Tesi di dottorato di ricerca
NEUROBIOLOGICAL EFFECTS OF DHEA IN FEMALES WITH SPECIAL REFERENCE TO SEXUAL FUNCTION: FINDINGS FROM IN-VIVO AND HUMAN STUDIES
Settore scientifico disciplinare
Corso di studi
FISIOPATOLOGIA DELLA RIPRODUZIONE E SESSUOLOGIA
tutor Prof. Genazzani, Andrea R.
- sexual function
Data inizio appello
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 anti-glucocorticoid 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.