Allolio and W Arlt

Contents

19.1

Introduction

19.2

DHEA secretion and age

19.3

Epidemiology

19.4

Mechanisms of action

19.4.1

DHEA

19.4.2

Androstenedione

19.5

Treatment with DHEA - clinical studies

19.5.1

Patients with adrenal insufficiency

19.5.2

Elderly subjects

19.5.3

Patients with impaired mood and wellbeing

19.5.4

Patients with immunological disorders

19.6

Androstenedione administration in clinical studies

19.7

The emerging therapeutic profile of DHEA

19.7.1

Effects on the central nervous system

19.7.2

Metabolism and body composition

19.7.3

Skeletal system

19.7.4

Skin

19.7.5

Immune system

19.8

Practical approach to the patient with DHEA deficiency

19.9

Future perspectives

19.10

Key messages

19.11

References

19.1 Introduction

Man together with higher primates have adrenals secreting large amounts ofdehy-droepiandrosterone (DHEA) and its sulfate ester, DHEAS. The physiological role of these steroid hormones has long been elusive. However, a growing number of

DHEAS (nmol/L)

DHEAS (nmol/L)

Age (years)

Fig. 19.1 Serum DHEAS concentrations during the human life cycle.

Age (years)

Fig. 19.1 Serum DHEAS concentrations during the human life cycle.

well-designed studies has helped to shed light on the role of DHEA in human health. Nevertheless, many aspects remain to be elucidated.

DHEA is distinct from other major adrenocortical steroids - cortisol and aldosterone - in declining with advancing age. Moreover, administration of DHEA to experimental animals has demonstrated a multitude of beneficial effects on the prevention of cancer, heart disease, diabetes and obesity (Svec and Porter 1998). This has led to the assumption that the age-related decline of DHEA may play a role in the degenerative changes observed in human aging and that administration of DHEA may reverse some of these changes. Moreover, the availability of DHEA as a food supplement in the USA resulted in aggressive marketing of DHEA as an anti-aging drug and in largescale self-administration without medical supervision.

However, in rodents circulating levels of DHEA and DHEAS are several orders of magnitude lower than in humans and no age-related decline in DHEA concentrations has been documented. This indicates that experimental studies in laboratory animals receiving high doses of DHEA have little bearing for human physiology.

This chapter, therefore, will focus mainly on data generated in humans. DHEA(S) will refer to both DHEA and DHEAS. In addition, clinical studies concerning androstenedione, another steroid hormone precursor, will also be covered.

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