Does Addison's disease directly cause low testosterone levels and how is it treated?

Does Addison's Disease Cause Low Testosterone?

Yes, Addison's disease does result in low testosterone levels, particularly in women, due to loss of adrenal androgen production including DHEA and androstenedione, which are precursors to testosterone. 1

Mechanism of Testosterone Deficiency

• The adrenal cortex normally produces androgens including dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS), and androstenedione, which serve as precursors to testosterone 1
• In Addison's disease, destruction of the adrenal cortex eliminates this source of androgen production 2
• Laboratory findings in primary adrenal insufficiency typically include low DHEAS, androstenedione, and testosterone levels 1
• This androgen deficiency is particularly clinically significant in women, as the adrenal glands are their primary source of androgens 1
• In men, testicular production of testosterone usually compensates, making adrenal androgen loss less clinically apparent 1

Clinical Manifestations

• Patients may experience persistent lack of libido and low energy levels despite optimized glucocorticoid and mineralocorticoid replacement 1
• These symptoms reflect the androgen deficiency that accompanies cortisol and aldosterone deficiency 2, 3
• Fatigue, weariness, and reduced stress tolerance are common complaints even with standard replacement therapy 3

Treatment Approach

For female patients with persistent lack of libido and/or low energy despite optimized glucocorticoid and mineralocorticoid replacement, offer a 6-month trial of DHEA replacement (25-50 mg daily), which can be continued if clinically effective. 1

Monitoring DHEA Replacement

• Guide dosing by monitoring serum DHEAS, androstenedione, and testosterone levels 1
• Measure these levels in the morning prior to DHEA ingestion 1
• Target hormone levels should be maintained in the normal range 1

Important Caveats

• There is only limited objective evidence of clinical benefit from large studies for DHEA replacement 1
• The long-term effects of DHEA or testosterone replacement therapy in patients with primary adrenal insufficiency are not known 1
• Such regimens should be used with caution due to lack of long-term safety data 1
• The evidence for benefit from DHEA replacement remains weak and inconsistent across studies 2, 3

Alternative Considerations

• Direct testosterone replacement may be considered in selected patients, though evidence is limited 1, 2
• The pragmatic approach prioritizes a time-limited trial (6 months) to assess individual response before committing to long-term therapy 1