DHEA deficiency can be seen in several disease states. Regardless of the etiology, patients with pri mary adrenal insufficiency manifest signs and symptoms associated with a deficiency or absence of all adrenal cortical hormones including cortisol, DHEA, and aldosterone [283,284]. Women with panhypopituitarism have severe androgen deficiency due to a lack of both ovarian and adrenal androgen production . Pituitary insufficiency can lead to a deficit of DHEA as the zona reticularis of the adrenal gland produces DHEA in response to stimulation by pituitary ACTH, similar to the stimulation of DHEA in the Leydig cell by LH .
Low DHEA levels have also been described in a variety of non-endocrine medical conditions. The age-related decline in circulating DHEA levels may correlate with many age-related phenomena such as diabetes and states of insulin resistance, hypertension, atherosclerosis, coronary artery disease, decreased bone mineral density, cancer, and dementia [287-291]. Low levels of DHEA have also been described in correlation with various conditions unrelated to aging, including obesity, depression, and other mood disorders, eating disorders, autoimmune disorders, immune deficiency states, and chronic stress states [287-289,292,293]. In the Massachusetts Male Aging Study (MMAS) DHEA-S was the only hormone which showed a strong (negative) correlation with the prevalence of ED among 17 investigated hormones, including T and estradiol .
Various drugs can contribute to decreased circulating levels of DHEA. Exogenous corticosteroids can decrease adrenal DHEA synthesis via negative feedback to the hypothalamus and pituitary gland, decreasing corticotropin-releasing hormone (CRH) and ACTH secretion, respectively. Both adrenolytic drugs, such as mitotane, and inhibitors of corticos-teroid synthesis, such as ketoconazole, can reduce adrenal production of DHEA along with cortisol [295,296].
More recently, a DHEA deficiency state has been reported in young, healthy, regularly menstruating premenopausal women presenting with decreased libido . The regular menstrual periods support normal cyclical ovarian function and ovarian testosterone production. However, since adrenal DHEA contributes to almost half of a premenopausal woman's circulating androgens, such a deficiency can manifest with symptoms of sexual dysfunction. The clinical manifestations of such a DHEA deficiency become more evident when ovarian function is diminished (use of hormonal contraceptives or ovarian failure), as DHEA is also produced by the ovaries.
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