Context: Patients with panhypopituitarism have impaired quality of life despite growth hormone replacement. They are profoundly androgen deficient and DHEA has been shown to have a beneficial effect on well-being and mood in patients with adrenal failure and possibly in hypopituitarism.

Objective: To determine the effect of DHEA administration on mood in hypopituitary adults on established growth hormone replacement, with a constant serum IGF-I.

Design: A double blind placebo controlled trial was conducted over an initial 6 months followed by open phase 6 months DHEA.

Setting: Tertiary referral endocrinology unit.

Patients: 30 female and 21 male hypopituitary patients enrolled. Data from 26 females and 18 males were analyzed after patient withdrawal.

Interventions: 50 mg DHEA was added to maintenance replacement including growth hormone.

Main outcome measures: The primary outcome objective was the effect on quality of life (QoL) and libido assessed by Qol-AGHDA, SF36, GHQ, EuroQol and SSES-E.

Results: Patients had impaired QoL at baseline compared with the age matched British population. Females showed improvement in Qol-AGHDA score (-2.9 ± 2.8 DHEA vs. -0.53 ± 3 placebo, P < 0.05), in SF36 social functioning (14.6 ± 23.1 DHEA vs. -4.7 ± 25 placebo, P = 0.047) and general health perception (9.6 ± 14.2 DHEA vs. -1.2 ± 11.6 placebo P = 0.036) after 6 months of DHEA. Men showed improvement in self-esteem (-1.3 ± 1.7 DHEA vs. 0.5 ± 1.5 placebo, P = 0.03) and depression (-1.6 ± 2.2 DHEA vs. 1.2 ± 2.4 placebo, P = 0.02) domains of GHQ, after 6 months DHEA.

Conclusions: DHEA replacement leads to modest improvement in psychological well-being in female and minor psychological improvement in male hypopituitary patients on growth hormone replacement.