentially enhance this effect 4