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Luciano Martini has been an internationally renowned endocrinologist and a remarkable ambassador of Italian endocrinology through the world. He brought important experimental contributions in support of the new science of intracrinology. After the menopause, the secretion of estrogens stops while serum DHEA attains its lowest values. Estrogens and androgens are produced intra cellularly from the small residual amounts of DHEA. They act within the cells and are released only after inactivation, thus avoiding stimulation of the endometrium and possible actions in other tissues. In three independent 12-week prospective, randomized, double- blind and placebo-controlled clinical studies, it was shown that intravaginal administration of DHEA (prasterone) improves the severity score of the most bothersome symptom of the menopause such as vaginal dryness and dyspareunia. Most importantly, all serum sex steroids remained within normal values, thus explaining the absence of systemic effects. In conclusion, the lack of DHEA availability, not the lack of estrogens, is the main cause of the symptoms of menopause and this notion should guide the therapeutic strategy.