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Estrogen - Hormone Replacement Therapy (hrt)

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Most animals in the wild do not live past menopause. By contrast, typical women in industrialized countries can expect to live more than one-third of their lives beyond their reproductive years. If living past menopause is a relatively recent phenomenon, then evolution will not have had time to adjust women's bodies to living with reduced postmenopausal hormone levels. From this perspective, perhaps HRT (used in this entry to designate both estrogen alone or in combination with progesterone) would be advantageous. On the other hand, if menopause arose during evolution as an adaptive mechanism, then women's bodies are likely to be physiologically adjusted to altered hormone levels, and upsetting that delicate balance with HRT might lead to unexpected health-damaging consequences. These two opposing theoretical possibilities are further complicated by an overwhelming amount of often conflicting data on the risks and benefits of HRT, leading to a great deal of confusion and uncertainty, even among experts, as to the optimal strategy for women who reach menopause. In this regard, decisions should also take into account the personal treatment goals, because therapy directed at some symptoms, such as hot flashes, can be short-term, whereas treatment of a chronic condition, such as osteoporosis, is usually lifelong. It should also be mentioned that the particular doses and routes of HRT can vary according to indication, with different amounts and regimens, including addition of progesterone to prevent endometrial hyperplasia.

The ideal method to scientifically evaluate all of the effects of HRT would be to conduct a randomized trial on a large group of women who are similar in many characteristics, with half the group being given HRT and the other half, a placebo. Indeed, one such study, the so-called Women's Health Initiative, was in progress in 2001, so ultimately, more definitive and comprehensive data on the risks and benefits of HRT will probably become available. At present, however, women reaching menopause are forced to rely predominantly on data from observational, retrospective epidemiological studies. Such studies are subject to a variety of biases, such as educational and socioeconomic backgrounds that might affect the decision of a woman to begin HRT. Nevertheless, it is interesting to note that although the observational studies differ in the details, such as differences in the ages of the subjects and length of estrogen use, virtually all of the analyses demonstrated reduced risk of death among estrogen users. The most comprehensive of these studies, which followed women for more than twenty-five years and had access to all medical records, including precise estrogen doses, showed that the yearly death rate among estrogen users was about half that of nonusers. Nonetheless, because all of these studies were observational, the findings must still be interpreted with caution.

In addition to the overall risk of death, a correlation has been suggested between several specific health parameters and the use of HRT. The most convincing effects are on the process of osteoporosis. Evidence from observational studies indicates that postmenopausal hormone users have fewer fractures than nonusers and show retardation of bone loss. However, the time at which HRT must be initiated in order to protect against fracture is not known. Controversy also exists regarding the maximum age at which HRT can be initiated to be of clinical utility. Although the beneficial effects of estrogen on bone have been demonstrated in women with established osteoporosis, to achieve maximum benefits, HRT should begin at the time of cessation of menses.

The putative beneficial effect of estrogen on cardiovascular status is controversial. Many observational studies on the relation between the use of estrogen and risk events from coronary heart disease suggested lower rates among post-menopausal estrogen users versus nonusers. However, three large prospective studies in the year 2000 concluded that HRT neither prevents cardiovascular problems in healthy women nor protects women with abnormal cardiac function against future cardiovascular episodes. Thus, despite the encouraging suggestions of earlier studies and the biological plausibility of protection against coronary heart disease associated with postmenopausal HRT, the cardioprotective effect of HRT is questionable. Indeed, the American Heart Association has recently issued an advisory statement discouraging the use of HRT in situations where the sole purpose is improvement of cardiovascular health.

Possible beneficial effects of HRT against arthritis, cognitive decline and Alzheimer's disease, periodontal disease, cataract formation, and colon cancer have been proposed based on epidemiological analyses, but further research is required to confirm these results. In any case, it is clear that at the very least, HRT alleviates such non-life-threatening symptoms of menopause as hot flashes, insomnia, and depression.

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