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There are gender-associated differences in blood pressure (BP) in humans, with men having higher BP than age-matched pre-menopausal women and being at greater risk for cardiovascular and renal diseases. The mechanisms responsible for the gender differences in BP control and regulation are not clear, although there is some evidence that interactions between sex hormones and the kidneys could play a role. However, the response to salt in pre- and post-menopausal women, and in particular the influence of exogenous and endogenous female sex hormones on renal hemodynamics and tubular segmental sodium handling, have been poorly investigated. Recently we have shown that both endogenous and exogenous female sex hormones markedly influence the systemic and renal hemodynamic response to salt. We have found that BP in young normotensive women, regardless of oral contraceptive use, is rather insensitive to salt. However, the renal hemodynamic and the tubular responses to salt vary significantly during the normal menstrual cycle and with the administration of oral contraceptives. Furthermore, after the menopause, BP tends to become salt sensitive, a pattern that could be due to aging as well as to the modification of the sex hormone profile. These observations provide new insights pertaining to potential mechanisms explaining the lower incidence of cardiovascular disease and progression of renal disease in pre-menopausal women (which tend to disappear with the menopause); these observations also emphasize the importance of considering more carefully the phase of the menstrual cycle whenever conducting physiologic studies in women and enrolling women in clinical studies. Finally, increased salt sensitivity in menopausal women strongly encourages the use of diuretics.Am J Hypertens 2004;17:994-1001 © 2004 American Journal of Hypertension, Ltd.