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SummaryMenopause is the permanent cessation of menses that occurs after the cessation of ovarian function, the climacteric is a phase in the aging process of women that marks the transition from the reproductive stage of life to the non reproductive stage and during which the ovarian function ceases.Menopause occurs at a median age of 51 years, the age of menopause appears to be determined genetically and does not seem to be related to race, nutritional status, age of menarche however it may occur earlier in cigarette smokers.The main mechanism underlying the menopause in depletion of the store of primordial follicle, another mechanism, however could be involved, namely loss of follicular responsiveness to the pituitary gonadotropins, this is supported by the presence of residual, dormant primordial follicles in postmenopausal ovaries and a significant increase in serum follicular stimulating hormone (FSH) concentration with distinct concomitant decrease in estradiol (E2) level. In some women however, ovarian function is lost earlier and more suddenly than expected as a result of natural causes, chemotherapy & radiotherapy, and surgery resulting in premature menopause.Menopause may be viewed as transition from middle age to old age by many women, although some may look up on this with pleasant anticipation as a time of relative freedom from such worries as undesired pregnancies and stress of child bearing, many women fear this period because it indicates the loss of femininity or the loss of reproductive potential, which may be especially painful to infertile women. For others, the menopause may represent the beginning of aging, with its diminishing abilities and competence. Although the majority of symptoms associated with climacteric are primarily due to the hypoestrogenemia that result from ovarian failure, the degree and quality by which the symptoms affect the patient are also dependent on socio-cultural and psychologic factors that in turn determined by the women’s environment and the structure of her character.The interaction between these three components (hypoestrogenemia social/ environmental, and psychologic make-up) explains the variable nature, severity and incidence of menopausal symptoms among different cultural, educational and racial population groups.Anatomic and physiologic changes associated with perimenopause include hot flushes, genitourinary atrophy manifested by incontinence and sexual dysfunction, bone loss and increased incidence of fracture, and unfavorable alteration in lipoproteins with increased risk of cardiovascular disease. There is no doubt that estrogen replacement therapy can manage these changes effectively.Unfortunately, estrogen replacement therapy has number of side-effects, such as breast tenderness headaches muscle cramps and vaginal bleeding, all of which lead to poor long-term compliance.Estrogen replacement therapy also increases the risk of endometrial cancer on long-term treatment especially if it is not associated with progesterone. It increases the risk of other cancers such as cervical cancer, ovarian cancer and breast cancer especially if there was a positive history in the family or if the patient had previous history of breast cancer or even a benign tumor. So, some women will not take estrogen as a therapy for menopausal symptoms because of its possible risks or because of its contraindications or they just refuse to take any hormone therapy.In such cases alternative medications to estrogen therapy may be given to these patients. These medications include several drugs such as, selective estrogen receptor modulator (SERM), the term SERM has been suggested to define more precisely chemical compounds which can bind to and activate the estrogen receptor (ER), but have effects on target tissues that are different from estrogen. The fundamental concept behind SERMs is retention of the beneficial effects of estrogen replacement therapy with avoidance of its drawbacks, especially with regard to endometrial stimulation, breast cancer and prothrombotic changes.There is some evidence that phytoestrogens may offer protection against a wide range of human conditions, including breast cancer, cardiovascular disease, brain dysfunction, osteoporosis, and menopausal symptoms. Previously available only in the diet, phytoestrogens are now widely available in pill or powder for, and are marketed to the public as ”natural” hormone.Phytoestrogens have chemical structures similar to those of estrogens and have been found to bind estrogen receptors. They exert both estrogenic and antiestrogenic effects on metabolism. Their actions at the cellular and molecular level are influenced by many factors, including concentration dependency, receptor status, presence or absence of endogenous estrogens, and the type of target organ or cell.Other non-steroidal drugs could be used for treatment of osteoporosis or even for its prevention, or for treatment of other menopausal symptoms as they have minimal complication and side-effects and no contraindication in many of them.By this way we give some hope for these patients in which estrogen replacement is contraindicated to manage short-term menopausal effects such as vasomotor instability, medium-term menopausal effects which include urogenital atrophy, and long-term menopausal effects as increase risk of coronary artery disease and osteoporosis with minimal or even no complication.ConclusionSafe and effective alternatives to HRT would be a welcome addition for the treatment of menopausal symptoms and to improve cardiovascular health and slow the rate of bone loss. There is now a substantial body of evidence to suggest that isoflavones offer benefits, but more interventional trials are required to reach definitive conclusions. Clinical applications for phytoestrogens are not firmly established, although they seem to represent a promising group of compounds, which may be used in the future for the treatment of the menopausal syndrome. They offer a safe, inexpensive and generally side effect-free alternative to current pharmaceutical measures.Tamoxifen, the first generation SERM is effective on patients with ER-positive metastatic breast cancer and in the adjuvant setting. The promising role for tamoxifen in ductal carcinoma in-situ for breast cancer prevention is evolving, and its use can be considered in certain patient groups, however tamoxifen also has the undesirable estrogenic effects of increasing risk for endometrial cancer and venous thrombo-embolism in women.Raloxifene hydrochloride, a second generation SERM, has been shown to increase women’s bone density without increasing risk for endometrial cancer. It was approved by food and drug administration (FAD) for treatment of post menopausal osteoporosis the drug appears to have a better side effect profile but less effect on bone loss than traditional estrogen replacement therapy.Furthermore its long-term benefit on cardiovascular disease prevention and is apparently protective action is still unknown.Other SERMs are in development, with the goal of reducing toxicity and/ or improving efficacy and future agents have the potential of providing a new paradigm for maintaining the health of women.
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