Practical approach to the patient with DHEA deficiency

At present there is no established indication and no generally accepted pharmacological preparation of DHEA for treatment. However, there is growing acceptance (Achermann and Silverman 2001; Arlt and Allolio 2003a; Oelkers 1999) of the view that DHEA replacement in patients with adrenal insufficiency may be beneficial in a substantial percentage of cases. In these patients not only very low or absent circulating DHEA(S) is demonstrated, but there is evidence of impaired wellbeing, reduced vitality and increased fatigue (Lovas et al. 2002), symptoms that are likely to respond to DHEA replacement (25-50 mg/day). Treatment usually starts with 25 mg/day. Serum DHEAS concentrations can easily be monitored and should be in the respective sex- and age-adjusted reference range (Orentreich etal. 1984). It is important to know that significant improvement may occur only after two to four months of treatment.

Treatment of elderlies with age-related low endogenous DHEA(S) is per se not justified. All available evidence indicates that an age-related decline in DHEA(S) concentration is not necessarily associated with impairment in wellbeing and mood or with increased fatigue. Accordingly, DHEA supplementation offers no apparent benefit for such a population. This is a situation very similar to postmenopausal hormone replacement: despite very low estradiol concentrations estrogen replacement may be more often detrimental than beneficial. This does not exclude the possibility that certain subgroups of elderly subjects may benefit from DHEA supplementation, but these subgroups need to be defined. In particular, to date there is little evidence that DHEA supplementation reverses relevant aspects of aging.

Much more plausible is an approach that focuses on specific complaints like anxiety, depression, increased fatigue or impaired female sexuality which may be amenable to DHEA treatment. In particular such complaints in patients receiving chronic glucocorticoid therapy with concomitant suppression of adrenal androgen secretion may occasionally justify an individual trial of DHEA therapy (25 mg/day). However, patients need to be informed about the experimental nature of such treatment. In particular, the possible risks of androgenic side-effects and the potential promotion of sex steroid-dependent tumor growth need to be addressed.

Table 19.1 Action profile of DHEA

Central Nervous System:

• mood f, well-being f, anxiety depression fatigue |

• libido ^ (f in women), sexual satisfaction ^ (f) Metabolism:

insulin sensitivity fasting glucose ^

• HDL-cholesterol | total cholesterol ^

sebum production f

• skin hydration f

• glucocorticoid demand in immunopathies (|)

• immune cell distribution ^ (B-cells, T-cells, natural killer cells)

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