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Abstract
The postmenopausal state is characterized by a decline in the level of circulating plasma oestrogens. This fall in oestrogen level is responsible for various symptoms affecting the quality of life of postmenopausal women such as hot flushes, moods, swings and sleep disorders, as well as metabolic changes including cardiovascular disease and osteoporosis. HRT given to postmenopausal women relieves these symptoms that accompany the decrease in oestrogen levels during the postmenopausal period. HRT has many benefits including prevention of early menopausal symptoms. It also reduces the incidence of postmenopausal urogenital complaints. It prevents bone loss and increase bone mass leading to very good prevention of osteoporosis. It also dramatically reduces the risk of cardiovascular disease by up to 50%. Although HRT has many beneficial effects, yet it has some risks including breast cancer, endometrial, cervical and ovarian cancer and metabolic problems. HRT does not suit every one. Each woman needs to be aware of the benefits and potential risks of HRT. Oestrogen will continue to be used for the prevention of unwanted sequelae of the menopause. Large randomized controlled trials are in progress to provide answers regarding HRT and the prevention of cardiovascular disease, Alzheimer’s disease and long-term morbidity and mortality. Therefore, there was a need for an ”ideal oestrogen” which will be designed to pinpoint desired tissues for oestrogen such as bones, liver and cardiovascular system, while acting as an anti-oestrogen in reproductive tissues such as the uterus and breast. Selective Estrogen Receptor Modulators (SERMs) are a new class of compounds that bind to and interact with ERs, acting as oestrogen agonists in some tissues and as oestrogen antagonists in others. SERMs should be considered only for patients who are at risk of osteoporotic fracture and do not wish to take HRT, or discontinued it because of poor compliance or whenever HRT is unwise to use. It can also follow HRT after the end of the sixth decade of life. SERM has still wide spectrum of tumor static activity which may be of value in managing cervical cancer, choriocarcinoma, cancer prostate, mesenteric desmoid tumors, and malignant melanomas of nasal and paranasal sinuses. The mechanism of action of antioestrogens was suggested that the act through binding to receptor sites and act as partial antagonists. Also in 1998, anti-oestrogens have been classified into short acting, long acting and physiological antagonists. In 1999, anti-oestrogens has been classified into pure anti-oestrogens and mixed agonist antagonist compounds. Other newly reported types of antioestrogens include Indole-3-Carbinol (I3C), environmental antioestrogens (phytoestrogens), and hydroxylated polychlorinated biphenyl metabolites. Also, newly reported types of antioestrogens include toremifene, idoxifene, droloxifene, TAT-59 and zindoxifene which are all triphenylethylene derivatives. Clomiphene citrate acts on the hypothalamus and pituitary leading to rise in LH and FSH. Although tamoxifen therapy has fringe benefits ion the prevention of bone loss and cardiovascular disease, wider clinical applications for these indications is controversial because of its agonist activities in non-target organs such as the uterus. In the prevention trials, the risk-benefit equation of tamoxifen therapy is different for the healthy volunteers and between pre- and post-menopausal women. For a breast cancer patient, hysterectomy and continued adjuvant tamoxifen may be appropriate if atypical endometrial hyperplasia occur. However, in a healthy subject participating in the chemoprophylaxis trials presents a different dilemma.
Objectives: The aim of this work was to review the advancement in the development of new antiestrogens and their possible clinical uses and comparison between them.