Dehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS, together represent the most
abundant steroid hormones in the human body. Nonetheless, their physiological significance, their
mechanisms of action and their possible roles in human disease are not well understood.
Highlighting the potential health significance of DHEA and DHEAS, concentrations of these
hormones in humans typically decrease steadily with age, approaching a nadir at about the time
many diseases of aging become markedly more prevalent. There is growing evidence in the
literature that a low DHEAS level, negatively correlates with the domains of sexual function in pre
and postmenopausal women to a greater extent than testosterone levels. Biological actions of
DHEA(S) involve neuroprotection, neurite growth, neurogenesis and neuronal survival, apoptosis,
catecholamine synthesis and secretion, as well as anti-oxidant, anti-inflammatory and antiglucocorticoid effects. In addition, DHEA affects neurosteroidogenis and endorphin
synthesis/release. We demonstrated in a model of ovariectomized rats that DHEA therapy increases
proceptive behaviors, already after 1 week of treatment, affecting central function of sexual drive.
In women, the analyses of clinical outcomes are far from being conclusive and many issues should
still be addressed. Although DHEA preparations have been available in the market since the 1990s,
there are very few definitive reports on the biological functions of this steroid, and it is still the case
that its regulation is unclear and its mechanisms of action largely yet to be established. We
demonstrate that one year DHEA administration at the dose of 10 mg provided a significant
improvement in comparison with vitamin D in sexual function and in frequency of sexual
intercourse in early postmenopausal women. Among symptomatic women, the spectrum of
symptoms responding to DHEA requires further investigation, to define the type of sexual
symptoms (e.g. decreased sexual function or hypoactive sexual desire disorder) and the degree of
mood/cognitive symptoms that could be responsive to hormonal treatment. In this regard, our
findings are promising, although they need further exploration with a larger and more representative
sample size.