Differential Effect of Oral Dehydroepiandrosterone-Sulphate on Metabolic Syndrome Features in Pre- and Postmenopausal Obese Women

Cecilia Gómez-Santos; Juan José Hernández-Morante; Francisco Javier Tébar; Esteban Granero; Marta Garaulet


Clin Endocrinol. 2012;77(4):548-554. 

In This Article

Abstract and Introduction


Objective To analyze the effect in obese pre- and postmenopausal women of a daily dose of 100 mg dehydroepiandrosterone-sulphate (DHEA-S) provided over a period of 3 months as replacement therapy against metabolic syndrome.
Context Although DHEA-S appears to be effective against certain features of metabolic syndrome, its usefulness against this syndrome as a whole has not been evaluated to date.
Design/Patients A randomized, double-blind placebo-controlled trial was conducted involving 61 postmenopausal women, who received DHEA-S (n = 41) or placebo (n = 20) for 3 months. The effect of DHEA-S treatment on the same postmenopausal women was compared with the effects observed in a group of premenopausal women (n = 20).
Measurements Anthropometric measurements were taken at the beginning and at the end of the treatment. Similarly, different parameters that define metabolic syndrome and other cardiometabolic variables were determined.
Results Dehydroepiandrosterone-sulphate replacement produced weight loss in the obese women studied. Moreover, waist circumference, glucose and systolic and diastolic blood pressure, among other metabolic syndrome parameters, improved in the postmenopausal group, who showed a significant reduction in the total metabolic syndrome score (P < 0·05). In contrast, in premenopausal women, the effect of DHEA-S was limited to obesity parameters, and no effect was observed on metabolic syndrome components. No significant changes were evident in the placebo group.
Conclusions An oral dose of DHEA-S is useful for weight loss. In obese postmenopausal women, the hormone significantly improves plasma biochemical levels and anthropometric characteristics, leading to a better metabolic profile, which highlights the usefulness of this therapy against metabolic syndrome in this group of women.


Metabolic syndrome (MetS), a disorder characterized by the manifestation of a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease,[1,2] is still treated considering every symptom individually.[3] However, as the aetiology of these alterations shares common features,[4,5] it might be considered a better approach to deal with this alteration as a whole.

In this respect, dehydroepiandrosterone-sulphate (DHEA-S), an adrenal-derived hormone, could be regarded as a promising agent against MetS in ageing women because plasma levels of this hormone decrease with age. Moreover, a large number of studies have shown an inverse relationship between plasma levels of DHEA-S and obesity;[6,7] likewise, the beneficial effects of this hormone on glucose and lipid metabolism parameters have been widely studied,[8,9] its effect as an insulin resistance decreasing agent[10,11] being of special interest. All these effects underline the beneficial properties of DHEA-S, as an anti-ageing, anti-obesity, insulin-sensitizing and cardiovascular-protective agent. Nevertheless, there is still some controversy about the precise effect of DHEA-S treatment on MetS, because some authors were not able to find any effect on cholesterol, triglycerides or insulin sensitivity.[12,13]

Our group has taken a deeper look at the metabolic effect of this hormone in experimental models and in in vitro adipose tissue cultures and found that the hormone is able to stimulate adipose tissue lipolysis, reduce fat accumulation and decrease energy intake.[14,15]

In addition, plasma levels of several peptides, such as leptin, adiponectin and ghrelin, which could play an important role in the genesis of MetS and cardiovascular diseases,[16–18] were also seen to be related with DHEA-S levels in experimental models.[18,19]

However, and in spite of this knowledge, no studies in humans have focused on a comprehensive evaluation of the effect of a replacement therapy with this hormone and the parameters that define MetS as a whole. The data that do exist are contradictory, because the effect of DHEA-S on MetS may differ according to the menopausal status.

For all the above, the present work represents an attempt to elucidate whether the aforementioned beneficial effects on different MetS components, which have been attributed to DHEA-S in experimental models, are conserved in vivo in obese women, and whether this hormone is able to decrease MetS risk as a whole. A second goal was to analyze the possible differential effect of DHEA-S in pre- and postmenopausal obese women.