Addison's Disease and Testosterone Deficiency

Mechanism of Testosterone Deficiency

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

Patients with Addison's disease may experience persistent lack of libido and low energy levels despite optimized glucocorticoid and mineralocorticoid replacement, reflecting the androgen deficiency that accompanies cortisol and aldosterone deficiency 1, 2

For female patients with persistent lack of libido and/or low energy despite optimized glucocorticoid and mineralocorticoid replacement, a 6-month trial of DHEA replacement (25-50 mg daily) can be offered, which can be continued if clinically effective, as recommended by the Endocrine Society 1, 2

DHEA replacement dosing should be guided by monitoring serum DHEAS, androstenedione, and testosterone levels, with target hormone levels maintained in the normal range, and the long-term effects of DHEA or testosterone replacement therapy in patients with primary adrenal insufficiency are not known, and such regimens should be used with caution due to lack of long-term safety data 1, 2
There is only limited objective evidence of clinical benefit from large studies for DHEA replacement, and the evidence for benefit from DHEA replacement remains weak and inconsistent across studies, highlighting the need for careful consideration and monitoring 1, 2