Endocrine Abstracts

Man is unique, with some other primates, in having adrenals that secrete large amounts of dehydroepiandrosterone (DHEA). The problem with DHEA, however, especially for women, is that its secretion from the adrenals starts decreasing at the age of 30 years and has already declined, on average, by 60% at menopause. Since there is no other source of sex steroids after menopause than those made locally in peripheral tissues by the mechanisms of intracrinology, it is logical to believe that low DHEA is responsible for the series of medical problems classically associated with the hormone deficiency of postmenopause. As strong support for the mechanism of intracrinology, recent randomized and placebo-controlled studies have shown that all the signs and symptoms of vulvovaginal atrophy can be rapidly improved or corrected by local administration of DHEA without systemic exposure to estrogens. In men, the combination of a pure antiandrogen with a GnRH agonist was the first treatment shown to prolong life in prostate cancer and can cure the disease in most cases if treatment is started at the localized stage. As a follow-up to our initial observations on the dual source of androgens and role of intracrinology in men, positive clinical data have been obtained with the new antiandrogen MDV3100 as well as with abiraterone, an inhibitor of 17α-hydroxylase (CYP17A1) in patients with prostate cancer progressing after castration, a benefit necessarily due to blockade of extratesticular androgens made in the prostate by intracrinology. On the other hand, the benefits of aromatase inhibitors and antiestrogens in breast cancer in postmenopausal women are necessarily secondary to the inhibition of the formation and action, respectively, of the estrogens made locally in the breast by the process of intracrinology.

In men, the combination of a pure antiandrogen with a GnRH agonist was the first treatment shown to prolong life in patients with prostate cancer and can cure the disease in most cases if treatment is started at the localized stage. As a follow-up to our initial observations on the dual source of androgens in men, positive clinical data have recently been obtained in studies with the new antiandrogen MDV3100 as well as with abiraterone, an inhibitor of 17α-hydroxylase (CYP17A1) in patients with prostate cancer progressing after castration, a benefit necessarily due to blockade of extratesticular androgens made in the prostate by intracrinology. On the other hand, the benefits of aromatase inhibitors and antiestrogens in breast cancer in postmenopausal women are necessarily secondary to the inhibition of the formation and action, respectively, of the estrogens made locally in the breast by the process of intracrinology.

Declaration of interest

President of EndoCeutics, Inc. Developping new DHEA medical indications.

Declaration of funding

This work was supported by EndoCeutics Inc.