Extragonadal synthesis of sex steroids: intracrinology.

All androgens and estrogens in post-menopausal women are synthesized locally in peripheral target tissues by tissue-specific steroidogenic enzymes according to the intracrine process. The importance of the intracrine or peripheral formation of sex steroids is illustrated by the success of aromatase inhibitors and antiestrogens in the prevention and treatment of breast cancer in post-menopausal women. On the other hand, a large series of problems are associated with the deficiency of sex steroids accompanying menopause and the decreased secretion of DHEA, osteoporosis being the best defined example. In this context, an important observation is that women at menopause are not only deprived from ovarian estrogens but are also lacking androgens due to the marked decrease of DHEA. In order to achieve a more physiological and tissue-specific hormone replacement therapy, DHEA, in combination with a SERM (selective estrogen receptor modulator) having pure antiestrogenic activity in the mammary gland and uterus could possibly meet the most important needs of women at menopause, namely control of hot flushes and, most importantly, prevent breast cancer, uterine cancer, ovarian cancer and osteoporosis with a potential improvement of cognitive functions and memory and prevention of Alzheimer's disease.