While life expectancy has grown by approximately 30 years in the last century in western countries, the age at menopause has increased by 2-3 years only. Thus, women are exposed to postmenopausal symptoms and disorders related to estrogens drop for a considerable period of their lifetime. The management of these frequent disorders is an important public health issue. Although recent data from the WHI randomized trial have demonstrated that late postmenopausal women (mean age 63.3 years) taking oral conjugated equine estrogens and medroxyprogesterone acetate in a continuous combined regimen for prevention of coronary heart disease have an increased risk of developing cardiovascular disease and breast cancer, there is no question that treatment of menopausal symptoms with HRT (Hormone Replacement Therapy) in younger women aged around 50 years is a clinically beneficial treatment. This is even truer for women who enter menopause earlier than 45 years. It is prudent not to extend the results of the WHI trial, as such, to other forms of HRT preparations, routes, dosages and regimens or to early postmenopausal women with no apparent risk factors for CVD. Recently data from a non-randomized study, the Million Women Study, have suggested that oral combined regimens are associated with an increased and that transdermal estradiol does not increase more than oral treatment, and in general may be less harmful: for instance, transdermal estradiol has no effect on vascular inflammatory markers in contrast to the increase observed with oral CEE (conjugated equine estrogens). Notably, more recent data on the estrogens-alone group of the WHI trial show a lower breast cancer risk than the combination, suggesting a important role of progestin in the risk, and a significant reduction in colon cancer.