DHEA for Addison's Disease

DHEA is worth considering in Addison's disease only in a narrow case. People with Addison's disease make almost no DHEA, and standard hydrocortisone and fludrocortisone don't replace it (Gurnell 2008). In women, adding DHEA restores normal androgen levels, but whether they feel better is less clear.

A meta-analysis of 10 trials in women with adrenal insufficiency found a small improvement in quality of life and depression and judged the evidence insufficient for routine use (Alkatib 2009). The Endocrine Society suggests a 6-month trial of DHEA for women with low libido, depressive symptoms or low energy despite otherwise optimised replacement, and stopping it if there is no sustained benefit (Bornstein 2016).

DHEA and DHEAS are the main hormones the adrenal glands release, and the body builds sex hormones from them. In Addison's disease, DHEA production fails almost completely alongside cortisol and aldosterone, but standard treatment replaces only the last two (Gurnell 2008).

In women with adrenal insufficiency, 50 mg of DHEA each morning raised DHEA, DHEAS, androstenedione and testosterone from low levels into the normal range (Arlt 1999). In the 12-month trial, testosterone reached low-normal levels only in women, not men (Gurnell 2008).

Restoring a hormone level is not the same as feeling better. Almost all women on 25 mg a day reached normal androgen levels in a 9-month trial, yet their health and sexuality scores changed no more than with placebo (Løvås 2003).

So correcting the deficiency is easy; the open question is who benefits from it, and the trials have not identified that group.

Trials used 50 mg once each morning (Arlt 1999; Gurnell 2008) or 25 mg a day (Løvås 2003). At 25 mg, most women reached premenopausal androgen levels, but side effects were frequent (Løvås 2003). At 50 mg, some older women reached above-normal DHEAS levels and had mild androgenic side effects (Gurnell 2008).

The Endocrine Society suggests monitoring with a morning DHEAS level taken before the daily dose, aiming for the middle of the normal range, and an initial 6-month trial (Bornstein 2016).

In a double-blind crossover trial, 24 women with adrenal insufficiency took 50 mg DHEA or placebo for 4 months each. DHEA improved overall well-being and depression and anxiety scores (global severity index -0.18 vs +0.03, P = 0.02) and increased sexual thoughts (P = 0.006) and sexual interest (P = 0.002) (Arlt 1999).

A 12-week double-blind crossover trial in 39 men and women with Addison's disease found that 50 mg a day improved self-esteem, mood and fatigue in both sexes, with no effect on cognition or sexual function (Hunt 2000).

In the longest trial, 106 men and women with Addison's disease took 50 mg micronized DHEA or placebo for 12 months. One SF-36 well-being subscale improved (P = 0.004), femoral neck bone loss was reversed (P < 0.05) and lean mass rose, but fatigue, cognition and sexual function did not change (Gurnell 2008).

In 39 women with adrenal failure randomised to 25 mg DHEA or placebo for 9 months, effects on health and sexuality questionnaires varied widely and were no different from placebo; 89% of those on DHEA reported side effects (Løvås 2003).

Pooling 10 trials in women, a meta-analysis found a small improvement in health-related quality of life (effect size 0.21, 95% CI 0.08 to 0.33) and a small benefit for depression, with no significant effect on anxiety or sexual well-being (Alkatib 2009). The authors described the gain as small and perhaps trivial.

No trial has identified which patients benefit, and the authors of the null trial suggested a subgroup may exist (Løvås 2003). Evidence in men comes from two trials with conflicting results on fatigue (Hunt 2000; Gurnell 2008), and no trial has run longer than a year.

For the wider picture of living with adrenal insufficiency, see our Addison's disease page.

Side effects were common in one trial: 89% of women taking 25 mg a day reported them, mainly increased sweat odour and scalp itching (Løvås 2003). In the 12-month trial, some older women developed above-normal DHEAS levels with mild androgenic effects (Gurnell 2008).

DHEA lowered total and HDL cholesterol in the crossover trial (Arlt 1999), and a meta-analysis across conditions found it lowers HDL in women by about 5 mg/dL (Qin 2020).

No formal interaction studies exist. The Endocrine Society suggests DHEA only on top of otherwise optimised glucocorticoid and mineralocorticoid replacement (Bornstein 2016). Because DHEA is converted into testosterone and estrogen, it adds to any hormone therapy you already take (Li 2020; Zhu 2021).