Endocrine-related chronic degenerative diseases (e.g. osteoporosis, senile dementia, cardiovascular disease) dominate together with endocrine-related cancer (e.g. breast and prostate cancer) as leading causes of mortality and morbidity in the elderly. Having a healthy life expectancy of around 72 years and a mean age at menopause of 50-52 years, european women spent a sizeable part of their life in a low estrogen state. Many of them will eventually develop one or more endocrine-related chronic degenerative diseases as a consequence, with profound direct and indirect impact on health care costs and the productivity and social wellbeing of their folks. Many ageing men and women eventually develop dementia as the result of atherosclerosis, stroke, trauma and other major neurodegeneraČtive diseases such as Parkinson's and Alzheimer's diseases, with the latter affecting about 15 million people worldwide. Hormone replacement therapy has been reported to delay or even prevent these degenerative diseases from developing, but its social acceptance was seriously damaged by reports that it increases the risk for breast cancer, cardiovascular disease, stroke and Alzheimer's diseases [1, 2].
Endocrine-related cancer: Breast and prostate cancer are the most frequent forms of endocrine-related cancer. Breast cancer, in particular, is a major cause of death among European women. According to recent reports, every 2.5 minutes a new case of breast cancer is diagnosed and every 7 minutes a woman dies of this disease in Europe. Despite major advances in biological and medical sciences, breast cancer risk keeps increasing by 1% annually, resulting in doubling of the number of new cases reported annually over the last 50 years. High levels of circulating estrogens during reproductive maturity and estrogen replacement therapies of various menopausal syndromes increase breast cancer risk. Estrogens are potent mitogens of mammary cells. By promoting cell proliferation, estrogens increase the number of random replication errors and the risk for breast cancer initiation and progression as a consequence. To treat hormone-dependent breast cancer while keeping degenerative diseases due to estrogen deprivation under control, selective estrogen receptor modulators (SERMs) acting as estrogen antagonists in the breast and uterus while exhibiting estrogen-like activity in the skeletal and cardiovascular systems have been developed. Prominent among these is Tamoxifen (NolvadexR), a SERM widely used to prevent breast cancer among high risk women as well as to treat estrogen receptor (ER)-positive breast tumours. However, one out of three ER+ tumours fails to respond to Tamoxifen and other means to prevent and treat the disease are presently under scrutiny .
 Rossouw JE et al; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002;288:321-33.
 Shumaker SA et al; WHIMS Investigators. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289:2651-62.
 Arpino G et al; Molecular mechanism and clinical implications of endocrine therapy resistance in breast cancer. Oncology. 2009;77 Suppl 1:23-37.